Thyroid Gland and Related Disease
‥Who would believe that there were mountaineers dewlapped like bulls, whose throats had hanging at ‘em, wallets of flesh‥
—Shakespeare, The Tempest (Act 3).
(This is an authentic description of the inhabitants of the Italian Alps, who had large iodine related goitres in the 16th century)2
HAKARU HASHIMOTO
Dr Hakaru Hashimoto was born on May 5, 1881, in the village of Midau, Nishi-tsuge in the Mie prefecture, Iga-Ueno, Japan. He was born in a family that had been practicing medicine for generations whose inspiration was his grandfather, Gen'I Hashimoto who was practicing Dutch medicine.
Dr Hashimoto was one of the first graduates from the Kyusyu Imperial University in Fukuoka in 1907. Between 1908 and 1912, while working in a surgical department, Dr Hashimoto took an interest in thyroid tissue. It was during this time that he extracted thyroid tissue samples from four patients and discovered new pathological characteristics.
In 1912, at the age of 31, Hashimoto published his findings as an independent new disease in Archiv Fur Klinishe Chirurgie, the German journal of clinical surgery. He published a 30 pages monograph with five figures, titled Notes of lymphomatous disease in the thyroid gland (struma lymphomatosa).
At age 52, Dr Hashimoto died on January 9, 1934 due to enteric fever, before receiving wide recognition for the discovery of goitrous lymphocyctic thyroiditis, or Hashimoto's disease.
However the eponym Hashimotos thyroiditis would not be reintroduced to Japan until the 1950s!
The thyroid is present in front of the neck,
The hormones produced are more than a speck,
A dwindling of levels can make you quite cold,
Cancerous swellings are in the young and the old.
The larger the gland it may stifle your voice,
Gets stuck to the trachea—leaves surgery the choice,
At times on removal,
the calcium may drop,
Take vitamin D and spasms will stop.
CASE 1
A 2-year-old girl presented with swelling under her chin from the age of 6 months. The swelling was insidious in onset, painless and gradually progressive in size. It was not associated with any discharge or skin changes. The child did not have any intraoral complaints. A 2 cm by 1 cm firm, nontender and mobile swelling was detected in the left submental region at level 1A. The skin over the swelling was normal and the swelling was not bidigitally palpable. The thyroid gland was not palpable. Ultrasound of the neck was done and images are displayed below.
WHAT IS THE DIAGNOSIS?
Laboratory test showed a normal thyroid functions. An Ultrasound scan of the neck showed an absent left lobe of the thyroid with multiple enlarged lymph nodes in level 2, 3, and 4 (Figure 1).
Subsequently, a thyroid uptake study was done which showed a normal right thyroid lobe, with agenesis of the left lobe (Figure 2). There was no evidence of functioning thyroid tissue in the submandibular swelling. The patient has been on regular follow-up with regular thyroid function tests.
Figure 2: Radioiodine uptake study showing an absent left lobe of thyroid (shown with arrow).
(SSN: Supra Sternal Notch).
DISCUSSION
Thyroid hemiagenesis is a rare embryological condition resulting from the developmental failure of one thyroid lobe. It is seen predominantly in females in a ratio of 3:1.1 Most patients diagnosed with this disorder have an associated pathology in the remaining thyroid lobe, including benign adenoma, multinodular goiter, hyperthyroidism, chronic thyroiditis, and rarely carcinoma. The most common pathology involved in thyroid hemiagenesis is hyperthyroidism.2 The molecular mechanism behind hemiagenesis of thyroid has not yet been described in detail. But, a mouse model with Shh-/- mutation showed hemiagenesis of the thyroid or of a nonlobulated gland. Hemiagenesis was also seen in mouse model with a double heterogeneous mutation of Pax8+/- and Tif+/+3. The presence of carcinoma in a patient with hemiagenesis is quite rare and only a few cases have been reported in the world literature.
REFERENCES
- Shaha AR, Gujarati R. Thyroid hemiagenesis. J Surg Oncol. 1997;65;137–40.
CASE 2
A young girl, 15 years of age, at present studying in 6th grade was brought by her mother for the evaluation of short stature. On clinical examination, she had a puffy face with a depressed nasal bridge. She also had dry, yellowish discoloration of skin. She was short stature and was mentally challenged (Figure 1). Her height was less than the third centile for her age.
Radiographic evaluation revealed a bone age that was markedly delayed (presence of only two carpal bones), of 3 years (Figure 2).
WHAT IS YOUR DIAGNOSIS?
Thyroid scintigraphy was done (Figure 3) and showed no tracer uptake in the neck in the region of thyroid but abnormal tracer accumulation was seen in the suprahyoid region.
This patient has congenital hypothyroidism (CH) associated with an ectopic lingual thyroid gland. The other hormonal axes in this patient were normal. The patient was started on oral thyroxine and has been kept on regular follow-up ever since.
DISCUSSION
Congenital hypothyroidism is one of the most common treatable causes of intellectual disability (mental retardation). Screening programs have been established in most developed and developing countries to detect and treat this disorder. Primary CH screening has been shown to be effective for the testing of cord blood or heel prick blood collected during the delivery, although the best “window” for testing is 3–5 days of age. Blood is spotted onto special filter paper (known as Guthrie cards), allowed to dry, and eluted into a buffer for thyroid-stimulating hormone (TSH) analysis. Normally serum TSH levels rise after birth (up to 60 μU/mL with the previous TSH assays) and falls less than 10 μU/mL after 48–72 hours. So a TSH level of up to 8–10 μU/mL can be considered as normal up to 12 week of infancy. With the newer assays TSH values are considered significant for the diagnosis of CH when it is around 20–25 μU/mL. The dose of thyroxine is as follows depending upon the age of the patient.
- 0–3 months: 10–15 µg/kg orally once per day
- 3–6 months: 8–10 µg/kg
- 6–12 months: 6–8 µg/kg
- 1–5 years: 5–6 µg/kg
- 6–12 years: 4–5 µg/kg
- 12 years or later: 2–µg/kg
- Patients in which growth and puberty are complete: 1.6 µg/kg orally once per day.
The Indian Academy of Pediatrics and the European Society for Paediatric Endocrinology recommend measurement of serum T4 or fT4 and TSH at 2 weeks after the initiation of L-T4 treatment, and every 2 weeks until serum TSH level is normalized. Subsequently every 1–3 months during the first 12 months of life, followed by every 2–4 months between 1 year and 3 years of age. A follow up once in 6–12 months thereafter until growth is complete is necessary. If a dose of thyroxine is changed with a visit, a review visit should be done in a 2 weeks’ time.1,2
REFERENCES
- Léger J, Olivieri A, Donaldson M, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014;99(2):363–84.
- Desai MP, Upadhye P, Colaco MP, et al. Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique. Indian J Med Res. 1994;100:36–42.
A 16-year-old boy, studying in 10th grade, presented with short stature and the boy was concerned about the same. He was born to nonconsanguineous parents, at term, by cesarean section, with a birth weight of 2.35 kg. He had neonatal jaundice for 5 days which eventually subsided. His mother gave a history of delayed milestones and had noticed that he was lagging behind his peers in height from the age of 10 years. There was no history of headache, visual disturbance or glucocorticoid usage. His academic performance was below average.
On physical examination he was found to be of short stature with a height of 124.5 cm (less than the 3rd centile) with an expected height of 153 + 6.5 cm. Clinically, there was no goiter. He did not have prepubertal testes and his pubic hair was of Tanner stage 4.
WHAT IS THE DIAGNOSIS?
He had a thyroid-stimulating hormone (TSH) level of 750 mIU/L with low free thyroxine and total thyroxine levels. He subsequently underwent a thyroid uptake study and images are displayed above. Tc-99m thyroid scan shows 2 areas of tracer uptake: at base of tongue and in the midline of the neck above the thyroid bed. It is suggestive of congenital hypothyroidism with ectopic thyroid in lingual and suprahyoid regions (Figure 1).
DISCUSSION
Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. In most cases, ectopic thyroid is located along the embryologic descent path of migration as either as a lingual thyroid or a thyroglossal duct cyst (TGDC).1 A lingual thyroid is the most common presentation of ectopic thyroid. In 70% of cases of ectopic thyroid, the normal thyroid gland is absent and this ectopic gland is the only functional thyroid tissue.2 Nearly 1–3% of all ectopic thyroids are located in the lateral neck.
REFERENCES
- Desai MP, Upadhye P, Colaco MP, et al. Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique. Indian J Med Res. 1994;100:36–42.
- Boyages S, Halpern JP, Maberly GF, et al. Effects of protracted hypothyroidism on pituitary function and structure in endemic cretinism. Clin Endocrinol (Oxf). 1989;30(1):1–12.
Case 1
A 29-year-old lady presented with history of menorrhagia and progressive weight gain and tiredness. The patient was looking dull and on examination was found to have dry and scaly skin (Figures 1 and 2). The clinical pictures of the upper limb are shown below.
The patient was evaluated and was found to have high levels of TSH and was started on thyroxine, following which the symptoms of dry skin resolved completely.
Case 2
A 50-year-old patient, Mr T, a known patient of hypothyroidism, presented with history of swelling in front of the lower limbs for the past 5 months. The swelling was slowly progressive, non pitting and not painful. The clinical picture of the patient is shown below (Figure 3).
He had a slow ankle reflex and also his TSH was more 150 mIU/mL. He was started on thyroxine with which the swelling completely subsided.
CASE 4
An 18-year-old girl presented with history of lethargy and easy fatigability along with complaints of difficulty in swallowing since 7 months. On examination, she had dry skin and her reflexes were slow. She was of normal stature. She was found to have a small mass in the midline at the base of her tongue (Figure 1). She did not have a palpable goitre. Examination of the neck revealed no palpable thyroid gland in the normal pre-tracheal position. Her clinical examination was negative for features of any other polyglandular endocrinopathy. An MRI of the neck showed a hyperintense lesion at the base of the tongue (Figure 2). Biochemical evaluation showed a TSH of 52.1 μIU/mL, total T4 of 2.8 μg/dL and free T4 of 0.50 ng/dL. Antithyroid antibodies were negative and other biochemical investigations were unremarkable.
WHAT IS THE DIAGNOSIS?
She was diagnosed with lingual thyroid and primary hypothyroidism. She was started on levothyroxine 100 μg/day and has been on regular follow up since then.
DISCUSSION
It is well known that the thyroid gland descends from the foramen caecum at the base of the tongue. Lingual thyroid is an ectopic thyroid tissue seen in the base of tongue caused due to aberrant embryological development. The differential diagnosis for lingual thyroid should include vascular tumors, telangiectatic granuloma, teratomas, and benign or malignant swelling in the posterior region of the tongue. Lingual thyroid is the most common type of ectopic thyroid, accounting for 90% of cases, whereas sublingual, thyroglossal, laryngotracheal, and lateral cervical types are less frequently encountered‥ Thyroid tissue can also be found, extremely rarely, in remote structures that were associated with the thyroid anlage during development, including the esophagus, mediastinum, heart, aorta, adrenal, pancreas, gallbladder, and skin.1,2
Figure 2: MRI of the neck showing a hyperintense lesion at the base of the tongue (shown with an arrow position).
REFERENCES
- Senthilraja M, Rajan R, Kapoor N, Paul TV, Cherian KE. An uncommon cause of dysphagia. J Family Med Prim Care. 2019;8(3):1282–83
- Massine RE, Durning SJ, Koroscil TM. Lingual thyroid carcinoma: A case report and review of the literature. Thyroid. 2001;11:1191–6.
A 21-year-old gentleman was referred to our thyroid clinic with a history of progressive proximal muscle weakness, muscle pain, and fatigue after minimal exercise. He complained of swelling of the calf muscles over the past few years and constipation.
On general examination, he had puffiness of the face, slowness of speech, and hypertrophy of the calf muscles bilaterally (Figure 1). Gower's sign was negative. He had a positive hung up ankle reflex. He had no palpable swelling in the neck and his oral cavity was normal. He did not have any other stigmata of polyglandular autoimmune syndrome type II (PGA-II) (Figures 1A and B).
WHAT IS THE DIAGNOSIS?
Laboratory tests including muscle biopsy showed features of rhabdomyolysis (Figure 2), creatine phosphokinase (CPK) 1500 U/L (25–90 U/L).
This gentleman was diagnosed as having primary hypothyroidism with Hoffmann's syndrome. Hoffmann's syndrome should be considered with other differential diagnoses (Becker's, Duchenne muscular dystrophy, amyloidosis, and focal myositis) when a patient with calf muscle hypertrophy is evaluated and a myopathic disorder is suspected, since it is treatable and mostly reversible.
The patient was put on replacement therapy with levothyroxine, started from 25 µg/day and increased to 100 µg/d. After this, the patient noticed improvement of his symptoms within 4 weeks.
Figures 1A and B: (A) Clinical features suggestive of hypothyroidism and (B) Pseudohypertrophy of calf muscles.
DISCUSSION
Myopathic changes are seen in 30–80% of patients with hypothyroidism. There are four variants of hypothyroid myopathy which are Hoffmann's syndrome, Kocher–Debré–Semelaigne syndrome, an atrophic form and a myasthenic syndrome. Hoffmann's syndrome was first described by Johann Hoffmann in 1897.
Hoffman's syndrome is an uncommon form of hypothyroid myopathy seen in adults with long standing untreated hypothyroidism. It is characterized by proximal limb muscle weakness and muscle pseudohypertrophy (Figure 1B). Patients present with muscle cramps, muscle stiffness, weakness, hyporeflexia, and delayed deep tendon reflexes. Muscle pseudohypertrophy is a very rare presentation and its etiology remains controversial.1 The gastrocnemius muscle is almost always involved. Postulated mechanisms for muscle pseudohypertrophy include an increased deposition of glycosaminoglycans, with increased muscle fiber size and number. Elevation of the serum CPK level is seen in 70–90% of patients with hypothyroidism indicative of muscle involvement but does not correlate with the severity of weakness. Electrophysiological studies may show myogenic, neurogenic or mixed patterns in hypothyroid myopathy. Biopsy of the affected muscles may show muscle fiber necrosis, atrophy, hypertrophy with increased number of nuclei and increased connective tissue (Figure 2).
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Muscle hypertrophy with weakness and slowness of movement in cretin children is called as Kocher–Debré–Semelaigne syndrome. The absence of painful spasms and pseudomyotonia differentiates this syndrome from Hoffmann syndrome.2
The blood sample of the patient mentioned above was centrifuged. The serum turned milky white as shown (Figure 3).
WHY DID THIS HAPPEN?
The milky white serum was seen due to elevated serum triglyceride levels (1800 mg/dL). In primary hypothyroidism there is a reduction in activity of lipoprotein lipase which then in turn causes hypertriglyceridemia. The mechanism of hypercholesterolemia is explained by a reduction in LDL-cholesterol hepatic receptor activity due to hypothyroidism.
REFERENCES
- Udayakumar N, Rameshkumar AC, Sirinivasan AV. Hoffmann syndrome: presentation in hypothyroidism. J Postgrad Med. 2005:51(4):332–3.
- Vasconcellos LF, Peixoto MC, de Oliveira TN, et al. Hoffmann's syndrome: pseudohypertrophic myopathy as initial manifestation of hypothyroidism. Arq Neuropsiquiatr. 2003:61(3B):851–4.
A 43-year-old gentleman presented with headache of 3 years duration, failure to gain height from the age of 8 years, underdeveloped secondary sexual characteristics and mental retardation.
On examination, he was disproportionately short statured with a height of 132 cm (<3rd centile) with an upper segment and lower segment ratio of 1.2:1 suggestive of shortened limbs. He looked dysmorphic, with prominent temporal bones and hypertelorism. He did not have a palpable thyroid gland (Figure 1A).
On biochemical evaluation, his thyroid-stimulating hormone (TSH) level was 775 µIU/mL with a T4 of 1.7 ng/dL. Other hormonal studies were normal. Radiology of the left hand revealed a bone age of 12 years (Figure 1B).
Computed tomography (CT) scan of the head was done, which revealed a sellar mass of the size 7.1 × 5.9 × 4.2 cm with supra sellar extension into the third ventricle causing obstructive hydrocephalus (Figures 2A to D, shown with an arrow).
WHAT IS THE DIAGNOSIS?
The presence of short stature, with intellectual disability, led to the clinical suspicion of congenital hypothyroidism (CH). His 131I uptake study was 0.3% which was grossly reduced, thereby suggestive of thyroid hypoplasia and confirmed the diagnosis.
The possibilities considered were nonfunctioning pituitary macroadenoma or a craniopharyngioma or a pituitary pseudotumor which could have been caused by long-standing untreated primary hypothyroidism.
He was started on thyroxine (100 µg/day). Following thyroid hormone replacement, he gained a height of 4.5 cm over a subsequent period of 3 years. An magnetic resonance imaging (MRI) done after 3 years showed significant reduction in the size of the pituitary mass with resolution of hydrocephalus favoring thyrotroph hyperplasia causing a pituitary pseudotumor.
Pituitary hyperplasia secondary to unrecognized and untreated primary hypothyroidism has been reported in both adults and children. The radiological diminution of the pituitary mass and the mass effects such as visual field improvement after thyroid replacement therapy confirms the possibility of pituitary hyperplasia, rather than a pituitary adenoma. There was a significant reduction in the sellar mass on treatment with thyroxine with normalization of TSH favoring a pituitary pseudotumor. The incomplete resolution may suggest the coexistence of a nonfunctioning adenoma or occurrence of a thyrotroph adenoma. Such thyrotroph adenomas are presumed to occur as the result of protracted pituitary stimulation secondary to long-standing thyroid deficiency.
DISCUSSION
Congenital hypothyroidism (CH) is a common preventable cause of intellectual disability. The estimated incidence in India is 1:2500–2800 live births with a varied age of onset and clinical features.1 Much of the etiology is due to thyroid ectopia, aplasia or hypoplasia. Disturbances of growth, puberty, and sexual function in those with CH as seen in our subject can be explained by the secondary effects of thyroid hormone deficiency on pituitary function.2 Severe protracted thyroid hormone deficiency may therefore result in thyrotropin adenomas of the pituitary gland.
Figures 1A and B: (A) Clinical features of short stature and dysmorphic features and (B) X-ray of hand showing bone age of around 10–12 years.
REFERENCES
- Thomas N. Thyroid disorders in the transitional age group—an Indian perspective. In: Mathew MC (Ed). Promoting Childhood Wellbeing-Vellore Experiences. 2002:38–46.
- Desai MP, Upadhye P, Colaco MP, et al. Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique. Indian J Med Res. 1994;100:36–42.
A 36-year-old gentleman presented with holocranial headache for over 2 months and weight gain of 10 kg in 5 months. He had a dull look with slow relaxation of the ankle reflexes. He did not have vomiting or postural hypotension (Figure 1).
The thyroid-stimulating hormone (TSH) levels were 320 mIU/mL (normal: 0.3–4.5 mIU/mL). The creatine phosphokinase (CPK) levels were markedly elevated. A CT scan brain showed a sellar mass with suprasellar extension (Figure 2).
WHAT IS THE DIAGNOSIS?
With the above clinical and investigative findings he was diagnosed to have primary hypothyroidism with pituitary pseudotumor. The patient was started with oral levothyroxine which relieved his headache.
DISCUSSION
Pituitary pseudotumor (pituitary thyrotroph hyperplasia) caused by unrecognized and untreated hypothyroidism has been described mostly in adults. Treatment with levothyroxine results in normalization of the size of the pituitary gland.1 The myolysis in hypothyroid patients are caused by the change of fast twitching type 2 muscle fiber to slow twitching type 1 muscle fiber, deposition of glycosaminoglycan, poor contractility of the actin-myosin filaments, low myosin ATPase activity, and low ATP turnover. This is associated with elevated CPK levels which usually normalize after levothyroxine treatment.2
REFERENCES
- Larson NS, Pinsker JE. Primary hypothyroidism with growth failure and pituitary pseudotumor in a 13-year-old female: a case report. J Med Case Rep. 2013;7:149.
- Al-Shraim M, Syro LV, Kovacs K, et al. Inflammatory pseudotumor of the pituitary: case report. Surg Neurol. 2004;62(3):264–7.
A 32-year-old lady presented with intolerance to heat, significant weight loss for over a month. Over the past 1 week she had also developed pain over the neck, fever, and tremors.
On examination, she had a palpable, painful diffuse thyroid swelling. There were no significant findings.
Laboratory investigations showed an erythrocyte sedimentation rate (ESR) of 110 mm and a thyroid-stimulating hormone (TSH) of 0.009 mIU/mL. Thyroid uptake study was done and showed very poor uptake of 99mTc in the thyroid bed (1.7% after 24 h) (Figure 1).
WHAT IS THE DIAGNOSIS?
A biopsy of the thyroid gland was done which showed neutrophils and epithelioid giant cells (Figure 2).
The clinical and investigative evidence led to the diagnosis of de Quervain's thyroiditis. The patient was given analgesics which relieved her pain.
DISCUSSION
Inflammatory disorders of the thyroid gland are divided into three groups according to their duration: acute, subacute and chronic. De Quervain's thyroiditis (also termed giant cell or granulomatous thyroiditis) is a subacute inflammation of the thyroid, which accounts for 5% of the thyroid inflammatory disorders. The etiology is unknown, but it generally appears two weeks after an upper viral respiratory infection.
Figure 1: Thyroid uptake study (131I) showing no uptake in the thyroid bed.
(SSN: suprasternal notch).
The natural history of granulomatous thyroiditis involves four phases: The destructive inflammation results in transient hyperthyroidism followed by euthyroidism. After transient hypothyroidism, the disease becomes inactive and thyroid function is normalized.1 Ultrasonography usually shows unilateral or bilateral hypoechoic, poorly defined, nonovoid, hypovascular, focal lesions and may mimic malignant thyroid nodule. Few may be diffuse and heterogeneously hypoechoic in appearance.2 The disease often remains unrecognized, or the first phase of the disease is diagnosed and treated as hyperthyroidism. The diagnosis can be confirmed by the presence of thyroid autoantibodies, cold gland (poor uptake) on scintigraphy and fine-needle aspiration cytology (FNAC). There is no definitive treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids can be given to relieve the pain.
REFERENCES
- Thomas N. Thyroiditis in India—profile and management. In: Das S (Ed). The Association of Physicians of India—Medicine Update, Volume 13. 2003. pp. 469–74.
- Frates MC, Marqusee E, Benson CB, et al. Subacute granulomatous (de Quervain) thyroiditis: grayscale and color Doppler sonographic characteristics. J Ultrasound Med. 2013;32(3):505–11.
A 38-year-old lady presented with the history of a painless swelling in front of the neck for the past 2 years. She had history of weight gain and cold intolerance for which she approached her family physician and was started on oral replacement of thyroxine, after preliminary thyroid function tests. She also had complaints of pain in the proximal interphalangeal joints of both her hand over the past 5 years for which she had taken analgesics off and on, for pain relief.
Clinical examination of the neck showed a diffuse thyroid swelling, rubbery in consistency, with an approximate weight of 40 g with pyramidal lobe enlargement (Figure 1). She also had deformity of the fingers (Figure 2). The rest of systemic examination was unremarkable.
WHAT IS THE DIAGNOSIS?
The biochemical evaluation showed a high thyroid-stimulating hormone (TSH) titer of 56 mIU/L and the thyroid peroxidase antibody (TPOAb) titers (normal: less than 35 IU/mL) were 1000 IU/mL. She also was rheumatoid factor (RF) positive (100 µ/mL). A biopsy of the thyroid swelling showed heterogeneous clusters of lymphocytes (Figure 3). With the above mentioned clinical features and investigations this patient was diagnosed to have Hashimoto's thyroiditis with rheumatoid arthritis (RA). She was started on methotrexate, hydroxychloroquine, and on replacement doses of thyroxine. She has been on follow-up ever since.
DISCUSSION
Hashimoto's thyroiditis is considered as an autoimmune disease whose detection was originally based on the tissue biopsy but which now can be reliably detected by the presence of high titer anti-microsomal antibodies. Its relationship to rheumatic diseases seems more frequent than might be expected, but this has not been definitely proved. Hashimoto's thyroiditis frequently leads to hypothyroidism, which in turn progresses to myxedema. Rheumatic syndromes associated with hypothyroidism include fibrositis, myositis, myalgias, carpal tunnel syndrome, Sjögren's syndrome, joint stiffness, and joint effusion.1,2 Thyroid dysfunction is seen at least three times more often in women with RA than in women with similar demographic features with noninflammatory rheumatic diseases such as osteoarthritis and fibromyalgia. Most of these manifestations are said to resolve with thyroxine replacement.
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Figure 3: Dense clusters of lymphocytes (shown with an arrow) with loss of normal thyroid architecture on biopsy.
REFERENCES
- Buchanan WW, Crooks J, Alexander WD, et al. Association of Hashimoto's thyroiditis and rheumatoid arthritis. Lancet. 1961;i:245–8.
- Buchanan WW. The relationship of Hashimoto's thyroiditis to rheumatoid arthritis. Geriatrics. 1965;20:941–8.
A 12-year-old boy presented with hair loss, a small thyroid swelling, lethargy and drooping of eyelids as shown in Figure 1. His thyroid-stimulating hormone (TSH) was 12.0 mIU/L.
WHAT IS THE DIAGNOSIS?
This patient was diagnosed to have autoimmune thyroid disease (AITD): Hashimoto's thyroiditis with myasthenia gravis (MG) and alopecia, suggestive of autoimmune polyglandular endocrinopathy syndrome type 2.
DISCUSSION
Graves’ disease and MG are both autoimmune diseases and the coexistence of these two diseases is rare but well recognized. Epidemiological studies have shown that AITD occurs in approximately 5–10% of patients with MG, whereas MG is reported in a fairly low frequency (0.2%) of patients with AITD.1 The association is thought to be uncommon, and it is generally believed that hyperthyroidism is far more commonly associated with MG than is hypothyroidism. However, no explanation has been offered to account for this difference.
The clinical presentation of MG associated with AITD is frequently restricted to the eye muscles. The reason for the association of AITD with ocular MG is unknown, but several hypotheses can be considered. First, ocular MG and generalized MG might actually represent separate diseases with different spectra of associated conditions. Second, an immunological cross-reactivity against epitopes or autoantigens shared by the thyroid and the eye muscles might be the basis of this association. In three-quarters of patients with both conditions, thyrotoxic symptoms occur before or concurrently with those of myasthenia.
PAS I, also known as APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) or MEDAC (multiple endocrine deficiency autoimmune candidiasis syndrome), usually appears in childhood in the age of 3–5 years or in early adolescence and, therefore, is also called juvenile autoimmune polyendocrinopathy. It is defined by a spectrum of persistent fungal infection (chronic mucocutaneous candidiasis), the presence of acquired hypoparathyroidism, and adrenal failure (Addison's disease).
REFERENCES
- Drachman DB. Myasthenia gravis and the thyroid gland. N Engl J Med. 1962;15:330–3.
- Christensen PB, Jensen TS, Tsiropoulos I, et al. Associated autoimmune diseases in myasthenia gravis. A population based study. Acta Neurol Scand. 1995;91:192–5.
A 30-year-old lady presented to the outpatient department with a swelling in front of the neck, hoarseness of voice, fatigue and progressively worsening muscle weakness. She had a significant weight loss of 5 kg over 6 months. She also complained of difficulty in chewing wheat pancakes, but no such symptoms with soft solids. She also gave a history of two episodes of sudden onset breathing difficulty in the past requiring invasive ventilation and subsequent tracheotomies. At presentation sequential photographs were taken and show the following clinical findings (Figure 1).
WHAT IS THE DIAGNOSIS?
Her blood investigations showed thyroid-stimulating hormone (TSH) of 0.007, FTC of 2.2, and a T4 of 21.2. Antiacetylcholine receptor antibody was 0.56 (normal < 2.1), antithyroglobulin antibodies: 22 (<100 IU/mL), and antimicrosomal (thyroid peroxidise) 400 (<50 IU/mL). A CT scan of the neck was done and had shown an enlarged thyroid gland with a bulky thymus inconsistent for her age (Figure 2).
WHAT IS THE DIAGNOSIS NOW?
This patient has a classical history suggestive of autoimmune hyperthyroidism with myasthenia gravis (MG). She was started on beta-blockers and was referred to the thoracic surgeons for a thymectomy.
DISCUSSION
It is well known that autoimmune thyroid disorders are known to be present only in 5–7.5% of the MG patients. However Myasthenia is seen in only 0.2% of the patients with thyroid disease.1 The higher frequency of ocular myasthenia in autoimmune thyroid disease could well be attributed to the genetic linkage. Certain human leukocyte antigen (HLA) specificity (B8, DR3, and BW46) between MG and thyroid disease has been reported to be associated with thyrotoxicosis.2
Figure 2: Computed tomography (CT) thorax showing a homogeneous soft tissue density mass in the anterior mediastinum in keeping with enlarged thymus (arrow)
REFERENCES
- Chhabra S, Pruthvi BC. Ocular myasthenia gravis in a setting of thyrotoxicosis. Indian J Endocrinol Metab. 2013;17(2):341–3.
- Weetman AP, McGregor AM. Autoimmune thyroid disease: further developments in our understanding. Endocr Rev. 1994;15(6):788–830.
A 19-year-old girl had early satiety toward the evening, tremors and weight loss and underwent radioactive 131I ablation 2 years ago. She presented now with weight gain, yellowish tinged skin and hoarseness of voice (Figure 1). On examination, she was found to have bilateral ptosis with easy fatigability after talking for 2 minutes.
WHAT IS THE DIAGNOSIS?
Her thyroid-stimulating hormone (TSH) before ablative treatment was <0.01 mIU/mL and FTC was 10 ng/dL. Preablation iodine uptake studies (131I) showed enlarged thyroid gland (both lobes) with uniform tracer uptake (Figure 2).
She initially had Graves’ disease associated with myasthenia gravis (MG). Following ablation with 131I, she went into hypothyroidism but ptosis persisted because of the MG.
DISCUSSION
PAS II is more common and occurs in adulthood, mainly in the third or fourth decade. It is characterized by primary adrenal failure with AITD (Schmidt's syndrome) and/or type 1 diabetes mellitus (Carpenter's syndrome). Adrenal failure may precede other endocrinopathies. Vitiligo and gonadal failure are occasionally associated with PAS II than with type 1. The other disorders like immunogastritis, pernicious anemia, and alopecia areata may occur in type 2. Immunogastritis, eventually leading to pernicious anemia, is an organ-specific autoimmune disease. PAS II is believed to be polygenic, characterized by an autosomal dominant inheritance. Some authors also mention there is APS type 3.APS type 3 (APS-3), is subdivided into three sub-types, based on their association with one thyroid autoimmune disease such as Hashimoto's thyroiditis, Graves’ disease, with one or more of the following diseases: type 1 diabetes mellitus (T1DM), chronic atrophic gastritis or pernicious anemia, and vitiligo, alopecia or MG.1,2
REFERENCE
- Lahner E, Centanni M, Agnello G, et al. Occurrence and risk factors for autoimmune thyroid disease in patients with atrophic body gastritis. Am J Med 2008. 121:136–141.
- Kahaly GJ. Polyglandular immune syndromes. Eur J Endocrinol 2009;161:11–20.
A 65-year-old lady who is a known patient of Graves’ disease presented to the thyroid specialty clinic with a history of redness of eyes.
WHAT IS THE CLINICAL ACTIVITY SCORE? WHAT POSSIBLE TREATMENT OPTIONS?
This patient had an active eye disease due to Graves’ ophthalmopathy (GO) with a clinical activity score (CAS) of 4/7 (Figures 1A and B).
This patient received intravenous glucocorticoid pulse therapy, once a week and intravenous methylprednisolone (0.5 g weekly for 6 weeks, then 0.25 g, weekly for 6 weeks each with a total cumulative dose of 4.5 g). A CT scan was performed (Figure 2).
DISCUSSION
For initial CAS, only items 1–7 are scored.
- Spontaneous orbital pain
- Gaze evoked orbital pain
- Eyelid swelling that is considered to be due to active (inflammatory phase) GO
- Eyelid erythema
- Conjunctival redness that is considered to be due to active (inflammatory phase) GO
- Chemosis
- Inflammation of caruncle or plicaPatients assessed during follow-up (after 3 months) can be scored out of 10 by including items 8–10
- Increase of >2 mm in proptosis
- Decrease in uniocular ocular excursion in any one direction of >5°
- Decrease of acuity equivalent to 1 Snellen line using a pin hole.1
The other treatment modalities for patients who are refractory to steroid therapy include intravenous rituximab or external beam radiation to the affected eyes. The usual dose for treatment of the retro-orbital area is 2000 rads (20 Gy), administered in 10 doses of 200 rads (2 Gy) over 2 weeks. Surgical decompression of the affected eye can be attempted in certain patients with sight threatening eye disease. Transantral decompression is a surgical procedure where the floor and medial wall of the orbit is removed to allow decompression of the orbital cavity.2
Figure 2: CT scan showing bilateral proptosis with thickening of the extraocular muscles (shown with an arrow) and retro-orbital fat stranding.
REFERENCES
- Subekti I, Boedisantoso A, Moeloek ND, et al. Association of TSH receptor antibody, thyroid stimulating antibody, and thyroid blocking antibody with clinical activity score and degree of severity of Graves ophthalmopathy. Acta Med Indones. 2012;44(2):114–21.
- Tortora F, Cirillo M, Ferrara M, et al. Disease activity in Graves’ ophthalmopathy: diagnosis with orbital MR imaging and correlation with clinical score. Neuroradiol J. 2013;26(5):555–64.
Figures 1A and B: (A) MRI T1 fat suppressed coronal image showing retro-orbital fat stranding and severe thickening of extraocular muscles. Note the relative sparing of the lateral rectus muscle on both the sides (shown with white arrow). (B) T2 axial MRI showing bilateral proptosis (both globes are entirely anterior to the intertemporal line) with coke bottle shaped extraocular muscles (shown with an arrow) (note that the central portion of the muscle is most severely enlarged and tendinous insertions are spared).
OTHER PATIENTS WITH EYE DISEASE
Figure 3: Mrs A, a new patient was diagnosed to have Graves’ disease presented with hyperthyroid/toxic symptoms of overactiveness, weight loss, and diarrhea. She also complained of a bilateral diffuse neck swelling. She was found to have a firm thyroid swelling and also proptosis which was graded with the clinical activity scoring (CAS) system, and she was found to have a score of 3/7. A case of Graves’ ophthalmopathy.
DIFFERENTIAL DIAGNOSIS FOR GRAVES’ OPHTHALMOPATHY
Figure 1: This patient a 26-year-old presented to the thyroid clinic with bilateral proptosis and was treated elsewhere as dysthyroid (hypothyroid) ophthalmopathy. On further evaluation he was found to have enlarged neck lymph nodes, swollen lacrimal and parotid glands for which MR imaging was done (Figure 2).
CASE 14
A 34-year-old gentleman presented with history of prominence of left eye which he noticed since the 1 year (Figure 1). He also reported weight loss of around 4 kg over a span of the last 4 months along with constant anxiety throughout the day.
WHAT IS THE LIKELY DIAGNOSIS?
Differential diagnoses for unilateral proptosis are infiltrative disorders like lymphoma, sarcoidosis, IgG4-related disease, primary orbital tumors, lachrymal gland tumors or dysthyroid ophthalmopathy. He was investigated and found to have suppressed TSH (<0.01 mIU/mL), elevated T4 levels −30 μg/dL and free T4–4.5 ng/dL. His TSH receptor antibody level was 10 IU/L. He was diagnosed to have Graves’ disease and was started on carbimazole. A plan was made for radio-iodine therapy with 131I at a later date, after his thyrotoxic symptoms settle. In addition, his clinical activity score (CAS) was 0/7 during the first visit and he was kept on follow-up for the same. He was counseled about the option of cosmetic surgery for the left exophthalmos, if required, as it was clinically inactive.
DISCUSSION
Clinical differential diagnoses for unilateral proptosis is innumerable.1 However, one should keep in mind that hyperthyroidism can present as unilateral propotosis. It should be ruled out before investigating for the other diagnosis.2 Although Graves’ ophthalmopathy (GO) is usually associated with hyperthyroidism, up to 20% may be euthyroid. Pure unilateral ophthalmopathy is rare, which is seen in up to 10% of patients with Graves’. TRAbs, a pathological marker for Graves’ disease, is present in almost every patient with the disease, which makes it a good marker in patients with uncertain oththalmopathy. Patients with euthyroid Graves’ ophthalmopathy (GO) typically have a mild, asymmetric disease with a lesser degree of soft tissue inflammation. These patients have to be placed on long-term follow-up as they can have worsening of thyroid function.
IgG4-related disease of the orbit typically causes proptosis by involvement of lacrimal gland, extraocular muscles or other pseudo-tumor. This diagnosis is typically made from biopsy findings, and an elevated IgG4 levels supports the diagnosis. The treatment for IgG4 disease is glucocorticoids.
REFERENCES
- Topilow NJ, Tran AQ, Koo EB, et al. Etiologies of Proptosis: A review. Intern Med Rev. 2020 Mar;6(3):10.18103/imr.v6i3.852.
- Marinò M, Ionni I, Lanzolla G, et al. Orbital diseases mimicking graves’ orbitopathy: a long-standing challenge in differential diagnosis. J Endocrinol Invest. 2020 Apr;43(4):401–11.
A 58-year-old man presented with complaints of neck swelling, protrusion of the eyes and “bumpy” swelling in the legs. He was evaluated and was found to have a thyroid swelling and deranged thyroid function parameters [thyroid-stimulating hormone (TSH) < 0.001 mIU/mL and T4 > 30 (µg/dL) and free T4 > 10 (ng/dL)] (Figures 1 to 3).
DISCUSSION
Histopathologically, pretibial myxedema shows deposition of mucin (glycosaminoglycans) throughout the dermis and subcutis. Deposited mucin promotes dermal edema by promoting the retention of fluid in the skin. This results in compression/occlusion of small peripheral lymphatics and lymphedema. There are four typical types seen:
- Diffuse, nonpitting edema (swelling)—the most common form.
- Plaque form—raised plaques on a background of nonpitting edema.
- Nodular form—sharply circumscribed tubular or nodular lesions.
- Elephantiasic form—nodular lesions with pronounced lymphedema (swelling due to accumulation of lymphatic tissue fluid). Lesions may coalesce to give the entire extremity an enlarged, warty appearance. This form is rare.
This affects 0.5–4.3% of patients with Grave's disease; it is seen in up to 13% in those with severe eye disease.
Dermopathy almost always is associated with ophthalmopathy and with acropachy in severe cases. A common antigen with thyroid, in tissues of the skin and the eyes, most likely TSH receptor, is involved in pathogenesis of extrathyroidal manifestations. Presence of dermopathy and acropachy are the predictors of severity of an autoimmune process. Local corticosteroid application is the standard therapy for dermopathy.1,2
Figures 1A and B: (A) Graves’ ophthalmopathy with a clinical activity score (CAS) of 4/7 with a diffuse bilateral firm thyroid swelling; (B) Pretibial myxedema (shown with an arrow) in hyperthyroidism (nodular type).
REFERENCES
- Tortora F, Cirillo M, Ferrara M, et al. Disease activity in Graves’ ophthalmopathy: diagnosis with orbital MR imaging and correlation with clinical score. Neuroradiol J. 2013;26(5):555–64.
- Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol. 2005;6(5):295–309.
A 34-year-old lady presented with a swelling in front of the neck for 2 years duration (Figure 1). There were no symptoms of thyroid dysfunction or compressive symptoms (dysphagia, dyspnea or hoarseness of voice). There was no significant past history or family history.
On examination, the swelling moved up with deglutition but not with protrusion of the tongue. The swelling was smooth-surfaced and firm in consistency. It was not fixed to the surrounding structures. There were no other clinical findings.
An ultrasonography of the thyroid swelling was done (Figures 2A and B) and the thyroid function tests were normal.
WHAT IS THE PROBABLE DIAGNOSIS?
Ultrasound showed a well-defined, solid, isoechoic nodule with positive halo sign (thin hypoechoic rim around the lesion) in the right lobe of thyroid. These are features of probably benign thyroid nodule. There were other small colloid nodules in both lobes. A radionuclide scan was done and revealed a cold nodule in the right lobe (Figure 3). Thus, dominant nodule in a multinodular goiter is the most likely diagnosis.
DISCUSSION
Preliminary studies suggest the potential use of an imaging staging system similar to that used for breast imaging. The thyroid imaging reporting and data system (TIRADS) system rates ultrasound findings on a score of 1–5 based upon ultrasonographic characteristics (Figure 4).1
30
Similar to the breast imaging-reporting and data system (BIRADS) category, sonographic TIRADS classification is as follows:
- TIRADS 1—normal thyroid gland
- TIRADS 2—benign lesions
- TIRADS 3—probably benign lesions
- TIRADS 4—suspicious lesions (subclassified as 4a, 4b, and later 4c with increasing risk of malignancy)
- TIRADS 5—probably malignant lesions (>80% risk of malignancy)
For benign nodules, surgery is indicated if any of the following are present:2
- Reaccumulation in the cystic nodule despite 3–4 repeated Fine-needle aspiration cytology (FNACs).
- Size more than 4 cm in some cases
- Compressive symptoms (dyspnea, dysphagia)
- Signs of malignancy (vocal cord dysfunction, lymphadenopathy.
Figure 4: Summary of American College of Radiology (ACR)—TIRADS.3
(FNA: fine-needle aspiration; FNAC: fine-needle aspiration cytology; TIRAD: thyroid imaging reporting and data system)
REFERENCES
- Russ G, Bigorgne C, Royer B, et al. Bienvenu-Perrard M. [The Thyroid Imaging Reporting and Data System (TIRADS) for ultrasound of the thyroid]. J Radiol. 2011;92(7-8):701–13.
- Middleton WD, Teefey SA, Reading CC, et al. Multi-institutional analysis of thyroid nodule risk stratification using the American College of Radiology Thyroid Imaging Reporting and Data System. AJR Am J Roentgenol. 2017;208(6):1331–41.
A 72-year-old lady gave a history of swelling in front of the neck for 50 years. She had been operated in 1972, with a probable subtotal thyroidectomy, for the thyroid swelling. Ten years after the surgery, she noticed a similar neck swelling, which had gradually progressed to the present size (Figures 1A and B). She had symptoms of dyspnea and hoarseness of voice. She also complained of dysphagia. There were no other symptoms suggestive of hyperthyroidism or hypothyroidism.
On examination, a large thyroid gland was palpable which had an irregular surface. It was firm in consistency and had a size of 16 × 15 cm. The lower border was not palpable. Pemberton's sign was positive (Figure 1B). Upper- and midcervical palpable lymph nodes were also palpable.
Plain radiograph a lateral view of the neck was done to assess the degree of tracheal compression (Figure 2).
An ultrasound of the neck swelling showed multiple solid, isoechoic nodules with a positive halo sign, coarse calcifications and peripheral vascularity in both lobes of the thyroid gland (TIRADS 3) (Figures 3 to 5).
Figure 2: Lateral radiograph of the neck showing a large goiter with macrocalcifications (shown with an arrow). There was no significant tracheal compression.
Figures 3A and B: USG thyroid showing multiple well defined, solid, isoechoic nodules in both lobes of the thyroid (shown with an arrow).
WHAT IS THE DIAGNOSIS?
Fine-needle aspiration (FNA) smears from the right thyroid nodule were suggestive of benign follicular 33nodule. In view of the large thyroid mass and compressive symptoms, she underwent total thyroidectomy. The surgical specimen on examination showed features of nodular hyperplasia. So the diagnosis of recurrent symptomatic benign nodular hyperplasia of thyroid was made. She was advised total thyroidectomy in view of the size and compressive symptoms.
Figures 4A and B: Color Doppler examination revealing peripheral vascularity in the thyroid nodules.
DISCUSSION
- Nodularity of thyroid tissue is extremely common. In a large population study (Framingham, MA), as an example, clinically apparent thyroid nodules were present in 6.4% of women and 1.5% of men.
- The prevalence of cancer is higher in several groups:
- Children
- Adults <30 years or over 60 years old.
- Patients with a history of head and neck irradiation.
- Patients with a family history of thyroid cancer. The National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference (“Bethesda Conference”) suggests the following classification scheme:
- Nondiagnostic
- Benign: This includes macrofollicular or adenomatoid/ hyperplastic nodules, colloid adenomas, nodular goiter, and Hashimoto's thyroiditis.
- Follicular lesion or atypia of undetermined significanc (FLUS or AUS): This includes lesions with atypical cells, or mixed macrofollicular and microfollicular nodules.
- Follicular neoplasm: This includes microfollicular nodules, including Hürthle cell lesions.
- Suspicious for malignancy
- Malignant
The Bethesda System for Reporting Thyroid Cytopathology with implied risk of malignancy is shown in shown below
- Non Diagnostic- 1- 4 %
- Benign - 0-3%
- AUS-5-15%
- Follicular Neoplasm- 15-30%
- Suspicious of Malignancy-60-75%
For benign nodules, surgery is indicated if any of the following are present:2
- Reaccumulation in the cystic nodule despite 3–4 repeated FNACs
- Size more than 4 cm in some cases
- Compressive symptoms (dyspnea, dysphagia)
- Signs of malignancy (vocal cord dysfunction, lymphadenopathy.
REFERENCES
- Wu HH, Rose C, Elsheikh TM. The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy. Diagn Cytopathol. 2012 May;40(5):399–403.
- Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017 Nov;27(11):1341–46.
A 46-year-old lady presented to us with complaints of multiple swellings in front of the neck for a period of 4 years. There were no specific symptoms of thyroid disturbances but she complained of difficulty in swallowing. There were complaints of change in voice.
On examination, she was found to have enlargement of lymph nodes in many levels of the neck including a thyroid swelling (Figure 1).
An ultrasound of the neck was done and it revealed multiple lymph node swellings with loss of fatty hilum (Figure 2).
WHAT IS THE DIAGNOSIS?
This patient most likely had a malignant thyroid swelling with nodular metastasis. A fine-needle aspiration cytology (FNAC) should be done to confirm the diagnosis.
A 43-year-old lady presented to the endocrinology clinic with complaints of swelling in the right side of the neck, which was slowly increasing in size over the past 3 years.
The ultrasound of the swelling showed features as given in Figure 1 After fine-needle aspiration (FNA) the swelling subsided markedly.
WHAT IS THE DIAGNOSIS? WHAT DIFFERENTIAL DIAGNOSES WILL YOU CONSIDER IN THIS PATIENT?
This patient has a cystic nodule in the right lobe of thyroid which explains the regression of the thyroid nodule after the FNAC. The differential diagnosis in this patient is a cystic parathyroid adenoma. Thyroid scintigraphy showed a hypofunctioning “cold” nodule, as these cystic nodules do not concentrate radioiodine or technetium. Aspiration cytology in this patient showed only colloid (Figures 2 and 3).
DISCUSSION
The majority of cystic thyroid nodules are benign degenerating thyroid adenomas. Autonomously functioning thyroid adenomas are more likely to undergo cystic degeneration than nonfunctioning adenomas. Purely cystic lesions rarely contain cancer.1 Size (>4 cm) of the cystic nodule may also be used as a criterion for surgery, although we do not use size as an absolute criterion for surgery.2
Figure 2: Ultrasound of thyroid showing an anechoic (cystic) nodule with thin internal septae (shown with an arrow).
Figure 3: Scanned film of the thyroid uptake scan showing a hypofunctioning right side nodule (shown with an arrow).
REFERENCES
- Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med. 1997;126:226–31.
- Massoll N, Nizam MS, Mazzagerri EL. Cystic thyroid nodules: diagnostic and therapeutic dilemmas. The Endocrinologist. 2002;12:185–98.
Figures 6A and B: Positive Pemberton's sign: Dilated veins on the anterior surface of the neck on raising the hands. This lady presented with a massive neck swelling that was extending retrosternally that pressed upon the superior vena cava on raising the hands, thereby causing dilatation of the veins in the upper part of the body.
Figure 7: Ultrasound thyroid showing a heterogeneous isoechoic nodule with eccentric hypoechoic component and an ill-defined lobulated margins, suggestive of malignant potential. This is a 40-year-old lady who presented with bilateral neck swelling more prominent on the left side. Clinically, she had a dominant nodule out of a multinodular goiter.
Figure 8: Thyroid ultrasound showing microcalcification (shown with an arrow), a feature of thyroid cancer. This patient, a 55-year-old patient presented with neck swelling, progressively increasing in size, weight loss, and loss of appetite. Fine-needle aspiration cytology (FNAC) of the thyroid was suggestive of papillary carcinoma of thyroid.
Figures 9A to C: This patient presented with a thyroid swelling and symptoms suggestive of malignancy. The Ultrasound of the neck showed multiple ill-defined, solid, markedly hypoechoic nodules, taller than wide in shape with microcalcifications and central vascularity. These features are highly suggestive of malignancy.
DOPPLER STUDIES OF THYROID
RADIONUCLIDE SCANNING IMAGES
This works on the principle of differential uptake of radioactive isotopes. Risk of malignancy is:
- Cold: 16%
- Indeterminate: 10%
- Hot: <1%.
Figure 2: A 48-year-old gentleman presented with a neck swelling for the past 8 months. He had no symptoms suggestive of hyperthyroidism or hypothyroidism. There was a history of mild change in voice over the past month. The figure above is a radionuclide scan of the patient showing a cold nodule in the right side (shown with an arrow).
WHAT DO YOU THINK IS THE DIAGNOSIS OF THE PATIENT?
The patient was diagnosed to have a malignancy in the thyroid swelling. There is an increased risk of malignancy in swellings that are “cold” on radionuclide scanning.
A 60-year-old lady, Ms S, presented with complaints of having had a fever with cough for 1 week and an anterior neck swelling for a fortnight. She was diagnosed to have a thyroid nodule at a clinic in her hometown. This had also been associated with dysphagia, dyspnea and hoarseness of voice. A fine-needle aspiration cytology (FNAC) was performed for the same which turned out to be inconclusive. She was known to have type 2 diabetes mellitus (T2DM) with poor glycemic control and had been using insulin for the treatment of the same.
Examination revealed a thyroid swelling—more prominent on the left, hard and very tender—which moved corresponding to deglutition. The overlying skin was erythematous (Figure 1). Pemberton's sign was positive with a right-sided tracheal deviation and lower border could not be visualized.
WHAT IS YOUR DIAGNOSIS?
Blood investigations revealed an HbA1c of 13.1% and a leukocyte count of 9,000 with 80% neutrophilia. Her albumin/gobulin ratio was 3:5, suggesting hyperglobulinemia. Blood cultures failed to elicit any growth which could be explained by the partial antibiotic course she had been subjected to elsewhere. She had been tested negative for HIV.
Ultrasonography of her neck—performed at presentation—showed a large hypoechoic lesion with internal echoes in the region of the left lobe measuring about 90 cc with overlying subcutaneous edema (Figure 2). Computed tomography (CT) initially showed a septic mass in the left lobe of thyroid while an FNAC of the same revealed clusters of neutrophils. When ultrasonography was performed for the second time in view of the worsening of her symptoms, a cystic nodule measuring approximately 165 cc was seen, along with internal septae replacing the entire left lobe of the thyroid gland (Figure 3).
Figure 1: Large neck swelling, L > R; note how the overlying skin is erythematous (shown within circle).
Spiking fever and increasing tenderness over the swelling suggested that the patient was rapidly declining and she was asked to undergo a left hemithyroidectomy. Histopathological examination of the tissue from the surgery displayed scanty thyroid parenchyma with abundant inflammatory granulation tissue containing dense infiltrates of neutrophils, lymphocytes, plasma cells, and histiocytes. Fibrosis, necrosis, degeneration, and hemorrhage were seen in the surrounding stroma. This was suggestive of acute suppurative thyroiditis (AST). There were no features of malignancy or granuloma. A culture obtained from this tissue grew Escherichia coli.
The patient was then treated with antibiotics and was asymptomatic at discharge. She was clinically euthyroid at follow up. Glycemic control was achieved solely with OADs and she did not require any insulin.
DISCUSSION
Acute suppurative thyroiditis is a life-threatening endocrine emergency which needs urgent surgical intervention.
43
Acute infection of the thyroid gland is an uncommon entity owing to its encapsulation that prevents dissemination. This is further supplemented by a high iodine content within the gland, a widespread lymphatic drainage surrounding it and its rich arterial vasculature. AST, as a differential, must be kept in mind in all patients with a tender thyroid nodule—in addition to de Quervain's thyroiditis—despite the fact it accounts for <1% of all thyroid illnesses.
Fine-needle aspiration cytology offers great utility in the diagnosis of thyroid pathologies as it has proven to be reliable while remaining minimally invasive and economical. While the formation of a local hematoma and pain are the most common complications of FNAC, AST may also rarely develop following the procedure.1
Major causative pathogens are Staphylococcus and Streptococcus species while gram-negative organisms and anaerobes are also seen in some cases.2 Mycobacteria and fungi are more likely to be pathogens in immunocompromised patients and these infections tend to be more chronic in nature, in comparison to bacterial infection.
The disease may progress rapidly and could prove to be fatal. This warrants heightened suspicion in susceptible cases. This could facilitate an early diagnosis which is pertinent. Ultrasonography is the preferred imaging methodology for the diagnosis of thyroid illnesses, having the added benefit of needle aspiration and subsequent cytological study. A CT scan or magnetic resonance imaging (MRI) is only required if the aforementioned imaging proves to be inconclusive. Abscess may appear as cold when seen on an iodine uptake scan. Antimicrobial therapy and surgical drainage of abscesses remain the treatments of choice.
REFERENCES
- Polyzos SA, Anastasilakis AD. Clinical complications following thyroid fine-needle biopsy: A systematic review. Clin Endocrinol. 2009;71:157–65.
- McLaughlin SA, Smith SL, Meek SE. Acute suppurative thyroiditis caused by Pasteurella multocida and associated with thyrotoxicosis. Thyroid. 2006;16(3):307–10.
A 72-year-old lady presented with the history of low backache which had worsened over the past 10 days and a progressively increasing neck swelling for the past 2 years. Previously, she had undergone a right hemithyroidectomy in 1990 for a solitary thyroid nodule.
On examination, the left lobe of thyroid was just palpable. The trachea was central and both carotids were normal. There was no enlargement of the cervical lymph nodes. There was a palpable sacral mass that was firm and nontender.
An ultrasound of the neck was done and showed a hypoechoic thyroid mass with calcifications and an absent peripheral halo (Figures 1A and B).
Figure 1B shows color Doppler with an increased vascularity.
WHAT IS THE PROBABLE DIAGNOSIS?
Magnetic resonance imaging (MRI) of the spine (Figures 2A to C) was done and it showed a sacral mass which was suggestive of metastasis. A whole body iodine uptake scan was done and showed similar evidence of sacral metastasis.
A bone scan was done and it showed an increased uptake in the sacral region suggestive of metastasis (Figures 3A and B).
Figures 1A to C: Ultrasound of the neck showing an absent right lobe (postoperative status), a solid, round, hypoechoic, heterogeneous nodule with vascularity in the lower pole of left lobe of thyroid. There were few benign right-sided neck nodes.
Figures 2A to C: Magnetic resonance imaging (MRI) of the spine showing a hypointense, ill-defined mass (shown with an arrow) replacing marrow and destroying sacral bone suggestive of metastasis.
Her bone scan and whole body uptake scan showed an increased tracer uptake in the sacral region (Figures 3 and 4). However, there were no uptake in the thyroid bed area. She underwent partial excision of the sacral mass in 2012 and the biopsy report at that time revealed metastatic papillary thyroid carcinoma (Figures 5A and B). She was given an 131I 100 mCi ablation and advised to come for follow-up after 6 months.
The follow-up whole body uptake scan after 1 year revealed an increased uptake in the thyroid region (Figure 6A). The subsequent ultrasound thyroid confirmed a 2 cm sized recurrence of the thyroid tumor. She underwent a completion thyroidectomy. The surgical specimen showed multifocal papillary microcarcinoma (follicular variant). She also was given an 131I 100 mCi ablation following surgery (Figure 6B).
DISCUSSION
Papillary thyroid carcinoma is well-differentiated and slow growing, with unique characteristics. Adjuvant therapy includes thyroid hormone suppression and radioiodine (131I) therapy rather than chemotherapy and radiotherapy. The prognosis is generally excellent and is influenced by factors related to the patient, the disease and the therapy. Factors associated with a less favorable outcome are male gender, age >40 years, family history of papillary cancer, tumor diameter > 4 cm, lymph node or distant metastases and invasive nature or poorly differentiated tumor. After total thyroidectomy and 131I ablation, the follow-up includes a diagnostic radioiodine scan and serum thyroglobulin estimation (after thyroxine withdrawal) at 6 months.46
Figures 3A and B: 99Tc bone scan showing an increased uptake in the sacral region suggestive of sacral metastasis (shown with an arrow).
(CBD: continuous bladder drainage).
Figure 4: 131I whole body scintigraphy postablation scan showing metastasis in the region of lumbar spine (shown with an arrow).
(SSN: suprasternal notch).
Figures 5A and B: Orphan Annie eye nuclei (shown with an arrow) in papillary carcinoma of thyroid, the nuclei looked similar to the eyes of all the characters of the American comic strip, Little Orphan Annie.
Further long-term follow-up includes clinical examination, thyroid-stimulating hormone (TSH) monitoring to ensure adequate suppression and serum thyroglobulin measurement.1 If thyroglobulin becomes detectable in a patient taking thyroxine then thyroxine is withdrawn, a diagnostic whole body scan is performed and the thyroglobulin measurement is repeated. Recombinant human TSH administration can be used to avoid the need for thyroxine withdrawal.2
Figures 6A and B: (A) Thyroid uptake study done before completion thyroidectomy showing an increased uptake in the left side of the thyroid region (shown with an arrow), (B) Thyroid uptake study done after completion thyroidectomy showing no uptake in the thyroid bed.
(SSN: suprasternal notch).
REFERENCES
- Jones MK. Management of papillary and follicular thyroid cancer. J R Soc Med. 2002;95(7):325–6.
- Unnikrishnan AG, Kalra S, Baruah M, et al. Endocrine Society of India management guidelines for patients with thyroid nodules: A position statement. Indian J Endocrinol Metab. 2011;15(1):2–8.
A 54-year-old patient Mr G was seen in the Endocrinology OPD with history of progressive swelling in the neck for 5 years, associated with a history of pain in the neck. He was clinically and biochemically euthyroid. He had no other compressive symptoms. On examination, there was a 6 × 5 cm firm to hard swelling more on the left than the right side, which moved up with deglutition. The trachea was deviated to the right. Computed tomography (CT) scan of the neck is shown in Figures 1 and 2. He underwent a total thyroidectomy and the specimens were sent for histopathological examination (Figures 3 and 4).
WHAT IS THE PROBABLE DIAGNOSIS?
The surgical specimen was evaluated and was found to have multifocal classical papillary thyroid carcinoma.
The follow-up 131I whole body survey revealed a residual thyroid and lymph nodal metastases (Figure 5).
Figures 1A and B: CT scan (coronal view) showing a heterogeneously enhancing large left thyroid nodule (arrow in 1B) with tracheal deviation to the right and a smaller nodule in the right lobe of the thyroid with calcification (arrow in 1A).
Figures 2A and B: CT scan (axial view) showing a necrotic left level III lymph node (shown with an arrow).
He underwent 131I ablation a few months later. He was started on suppressive doses of thyroxine and was followed up on a regular basis.
Figure 4: Capsular invasion and extracapsular disease, a classical feature of papillary carcinoma of the thyroid (shown with an arrow).
Figure 5: Thyroid scintigraphy revealing a bulky residual thyroid and lymph node metastasis (shown with circle).
Figure 6: MRI of spine revealing T1 vertebral body collapse with posterior bulge and cord compression (shown with an arrow).
A few months later, he presented with progressive weakness of both lower limbs for 10 days. He also had decreased sensation in both the lower limbs, more on the right than the left. There was no history of urinary or fecal incontinence. Shown below is the MRI of the spine (Figure 6). His chest X-ray shown heterogeneous infiltrates with CT thorax also confirming the same (Figures 7 and 8).
WHAT DO YOU THINK HAPPENED?
Mr G was evaluated for rapidly progressing paraparesis. An MRI spine showed features of skeletal metastases in multiple vertebrae. The first thoracic vertebra showed collapse and epidural component causing cord compression (Figure 6). A CT scan of the thorax also revealed multiple nodules in both the lungs (Figure 8). He was planned for palliative radiotherapy to the spine and was also referred to the spinal surgery department for urgent decompressive surgery.50
Figure 7: Chest radiograph showing numerous basal predominant bilateral lung nodules of varying sizes (metastases, shown with an arrow).
Figures 8A and B: CT thorax, axial and coronal sections, showing numerous bilateral lung metastases (shown with an arrow).
A 61-year-old patient, Mrs S, presented to the casualty with a history of slipping and falling in the bathroom and sustained a closed injury to her left thigh. She had undergone a total thyroidectomy and Sistrunk's operation few months earlier. On examination, she had swelling and tenderness over the left thigh with an abnormal mobility and crepitus. The X-ray of the left femur is shown below.
WHAT IS THE DIAGNOSIS?
Mrs S was diagnosed to have a papillary carcinoma thyroid who underwent a total thyroidectomy elsewhere came to our center for further management. She developed a pathological fracture of the left femur and she underwent intramedullary nailing and fixation for the same purpose (Figure 1). The histopathology from the left femur was reported as metastatic adenocarcinoma and the thyroid pathology slides, which were reviewed, was reported as classical papillary carcinoma thyroid. Chest X-ray and computed tomography (CT) thorax revealed features of metastasis (Figures 2A and B). CT abdomen showed a metastasis in the vertebrae (Figure 3). The 131I whole body scan showed an increased uptake in the thyroid residue (Figure 4). She was further evaluated with a positron-emission tomography-computed tomography (PET-CT) for the disease status and was found to have disseminated metastatic disease (Figures 5A to D).
Figure 1: Radiograph of the left femur showing a lytic lesion in the left mid shaft of femur with pathological fracture (shown with an arrow).
Figures 2A and B: Chest radiograph and CT of thorax showing multiple lung metastasis (canon ball appearance, shown with an arrow).
Figure 4: 131I Whole body scan revealing uptake in the thyroid bed suggesting a residual lesion (shown with an arrow).
(SSN: suprasternal notch).
Figures 5A to D: Positron-emission tomography-computed tomography (PET-CT) showing various areas of metastases including metastatic neck and mediastinal nodes, bone and lung metastases [areas in red indicate areas of increased fluorodeoxyglucose (FDG)-uptake].
(CECT: contrast-enhanced computed tomography)
She was planned for diagnostic iodine scan followed by a therapeutic radioiodine ablation. She was managed conservatively in the ward with analgesics and symptomatic, palliative care.
DISCUSSION
The overall incidence for papillary thyroid cancer (PTC) is 16.3/100,000 for women and 5.6/100,000 for men. A history of rapid growth, a thyroid nodule or fixation of the nodule to surrounding tissues, and compressive symptoms like new onset hoarseness or vocal cord paralysis, dysphagia or dyspnea or the presence of ipsilateral cervical lymphadenopathy should raise the suspicion that a nodule may be malignant. Risk factors for PTC include a history of radiation exposure during childhood, a history of thyroid cancer in a first-degree relative, or a family history of a thyroid cancer.1
Mutations in the genes encoding for the proteins in the mitogen-activated protein kinase (MAPK) pathway are critical to the development and progression of differentiated thyroid cancer. Mutations in REarranged 54during Transfection (RET)/PTC, neurotropic tyrosine kinase receptor type 1 (NTRK1), RAS, or BRAF occur in as many as 70% of well-differentiated thyroid cancers.
Papillary cancers are typically unencapsulated and may be partially cystic. Microscopically, most are characterized by the presence of papillae consisting of one or two layers of tumor cells surrounding a well-defined fibrovascular core; follicles and colloid are typically absent. Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty) and psammoma bodies seen on light microscopy are characteristic for PTC. The former is useful in identifying the follicular variant of papillary thyroid carcinomas. The morphologic diagnosis is based upon an aggregate of typical cytological features which itself is a pathognomonic feature of PTC. The nuclei are large, oval, and appear crowded and overlapping on microscopic sections. They may contain hypodense powdery chromatin, cytoplasmic pseudoinclusions due to a redundant nuclear membrane, or nuclear grooves. Lymphatic spread is more common than hematogenous spread. The so-called lateral aberrant thyroid is actually a lymph node metastasis from papillary thyroid carcinoma.
Most patients with papillary cancer do not succumb to disease itself. Variant forms of papillary cancer include the follicular variant (about 10%) and the tall-cell variant (a more aggressive tumor, 1%).255
REFERENCES
- DM, TMK, Khan DM, et al. Follicular variant of papillary thyroid carcinoma: cytological indicators of diagnostic value. J Clin Diagn Res. 2014;8(3):46–8.
- Schneider AB, Sarne DH. Long-term risks for thyroid cancer and other neoplasms after exposure to radiation. Nat Clin Pract Endocrinol Metab. 2005;1:82–91.
A 75-year-old lady presented with a progressive swelling in front of the neck for 30 years. There was no history of hyperthyroidism or hypothyroidism. There were no pressure symptoms like dysphagia or hoarseness of voice. She complained of a choking feeling for the past 2 years, when she lies flat in bed. Her husband and three of her children were taking medicines for hypothyroidism. On examination, she had a 10 × 8 cm size, firm swelling in front of the neck which was more on the right side, which moved up with deglutition. There was no retrosternal extension but the trachea was deviated to left side.
WHAT IS THE PRELIMINARY DIAGNOSIS? WHAT ARE THE DIFFERENTIAL DIAGNOSES?
The diagnosis was that of a dominant nodule in a multinodular goiter. The patient underwent a total thyroidzectomy and the surgical specimen was diagnosed to be a follicular variant of papillary carcinoma involving left lobe. Hürthle cell nodules were also evident in the left lobe. Postsurgery, she was put on suppressive doses of thyroxine.
The following year an ultrasound neck was done which showed enlarged lymph nodes (Figure 1). She underwent 131I whole body scan which revealed a residual thyroid (Figure 2). She was then admitted for 131I ablation.
After 6 months she was found to have elevated serum thyroglobulin and a repeat 131I whole body scan there was an increased tracer activity in the left thyroid region and T6 thoracic vertebrae which is highly suggestive of skeletal metastases (Figure 3).
This patient was given 100 mci of 131I and then kept on suppressive dose of thyroxine, with regular follow-up.
DISCUSSION
The importance in the management of thyroid cancer is early identification of those patients with more advanced or high-risk disease requiring aggressive treatment. The revision of the tumor, node, and metastasis (TNM) staging; and American Thyroid Association risk stratification systems has changed the categories of many patients in recent times. The main follow up tools for those had treatment for PTC are ultrasonography of the neck US and stimulated serum Thyroglobulin levels.
RAI-refractory PTC needs alternative treatment protocol for the control of the disease. In these patients treatment with tyrosine kinase inhibitors (TKIs) such as Sorafenib or Lenvatinib may be considered. However Sorafenib is a time tested drug with good response been shown in these patients with TENIS (Thyroglobulin elevation with Negative Iodine Scintigraphy).1,2
Figure 1: Postoperative ultrasonography (USG) of the neck showing level 3 cervical lymph nodes (shown with an arrow).
Figure 2: Thyroid whole body scintigraphy showing a mild tracer uptake in the thyroid bed suggestive of mild residual thyroid (shown with an arrow).
(SSN: suprasternal notch).
Figure 3: Thyroid whole body (WB) scintigraphy done 6 months later, showing tracer accumulation in the left side of the neck and in the region of the T6 vertebra, suggestive of functioning metastases to the left supraclavicular lymph node (shown with white arrow) and the T6 vertebra (shown with black arrow).
REFERENCES
- Araque KA, Gubbi S, Klubo-Gwiezdzinska J. Updates on the Management of Thyroid Cancer. Horm Metab Res. 2020 Feb 10.
- Jayarangaiah A, Sidhu G, Brown J, et al. Therapeutic options for advanced thyroid cancer. Int J Clin Endocrinol Metab. 2019;5(1):26–34.
A 60-year-old lady presented with swellings on head for the past 2 years and in front of her neck for the past 6 years (Figure 1).
WHAT IS YOUR PRELIMINARY DIAGNOSIS?
On further history she had symptoms of hypothyroidism (lethargy, tiredness) and complained of pain in the swelling of the head. She also complained of lower back ache.
On examination, the neck swelling moved up with deglutition and was bilateral and diffusely enlarged, the surface of which was irregular. She also had multiple enlarged cervical lymph nodes.
On investigations, the Chest X-ray showed multiple well defined infiltrates bilaterally (Figure 2). Whole body uptake scan showed increased uptake in both the lungs (Figure 3). The clinical picture was highly suggestive of a thyroid primary malignancy with distant metastases. A fine needle aspiration (FNA) biopsy revealed epithelial cells arranged in a pattern of microfollicles, scant or absent colloid, and few macrophages and defined the lesion of follicular lesion of undetermined significance.
With the clinical picture and investigations she was diagnosed with follicular thyroid carcinoma with distant metastasis.
59
DISCUSSION
Follicular thyroid cancer is the second most common type of thyroid cancer after papillary thyroid cancer (PTC).1 Follicular thyroid cancer typically spreads via hematogenous dissemination. Common sites of distant metastases are bone (with lytic lesions) and lung and, less commonly, the brain, liver, bladder, and skin. Unlike PTC, FNA biopsy cannot diagnose or distinguish between the follicular adenomas and cancers. Microscopically, the diagnosis of follicular cancer requires distinguishing adenoma from cancer, through identification of tumor extension through the tumor capsule and/or vascular invasion, given the fact that follicular cancer commonly occurs in older patients and is more often associated with an aggressive clinical course and distant metastases. It has higher mortality than PTC.2
REFERENCES
- D'Avanzo A, Treseler P, Ituarte PH, et al. Follicular thyroid carcinoma: histology and prognosis. Cancer. 2004;15;100(6):1123–9.
- Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer. 2005;1;103(11):2269–73.
A 48-year-old lady presented to our clinic with a history of progressive, painless swelling in front of the neck over the past 25 years. However, more recently, she had developed dyspnea on exertion with hoarseness of her voice. She was not known to have hypertension or any associated skin lesions.
Upon examination, she was found to have thyroid swelling of 10 × 7 cm which was of variegated consistency. She had stridor on palpation of the gland (Figure 1A). Pemberton's sign was positive (Figure 1B). There were no other clinical features.
An ultrasound of the neck revealed bilateral thyroid masses with heterogeneous echotexture, central pattern of vascularity, macro- and microcalcifications. Chest X-ray showed deviated trachea with probable compression or infiltration of the trachea (Figure 2). Fine-needle aspiration cytology (FNAC) of the thyroid showed amyloid deposits in the background of colloid and the cells were positive for calcitonin (Figures 3 and 4).
Computed tomography (CT) scan neck showed a thyroid mass with infiltration of the trachea (Figure 5).
WHAT IS THE DIAGNOSIS?
Based on the clinical, pathological, and radiological findings, she was diagnosed with medullary thyroid carcinoma (MTC) with tracheal invasion.
61
Figures 5A to C: Serial sections of the CT scan of the neck showing a large heterogeneously enhancing thyroid mass infiltrating the trachea (black arrow) and left internal jugular vein (white arrow).
Subsequently, she underwent total thyroidectomy with central compartment dissection and resection and anastomosis of the tracheal infiltration segment.
DISCUSSION
Medullary thyroid carcinoma is an uncommon neuroendocrine malignancy that accounts for 5% of all the thyroid cancers.1 MTC presents in sporadic and familial forms [multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial MTC syndromes]. The familial forms are secondary to germline mutations in the REarranged during Transfection (RET) proto-oncogene. Early diagnosis and treatment is most important. Genetic testing has made possible, the early detection in asymptomatic carriers and high-risk patients, with early or prophylactic surgery being curative in many. All carriers of an RET mutation should be evaluated and treated surgically for MTC. The primary treatment in all patients diagnosed with MTC is total thyroidectomy with central lymph node dissection.2
Calcitonin and carcinoembryonic antigen (CEA) levels can be used as prognostic factors and as tumor markers. If elevated, further investigation, including use of imaging modalities, may be necessary for evaluation of metastatic disease.62
REFERENCES
- Finny P, Jacob JJ, Thomas N, et al. Medullary thyroid carcinoma: a 20-year experience from a centre in South India. ANZ J Surg. 2007;77(3):130–4.
- Griebeler ML, Gharib H, Thompson GB. Medullary thyroid carcinoma. Endocr Pract. 2013;19(4):703–11.
A 56-year-old non-smoking farmer presented to our thyroid clinic with the rapid progression of the thyroid swelling over the past 20 days with simultaneous hoarseness of voice during the same period. He had a thyroid swelling for the past 20 years whose size was static in nature (Figure 1).
Clinical examination showed a massive deviation of the trachea to the left side with a predominant right lobe thyroid enlargement. Chest X-ray image is shown in Figure 2.
WHAT COULD BE THE PROBABLE CLINICAL DIAGNOSIS?
This gentleman had probable anaplastic carcinoma clinically in view of the rapid progression of the symptoms. The hoarseness of voice could be well due to the external laryngeal nerve involvement. The Chest X-ray showed a massive deviation of trachea to the left side.
The computed tomography (CT) scan neck and thorax showed a large heterogeneously enhancing mass with chunky calcifications in the right lobe of thyroid measuring 5.9 × 8 × 12 cm (Figure 3).
The patient underwent a trucut biopsy of the right lobe of thyroid which was also suggestive of a possible anaplastic carcinoma of the thyroid and the patient was advised external beam radiotherapy.
DISCUSSION
Anaplastic thyroid cancers are undifferentiated tumors of the thyroid follicular epithelium. In marked contrast to the differentiated thyroid cancers, anaplastic cancers are extremely aggressive, with a disease-specific mortality approaching 95%. The few exceptions are patients whose tumors are small and who are treated very aggressively. Approximately 20% of patients have a history of differentiated thyroid cancer and 20–30% have a coexisting differentiated cancer. The primary symptom of anaplastic cancer is a rapidly enlarging neck mass, occurring in about 85% of patients.1
The diagnosis of anaplastic cancer is usually established by cytologic examination of cells which show spindle cells, pleomorphic giant cells, and/or squamoid. Many anaplastic thyroid cancers have a mixed morphology of two or all three patterns. For patients with a small intrathyroidal anaplastic cancer associated with a differentiated thyroid cancer, we suggest total thyroidectomy. Total thyroidectomy will facilitate subsequent treatment of the differentiated thyroid cancer. However, for the rare patients with intrathyroidal anaplastic thyroid cancer, without a coexistent well-differentiated thyroid cancer component, thyroid lobectomy with wide margins of adjacent soft tissue by the side of the tumor is an appropriately aggressive alternative surgical approach.2
Figure 2: Chest radiograph showing a large soft tissue density mass in the right side of the neck causing compression and deviation of the trachea to the left side.
Figure 3: Computed tomography (CT) showing a large right thyroid mass (shown with an arrow) with areas of necrosis and calcifications.
REFERENCES
- Neff RL, Farrar WB, Kloos RT, et al. Anaplastic thyroid cancer. Endocrinol Metab Clin North Am. 2008;37:525–38.
- Smallridge RC, Copland JA. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol). 2010;22:486–97.
fine-needle aspiration cytology from the left side nodule was suggestive of papillary carcinoma of thyroid. She underwent total thyroidectomy with Sistrunk procedure for the thyroglossal cyst. Biopsy of the surgical specimen confirmed papillary carcinoma of thyroid arising from the thyroglossal cyst with normal thyroid tissue.
CASE 27
A 34-year-old lady presented with an insidious onset and slowly progressive neck swelling for over 12 years. She did not have features suggestive of either hypothyroidism or hyperthyroidism. There was no previous history of pressure symptoms.
On physical examination there was a 3 cm × 4 cm submental swelling which moved on deglutition and protrusion of the tongue (Figures 1A and B). The swelling was variegated in consistency with cystic and few firm areas. She did not have any lymph nodal enlargement.
Her thyroid function tests were normal. Ultrasound of the neck showed a complex cystic lesion with an irregular papillary solid component with microcalcifications in the midline of the neck at the level of hyoid bone. The normal thyroid gland was separately seen.
WHAT IS THE DIAGNOSIS?
Figures 2A and B could represent malignancy in a thyroglossal cyst.
Figures 2A and B: Ultrasound of the neck (A) Midline subhyoid complex cystic lesion with irregular solid component and microcalcification and (B) Normal thyroid gland.
Subsequently, she underwent fine-needle aspiration cytology (FNAC) which showed clusters of colloid and psammoma bodies with occasional follicular cells suggestive of papillary carcinoma thyroid in a thyroglossal cyst (Figure 3). She underwent a Sistrunk operation with total thyroidectomy for the swelling and was put on replacement doses of thyroxine.
DISCUSSION
The thyroglossal duct cyst (TGDC) is the most common anomaly associated with thyroid development. The thyroid gland descends from the foramen cecum to a point below the thyroid cartilage and leaves an epithelial tract known as the thyroglossal tract. The tract disappears during the 5th to the 10th gestational week. Incomplete atrophy of the tract forms the basis of origin of the cyst.1 Malignancy within a TGDC is rare and occurs in only about 1.5% of cases, and diagnosis is usually made postoperatively as clinically it may be difficult to distinguish from benign neoplasms. Features that should arouse suspicion of malignancy include large or increasing size, hardness, fixity, irregular shape, and previous exposure to ionizing radiation. There is no role for routine FNAC of a TGDC in the absence of suspicious features.2
REFERENCES
- Aculate NR, Jones HB, Bansal A, et al. Papillary carcinoma within a thyroglossal duct cyst: significance of a central solid component on ultrasound imaging. Br J Oral Maxillofac Surg. 2014;52(3):277–8.
- Senthilkumar R, Neville JF, Aravind R. Malignant thyroglossal duct cyst with synchronous occult thyroid gland papillary carcinoma. Indian J Endocrinol Metab. 2013;17(5):936–8.
A 69-year-old lady, who was known to have type 2 diabetes mellitus (T2DM), hypertension and coronary artery disease presented with neck swelling for a duration of 9 years (Figure 1). The swelling was cystic in nature and was pulsatile. There was no history suggestive of either hypothyroidism or hyperthyroidism. There was no history of associated pressure related symptoms. On examination, the thyroid gland was normal in size. There was no tracheal tug and the swelling did not move up with deglutition or protrusion of the tongue. Thyroid function tests were normal.
WHAT IS THE PROBABLE DIAGNOSIS?
A color Doppler of the swelling revealed dilatation of the right innominate artery, which was suggestive of an aneurysm. This swelling was mimicking a thyroid swelling (Figure 2). This is a unique patient wherein the aneurysms of the innominate artery (AIA) presented as a thyroid swelling. Since she was clinically and biochemically euthyroid, she was referred to vascular surgery department for further management.
DISCUSSION
Here are some differential diagnoses for a neck mass:
- Branchial cleft cyst
- Thyroglossal duct cyst (TGDC)
- Vascular anomalies
- Laryngocele
- Ranula
- Teratoma
- Dermoid cyst
- Thymic cyst
Inflammatory neck mass:
- Infectious inflammatory disorders
- Reactive viral lymphadenopathy
- Bacterial lymphadenopathy
- Parasitic lymphadenopathy
- Noninfectious inflammatory disorders
Neoplastic disorders:
- Metastatic head and neck carcinoma
- Thyroid masses
- Salivary gland neoplasm
- Paragangliomas
- Schwannoma
- Lymphoma
- Lipoma and benign skin cysts.
REFERENCES
- Kraus R, Han BK, Babcock DS, et al. Sonography of neck masses in children. Am J Roentgenol. 1986;146(3):609–13.
- Josephson GD, Spencer WR, Josephson JS. Thyroglossal duct cyst: the New York Eye and Ear Infirmary experience and a literature review. Ear Nose Throat J. 1998;77(8):642–4, 646–7, 651.
69MULTIPLE CHOICE QUESTIONS
1. A 26-year-old lady presents with recurrent episodes of palpitations over a period of 3 years. Clinical examination reveals a smooth symmetrical goiter, just visible in the anterior part of the neck. Biochemical tests show a total T4 of 19.0 µg/dL (Normal 4.5–11.5 µg/dL) and a TSH of 8.0 mIU/mL (Normal 0.5–4.5 mIU/mL). Which of the following is FALSE:
- It could be a TSH producing tumor
- It could be thyroid hormone receptor resistance
- The biochemical values could be present in a euthyroid normal pregnancy
- A visual field test may be indicated
2. All of the following are associated with normal/raised radioactive iodine uptake activity over the neck with an intact thyroid, EXCEPT:
- Graves’ disease
- Trophoblastic disease
- Thyroid hormone resistance
- Excessive metastasis from thyroid cancer
3. All of the following therapies are useful in the management of thyroid eye disease, EXCEPT:
- Azathioprine
- Etanercept
- Selenium
- Chromium
4. All of the following drugs are associated with thyroiditis, EXCEPT:
- Amiodarone
- Interferon alpha
- Interleukin-2
- Amitriptyline
5. All of the following mutations are described in follicular carcinoma, EXCEPT:
- RAS
- PAX8
- PPAR gamma
- BRAF
6. Hyperthyroidism in children, all of the following statements are true EXCEPT:
- Sufficient 131I therapy is advisable for GD management as a single dose to reach a state of hypothyroidism
- Pediatric patients with Graves’ disease who are not in remission following 1–2 years of methimazole therapy should be considered for treatment with RAI therapy/thyroidectomy
- 131I therapy should be completely avoided in children less than 5 years
- PTU is associated with a lower number of reported side effects pertaining to hepatotoxicity in children
7. All of the following drugs are associated with thyroiditis, EXCEPT:
- Amiodarone
- Interferon alpha
- Interleukin-2
- Amitriptyline
8. All of the following can be secreted by medullary carcinoma thyroid EXCEPT:
- Carcinoma embryonic antigen
- Somatostatin
- Cortisol
- TRH
9. A 23-year-old lady presented with features suggestive of thyrotoxicosis. Her evaluation for the same with blood investigations and nuclear medicine studies are suggestive of thyrotoxicosis factitia. Which one of the following is not a feature of thyrotoxicosis factitia?
- Suppressed—TSH, and elevated T4 and FT4
- Elevated thyroglobulin level
- Low radioiodine uptake
- Absent thyroid autoantibodies
10. A 25-year-old lady with bipolar disorder has been on lithium therapy since 2 years. She is married for 4 years and has not conceived yet. She has also a recent history of polydipsia, weight loss, and palpitation. She was referred by the psychiatry department for further evaluation. Which of the following endocrine disorder is NOT common with long-term lithium therapy?
- Hypothyroidism
- Thyrotoxicosis
- Nephrogenic diabetes insipidus
- Hypocalcemia
11. An 18-year-old lady presented with painful thyroid swelling since 2 weeks. On examination, she has a grade-2 thyroid swelling with tenderness. Her blood investigation revealed TSH—0.34 µIU/mL (Normal 0.5–4.5 mIU/mL). T4 of 12.5 µg/dL (Normal 4.5–11.5 µg/dL), FT4 of 1.8 ng/dL (Normal 0.8–1.8 ng/dL), and a high ESR. Radioiodine uptake study showed 10% uptake at 24 hours. She was initially treated with naproxen 1 tab twice daily for 1 week. However, she continued to have pain, so later on she was treated with prednisone. All of the following are the indications of prednisolone (steroid) therapy in thyroid disorders EXCEPT:
- Hashimoto's encephalopathy
- Thyrotoxicosis storm
- Myxedema coma
- Prior to radioiodine therapy in the absence of eye disease
12. All of the following clinical condition are associated with increase in radioiodine uptake in the region of thyroid EXCEPT:
- Graves’ disease
- Metastatic thyroid cancer
- Choriocarcinoma
- Struma ovarii
13. A 60-year-old lady, a known patient of Hashimoto's thyroiditis, primary hypothyroidisms presented with rapidly increasing thyroid swelling since 3 months. The thyroid swelling 70was associated with pressure symptoms and pain. On examination, both lobes of the thyroid were enlarged (right was larger than left). FNAC of the thyroid was suggestive of lymphoma. Which type of lymphoma is more common in the setting of Hashimoto's thyroiditis?
- Adult T-cell lymphoma
- Mixed cellularity Hodgkin's lymphoma
- Hairy cell leukemia
- MALT lymphoma
14. A 34-year-old lady, teacher by profession, presented with history of a thyroid swelling since 2 years. On examination, the thyroid swelling appears firm to hard in consistency and there were no palpable lymph nodes. The FNAC of thyroid nodule was suggestive of medullary carcinoma. She had no prior family history of thyroid carcinoma. She is married with 3 children. Her genetic analysis showed mutation at codon 609. Monitoring of kindred with positive for RET mutation include all EXCEPT:
- Annual monitoring of stimulated calcitonin
- Annual monitoring of urinary metanephrines and normetanephrines
- 1–2 yearly monitoring of serum calcium and iPTH levels
- Annual monitoring of prolactin level
15. A 45-year-old gentleman presented with thyroid swelling since 5 years. Patients noticed that the size of swelling increased 1 and ½ times recently. On examination, there was a large nodule of size >3 cm on the right upper pole of thyroid and clinically there was no significant lymph node enlargement. His ultrasound of the thyroid showed a TIRAD score of 4C. Which of the following is not a feature of this scoring system?
- Solid component
- Markedly hyperechoic nodule
- Taller than wider shaped nodule
- Microcalcification
16. All of the following clinical conditions can be associated with an increase in radioiodine uptake EXCEPT:
- Graves’ disease
- Metastatic thyroid cancer
- Choriocarcinoma
- Struma ovarii
17. A 34-year-old lady, a known case of Graves’ disease diagnosed since 3 years, but on irregular treatment with antithyroid drugs. Simultaneously she had developed prominence of her both eye balls which was associated with redness off and on. Since last 1 month she noticed rapid deterioration of her vision in her right eye. All of the following are the causes of rapid deterioration of vision in Graves’ ophthalmopathy EXCEPT:
- Globe subluxation
- Exposure keratitis
- Central serous retinopathy
- Optic nerve compression
18. A 23-year-old male was evaluated for his thyroid disorders. His thyroid function revealed TSH—8µIU/mL, T4 of 15.2 µg/dL (Normal 4.5–11.5 µg/dL) and FT4 of 3.2 ng/mL (Normal 0.8–1.8 ng/mL). He had no history of prior medication. He was diagnosed with Refetoff syndrome based on clinical features and biochemical evidence. In which clinical condition does thyroid hormone function simulate like a thyroid hormone resistance syndrome?
- Sick euthyroid syndrome
- Thyrotoxicosis factitia
- TSH secreting pituitary tumor
- Grave's thyrotoxicosis
19. Mark True/False for the following statements on management of thyroid nodules during pregnancy:
- Surgery for suspected PTC detected during pregnancy is best operated around 24 weeks. True/False
- It may be beneficial to use thyroxine in a suppressive dose to maintain TSH between 0.1–1 mIU/L. True/False
- TSH levels if suppressed in first trimester will require a RAI uptake study after delivery. True/False
- TSH receptor antibody is useful in differentiating Graves’ disease versus thyroiditis. True/False
20. Mark True/False on the following statements on thyroid nodules:
- Thyroglobulin is a sensitive and specific test for diagnosis of thyroid carcinoma. True/False
- The risk of malignancy in FNAC reported as suggestive of malignancy could be as high as 96%. True/False
- Ultrasound-guided FNAC is recommended for those nodules that are nonpalpable, cystic, and anteriorly placed. True/False
- Molecular markers like galectin-3 can be used to identify high-risk patients with indeterminate cytology. True/False