Professional Documents
Culture Documents
Thyroid gland
- 30 g, just inferior to the larynx
- Right and left lobes connected by isthmus (in 50% a small pyramidal lobe extends upward from isthmus)
- ↓ T3 & T4 stimulate release of TRH and TSH , ↑ T3 & T4 feed back to suppress the secretion of both TRH and TSH
- TSH binds to TSH receptor on thyroid follicular epithelium, causing activation of G proteins, cAMP-mediated synthesis
and release of T3 & T4
- In the periphery, T3 & T4 interact with the thyroid hormone receptor (TR) to form a hormone receptor complex that
translocates to the nucleus and binds to thyroid response elements (TREs) on target genes to initiate transcription
Structure of thyroid follicles
- Single layer of follicular epithelial cells, Basement membrane, Lumen filled with colloid: Synthesis of thyroid hormones
(T3 & T4)
- Parafollicular (C) cells : Synthesis of calcitonin
- The follicle is the morpho-functional unit of the thyroid gland
Follicular cells: effect of activity
- In inactive gland
o Follicles are large, Lining cells are flattened, Abundant colloid
- In active gland
o Follicles are smaller, Lining cells are increased in size, Colloid is reduced (cells absorb colloid adjacent to their
apical surface)
- Ex. A 47-year-old woman has had increasing fatigue with dyspnea and reduced exercise tolerance for the past year. On examination she has nonpitting edema of the
lower extremities. Laboratory studies show a serum TSH level of 10 mU/L and T4 level of 2 μg/dL. She is most likely to have pathologic findings affecting which of the
following cells? Thyroid follicular cells
o The normal feedback loop of peripheral thyroid hormones (T3 and T4) onto the basophils (thyrotrophs) of the adenohypophysis regulates TSH release (under
tropic control of TRH from the hypothalamus). When patients with primary thyroid failure, the most common cause for hypothyroidism with myxedema in
adults, do not have sufficient residual functioning thyroid follicular cells producing thyroid hormones, then the TSH will rise, as in this case, in conjunction
with a low T4 level.
Functions of thyroid hormone
1. Controls basal metabolic rate
2. Growth and maturation of tissue (Brain)
3. Turnover of hormones and vitamins
4. Cell regeneration
5. Synthesis of low-density lipoprotein (LDL) receptors for LDL (main vehicle for transporting cholesterol)
6. Synthesis of β-adrenergic receptors for catecholamines
Thyroid function tests
Total serum T4 {T4 bound to TBG + free T4 (FT4)}
1. Normal TBG, ↑ FT4/FT3 - Graves disease or Thyroiditis (release of FT4 from colloid in the damaged thyroid)
2. Normal TBG, ↓FT4/FT3 - Hypothyroidism
3. ↓TBG, Normal FT4/FT3 - Anabolic steroids, or nephrotic syndrome with loss of TBG (↓TBG: ↓total serum T4 but FT4 and TSH
remain normal, hence no hypothyroidism)
4. ↑TBG, Normal FT4/FT3 - Woman taking estrogen or during pregnancy (Estrogen: ↑TBG → ↑total serum T4 but not FT4, TSH is normal because FT4 is normal, hence
no hyperthyroidism)
- Lingual thyroid- mass lesion at the base of the tongue (white arrow).
- Treatment
o Suppression with thyroxine
o Ablation with radioactive iodine
o Surgery if obstructive
Thyroglossal duct cyst
- Cystic midline mass that is close to or within the hyoid bone
- Moves with deglutition
- Surgery with removal of the proximal duct and a portion of the hyoid bone
Hypothyroidism
- Cretinism (Hypothyroidism in infancy/early childhood)
o Dietary iodine deficiency endemic to certain regions (Himalayas, inland China, Africa)
o Genetic defects that interfere with the biosynthesis of thyroid hormone
o Severe mental retardation, (severity related to time of deficiency) if maternal thyroid deficiency before development of the fetal thyroid gland (starts in 7th
week, produces hormone by 12th week)
o In congenital hypothyroidism, the child is born normal because during pregnancy, it receives thyroid hormones from the mother (lipid soluble, can cross the
placenta)
o Short stature, ↑ weight, coarse facial features, protruding tongue, umbilical hernia
o Ex. A 2-year-old child has failure to thrive since infancy. Physical examination shows that the child is short and has coarse facial features, a protruding tongue,
and an umbilical hernia. As the child matures, profound intellectual disability becomes apparent. A deficiency of which of the following hormones is most
likely to explain these findings? Thyroxine (T4)
Cretinism is a condition that is uncommon whenever routine newborn screening is available for testing and treatment at birth for hypothyroidism.
Hypothyroidism that develops in older children and adults is known as myxedema
o Ex. The parents of a 4-week-old girl complain that their baby is apathetic and sluggish. On physical examination, the child’s abdomen is large and exhibits an
umbilical hernia. The skin is pale and cold, and the temperature is 35°C (95°F). Which of the following provides a plausible explanation for the signs and
symptoms of this child? Thyroid agenesis
Cretinism denotes physical and mental insuffi ciency that is secondary to congenital hypothyroidism. Cretinism may be endemic, sporadic, or
familial and is twice as frequent in girls as in boys. Iodination of salt has reduced the incidence of cretinism in the United States and other
countries. The most common cause of neonatal hypothyroidism today is agenesis of the thyroid, which occurs at a rate of 1 in 4,000 newborns.
Hypothyroidism in pregnant women also has grave neurologic consequences for the fetus, expressed after birth as cretinism. Symptoms of
congenital hypothyroidism appear in the early weeks of life and include sluggishness, a large abdomen often with umbilical herniation, low body
temperature, and refractory anemia. Mental retardation, stunted growth, and characteristic facies become evident. If thyroid hormone
replacement therapy is not promptly provided, congenital hypothyroidism results in mentally retarded dwarfs.
- Myxedema (Hypothyroidism in older child/adults)
o Generalized fatigue, apathy, mental sluggishness (may mimic depression)
o Speech and intellectual functions are slowed (no mental retardation)
o Listlessness, cold intolerance, and overweight
o ↓Sympathetic activity – constipation, ↓sweating, ↓ blood flow – cool/pale skin
o ↓Cardiac output - shortness of breath and decreased exercise capacity
o Atherogenic profile - an increase in total cholesterol and LDL levels
o Accumulation of matrix substances (glycosaminoglycans and hyaluronic acid) in skin/ other sites - Non-pitting edema
o EDEMA caused by accumulation of interstitial substance, NOT WATER (hence non-pitting), swollen puffy face
- Diagnosis of Hypothyroidism
o Patients with unexplained increases in body weight or hypercholesterolemia
o Diastolic hypertension (due to retention of sodium and water)
o Dilated cardiomyopathy with biventricular heart failure
o Muscle weakness common complaint
o Delayed relaxation of deep tendon reflexes (Woltman sign)
o Primary: TSH ↑, Secondary (hypothalamic/pituitary) – TSH not increased
o T4 ↓in individuals with hypothyroidism of any origin
- Hashimoto Thyroiditis
o Autoimmune destruction of thyroid gland with thyroid failure
o Most common cause of hypothyroidism in non-endemic areas, children
o 45 to 65 years of age, HLA-DR3 and HLA-DR5 associations
o Female predominance of 10 : 1 to 20 : 1, 45 to 65 yrs, HLA-DR3 & HLA-DR5
o Breakdown in self-tolerance to thyroid autoantigens, circulating autoantibodies against thyroglobulin and thyroid
peroxidase
o Morphology
Diffusely enlarged thyroid, cut surface is pale, yellow-tan and firm
Parenchymal infiltration by small lymphocytes and plasma cells
Thyroid follicles are atrophic and are lined by Hürthle cells
Interstitial connective tissue is increased and may be abundant but unlike Reidel thyroiditis, the fibrosis does not extend beyond the capsule of
the gland
o Clinical Course
Painless enlargement of thyroid + hypothyroidism, middle-aged woman
Hypothyroidism may be preceded by transient thyrotoxicosis caused by disruption of thyroid follicles,
leading to release of thyroid hormones (“Hashitoxicosis”)
Risk for developing other autoimmune diseases
Endocrine (Type 1 diabetes, Autoimmune adrenalitis)
Non-endocrine (SLE , Myasthenia gravis, and Sjögren syndrome)
↑risk for extranodal marginal zone B-cell lymphomas within thyroid
Possible predisposition to Papillary carcinoma thyroid
o Ex. A 43-year-old woman has had increasing lethargy and weakness over the past 3 years. She has cold intolerance and
wears a sweater in the summer. One year ago, she had menorrhagia, but now she has oligomenorrhea. She has difficulty
concentrating, and her memory is poor. She has chronic constipation. On physical examination, her temperature is
35.5Åã C, pulse is 54/min, respirations are 13/min, and blood pressure is 110/70 mm Hg. She has alopecia, and her skin
appears coarse and dry. Her face, hands, and feet appear puffy, with doughlike skin. Laboratory findings show
hemoglobin, 13.8 g/dL; hematocrit, 41.5%; glucose, 73 mg/dL; and creatinine, 1.1 mg/dL. The representative
microscopic appearance of her causative disease is shown in the figure. Which of the following serologic test findings is
most likely to be positive in this woman? Anti–thyroid peroxidase antibody
The lymphoid follicles and the large, pink nodules of Hü rthle cells in this photomicrograph are typical for
Hashimoto thyroiditis. The anti–thyroid peroxidase (antimicrosomal) and antithyroglobulin antibody titers
typically are increased in patients with Hashimoto thyroiditis when thyroid enlargement is still present. In
the later, “burnt-out” phase of Hashimoto thyroiditis, the antibodies are sometimes undetectable— only the hypothyroidism is. The thyroid-
stimulating hormone (TSH) level is an indication of whether there is a primary disease in the thyroid. If the patient appears hypothyroid and a
primary thyroid disease (e.g., Hashimoto thyroiditis) is suspected, the TSH level is elevated.
- Subacute Lymphocytic (Painless) Thyroiditis
o Postpartum/Sporadic thyroiditis, mostly middle-aged women
o Circulating anti-thyroid peroxidase antibodies or a family history of other autoimmune disorders
o Lymphocytic infiltration with large germinal centers within the thyroid parenchyma and patchy disruption and collapse of thyroid follicles
o NO Fibrosis or Hürthle cell metaplasia
o Painless and postpartum thyroiditis are variants of autoimmune thyroiditis
o Ex. A 30-year-old woman has given birth to her second child. She develops heat intolerance and loses more weight than expected postpartum. On physical
examination, her thyroid gland is enlarged but painless; there are no other remarkable findings. Laboratory studies show a serum T4 level of 12 μg/dL and a
TSH level of 0.4 mU/L. A year later she is euthyroid. Which of the following is most indicative of the pathogenesis of this
patient’s disease? Anti–thyroid peroxidase antibodies
The presence of autoantibodies in the serum in this patient with transient hyperthyroidism would suggest
Hashimoto thyroiditis (“hashitoxicosis”), but the variant called subacute lymphocytic painless thyroiditis may
affect 1 in 20 postpartum women, and a minority progress to hypothyroidism.
o Ex. A 46-year-old woman complains of increasing fatigue and muscle weakness over the past 6 months. She reports an
inability to concentrate at work and speaks with a husky voice. The patient denies drug or alcohol abuse. Physical
examination reveals cold and clammy skin, coarse and brittle hair, boggy face with puffy eyelids, and peripheral edema.
There is no evidence of goiter or exophthalmos. Laboratory studies show reduced serum levels of T3 and T4. Which of the
following is the most likely underlying cause of these signs and symptoms? Autoimmune thyroiditis.
Hypothyroidism refers to the clinical manifestations of thyroid hormone deficiency. It can be the consequence
of three general processes: (1) defective synthesis of thyroid hormone; (2) inadequate function of thyroid
parenchyma; and (3) inadequate secretion of TSH. Dominant clinical manifestations of hypothyroidism include muscular weakness, peripheral
edema, “myxedema madness,” pallor, and enlarged tongue. Women with hypothyroidism suffer ovulatory failure, progesterone defi ciency, and
irregular and excessive menstrual bleeding. Erectile dysfunction and oligospermia are common symptoms of hypothyroidism in men. Primary
(idiopathic) hypothyroidism is often autoimmune. Three fourths of patients with primary hypothyroidism have circulating antibodies to thyroid
antigens, suggesting that these cases represent the end stage of autoimmune thyroiditis.
- Granulomatous Thyroiditis
o De Quervain thyroiditis, most common cause of thyroid pain
o Women, 40 - 50 years
o Triggered by a viral infection, seasonal incidence
o Aggregates of lymphocytes, activated macrophages, and plasma cells associated with collapsed and damaged thyroid
follicles
o Multinucleate giant cells enclose naked pools or fragments of colloid
o Unlike autoimmune thyroid disease, the immune response is virus-initiated and not self-perpetuating, so the process is
limited
o Ex. A 37-year-old woman has had difficulty swallowing and a feeling of fullness in the anterior neck for the past week. She is recovering from a mild upper
respiratory tract infection 1 month ago. On physical examination, her temperature is 37.4 deg C, pulse is 74/min, respirations are 16/min, and blood pressure
is 122/80 mm Hg. Palpation of her diffusely enlarged thyroid elicits pain. Laboratory studies show an increased serum T4 level and a decreased TSH level. Two
months later, she no longer has these complaints. The T4 level is now normal. Which of the following conditions is most likely to have produced these
findings? Subacute granulomatous thyroiditis
Subacute granulomatous thyroiditis (de Quervain thyroiditis) is a self-limited condition that can be of viral origin because many cases are
preceded by an upper respiratory infection. The transient hyperthyroidism results from inflammatory destruction of the thyroid follicles and
release of thyroid hormone. The released colloid acts as a foreign body, producing florid granulomatous inflammation in the thyroid.
o Ex. A 43-year-old woman complains of low-grade fever and has a 3-day history of pain in her neck. Physical examination reveals a slightly enlarged thyroid. A
CBC is normal. A biopsy of the thyroid reveals granulomatous infl ammation and the presence of giant cells (shown in the image). What is the appropriate
diagnosis? Subacute (DeQuervain) thyroiditis
- Riedel thyroiditis
o Extensive fibrosis involving thyroid and contiguous neck structures with extension of fibrosis into surrounding tissue
(unlike Hashimoto)
o Hard and fixed thyroid mass (clinically simulates a thyroid carcinoma)
o Associated with fibrosis in other sites (retroperitoneum, mediastinum)
o Treatment: Corticosteroids, Tamoxifen, Surgery
o Ex. A 33-year-old woman complains of swelling in the anterior portion of her neck, which she fi rst noticed 8 months
ago. Except for some discomfort during swallowing and hoarseness, the patient does not report any symptoms.
Physical examination reveals a stony, hard thyroid gland that is adherent to other neck structures. A thyroid biopsy is
shown in the image. The pathologist reports that the thyroid parenchyma is replaced by dense, hyalinized fibrous tissue and a chronic
inflammatory infiltrate. What is the appropriate diagnosis? Riedel thyroiditis
Hyperthyroidism
Thyrotoxicosis - hypermetabolic state caused by ↑free T3 and T4
1. Diffuse hyperplasia of thyroid with Graves disease (85% of cases)
2. Hyperfunctional multinodular goiter
3. Hyperfunctional thyroid adenoma
- Hyperthyroidism
o ↑Basal metabolic rate, heat intolerance, weight loss despite ↑appetite
o Heart: tachycardia, palpitations, cardiomegaly, arrhythmias, CHF
o Overactivity of sympathetic nervous system - tremor, hyperactivity, emotional lability, anxiety, inability to concentrate, and insomnia
o GIT: hypermotility, diarrhea, and malabsorption
o Ocular changes
o Skeletal system: osteoporosis
o Muscle atrophy with fatty infiltration and focal lymphocytic infiltrates
o Minimal hepatomegaly due to fatty changes in the hepatocytes
o Generalized lymphoid hyperplasia and lymphadenopathy
o A person with hyperthyroidism showing wide-eyed, staring gaze, caused by overactivity of the sympathetic nervous system
o In Graves disease, accumulation of loose connective tissue behind the eyeballs adds to the protuberant appearance of the eyes
o Ex. A 65-year-old woman with a history of multinodular goiter complains of increasing nervousness, insomnia, and heart palpitations. She has lost 9 kg (20 lb)
over the past 6 months. Physical examination reveals a diffusely enlarged thyroid. There is no evidence of exophthalmos. Laboratory studies show elevated
serum levels of T3 and T4. Serologic tests for antithyroid antibodies are negative. Which of the following is an important complication of this patient’s
endocrinopathy? Cardiac arrhythmia
- Thyroid Storm
o Abrupt onset of severe hyperthyroidism
o Patients with underlying Graves disease
o Acute elevation in catecholamine levels, during infection, surgery, cessation of antithyroid medication, or any form of stress
o Patients - febrile , tachycardia out of proportion to the fever
o Medical emergency - significant number of untreated patients die of cardiac arrhythmias
o Ex. A 42-year-old woman has a sudden onset of fever with headache, nausea, diaphoresis, and palpitations. On physical examination her temperature is
39.2Åã C; pulse, 115/min; irregular respiratory rate, 30/min; and blood pressure, 150/85 mm Hg. Deep tendon reflexes are 4+ bilaterally. Her outstretched
hands exhibit a high frequency tremor. Which of the following drugs should she receive emergently? Propranolol
Thyroid storm is a medical emergency. There is not enough time to wait for confirmatory laboratory thyroid testing. There are increased
catecholamine levels, and the β-blocker propranolol will help prevent emergent
death from cardiac failure.
- Apathetic hyperthyroidism
o Thyrotoxicosis occurring in older adults
o Advanced age and co-morbidities blunt the features of hyperthyroidism
o Diagnosis made during laboratory work-up for unexplained weight loss or worsening cardiovascular disease
- Diagnosis of hyperthyroidism
o Primary Hyperthyroidism: ↓ TSH, ↑ free T3 &T4
o Secondary Hyperthyroidism: pituitary associated, TSH may be ↑
o TRH stimulation test - to evaluate cases of suspected hyperthyroidism with equivocal changes in the baseline serum TSH level (Normal rise in TSH after
administration of TRH excludes secondary hyperthyroidism)
o Measurement of radioactive iodine uptake by the thyroid gland
Graves disease: diffusely increased uptake in the whole gland
Toxic adenoma: increased uptake in a solitary nodule
Thyroiditis: decreased uptake
o TSH is usually not stimulated by TRH in TSH-omas
- Management of hyperthyroidism
o β-blocker to control symptoms induced by ↑ adrenergic tone
o Thionamide to block new hormone synthesis
o Iodine solution to block the release of thyroid hormone
o Agents that inhibit peripheral conversion of T4 to T3
o Radioiodine, incorporated into thyroid tissues, results in ablation of thyroid function over a period of 6 to 18 weeks
- Graves Disease
o Triad of findings
Hyperthyroidism associated with diffuse enlargement of the gland
Infiltrative ophthalmopathy with resultant exophthalmos
Localized, infiltrative dermopathy, pretibial myxedema, in fewpatients
o More often in women, 20 to 40 years of age
o Autoantibodies against multiple thyroid proteins (TSH receptor)
Thyroid stimulating immunoglobulin (TSI) in 90% of patients
o A: The patient has exophthalmos and a diffuse enlargement of the thyroid gland (goiter)
o B: Severe exophthalmos - proptosis of the eye, increased vascularity of the conjunctiva, and the enlarged lacrimal gland
o C: Pretibial myxedema (thickened area of erythema involving the pretibial area and dorsum of the foot)
o Infiltrative ophthalmopathy
Protrusion of the eyeball (Exophthalmos) is associated with ↑volume of the retro-orbital connective tissues and extraocular
muscles
Marked infiltration of the retro-orbital space by mononuclear cells, mainly T cells
Inflammation with edema and swelling of extraocular muscles
Accumulation of ECM components, specifically hydrophilic glycosaminoglycans (hyaluronic acid and chondroitin
sulfate)
↑numbers of adipocytes (fatty infiltration)
Studies performed in animal models suggest that orbital preadipocyte fibroblasts, which express the TSH receptor, appear to stimulate the
autoimmune reaction
o Morphology
Symmetric enlargement
Parenchyma has a soft, meaty appearance resembling muscle
Untreated cases
Follicular epithelial cells are taller and more crowded
Small papillae lacking fibrovascular cores encroaching on the colloid
Colloid within the follicular lumen is pale, with scalloped margins
Diffusely hyperplastic thyroid in Graves disease showing follicles lined by tall, columnar epithelium. The
crowded, enlarged epithelial cells project into the lumens of the follicles. These cells actively resorb the
colloid in the centers of the follicles, resulting in the scalloped appearance of the edges of the colloid
o Morphology after treatment
After administration of iodine: involution of epithelium and accumulation of colloid (blocks thyroglobulin
secretion)
Treatment with the anti-thyroid drug propylthiouracil: exaggerates epithelial hypertrophy and hyperplasia (stimulates TSH secretion)
Changes in other organs
Enlargement of the thymus in younger patients
Hypertrophy of heart
Hydrophilic mucopolysaccharide deposition in the tissues of the orbit
Deposition of glycosaminoglycans and lymphocyte infiltration in dermis
o Clinical course
Thyrotoxicosis
Diffuse hyperplasia of the thyroid: audible “bruit”
Ophthalmopathy: wide, staring gaze and lid lag
Dermopathy: most common in the skin overlying the shins
Cardiac findings: Atrial fibrillation, Sinus tachycardia, Systolic HTN, High output failure
↑glucose, calcium, lymphocytes; ↓cholesterol
↑free T4 and T3 levels and ↓TSH levels
Radioiodine scans - diffusely increased uptake of iodine
Treatment: β-blockers, thionamides, radioiodine ablation, thyroidectomy and surgery
o Ex. A 20-year-old woman and her twin sister both experience increasing diplopia. Their conditions develop within 3 years of each other. On physical
examination, they have exophthalmos and weak extraocular muscle movement. The thyroid gland is diffusely enlarged but painless in each sister, and there is
no lymphadenopathy in either woman. Which of the following serum laboratory findings is most likely to be reported in these sisters? Decreased thyroid-
stimulating hormone level
Exophthalmos is a feature seen in about 40% of individuals with Graves disease. The hyperfunctioning thyroid gland leads to an increased T4 level,
with positive feedback from the pituitary to decrease thyroid-stimulating hormone (TSH) secretion. There is about 50% concordance of Graves
disease among identical twins. The autoimmune character of this disorder is evidenced by an association with HLA-DR3 and by the presence of an
autoantibody against TSH receptor that activates T4 secretion.
o Ex. A 21-year-old woman has noted increasing fatigue and a 7-kg weight loss without dieting over the past 4 months. She also has increasing anxiety and
nervousness with diarrhea. Physical examination shows a diffusely enlarged thyroid gland. Her temperature is 37.5 deg C, pulse is 103/min, respirations are
28/min, and blood pressure is 140/75 mmHg. A radionuclide scan of the thyroid shows a diffuse increase in uptake.
The figure shows the representative microscopic appearance of the thyroid gland. What is most likely to produce these
findings? Antibodies against TSH receptor
The tall columnar epithelium with papillary infoldings and scalloping of the colloid is characteristic of
Graves disease, which leads to hyperthyroidism. This disease is caused by autoantibodies that bind to the
thyroid-stimulating hormone (TSH) receptor and mimic the action of TSH.
o Ex. A 40-year-old man notes weight loss, increased appetite, and double vision for 6 months. On physical examination,
his temperature is 37.7deg C, pulse is 106/min, respirations are 20/min, and blood pressure is 140/80 mm Hg. A fine
tremor is observed in his outstretched hands. He has bilateral proptosis and corneal ulceration. Laboratory findings
include a serum TSH level of 0.1 mU/L. A radioiodine scan indicates increased diffuse uptake throughout the thyroid.
He receives propylthiouracil therapy, and his condition improves. Which of the following best describes the
microscopic appearance of his thyroid gland before therapy? Papillary projections in thyroid follicles and lymphoid aggregates in the stroma
The clinical findings in this case point to hyperthyroidism, and the increased, diffuse uptake corroborates Graves disease as a probable cause
because the thyroidstimulating hormone (TSH) level is quite low. The thyroidstimulating immunoglobulins that appear in this autoimmune
condition result in diffuse thyroid enlargement and hyperfunction, and papillary projections lined by tall columnar epithelial cells.
Differential: Destruction of thyroid follicles with lymphoid aggregates and Hürthle cell metaplasia is characteristic of Hashimoto thyroiditis. A
goiter has enlarged follicles and flattened epithelial cells; most of these patients are euthyroid. Follicular destruction and the presence of giant
cells occur in granulomatous thyroiditis. Nests of cells in a Congo red–positive hyaline stroma characterize a medullary carcinoma, which can be
multifocal, but is not diffuse and
does not lead to hyperthyroidism.
o Ex. A 55-year-old man complains of severe muscle weakness and drooping eyelids. He states that his symptoms worsen with repetitive movements but then
resolve after a short rest. A chest X-ray reveals an anterior mediastinal mass. A biopsy of this mass would most likely reveal which of the following pathologic
changes? Thymic hyperplasia
Myasthenia gravis is an acquired autoimmune disease characterized by abnormal muscular fatigability and is caused by circulating antibodies to
the acetylcholine receptor at the myoneural junction. In two thirds of patients, thymic hyperplasia is closely associated with myasthenia gravis,
and 15% have thymoma. Conversely, one third to one half of patients with thymoma develop myasthenia gravis. Thymectomy is often an effective
treatment for
these patients.
o Ex. A 29-year-old woman complains of nervousness and muscle weakness of 6 months in duration. She is intolerant of
heat and sweats excessively. She has lost 9 kg (20 lb) pounds over the past 6 months, despite increased caloric intake.
She frequently finds her heart racing and can feel it pounding in her chest. She also states that she has missed several
menstrual periods over the past few months. Physical examination reveals warm and moist skin and bulging eyes
(exophthalmos). Laboratory studies will likely reveal which of the following endocrine abnormalities in this patient? Anti-
TSH receptor antibodies
Ex. A thyroid biopsy obtained from the patient described in Question above is shown in the image. Which of
the following best describes the pathologic findings? Follicular hyperplasia with scalloping of colloid
o Ex. A 33-year-old woman presents with a swelling in her neck, which she fi rst noticed 2 months ago. Physical
examination reveals a solitary, nontender nodule of the thyroid gland measuring 2 cm in diameter. Thyroid function tests
are within normal limits. The nodule does not accumulate 125Iodine on thyroid scintiscan. A biopsy of the nodule is
shown in the
image. Which of the following is the most likely diagnosis? Follicular adenoma
Goiters
- Diffuse and Multinodular Goiters
o Goiter: enlargement of the thyroid due to impaired synthesis of thyroid hormone, mostly due to dietary iodine deficiency
o Impaired thyroid hormone synthesis compensatory rise in serum TSH hypertrophy & hyperplasia of thyroid follicular cells Gross enlargement
o Compensatory increase in functional mass Euthyroid state
o If iodine deficiency is severe Goitrous hypothyroidism
- Diffuse Nontoxic (Simple) Goiter
o Colloid goitre, enlargement of the entire gland, NO nodularity
o Endemic goiter
Geographic distribution (mountainous regions)
Variations in prevalence suggest role of Goitrogens (Brassicaseae family – cabbage, cassava)
o Sporadic goiter
Female preponderance, puberty/young adults
Ingestion of substances that interfere with thyroid hormone synthesis
Hereditary enzymatic defects (dyshormonogenetic goiter)
In most cases, the cause is not apparent
o Cassava contains a thiocyanate that inhibits iodide transport within the thyroid, worsening any possible concurrent iodine deficiency
o Ex. A 45-year-old woman from Kathmandu, Nepal, reports a feeling of fullness in her neck, but has no other concerns. The enlargement has been gradual and
painless for more than 1 year. Physical examination confirms diffuse enlargement of the thyroid gland without any apparent masses or lymphadenopathy.
Laboratory studies of thyroid function show a normal free T4 level and a slightly increased TSH level. What is the most likely cause of these findings? Diffuse
nontoxic goiter
Diffuse nontoxic goiter is most often caused by dietary iodine deficiency. This condition is endemic in regions of the world where there is a
deficiency of iodine (e.g., inland mountainous areas); it also may occur sporadically. As in this case, patients are typically euthyroid.
Differential: A follicular adenoma rarely functions to produce excess thyroid hormone; most are “cold,” nonfunctioning nodules that do not
involve the thyroid diffusely. A chronic lymphocytic thyroiditis, such as Hashimoto thyroiditis, initially can produce
thyroid enlargement, but atrophy eventually occurs with resulting hypothyroidism. Papillary carcinomas most often
produce a mass effect or metastases and do not affect thyroid function. Subacute granulomatous thyroiditis can lead
to diffuse enlargement, and transient hyperthyroidism can occur, but the disease typically runs a course of no more
than 6 to 8 weeks. Plummer disease, or toxic multinodular goiter, occurs when there is a hyperfunctioning nodule in
a goiter.
o Ex. A 14-year-old girl noticed gradual neck enlargement during the past 8 months. On physical examination her thyroid gland is
diffusely enlarged. Her serum TSH level is normal. A dietary history is most likely to reveal that she has begun eating more of
which of the following foods? Cabbage
She has developed a sporadic goiter. Vegetables of the Brassicaceae family, including cabbage, turnips, and Brussels
sprouts, contain glucosinolate, which can decompose to release thiocyanate, a by product that interferes with
thyroid hormone synthesis. Thus such substances are known as goitrogens. Young persons with increased demand
for thyroid hormone are at increased risk.
o Ex. A 55-year-old woman presents with a large anterior neck mass (patient shown in the image). She also complains of dysphagia and hoarseness. Physical
examination reveals inspiratorystridor. Laboratory evaluation of this patient would most likely demonstrate which of the following? Euthyroidism
o Ex. A 52-year-old woman complains of swelling in the anterior portion of her neck, which she first noticed 6 months ago. Except for some discomfort during
swallowing, the patient does not report any significant symptoms. Physical examination reveals a symmetrically enlarged thyroid. A thyroid biopsy is shown in
the image. Which of the following is the most likely diagnosis? Nontoxic goiter
o Ex. Five years later, the patient described in Question 30 returns with symptoms of hyperthyroidism. Which of the following best summarizes the clinical
symptoms expected in this patient? Tremor, tachycardia, weight loss
- Goiter
o Enlarged thyroid
Does not indicate functional status of gland - may be associated with hypo, hyper or euthyroidism
Low dietary intake of iodine leads to less production of thyroid hormone – stimulates release of TSH –
leads to thyroid enlargement
ENDEMIC GOITER: in restricted geographical regions where natural iodine supply is low
- Multinodular Goiter
o Recurrent episodes of hyperplasia and involution
o Extreme thyroid enlargements
o Frequently mistaken for neoplasms
o Intrathoracic or plunging goiter - grows behind sternum and clavicles
o Morphology
C/s: Irregular nodules containing variable amounts of colloid
Older lesions show hemorrhage, fibrosis, calcification, and cystic
change
Microscopic appearance
Colloid-rich follicles lined by flattened, inactive epithelium
Areas of follicular hyperplasia with degenerative changes
No capsule between the hyperplastic nodules and residual compressed thyroid parenchyma (unlike follicular neoplasms)
o A: Gross morphology demonstrating a coarsely nodular gland, containing areas of fibrosis and cystic change
o B: Photomicrograph of a hyperplastic nodule, with compressed residual thyroid parenchyma on the periphery. There is no capsule (distinguishing feature
from follicular neoplasms)
o Clinical Course
Mostly euthyroid
Mass effects from enlarged thyroid
Hemorrhage into cysts produces sudden, painful, gland enlargement
Pemberton sign: compression of the jugular vein causing neck congestion
T3 and T4 levels are normal, TSH is usually elevated or upper normal
Plummer syndrome: an autonomous nodule develops within a long-standing goiter and produces hyperthyroidism (toxic multinodular goiter)
Dyshormonogenetic goiter In children may induce cretinism
o Ex. A 70-year-old man has had greater difficulty swallowing for the past 2 years. Over the past 6 months, he has lost 3 kg. On physical examination, his
temperature is 37.3 deg C, and pulse is 102/min. There is fullness to the anterior neck, with a 5 Å~ 10 cm irregular mass on palpation. Laboratory studies show
serum TSH of 0.2 mU/L. A thyroid scintigraphic scan shows a 1.5-cm nodule with increased uptake in the right thyroid lobe, and decreased uptake into the
remaining enlarged thyroid. What is the most likely diagnosis? Toxic multinodular goiter
A long-standing diffuse goiter can evolve into a multinodular goiter, and one of the nodules can begin hyperfunctioning to cause so-called
Plummer disease. This “toxic” nodule has acquired growth and functional characteristics similar to a benign neoplasm, such as a follicular
adenoma, but one that is functional.
Differential: Rare toxic follicular adenomas can function and produce “hot” nodules, but the remaining gland is often atrophic, not enlarged. In
Graves disease, the thyroid is enlarged, but usually diffusely, without pronounced nodularity, so that there is increased uptake into the entire
gland. In addition, clinical features such as dermopathy and ophthalmopathy that are lacking with Plummer disease are associated with Graves
disease. There may be initial diffuse thyroid enlargement with Hashimoto thyroiditis and transient hyperfunction, but over time the thyroid
atrophies, and hypothyroidism ensues. It is extremely rare for a papillary carcinoma to function, and although this would be a hot nodule,
the remaining thyroid would not be enlarged.
- Euthyroid sick syndrome (ESS)
o Serum T3 and T4 are abnormal but gland function appears normal
o Associated with: malignancy, heart failure, anorexia nervosa, chronic renal failure, sepsis, myocardial infarction
o Pathogenesis: block in outer ring deiodinase conversion of FT4 to FT3; FT4 is converted to inactive reverse T3