Endocrine Pathology

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ENDOCRINE PATHOLOGY

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Case 1: Enlarging neck (Grave’s disease) A 43 year old female noted gradual neck enlargement every time she got pregnant. She had occasional irritability & palpitations, excessive sweating & easy fatigability. Since 1 year ago, she lost 15 kg despite eating adequately. Later, the patient developed exopthalmos, prompting consult. On physical examination, PR 105/minute, regular; RR 24/ minute; BP: 130/80; BW: 52.7 kg. Thyroid lobes are easily palpable, moves with deglutition, soft, nontender, no nodules noted. Chest & abdominal findings are normal Explain the signs & symptoms of the patient. Discuss the etipathogenesis of exopthalmos & weight loss. o Signs & symptoms are due to excessive secretion of thyroid hormones o Thyroid hormones increase basal metabolic rate o Increased basal metabolic rate & increase in uncoupling protein levels → Increased oxygen consumption, decreased ATP production, increased heat production → Activation of heat losing mechanism of the body → excessive sweating o Palpitations: increased cardiac rate due to increased thyroid hormones & effects of increased oxygen requirement o Exopthalmos  T cells are sensitized to antigens shared by thyroid follicles & orbital fibroblasts, accumulate around the eye, where they secrete cytokines that activate fibroblasts.  Enlargement of the extraocular muscles around the orbit. The muscles are normal but they are swollen by mucionous edeme & accumulation of fibroblasts & infiltration by lymphocytes. The increased orbital contents caused forward displacement of the eye o Weight loss: Increased metabolic rate with subsequent loss of subcutaneous fat o Pregnancy: Stimulation of human chorionic gonadotropin on thyroid She has been diagnosed with diffuse toxic goiter o Colloid goiter o Goiter:  Any enlargement of the thyroid  Graves disease  Iodine deficiency  Tumor Which laboratory ancillary procedures are necessary to evaluate patient’s condition? What would be the expected results? o Thyroid function tests: Free T3, Free T4, TSH levels o Expected results: Increased free T3 & T$, decreased TSH levels Slide A: Normal thyroid gland o Lining epithelium: Cuboidal o Colloid: Acidophilic intraluminal deposit: thyroid globulin o Physiologic enlargement of thyroid due to pregnancy o Early in pregnancy: Increase renal blood flow & glomerular filtration which increased iodine clearance from plasma. This results in a fall in plasma iodine concentration & an increase in the iodide requirements in the diet o Near the end of 1st trimester: Direct stimulatory effects of hCG on the thyroid induces a small & transient increase in the free thryoxine levels & in turn a partial decrease in TSH secretion

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First half of gestation: Marked increase in thyroid binding globulin which causes an increased increase in total serum thyroid levels. Patient may develop transient hyperthyroid state Slide B: Multinodular Goiter o Gross: Enlarged nodular gland o Microscopic  Flattened squamous to cuboidal epithelium  Varisized glands with enlarged glands  Distention of the follicles filled with colloid  Cystic follicles/ Colloid cyst o Cyclical variations in the need for thyroid hormones & alternating episodes of stimulation & involution. Some patients have thyroid growth immunoglobulins that promote thyroid growth without activating hormone production o Signs & symptoms: Asymptomatic thyroid enlargement o Complications:  Dysphagia & stridor: Large goiter compressing the esophagus & trachea  Venous congestion of head & face: Pressure on neck veins  Hoarseness: Compression of recurrent laryngeal nerves  Local pain: Hemorrhage into a nodule or cysts Slide C: Grave’s disease o Gross: Diffuse, symmetrically enlarged o Microscopic  Diffusely hyperplastic  Tall columnar epithelial cells  Papillae that project into lumen  Depleted colloid (scalloped or moth eaten appearance) o IgG antibodies are present which are directed against components of thyroid follicular epithelium, stimulating TSH receptor & increasing thyroid hormone secretion o Most frequent cause of hyperthyroidism in patient younger than 40 o Signs & symptoms:  Enlarged thyroid gland  Hyperthyroid state: Nervousness, irritability, weight loss, exopthalmus, tremor, excessive sweating o Complication: Progressive thyroid failure Slide D: Hashimoto’s thyroiditis o Gross: Diffusely enlarged gland o Microscopic:  Infiltration by mononuclear cells & lymphocytes  Presence of germinal centers  Destruction & atrophy of follicles  Hurthle cell change: Oxyphilic metaplasia of follicular cells o Autoimmune process: Activation of CD4 T cells that have been sensitized by to thyroid follicles. The activated T cells recruit both autoreactive B cells & cytotoxic CD 8 T cells o More common during the 4th to 5th decade of life; women more affected than men o Signs & symptoms: Gradual onset of goiter; initially euthyroid becoming hypothyroid o Complications: Overt hyperthyroid state Slide E: De Quervain’s thyroditis (Subacute) o Gross: Enlarged gland o Microscopic  Patchy leukocytic infiltrate, plasma cells & macrophages o

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Destruction of follicles allow release of colloid that elicits granulomatous reaction  Numerous foreign body type Multinucleated giant cells A self-limiting viral infection characterized by granulomatous inflammation. Typically occurs after an upper respiratory tract infection caused by influenze virus, adenovirus, echovirus & coxsackie virus Affects women between 30 to 50 years Signs & symptoms  Pain in anterior neck  Fever  Tender thyroid gland 

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Case II: Firm mass on neck (Papillary carcinoma A 34 year old female noted slight swelling of the neck during pregnancy. After giving birth, the swelling persisted on one side. Consult revealed a palpable, non-tender, firm, nodule on the swollen side that moves with deglutition. Aside from the swollen neck, the patient is apparently normal o Recent growth: mass with tenderness & hoarseness, with radiation to head & neck → thyroid cancer o Significance of palpable nodule: Enlarged cervical lymph nodule o Diagnostic work up could be done to evaluate patient’s condition? What will be the expected results?  Fine needle aspiration biopsy: Lymphocytes & psamomma bodies  Radionuclide scan: Hot (Hyperthyroidism) Slide A: Papillary Carcinoma o Gross  Solitary, with fibrosis & calcifications  Firm, hard gritty nodule with pale cut surfaces o Microscopic  Branching papillae  Fibrovascular core with single row of stratified cuboidal to columnar epithelium  Nuclear atypia  Ground glass appearance  Orphan annie eye nuclei  Eosinophilic pseudoinclusion & nuclear grooves o Malignant neoplasm associated with iodine excess, radiation & genetic factors o Most common form of thyroid cancer o More common in women between ages 20 to 50 o Signs & symptoms  Painless, palpable nodule  Enlarged cervical lymph nodes  Cervical lymphadenopathy without palpable nodule o Complications  Hoarseness, dysphonia, cough & dyspnea: Obstruction to trachea & esophagus  Metastasis to regional lymph nodes, lungs & brain Slide B: Follicular adenoma o Gross  Solitary, spherical well demarcated  Area of hemorrhage  Encapsulated o Microscopic  Proliferating epithelium with fibrous capsule without invasion (Usually not

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demonstrated in fine needle aspiration biopsy)  No vascular invasion o Signs & symptoms  Unilateral painless mass  Cold nodule: Takes up less iodine o Benign thyroid neoplasm o Complications: Compression of contiguous structures (Trachea & esophagus) o Common in young women but occurs in all ages Slide C: Follicular carcinoma o Gross: Solitary encapsulated nodule o Microscopic  Proliferating thyroid epithelial cells  Variable nuclear pleomorphism  Definitive fibrous capsule with capsular invasion (arrow) o 2nd most common thyroid carcinoma o More common in 40 to 50 o Signs & symptoms: Palpable thyroid nodule (Cold) o Complications: Metastasis (Hematogenous) to bone & lungs Slide D: Medullary carcinoma o Gross  Hemorrhage, necrosis  Tends to arise in the superior portion of the thyroid where it is richest in C cells o Microscopic  Polygonal granular cells separated by a distinct vascular stroma  Upper inset: Acellular stromal amyloid (deposition of procalcitonin)  Lower inset: Positive reaction with calcitonin marker o Signs & symptoms  Increased vasoactive peptide: Might manifests as diarrhea  Carcinoid syndrome: Serotonin o Tumor derived from the parafollicular or C cells of the thyroid which are distinguished by their secretion of calcium lowering calcitonin o Mean age: 50, more in female o Complications: Widespread metastasis Case III: Body weakness: Parathyroid adenoma A 65 year old female complained of bone pains, recurrent abdominal cramps & constipation. She is also often lethargic & weak She had recurrent UTI due to presence of calcium oxalate stones in urine. She had been told of possible parathyroid pathology o Hyperparathyroidism  Increase bone resorption (activation of osteoclasts, which makes the bone weak)  Increase gastric absorption of calcium  Increase excretion of phosphates  Increase renal absorption of calcium o Renal stones: Increased resorption from renal tubules, urinary retention o Laboratory/ ancillary procedures  Increased serum ionized calcium  Increased chlorine  Decreased phosphate Slide A: Parathyroid hyperplasia o Microscopic  Normal adipose tissue is replaced by hyperplastic chief cells arranged as sheets  Small foci of adipose tissue is still noticeable

Non specific proliferation of parathyroid chief cells leading to excessive secretion of parathyroid hormone o Gross: all 4 parathyroid glands are enlarged o Signs & symptoms: Asymptomatic hypercalcemia to systemic renal & skeletal disease o Complications  Chondrocalcinosis  Pathological fracture  Renal failure secondary to nephrocalcinosis  Chronic pancreatitis  Gastrointestinal disturbances  Lethargy, depression, seizures  Aortic & mitral valve calcifications Slide B: Parathyroid Adenoma o Gross: Solitary circumscribed mass o Microscopic  Sheets of neoplastic chief cells embedded in rich capillary network o 80% of all cases o

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Case IV: Galactorrhea: Pituitary adenoma (Prolactinoma) A tall voluptuous 24 year old female experienced double vision upon waking up. Since adolescence, her menses were irregular but she had been amenorrheic for the past 3 months Physical examination revealed large breasts, with minimal white secretions expressed from the nipples o Tumor cells secrete prolactin o Double vision  Increase in the size impinges on the optic chiasm  Cranial nerves 3,4 & 6: Weakness of ocular muscles o Amenorrhea: Increase in prolactin exerts antagonistic effect on FSH & LH o Laboratory/ Ancillary procedures  Serum prolactin elevation  CT scan, MRI  Enlarged sella turcica  Tumor enlargement o Causes  Physiologic: Pregnancy, stress, nipple stimulation  Patholgic: Dopamine antagonists & antihypertensives (Reserpine) o More common in men between 20 to 50 years Slide A o Acidophiles or chromophobe hypersecreting prolactin o Gross: Usually a macroadenoma o Signs & symptoms: Galactorrhea, infertility, decreased libido & erectile dysfunction o Complications: Expansile growth of the tumor into sphenoid sinus, cavernous sinus & optic chiasm may damage optic nerves & grow into brain & disrupt morphology & function of hypothalamus Slide B: Corticotroph adenoma o Tumor cells secrete corticotrophin which induces adrenal cortical hypersecretion to produce Cushing disease o Gross: Usually a microadenoma o Microscopic: Intensely basophilic tumor cells o Signs & symptoms: Due to excessive corticosteroid  Obesity: Face, neck, trunk, abdomen  Atrophic skin  Hirsuitism  Hyperpigmentation  Osteoporosis  Hypertension

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Glucose intolerance Virilized female Erectile dysfunction

Case V: Uncontrolled hypertension: Pheochromocytoma A 53 year old male, experienced episodes of “headiness” & nape discomfort, increasing frequency & severity. His symptoms were relieved upon intake of antihypertensive medication. In between attacks, he is apparently normal During the last attack, BP was 190/110, PR 102/minute, RR 26/minute, temp 36.8°C. Initial workup revealed slight tachycardia on ECG, normal chest x ray, & elevated 24 hour VMA He was informed of possible pathology in adrenal gland causing hypertension o Vanylylmandellic acid  Metabolite of epinephrine  Mediates systemic actions of epinephrine Laboratory/ ancillary procedures o Plasma catecholamines o CT scan o MRI o Tumor related metabolite for diagnosis, adequacy of excision & follow up (Elevation: recurrence/metastasis) Slide A: Cortical Adenoma o Benign tumor of adrenal cortex o Gross  Solitary lesion  Well circumscribed with delicate capsule  Firm yellow lobulated mass  Thin rim of compressed adrenal cortex surrounds tumor o Microscopic  Brown oval nuclei with clear cytoplasm  Clear, lipid laden cells arranged in sheets & nests Slide B: Adrenal cortical adenoma o Gross: Encapsulated lobulated bulky tumor with yellow cut surfaces o Microscopic: Clear & compact cells with varying degrees of nuclear pleomorphism o Malignant neoplasm of the adrenal cortex Slide C: pheochromocytoma o Tumor of chromaffin cells of the adrenal medullar that secretes cathecholamines o Gross: Sharply circumscribed, reddish brown mass occupying adrenal medulla, adrenal cortex compressed o Microscopic  Membrane bound vesicles with catecholamine  Polyhedral to fusiform tumor cells exhibiting marked pleomorphism o Signs & symptoms: sustained or episodic hypertension o Complications  Angina & myocardial infarction: due to myocardial necrosis caused by elevated catecholamine Slide D: Neuroblastoma o Malignant tumor of neural crest origin that is composed of neoplastic neuroblasts & originates in adrenal medulla & sympathetic ganglia o Neuroblasts: from primitive sympathogonia represents intermediate stage of development of sympathetic ganglionic neurons o Persistence & transformation of this embryonal structure o Gross  demarcated with fibrous pseudocapsule

Large lobulated hemorrhagic mass adherent to upper pole of the kidney o Microscopic  Small cells with dark nucleus & scanty cytoplasm  Dense sheets of small round to fusiform cells with hyperchromatic nuclei & scanty cytoplasm o Signs & symptoms  Enlarging abdomen  Firm, irregular non-tender mass  Marked irritability: Due to pain from bony metastasis  Gait disturbance: Due to spinal cord compression Complications: Widespread metastasis (Bone, liver, thorax) 

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