Name Incidence Pathology Clinical Histology Px TxWaterhouse-Friederichsen Syndrome

More common in children; results from acute bacterial infection (Neisseria meningitidis)

Primary acute adrenocortical insufficiency; bilateral hemorrhagic infarct of adrenal glands; glands enlarged.

Sepsis and DIC; Hypotension, shock, petechiae and/or purpura; hyponatremia, hyperkalemia, hypoglycemia

Hemorrhage starts within medulla and suffuses peripherally into cortex often leaving islands of recognizable cortical cells. Micro: little residual cortical architecture is discernable.

Often fatal if not treated immediately; death follows w/in hrs to a few days without Tx.

Antibiotics and Steroid Replacement; fludrocortisone.

Addison Disease

More common in white women (autoimmune adrenalitis); TB, AIDS or metastatic cancers

Primary Chronic Adrenocortical Insufficiency; destruction of adrenal cortex leading to deficiency of glucocorticoids, mineralocorticoids, androgens; ACTH is elevated

Gradual onset of weakness, skin hyperpigmentation, hypotension, hypoglycemia, poor response to stress, loss of libido.

Adrenals are small and scarred; loss of all but a subcapsular rim of cortical cells, there is extensive mononuclear cell infiltrate.

Death is rapid unless therapy begins immediately.

Steroid replacement, corticosteroid therapy.

Cushing Syndrome

More common in women (5:1) than men; 20-30 years due to Cushing’s Disease (adenoma) ; Ectopic ACTH production (oat cell carcinoma); iatrogenic (chronic corticosteroid use) – most

Hypercortisolism: condition that produces an elevation in glucocorticoid levels

HTN, truncal obsesity; “moon facies”, buffalo hump; proximal muscle weakness; striae; osteoporosis; hirsuitism; DM; emotional.

Adrenals will have cortical atrophy (if due to exogenous ACTH), diffuse hyperplasia, nodular hyperplasia or adenoma depending on cause of syndrome.

Prognosis depends on cause. Most cases can be cured. Some tumors may recur.

Pituitary adenomas are resected. use adrenal enzyme inhibitors (if unresectable tumor) including ketoconazole and aminoglutethimide

cases

Conn Syndrome Caused by adenoma; more common in women

Primary Hyperaldosteronism; chronic excess of aldosterone secretion.

HTN or hypokalemia; see decreased renin (contrast to secondary hyperaldosteronism)

Adenomas are usually solitary, small, well-circumscribed lesions (mostly on left) and yellow on cut section; composed of lipid-laden cortical cells of uniform size; presence of spironolactone bodies (eosinophilic, laminated cytoplasmic inclusions)

ECG changes and cardiac decompensation

Remove adenoma if possible. Medical treatment with aldosterone antagonist (spironolactone)

AtrophicAdrenal hyperplasia, bilateral; cortex is very thickened

Pheochromocytoma

Uncommon; tumor of chromaffin cells of medulla.10% malignant; 10% extra-adrenal; 10% bilateral; 10% pediatric; associated with MEN

Tumor of chromaffin cells which secrete catecholamines.

HTN, headache, flushing diaphoresis, palpitations, tachycardia, DM, anxiety; see increased catecholamines (plasma or urine); urine VMA and urine metanephrine

Gross: grey to red on cut surface; micro: nests of polygonal cells; EM: neurosecretory granules.

May lead to cardiac failure, sudden death.

Isolated benign tumors are surgically removed; use of adrenergic blockers to prevent HTN crisis; multi-focal lesions require long-term treatment.

Neuroblastoma Most common malignant childhood neoplasm (extracranial); kids < 5 yrs; 15% of childhood deaths from cancer. Whites males more common.

Tumor of sympathetic ganglion cells that can secrete catecholamines, VMA, HVA

Abdominal enlargement; HTN is uncommon since catecholamine secretion is in small amounts; fever and possible weight loss.

Micro: small round blue cell tumor; small cells embedded in finely fibrillar matrix.

Metastatic in 90% of patients at Dx.Better Px in patients less than 11 months at Dx, low stage, high VMA/HVA ratio and absent n-myc gene.

Depends on risk; most low risk are resected and higher risk are additionally treated with ChemoTx.

Congenital Adrenal Hyperplasia aka Adrenogenital Syndrome

Autosomal recessive

Enzymatic defects in production of cortisol ↓ cortisol, ↑ ACTH, and adrenal hyperplasia (most common type is 21-hydroxylase deficiency)

Presents soon after birth with salt wasting (lack of mineralocorticoids and glucocorticoids); virilization 2° to ↑ androgens

Cortex undergoes hyperplasia (bilateral); cortex is thickened and nodular; on cut section appears brown due to total depletion of lipid; proliferating cells are compact, eosinophilic, lipid-depleted cells mixed with lipid laden clear cells.

Hypotension, circulatory collapse.

Exogenous glucocorticoids; surgery depending on extent of virilization.

Primary Hyperparathyroidism

Adenoma (75-80%); Hyperplasia (10-15%); carcinoma < 5%

Excess production of PTH leading to hypercalcemia; lab findings of elevated ionized serum calcium, elevated or high normal PTH, hypophosphatemia

Often no symptoms just elevated serum Ca2+; bones: pain from osteoporosis, osteitis fibrosa cystica, “brown tumor”; kidney stones; Groans from PUD, pancreatitis, gallstones; moans from depression, coma, seizures; metastatic calcification; arrhythmias (shorted QT); neurologic changes;

See specific cause

See specific cause

Parathyroid Adenoma

95% sporadic; rest assoc w/MEN-I; 85% of cases of primary hyperparathyroidism

Primary Hyperparathyroidism; neoplastic cells grow and compress adjacent normal gland; not admixed w/fat

Bones, stones, groans and moans

Adenomas not that large and variable in location; difficult to differentiate from hyperplasia; cellular pleomorphism, mitoses are rare; absence of fat; rim of normal tissue

Good prognosis with few complications.

If mild, monitor for escalation in symptoms. A single adenoma may be surgically removed. If asymptomatic, surgery is recommended for patients under 50.

Monotonous cells, many capillaries, lack of fat.

After surgery, monitor for postoperative hypocalcemia.

Parathyroid Hyperplasia

20% of cases associated w/MEN I and II; monoclonal; 15% of cases of primary hyperparathyroidism.

All glands increased in size but may be asymmetrical sparing 1 or 2 glands; usually multinodular pattern with decreased fat and usually involves chief cells.

Symptoms due to hypercalcemia; fatigue, anorexia and drowsiness.

20% recurrence; prognosis is less than that of parathyroid adenoma; advanced complications include nephrocalcinosis and osteitis fibrosa cystica.

Removal of 3 and ½ glands; remaining tissue is sometimes implanted in forearm to ensure easy access in case of recurrence.

Parathyroid Carcinoma

Rare cause (1%) of primary hyperparathyroidism;

Malignant tumor secreting PTH; parenchyma predominantly chief cells (larger than in adenomas) and have bland cytological appearance; 2/3 of cases have extracapsular invasion by tumor.

1/3 are large enough to be palpable at diagnosis; serum calcium may be very high (exceeds 14 mg/dL); Symptoms of hypercalcemia.

A very large grey tumor - nodules. Micro: nuclear pleomorphism, fibrosis and invasion of adjacent tissues;

2/3 of cases recur.

Surgical resection is the only effective treatment. Removal of tumor, thyroid lobe, parathyroid, lymph nodes, and soft tissue.

Secondary Hyperparathyroidism

Most common cause is chronic renal failure w/ increased PTH; rare causes: malabsorption of Vitamin D and calcium and steatorrhea

Chronically depressed serum calcium, leading to increased PTH causing compensatory hyperplasia.

Skeletal pain from bone lesions (osteitis fibrosa cystica)

Parathyroids are enlarged but not symmetrically; chief cell nodular hyperplasia and decreased fat cells

May lead to calciphylaxis, significant ischemic damage to skin and other organs.

Subtotal parathyroidectomy, leaving 50 mg of tissue.

Hypoparathyroidism

Less common than hyperparathyroidism; due most often to thyroid surgery (accidental removal); DiGeorge Syndrome (congenital absence); Idiopathic atrophy (autoimmune); familial

PTH deficiency; ionized calcium falls below reference range;

Hypocalcemia, hyperphosphatemia with decreased PTH; tetany, muscle spasms, seizures, “Chvostek and Trousseau’s” signs; psychiatric disturbances; prolonged QT; cataracts; dental changes in kids.

Atrophy of parathyroid or complete absence. Many complications.

Vitamin D and calcium