Arthur S. Schneider, M.D. Department of Pathology Adrenal Disorders Arthur S. Schneider, M.D. Department of Pathology

Adrenal hyperfunction

Diffuse hyperplasia of adrenal (bottom illustration) from Robbins-Cotran PBD, 8e

Cushing syndrome hypercorticism regardless of cause medical use of exogenous adrenal corticoids – most frequent cause hyperproduction of ACTH by corticotrophs of the pituitary (“Cushing disease”) Ectopic ACTH production primary adrenal causes 

Adrenal hypercorticism secondary to pituitary disease (Cushing Disease) corticotropic adenoma (basophilic adenoma) hypersecretion of adrenocorticotropic hormone (ACTH) increased production of adrenal cortical hormones also may be caused by basophilic microadenomas– often multiple

Other causes of Cushing syndrome adrenal causes adrenal cortical adenoma adrenal carcinoma (less common than adenoma) ectopic ACTH production small cell lung carcinoma various other tumors Hypercorticism autonomous--not suppressed by exogenous adrenal steroids as in dexamethasone suppression tests  

Dexamethasone suppression tests test given at low (usually 1–2 mg) and high (8 mg) doses of dexamethasone levels of cortisol are measured low dose dexamethasone suppresses cortisol when there is no pathology in endogenous cortisol production high dose dexamethasone exerts negative retro-control on pituitary ACTH producing cells but not on ectopic ACTH producing cells or adrenal adenoma

ACTH measurements in hypercorticism increased in pituitary hypercorticism and in ectopic ACTH production low when hypercorticism is of adrenal origin

Morphologic changes bilateral hyperplasia of adrenal zona fasciculata occurs when syndrome results from ACTH stimulation adrenal cortical atrophy when exogenous glucocorticoid medication is cause adrenal cortical adenoma or carcinoma: adenoma more common

Cushing syndrome from Robbins-Cotran PBD, 8e

Cushing syndrome – clinical characteristics round moon face dorsal “buffalo hump” relatively thin extremities muscle wasting and weakness skin atrophy easy bruising and purplish striae over abdomen hirsutism muscle weakness osteoporosis, amenorrhea, hypertension, hyperglycemia, psychiatric dysfunction

Summary—Pituitary Cushing disease Increased corticotropin (ACTH) corticotropic (basophilic) adenoma or multiple corticotropic microadenomas

Summary -- Cushing syndrome (hypercorticism) Bilateral hyperplasia of adrenal zona fasciculata secondary to hyperactivity of pituitary corticotrophs or to ectopic ACTH-like production by a variety of tumors; adrenal cortical adenoma May be of pituitary, adrenal, or ectopic origin; can also result from administration of exogenous hormone

From Rubin’s Pathology

From Rubin’s Pathology

Primary aldosteronism (Conn syndrome)   primary hyperproduction of adrenal mineralocorticoids. usual cause: adrenocortical adenoma (aldosteronoma) also can result from hyperplasia of zona glomerulosa adrenocortical carcinoma much less common than adenoma or hyperplasia.

Clinical characteristics -- primary aldosteronism hypertension sodium and water retention hypokalemia decreased serum renin negative feedback of increased blood pressure on renin secretion

Primary aldosteronism from Robbins-Cotran PBD, 8e

Secondary aldosteronism secondary to renal ischemia, renal tumors, and profound edema of any cause such as cirrhosis, nephrotic syndrome, cardiac failure caused by stimulation of renin-angiotensin system serum renin increased (contrast to primary aldosteronism)

Serum renin in secondary aldosteronism increased (contrast to primary aldosteronism) synthesized in juxtaglomerular apparatus promotes conversion of angiotensinogen to angiotensin I angiotensin I converted by angiotensin-converting enzyme (mainly in the lung) to angiotensin II angiotensin II facilitates release of aldosterone

Summary -- hyperaldosteronism (aldosteronism) primary adenoma or hyperplasia of zona glomerulosa serum renin decreased secondary bilateral hyperplasia of zona glomerulosa caused by stimulation of renin-angiotensin system serum renin increased; frequently secondary to edema, regardless of the cause

Adrenal virilism (adrenogenital syndrome) congenital enzyme defects lead to diminished cortisol production compensatory increased ACTH adrenal hyperplasia androgenic steroid production 21-hydroxylase deficiency most common. in most severe “salt-wasting” form  salt loss and hypotension 11-hydroxylase deficiency, much less common salt retention and hypertension.

Adrenogenital syndrome clinical characteristics virilism in females precocious puberty in males

21-hydroxylase deficiency from Robbins-Cotran PBD, 8e

Summary--adrenal virilism adenoma, carcinoma, or hyperplasia of zona reticularis Can be due to hyperplasia resulting from congenital enzyme deficiencies such as 21-hydroxylase and 11-hydroxylase deficiencies

Adrenal hypofunction

Deficiency of pituitary ACTH adrenal failure is secondary no hyperpigmentation of the skin lack of b-melanocyte-stimulating hormone (β-MSH ) as well as ACTH contrasts with primary adrenal failure (Addison disease) in which ACTH and β-MSH is increased and hyperpigmentation is the rule

Hypocorticism (adrenal hypofunction) cause is primary in adrenal or secondary to hypothalamic or pituitary dysfunction deficiency of glucocorticoids (primarily cortisol), often with associated mineralocorticoid deficiency

Addison disease (primary adrenocortical deficiency) idiopathic adrenal atrophy (autoimmune lymphocytic adrenalitis) most common cause tuberculosis (former most common cause) metastatic tumor, and various infections

Addison disease -- characteristics hypotension increased pigmentation of skin decreased serum sodium, chloride, glucose, and bicarbonate increased serum potassium

Addison disease secondary to tuberculosis

Addison disease secondary to tuberculosis

Waterhouse-Friderichsen syndrome catastrophic adrenal insufficiency and vascular collapse due to hemorrhagic necrosis of the adrenal cortex.often associated with disseminated intravascular coagulation (DIC) classically due to meningococcemia, most often in association with meningococcal meningitis

Waterhouse-Friderichsen syndrome from Robbins-Cotran PBD, 8e

Waterhouse-Friderichsen syndrome

Waterhouse-Friderichsen syndrome from Robbins-Cotran PBD, 8e

Autoimmune adrenalitis from Robbins-Cotran PBD, 8e

Tumors of adrenal medulla

Adrenal cortical adenoma from Robbins-Cotran PBD, 8e

Adrenal cortical adenoma from Robbins-Cotran PBD, 8e

from Robbins-Cotran PBD, 8e

Adrenal cortical carcinoma (left) from Robbins-Cotran PBD, 8e

Pheochromocytoma derived from chromaffin cells of the adrenal medulla; when derived from extra-adrenal chromaffin cells, called paraganglioma most often benign; 10% malignant. surgically correctable hypertension

Pheochromocytoma hypertension usually paroxysmal (episodic) may be persistent results from hyperproduction of catecholamines (epinephrine and norepinephrine) increased urinary excretion of catecholamines and their metabolites (metanephrine, normetanephrine, vanillylmandelic acid)

Pheochromocytoma tumor can also cause hyperglycemia can be part of MEN IIa or MEN IIb (III)

Pheochromocytoma other associations von Hipple-Lindau disease renal, hepatic and pancreatic cysts renal cell carcinomas cerebellar hemangioblastomas von Recklinghausen disease neurofibromatosis schwannomas, gliomas Sturge-Weber cavernous hemangiomas

Pheochromocytoma from Robbins-Cotran PBD, 8e

Pheochromocytoma from Robbins-Cotran PBD, 8e

Pheochromocytoma from Robbins-Cotran PBD, 8e

Neurosecretory granules in a pheochromocytoma

Neuroblastoma highly malignant catecholamine-producing tumor occurs in early childhood urinary catecholamines and catecholamine metabolites are same as in pheochromocytoma tumor causes hypertension usually originates in adrenal medulla often presents as large abdominal mass

Neuroblastoma amplification of N-myc oncogene thousands of gene copies per cell characteristic karyotypic changes (homogeneously staining regions or double minute chromosomes) number of N-myc gene copies related to aggressiveness of the tumor. occasionally converts into more differentiated form – ganglioneuroma change reflected by marked reduction in number of gene copies

Summary – adrenal medullary tumors pheochromocytoma chromaffin cell tumor; benign or malignant tumor secretes catecholamines (epinephrine and norepinephrine) and causes secondary hypertension neuroblastoma malignant “small blue cell” tumor of adrenal medulla catecholamine-secreting malignancy of early childhood; hypertension 

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