Adrenal gland and paraganglia
Last revised 21 February 2008
Last major update February 2005
(c) 2002-2008 PathologyOutlines.com, Inc.
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Table of Contents-Adrenal gland
Primary references, anatomy, embryology, histology, grossing, adrenal cortex-physiology
Congenital anomalies: accessory adrenal tissue, adrenal cytomegaly, adrenal hypoplasia, adrenal union or adhesion, Beckwith-Wiedemann syndrome, congenital adrenal hyperplasia, hereditary ACTH unresponsiveness, storage diseases
Adrenal insufficiency: primary-general, secondary, Addison’s disease, amyloidosis, autoimmune adrenalitis, drugs, infections, isolated mineralocorticoid deficiency, polyglandular autoimmune syndromes, radiation, Waterhouse-Friderichsen syndrome,
Adrenal hyperfunction/hyperplasia: general, Cushing’s syndrome, hyperaldosteronism, acquired hyperplasia, macronodular hyperplasia, micronodular hyperplasia, pigmented hyperplasia, unilateral hyperplasia
Adrenocortical adenoma: children, adenoma-general, oncocytoma, corticomedullary mixed tumor
Other benign cortical lesions: adenomatoid, cysts, focal adrenalitis, hemangioma, malakoplakia, massive macronodular adrenocortical disease, myelolipoma, ovarian thecal metaplasia, solitary fibrous tumor
Adrenocortical carcinoma: general, staging, features to report
Adrenal medulla: physiology, hyperplasia, tumors-general, malignant melanotic tumors, pheochromocytoma
Neuroblastic tumors: general, ganglioneuroblastoma, ganglioneuroma, neuroblastoma, staging, prognostic factors, grossing
Other adrenal malignancies: angiosarcoma, Ewing’s/PNET, leiomyosarcoma, lymphoma, metastases, plasmacytoma
Paraganglia: general, hyperplasia, paraganglioma, paraganglioma-report
American Journal of Surgical Pathology (AJSP), March 1977 to February 2005
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to February 2005
Human Pathology (Hum Path), March 1970 to November 2004
Modern Pathology (Mod Path), Jan 1988 to February 2005
Atlas of Nontumor Pathology, Series I: Endocrine Disease; AFIP, 2002
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004
Sternberg, S: Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
University of Pittsburgh case histories: through #417
Journal search terms: adrenal, paraganglia, paraganglioma
Please refer to these primary references for more detailed discussions and photographs
A composite of two neuroendocrine organs, the adrenal cortex (mesodermal) and adrenal medulla (neuroectodermal)
Also called suprarenal glands
Left and right-sided glands; left gland is crescentic and right gland is pyramidal in adults; each is 5 x 3 x 1 cm
On superiomedial kidneys in retroperitoneum
Gland has head (medial), body (middle) and tail (lateral)
Normal weight 4-6 grams each after dissection of fat; acute stress reduces lipid content and weight; prolonged stress induces hypertrophy and hyperplasia and increases weight
Has complete fibrous capsule, which may merge with capsule of kidney (either gland), and liver (right sided gland)
Cortex is bright yellow due to lipid; zona reticularis is thinner and darker
Medulla has ellipsoid shape, is gray-tan and <10% of gland volume (1% in neonates); is more prominent with cortical atrophy; majority of medulla is within head of gland
Neonatal gland is dark red-brown due to congestion, with no visible medullary tissue
Adrenal glands are supplied by three arteries, drained by shorter right adrenal vein and longer left adrenal vein
Lymphatics only in capsule, not elsewhere
Gross images: adrenal glands; cross section
Gross drawings: (1) view from front; (2) view from behind; (3) relationship to kidneys; (4) cross section
By day 25 of gestation, bilateral adrenal primordium develops as cords of large polyhedral cells in coelomic epithelium medial to mesonephros and urogenital ridge
By day 45, adrenal glands enlarge to 1 mg, and primitive sympathetic cells with nerve tracts migrate to form medulla
By week 7, paraganglionic cells replicate and differentiate into chromaffin cells; primitive sympathicoblasts form neuroblastic nodules that peak at weeks 17-20 and usually regress; persistent nodules may be confused with small neuroblastomas
By week 8, each gland weighs 4 mg, with outer (definitive) cortex distinct from inner (fetal) cortex
Inner (fetal) cortex has large eosinophilic cells mixed with small nodules of primitive neuroblastic cells, represents 75% of cortical volume at birth, but then involutes due to apoptosis, with only stroma present by one year
By week 20, adrenals are larger than kidneys, and composed mostly of fetal cortex
At birth, each adrenal gland weights 5 grams
Premature, stillborn and some neonates with in utero stress have microscopic cystic changes in adrenal glands
Micro images: fetal and adult cortex
Adrenal cortex
Normal cortex in adults is 2 cm thick
Adrenal cortex anatomical zones (“gfr”):
Zona glomerulosa: just beneath the adrenal capsule; composed of small clusters and short trabeculae of relatively small, well defined cells, less cytoplasm than other cortical cells, lipid-poor, 15% of cortical volume
Zona fasciculata: forms broad band of large cells with distinct membranes arranged in cords two cells wide; cytoplasm has numerous small lipid vacuoles which may indent the central nucleus and resemble lipoblasts, 70-80% of cortical volume, lipid stores are depleted by ACTH
Zona reticularis: grossly brown; haphazardly arranged cells, smaller than zona fasciculata cells, with granular and eosinophilic cytoplasm with lipofuscin but minimal lipid; thinner than zona glomerulosa or fasciculata
Cortical extrusions: common into periadrenal fat; usually maintain attachment to adrenal gland
Cortical cuff: adrenal cortical cells around adrenal central vein and its branches
Cytology: may have aggregates of bare nuclei resembling metastatic small cell carcinoma (Mod Path 1991;4:594)
Positive stains: low molecular weight cytokeratin, alpha inhibin, MelanA/A103, bcl2, synaptophysin (weak), variable vimentin
Negative stains: chromogranin, epinephrine
Micro images: cross section #1; #2; cortical layers #1; #2; #3; #4; various images (low and high power); fasciculata; reticularis; fasciculata, reticularis and medulla; reticularis lipid stain
EM: zona glomerulosa-sparse intracellular lipid, elliptical mitochondria with lamellar (plate-like) cristae; may have microvillous projections; no/rare lysosomes, lipofuscin or smooth endoplasmic reticulum
EM: zona fasciculata-round/oval mitochondria with short and long tubular cristae; prominent lipid droplets, prominent smooth endoplasmic reticulum, moderate amounts of rough endoplasmic reticulum, microvillus cytoplasmic projections, more lysosomes than zona glomerulosa
EM: zona reticularis-spherical/ovoid mitochondria with short and long tubular invaginations of inner membrane; abundant lipofuscin granules, lysosomes and microvilli; sparse lipid droplets
EM images: zona fasciculata
Adrenal medulla
Composed of neural crest cells called chromaffin cells (also called pheochromocytes, medullary cells) with a multilineage differentiation potential; also sustentacular cells
Chromaffin cells: arranged in small nests and cords separated by prominent vasculature; take up chromium salts strongly, turn brown-black after exposure to Zenker’s solution (potassium dichromate); large polygonal cells with poorly outlined borders, abundant granular and usually basophilic cytoplasm, mild variation in cell size; occasionally has PAS+ hyaline droplets
Sustentacular cells: supporting cells, spindle cells at periphery of nests of chromaffin cells; associated with rich vasculature; S100+, difficult to identify with routine staining
Ganglion cells: occasional single cells or small clusters associated with myelinated nerve bundles
Central vein: has thick wall of smooth muscle
Micro images: adrenal medulla; images 45-48 (low and high power)
Positive stains: chromogranin, synaptophysin, neurofilament, tyrosine hydroxylase, epinephrine, S100 (sustentacular cells)
Negative stains: keratin, vimentin
EM: numerous mitochondria; norepinephrine producing cells have 250 nm electron opaque neurosecretory granules, with prominent halo between granule membrane and dense core; epinephrine producing cells have 190 nm finely granular neurosecretory granules, filling the enclosing membrane and no halo; moderate amount of rough endoplasmic reticulum, interdigitating blunt cytoplasmic processes with poorly developed cell junctions; sustentacular cells have moderate amounts of rough endoplasmic reticulum and occasional lipid droplets, but no neurosecretory granules
Protocol for examining specimens (nothing unusual compared to other specimens), Archives 2000;124:17
Adrenal cortex: synthesizes and secretes corticosteroids (mineralocorticoids, glucocorticoids and sex hormones), all derived from cholesterol
Zona glomerulosa (outer): produces mineralocorticoids (aldosterone-increases sodium and water absorption and potassium secretion)
Zona fasciculata (middle): produces glucocorticoids, some sex hormones
Zona reticularis (inner): produces estrogens and androgens, some glucocorticoids
Normal pathways of hormone production in adrenal cortex (via cytochrome P450 enzymes):
Circulating low-density lipoproteins are internalized into cortical cells, lipoproteins are hydrolyzed, producing cholesterol esters, which break down to cholesterol and free fatty acids
Cholesterol => 20 alpha hydroxycholesterol => (via 20,22 desmolase complex)
pregnenolone => progesterone - (21) => 11 deoxycorticosterone => corticosterone => aldosterone
| (17) | (17)
17 alpha hydroxyprogesterone => (21) - deoxycortisol => cortisol
|
dihydroxyepiandrosterone => androstenedione => estradiol 17 beta
|
testosterone
17: 17 hydroxylase
21: 21 hydroxylase
Extra-adrenal regulation
Hypothalamic corticotropin-releasing hormone (CRH) enters hypophyseal portal system, reaches anterior pituitary gland, stimulates release of ACTH
ACTH travels in blood to adrenal cortex, is bound to cortical cell membranes, activates intracytoplasmic cyclases that form cAMP and GMP; both cortisol and ACTH inhibit release of CRH, and cortisol also inhibits secretion of ACTH
ACTH normally is secreted episodically, with more and longer episodes in early morning, and nadir in evening; this pattern causes circadian rhythm for cortisol seen in normals
Volume changes affect renin-angiotensin system, leading to aldosterone secretion
ACTH, potassium ions and aldosterone-stimulating factor also regular aldosterone synthesis
Fetal adrenal gland lacks 3 beta hydroxysteroid dehydrogenase (converts pregnenolone to progesterone); as a result produces abundant dihydroepiandosterone, but little cortisol
Types of hormones:
Autocrine: hormone binds to receptors on cell that produces it
Paracrine: hormone binds to receptors of nearby cells of a different type
Endocrine: hormone acts on target organs distant from site of synthesis
Hormones are either signaling molecules that interact with cell surface receptors or steroids that interact with intracellular receptors; signaling molecules often act via second messengers, such as cAMP, inositol triphosphate, or calcium levels
Congenital anomalies
Nests of adrenal tissue located away from adrenal gland
Also called heterotopia, although technically this term refers to displacement to an abnormal location, not the presence of accessory tissue elsewhere in body
Due to migration of adrenocortical primordial cells with gonads
Usually without accompanying medullary tissue; cases near celiac ganglion may also contain medullary tissue
Retroperitoneal space along urogenital ridge, beyond renal capsule in upper pole, hilum of ovary or testes, along course of spermatic cord
Present in 1% of inguinal hernia sacs
May be accompanied by malformation of epididymis
May be fused with liver or kidney and surrounded by a common capsule
May undergo same disease processes as ordinary adrenal glandular tissue
Micro images: adrenal rest in hernia sac #1; #2
DD: metastatic renal cell carcinoma or other clear cell tumors
Non-adrenal tissue present in adrenal gland
Very rare (except for metastases)
Case report of benign intraadrenal thyroid tissue (Hum Path 1999;30:105)
Relatively common finding within fetal cortex in newborns, particularly premature infants (3-7%) or infants with Rh incompatibility
May be associated with Beckwith-Wiedemann syndrome
Cells do NOT represent carcinoma in situ
Case reports: occurrence in two apparently normal adults (Archives 1986;110:1072)
Gross: hyperplastic adrenal glands
Micro: numerous markedly enlarged (up to 150 microns) and bizarre polyhedral cells with eosinophilic granular cytoplasm and large hyperchromatic nuclei with pseudoinclusions in adrenal cortex; no/rare mitotic figures
DD: CMV infection (usually infants, basophilic cytoplasm, large intranuclear inclusion surrounded by a clear halo)
References: Archives 1981;105:358 (pseudoinclusions)
Congenital aplasia is very rare; found in 10% with unilateral renal agenesis
Bilateral hypoplasia is associated with anencephaly due to lack of ACTH cells; causes adrenal insufficiency
Unilateral absence occurs in 1 per 10,000 live births
May be associated with sudden infant death syndrome (Archives 1977;101:168)
Infant symptoms: weight loss, vomiting, dehydration, severe electrolyte disturbances-due to adrenal insufficiency
Primary hypoplasia: X linked, associated with mutations or deletions of DAX-1 gene at Xp21; cortex is hypoplastic, but fetal zone is intact, often has cytomegalic features; associated with hypogonadotrophic hypogonadism in young men
Miniature adult type of hypoplasia: sporadic or autosomal recessive; small glands but normal architecture
Gross: small for age adrenal glands, decreased fetal zone in newborns, scattered cytomegalic cells, cells have decreased lipid
DD: chronic exogenous glucocorticoids causes acquired hypoplasia
Rare
Adrenal union (fusion): adrenal glands are fused above the aorta with butterfly or horseshoe shape, with common connective tissue capsule and intermingling of cells; associated with midline congenital defects, including spinal dysraphism, indeterminate visceral situs, bilateral renal agenesis, Cornelia de Lange syndrome (mental and growth retardation, low set ears, antiverted nostrils, spade-like hands with short tapering fingers); normal histology
Unions also to kidney or liver in 0.4-3.0% of unselected autopsies; common capsule, but no intermingling of cells
Adrenal adhesion: adrenal gland is attached to opposite adrenal gland, but with an intervening connective tissue capsule
Visceromegaly, gigantism, macroglossia, abdominal wall defects, craniofacial abnormalities, midfacial hypoplasia, adrenocortical hyperplasia
Incidence of 1 per 13,000 births, usually sporadic
May have brain damage due to hypoglycemia, causing mental retardation or death
May develop Wilm’s tumor, adrenocortical carcinoma, neuroblastoma, pancreatoblastoma, pheochromocytoma
Due to abnormality of 11p15.5
Gross: enlarged adrenal glands up to 16g, may be cerebriform and nodular
Gross images: large lobulated adrenal glands
Micro: bilateral cytomegaly with large and pleomorphic nuclei and cytoplasmic nuclear pseudoinclusions; also medullary hyperplasia; variable hemorrhagic macrocysts
Micro images: adrenal cytomegaly
Congenital adrenal hyperplasia
Various autosomal recessive syndromes due to enzyme deficiencies in biosynthesis of adrenal steroids, diverting production to other pathways and causing elevated ACTH levels and adrenocortical hyperplasia
No gender preference, usually presents in children, rarely in adults
Symptoms depend on specific defect; include salt wasting, virilization, adrenogenital syndrome, hypertension
Salt wasting syndrome: usually evident soon after birth (in utero, maternal kidneys maintain electrolytes and fluids); hypotension due to decreased serum sodium and increased serum potassium [from lack of aldosterone production], acidosis, cardiovascular collapse, death
Simple virilizing syndrome: easier to detect in females (clitoral hypertrophy) than males
Nonclassic virilizing syndrome: more common than simple virilizing syndrome; asymptomatic or only hirsutism
Adrenogenital syndrome: adrenal secretes excess androgens, causing changes towards adult masculinity in children or female adults; 50% occur before puberty, 80% are female; diagnosed based on elevated dehydroepiandrosterone; rarely associated with male adult feminization due to increased 17-ketosteroids
Congenital adrenal hyperplasia tumors:
Virilization in adult women is usually associated with carcinoma, particularly if Cushing’s syndrome also present
Feminization in adult men is almost always associated with carcinoma
Congenital adrenal hyperplasia is associated with testicular tumors that arise from ectopic adrenal cortical rests (Archives 2000;124:785), and rarely with similar ovarian tumors (AJSP 2001;25:1443)
21-hydroxylase deficiency: causes 95% of cases; incidence of 1 per 5,000 to 14,500 births (1 in 60 in the normal population are heterozygotes); block in production of aldosterone and cortisol leads to accumulation of 17-hydroxypregnenolone and its catabolite pregnanetriol, also high plasma ACTH; causes virilizing syndrome, cortisol deficiency and variable salt wasting syndrome; also Leydig cell hyperplastic nodules without Reinke crystalloids
Nonclassic 21-hydroxylase deficiency: very common autosomal recessive disorder (1% incidence in parts of US), with mild cortisol deficiency, excessive adrenal androgens, no salt wasting; usually diagnosed by early adulthood
11-beta hydroxylase deficiency: second most common form (5%), incidence of 1 per 100,000 live births; associated with increased androgens and deoxycorticosterone; causes virilization and hypertension
17-alpha hydroxylase deficiency: causes 1% of cases, all patients have female external genitalia due to increased deoxycorticosterone; also hypertension
3 beta hydroxysteroid dehydrogenase deficiency: impaired synthesis of all steroid hormones, adrenal gland is similar to normal fetus; patients present in early infancy with adrenal insufficiency, variable virilization in females
Congenital lipoid adrenal hyperplasia: very rare, low cortisol and aldosterone secretion, high levels of ACTH, FSH, LH and plasma rennin; present with severe adrenal insufficiency in neonatal period; usually die in infancy
Treatment: exogenous glucocorticoids and mineralocorticoids to provide cortisol and suppress ACTH levels, surgical correction of external genitalia
Gross: marked adrenal enlargement (15g each gland) with cerebriform appearance, tan-brown; secondary to elevated ACTH (due to reduced cortisol secretion)
Micro: diffuse cortical hyperplasia, particularly of zona reticularis-like compact cells
DD: bilateral hyperplasia due to ectopic ACTH (not grossly cerebriform, may have metastatic carcinoma, differentiate clinically)
Hereditary unresponsiveness to ACTH
Rare; due to abnormalities of ACTH receptor in adrenocortical cells
Seizures, hypoglycemia, muscle weakness, hyperpigmentation similar to Addison’s disease
Low plasma cortisol levels, increased serum ACTH
Micro: normal zona glomerulosa, atrophic zona fasciculata and reticularis
Adrenoleukodystrophy
Also called Addison-Schilder’s disease
Rare, X linked recessive, affects 1 in 120,000 males
Progressive demyelination of central and peripheral nervous system (dementia, blindness, quadriplegia) and adrenocortical insufficiency
Due to mutations of adrenoleukodystrophy protein (ADLP) in peroxisomal membrane at Xq28, which cause defective oxidation of long-chain fatty acids; cholesterol esters and gangliosides accumulate in membranes of adrenal cortex, brain, other organs
Diagnosis: presence of hexacosanoate and other very long-chain saturated fatty acids in cultured skin fibroblasts
Carriers: women may have a variant form of disease or no neurologic symptoms (Archives 1987;111:151)
Adrenomyeloneuropathy: related disorder with onset in teens to 20’s; adrenal insufficiency but no neurologic disorder at initial presentation; develop weakness, spasticity and distal polyneuropathy, slowly progressive
Treatment: dietary therapy (Lorenzo’s oil) may delay neurologic progression
Gross: atrophic adrenal glands, 1-2 g
Micro: ballooning and striation of zona fasciculata and reticularis cells, often in nodules; cells may have large cortical vacuoles and clefts (representing lipid dissolved during processing); medulla unchanged
Other: cerebral white matter exhibits demyelination, inflammation, gliosis and macrophages; also abnormalities of schwann cells in peripheral nerves and Leydig cells in testis
EM: proliferation of smooth endoplasmic reticulum and trilaminar lamellar inclusions
DD: autoimmune adrenalitis (lymphocytes and no balloon cells)
Pompe’s disease
Also called type II glycogenosis
Infantile form of generalized glycogenosis, due to deficiency of lysosomal acid alpha-1,4-glucosidase
Intralysosomal glycogen storage in CNS, heart, liver, skeletal muscle, thyroid, parathyroid, pituitary, pancreatic islets; also in adrenal cortex and medulla, with severe accumulation in zona fasciculata (Archives 1985;109:921)
Wolman’s disease
Primary familial xanthomatosis
Rare, autosomal recessive lipid storage disorder
Due to deficiency of lysosomal acid lipase, causing accumulation of triglycerides and cholesterol esters in liver, spleen and adrenal glands
Usually causes death by age 6 months
Gross: markedly enlarged adrenal glands with dystrophic calcifications but normal architecture
Gross images: markedly enlarged adrenal glands
Micro: necrosis, fibrosis, calcification; zona fasciculata and reticularis cells have vacuolated cytoplasm
DD: Niemann-Pick disease, other storage diseases
Adrenal insufficiency
Primary acute adrenal insufficiency-general
Often insidious in onset, patients may present in shock due to increased stress
Causes:
(a) patients with chronic adrenal insufficiency (primary or secondary) and acute stress requiring immediate increase in steroids
(b) rapid withdrawal of exogenous steroids (i.e. no taper) or failure to increase steroids with acute stress
(c) massive adrenal hemorrhage destroying adrenal cortex due to anticoagulation, coagulopathy, newborns with physiologic deficiencies in prothrombin time
(d) hypotension/shock that causes mild or massive corticomedullary necrosis, including Waterhouse-Friderichsen syndrome
(e) infections that destroy substantial adrenal cortical tissue
(f) amyloidosis
(g) drugs, radiation
(h) autoimmune disorders (autoimmune adrenalitis or polyglandular autoimmune syndromes)
Patients usually live normal lives after diagnosis (depending on cause); may be at higher risk for heart failure, hypertension or osteopenia
Treatment: glucocorticoids, mineralocorticoids, IV fluids; in chronic patients, must give steroid boost during infections, prior to surgery or during pregnancy
Virtual slides: atrophy (caused not specified)
Secondary adrenocortical insufficiency
Caused by any disorder of pituitary gland which decreases ACTH production and causes adrenal cortical atrophy
Causes: pituitary macroadenoma, craniopharyngioma, tuberculosis or other infections, sarcoidosis, lymphocytic hypophysitis, head trauma, aneurysms, postpartum pituitary necrosis (Sheehan’s syndrome), pituitary apoplexy, metastases; also mutations in pro-opiomelanocortin gene
Tertiary adrenocortical insufficiency: due to disorders of hypothalamus reducing release of corticotropin releasing hormone (CRH); some include this within secondary adrenocortical insufficiency
Similar atrophic changes are caused by exogenous steroids, which also decrease ACTH production
No hyperpigmentation since ACTH levels are low
Laboratory: serum aldosterone, sodium and potassium levels are usually normal, since they are controlled by renin-angiotensin axis, which is not under the control of ACTH; androgens and cortisol levels are low since their production is influenced by ACTH, although androgens are less affected in males since they are also produced by testis; hypoglycemia is more common than with primary adrenal insufficiency
May be associated with hypopituitarism
Treatment: exogenous ACTH; causes rise in serum cortisol levels; may also need to replace other pituitary hormones
Gross: atrophic adrenal glands with retention of architecture, often fibrotic capsule, bright yellow (due to lipid accumulation), prominent medulla
Micro: normal thickness of zona glomerulosa, thinner fasciculata and reticularis; usually no lymphoplasmacytic infiltration
Also called primary chronic adrenal insufficiency
No symptoms until 90% of cortex is compromised; affects 3-6 individuals per 100,000 population
More common in white women
Causes: autoimmune disorders, infections (Histoplasma, Coccidiodes, tuberculosis), space occupying lesions (metastases, lymphomas), hemorrhage, amyloid, sarcoid, hemochromatosis
Symptoms: progressive weakness, easy fatigability, anorexia, weight loss, depression, irritability, menstrual abnormalities, GI disturbances, hyperpigmentation (primary adrenal disease causes elevated ACTH, which stimulates melanocytes at sun-exposed areas and pressure points), small heart (due to chronic hypovolemia), hypotension; infections may precipitate an acute crisis
Laboratory: elevated ACTH levels, low cortisol levels that don’t respond to exogenous ACTH (since adrenal gland is damaged), hyponatremia, hypoglycemia, hyperkalemia, occasionally hypercalcemia
Gross: irregularly shrunken glands, may be hard to find
Virtual slides: Addison’s disease
Rarely causes cortical hypofunction, only if extensive bilateral involvement
Usually associated with systemic amyloidosis-AA type
68% of consecutive autopsies had adrenal amyloid deposits, often multinodular, probably due to aging
Gross: adrenal gland normal or enlarged; gray-yellow cut surface
Micro: typically affects zona fasciculata and reticularis, acellular salmon-pink amorphous material is present between cortical cells, which ultimately become atrophic; amyloidosis-AL type is typically deposited intravascularly
Virtual slides: amyloidosis
DD: infarction related changes
Also called idiopathic primary adrenal insufficiency
No clinical findings until 90% of adrenal cortex is destroyed
Causes 70-90% of cases of adrenal insufficiency; usually women ages 20-50, sporadic or familial
Up to 75% have autoantibodies against adrenal cortical zones not present in normal patients; antibodies appear months to years before onset of adrenal insufficiency
50% of autoimmune cases have circulating autoantibodies to 21 hydroxylase and 17 alpha-hydroxylase enzymes
60% are associated with Hashimoto’s thyroiditis, pernicious anemia, type 1 diabetes or idiopathic hypoparathyroidism (although patients with these common disorders only rarely develop adrenal insufficiency)
Associated with HLA-B8, DR3, DR4
45% with circulating autoantibodies but without symptoms develop impaired adrenocortical function within 2 1/2 years
Case reports: 24 year old woman with death due to pituitary and adrenal insufficiency, with heavy lymphocytic infiltration of adenohypophysis, thyroid, and adrenals, and diffuse retroperitoneal fibrosis with perivascular lymphocytic infiltrates, 2 years after delivery of normal infant (Archives 1985;109:230), due to intravascular B cell lymphoma (Hum Path 1996;27:209)
Gross: small adrenal glands with replacement by hyalinized fibrous tissue
Micro: fibrotic capsule; lymphocytes, histiocytes and plasma cells in all cortical layers; rare or small islands of remaining cortical cells with eosinophilic cytoplasm and lipid depletion; medulla is unchanged
DD: normal adrenal cortex (focal lymphocytic aggregates, but cortical cells present and no symptoms of adrenal insufficiency), chronic glucocorticoid therapy (causes atrophic adrenal glands but no inflammation, no adrenal insufficiency except in times of crisis), myelipomatous change (fat cells, lymphocytes and bone marrow elements), Carney’s complex (lymphocytes and nodules of enlarged zona reticularis-type cells, no glandular atrophy)
Drugs causing adrenal insufficiency
Aminoglutethimide: inhibits enzyme converting cholesterol to pregenolone, causes decrease in cortisol and aldosterone
Metapyrone: inhibits 11 beta hydroxylase, which inhibits cortisol and aldosterone synthesis
Mitotane: cytotoxic to zona fasciculata and reticularis, produces medical adrenalectomy; produces atrophic adrenal glands with fibrosis and residual islands of cortical cells
Cytomegalovirus (CMV): common in adrenal glands of AIDS patients, causes adrenocortical necrosis; if severe, may cause adrenal insufficiency
Echovirus: case reports at Archives 1983;107:361, Hum Path 1983;14:818
Fungi: due to Histoplasma, Cryptococcus, Paracoccidioides; enlarged glands with fibrosis, necrosis and granulomatous inflammation
Herpes simplex / varicella zoster: may involve adrenal glands, associated with extensive cortical necrosis; may cause adrenal insufficiency (Hum Path 1985;16:1091)
HIV: changes due to HIV virus itself, opportunistic infections (Mycobacterium avium-intracellulare, CMV, HSV) or associated neoplasms; may have defect in 17-deoxcorticosteroid production or peripheral resistance to glucocorticoids
Mycobacterium avium-intracellulare: sheets of histiocytes with abundant acid-fast organisms detected with acid-fast stains
Tuberculosis
Rare cause of adrenal insufficiency in US and Western Europe, more common elsewhere