The Adrenal Glands Thomas Jacobs, M.D. Diane Hamele-Bena, M.D. I. - - PDF document

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The Adrenal Glands Thomas Jacobs, M.D. Diane Hamele-Bena, M.D. I. - - PDF document

Sep 25, 2023 206 likes •573 views

The Adrenal Glands Thomas Jacobs, M.D. Diane Hamele-Bena, M.D. I. Normal adrenal gland A. Gross & microscopic B. Hormone synthesis, regulation & measurement II. Hypoadrenalism -- Break -- III. Hyperadrenalism; Adrenal cortical

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The Adrenal Glands

Thomas Jacobs, M.D. Diane Hamele-Bena, M.D.

  • I. Normal adrenal gland
  • A. Gross & microscopic
  • B. Hormone synthesis, regulation & measurement
  • II. Hypoadrenalism
  • - Break --
  • III. Hyperadrenalism; Adrenal cortical neoplasms
  • IV. Adrenal medulla
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  • Normal adult adrenal gland: 3.5 - 4.5 grams

Normal Adrenal Gland

  • Cortex: 3 zones:

– Glomerulosa – Fasciculata – Reticularis

Adrenal Cortex Morphology

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Capsule lomerulosa asciculata eticularis

C O R T E X

G F R

Fasciculata Reticularis

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Hormone synthesis, regulation, and measurements

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Hypoadrenalism Hypoadrenalism

  • Primary Adrenocortical Insufficiency
  • Secondary Adrenocortical Insufficiency

–Due to primary failure of adrenal glands –ACTH is elevated –Due to disorder of hypothalamus or pituitary –ACTH is decreased

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Hypoadrenalism

Clinical Manifestations

  • Fatigue, weakness, depression
  • Anorexia
  • Dizziness
  • N&V, diarrhea
  • Hyponatremia, hyperkalemia
  • Hypoglycemia
  • Hyperpigmentation

Hypoadrenalism

Clinical Manifestations

Primary adrenal insufficiency: Deficiency of glucocorticoids, mineralocorticoids, and androgens

Hypoglycemia Fatigue Anorexia Weight loss Hyponatremia Hyperkalemia Hypotension Dizziness

aldosterone

Reduced pubic and axillary hair in women

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Hypoadrenalism

Clinical Manifestations

Primary adrenal insufficiency: Concomitant hypersecretion of ACTH Hyperpigmentation

MSH-like effect

Hypoadrenalism

Clinical Manifestations

Secondary adrenal insufficiency: Deficiency of ACTH NO hyperpigmentation

  • Other manifestations of hypopituitarism may also be present,

e.g., other endocrine deficiencies & visual field defects

  • Aldosterone secretion is usually normal and the renin-

angiotensin system is preserved, so NO hyperkalemia

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Pathology of Hypoadrenalism

  • Primary Adrenocortical Insufficiency

– Acute – Chronic = Addison Disease

  • Secondary Adrenocortical Insufficiency
  • Waterhouse-Friderichsen Syndrome

Acute hemorrhagic necrosis, most often due to Meningococci

Meningococci

Waterhouse-Friderichsen Syndrome

  • Hypotension
  • Purpura
  • Cyanosis

Adapted from Netter

Massive adrenal hemorrhage

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Waterhouse-Friderichsen Syndrome Waterhouse-Friderichsen Syndrome

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Pathology of Hypoadrenalism

  • Primary Adrenocortical Insufficiency

– Acute – Chronic = Addison Disease

  • Waterhouse-Friderichsen Syndrome

Acute hemorrhagic necrosis, most often due to Meningococci

  • Autoimmune adrenalitis
  • Tuberculosis
  • AIDS
  • Metastatic tumors
  • Other: fungi, amyloidosis, hemochromatosis

Addison Disease

Clinical findings

Mineralocorticoid deficiency Glucocorticoid deficiency Androgenic deficiency

  • Hypotension
  • Hyponatremia
  • Hyperkalemia
  • Loss of pubic and axillary

hair in women

  • Weakness and fatigue
  • Weight loss
  • Hyponatremia
  • Hypoglycemia
  • Pigmentation
  • Abnormal H2O metabolism
  • Irritability and mental

sluggishness

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Autoimmune Adrenalitis

Three settings:

  • Autoimmune Polyendocrine Syndrome type 1 (APS1) =

Autoimmune Polyendocrinopathy, Candidiasis, and Ectodermal Dysplasia (APECED)

  • Autoimmune Polyendocrine Syndrome type 2 (APS2)
  • Isolated Autoimmune Addison Disease

Pathologic Changes in Autoimmune Adrenalitis

  • Gross:

–Very small glands (1 - 1.5 grams) –Cortices markedly thinned

  • Micro:

–Diffuse atrophy of all cortical zones –Lymphoplasmacytic infiltrate –Medulla is unaffected

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Tuberculosis involving adrenal

Multinucleated giant cells Cortex and medulla are affected

Metastatic carcinoma in adrenal

Tumor

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Pathology of Hypoadrenalism

  • Primary Adrenocortical Insufficiency

– Acute

  • Waterhouse-Friderichsen Syndrome

– Chronic = Addison Disease

  • Secondary Adrenocortical Insufficiency

– Any disorder of the hypothalamus or pituitary leading to diminished ACTH; e.g., infection; pituitary tumors, including metastatic carcinoma; irradiation

Diagnosis of Hypoadrenalism

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Hyperadrenalism

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Hyperadrenalism

Three distinctive clinical syndromes:

  • Cushing Syndrome: excess cortisol
  • Hyperaldosteronism
  • Adrenogenital or Virilizing Syndrome: excess androgens

Hyperadrenalism

In clinical practice, most cases of Cushing Syndrome are the result of administration of exogenous glucocorticoids (“exogenous” or iatrogenic Cushing Syndrome).

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Endogenous Exogenous (Iatrogenic)

Cushing Syndrome

Pituitary adenoma Adrenal neoplasm or hyperplasia ACTH-producing tumor

“Endogenous” Cushing Syndrome

Etiology Pathology

  • Cushing Disease
  • Ectopic ACTH production
  • Hypersecretion of cortisol by

adrenal neoplasm or autonomous adrenal cortical hyperplasia

  • I. ACTH-dependent:
  • II. ACTH-independent:

Pituitary adenoma or hyperplasia Extra-adrenal ACTH-producing tumor Adrenal neoplasm or cortical hyperplasia Adrenal cortical hyperplasia Adrenal cortical hyperplasia

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Adapted from Netter

Adrenal carcinoma Adrenal adenoma Pituitary adenoma Adrenal cortical hyperplasia Dorsal fat pad Ecchymoses Thin skin Thin arms & legs Poor wound healing Moon face Striae Pendulous abdomen

C O R T I S O L

Cushing Syndrome

ACTH-producing tumor

Hydrocortisone Excess

  • Abnormal fat distribution

–Moon face –Central obesity

  • Increased protein catabolism

–Thin skin –Easy bruisability –Striae –Osteoporosis with vertebral fractures –Impaired healing –Muscle wasting –Suppressed response to infection

  • Diabetes
  • Psychiatric symptoms
  • Hirsutism
  • Deepened voice in women
  • Acne
  • Abnormal menses

Cushing Syndrome

  • Hypokalemia with alkalosis
  • Usually occurs in cases
  • f ectopic ACTH production

Adrenal Androgen Excess Mineralocorticoid Excess

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Pituitary adenoma

Cushing Disease

Usually not so large!

Normal Cortical hyperplasia

Cortex

Adrenal cortical hyperplasia

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Adrenal cortical adenoma

Tumor Adrenal gland

Pathology of Primary Hyperaldosteronism

  • Aldosterone-secreting adenoma
  • Bilateral idiopathic cortical hyperplasia
  • Adrenal cortical carcinoma

– Conn Syndrome – Uncommon cause of hyperaldosteronism

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Conn Syndrome

Adapted from Netter

Adrenal adenoma

  • Hypertension
  • Polydipsia
  • Polyuria
  • Hypernatremia
  • Hypokalemia

Aldosterone

Adenomas and Carcinomas

* May produce:

  • Cortisol
  • Sex steroids
  • Aldosterone

Cortical Neoplasms

Functioning * Non-functioning

(Cushing Syndrome)) (Conn Syndrome))

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Cortical Neoplasms

  • Discrete, but often unencapsulated
  • Small (up to 2.5 cm)
  • Most <30 grams
  • Yellow-orange, usually without

necrosis or hemorrhage

  • Usually unencapsulated
  • Large (many >20 cm)
  • Frequently > 200-300 grams
  • Yellow, with hemorrhagic,

cystic, & necrotic areas

  • Adenomas

– Gross: – Micro:

  • Carcinomas

– Gross: – Micro:

  • Lipid-rich & lipid-poor cells with

little size variation

  • Ranges from mild atypia to

wildly anaplastic

Residual adrenal gland

Adrenal cortical adenoma

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Adrenal cortical adenoma

Tumor Kidney

Adrenal cortical carcinoma

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Adrenal cortical carcinoma

Mitosis

Diagnosis of Hyperadrenalism

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Adrenal Medulla

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  • Specialized neural crest (neuroendocrine) cells
  • Part of the chromaffin system, which includes the

adrenal medullae & paraganglia

  • Major source of catecholamines (epi, norepi, &

dopamine)

Adrenal Medulla

Carotid bodies Aortic bodies Thoracic sympathetic paraganglia Adrenal medullae Aortic sympathetic paraganglia Visceral autonomic paraganglia

Paraganglion System

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Adrenal Medulla

  • Neuroblastoma
  • Ganglioneuroblastoma
  • Ganglioneuroma
  • Pheochromocytoma

Tumors of the Adrenal Medulla

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Ganglioneuroma Ganglioneuroblastoma Neuroblastoma

B E N I G N M A L I G N A N T

  • Poorly differentiated malignant neoplasm derived

from neural crest cells

  • Usually occurs in infants & small children
  • “Small round blue cell tumor” of childhood

Neuroblastoma

Rhabdomyosarcoma Lymphoma Retinoblastoma Wilms tumor Ewing sarcoma/PNET Medulloblastoma

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Neuroblastoma: primary sites

  • Head
  • Neck
  • Chest
  • Adrenal
  • Abdomen, nonadrenal
  • Pelvis
  • Other sites & unknown

2% 5% 13% ~ 40% 18% 4% 21%

  • Gross:

– Large tumor with hemorrhage, necrosis, & calcification

Neuroblastoma: Pathology

  • Micro:

– Undifferentiated small cells resembling lymphocytes (“Small, round, blue cell tumor”) – May show areas of differentiation (larger cells with more cytoplasm and Schwannian stroma)

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Neuroblastoma Neuroblastoma

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  • Patient age
  • Stage
  • Site of 10 involvement
  • Histologic grade
  • DNA ploidy
  • N-myc oncogene amplification
  • Others: Chromosome 17q gain, Chromosome 1p loss, Trk-A

expression, Telomerase expression, MRP expression, CD44 expression

Neuroblastoma: Prognostic Factors

  • Differentiated neoplasm of neural crest origin
  • Benign
  • Occurs in older age group
  • Pathology:

– Gross: Encapsulated, white, firm – Micro: Ganglion cells & Schwann cells

Ganglioneuroma

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Ganglioneuroma

  • Composed of malignant neuroblastic elements &

ganglioneuromatous elements

  • Prognosis depends on % of neuroblasts

Ganglioneuroblastoma

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Ganglioneuroblastoma

Pheochromocytoma

  • Rare, but important: surgically curable form of

hypertension

  • May arise in association with familial syndromes, e.g.,

MEN2, von Hippel-Lindau, von Recklinghausen (NF1)

  • May be “sporadic”: ~24% have germline mutations,

including mutations of RET, VHL, SDH-B, and SDH-D genes

  • Extra-adrenal tumors (e.g., carotid body) are called

“paragangliomas”

  • Catecholamine-secreting neoplasm: HYPERTENSION
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  • Gross:

– 1 - 4000 grams (average = 100 grams) – Areas of hemorrhage, necrosis, & cystic degeneration

Pheochromocytoma: Pathology

  • Micro:

– Balls of cells resembling cells of medulla, with bizarre, hyperchromatic nuclei; richly vascular stroma

  • Benign & malignant tumors are histologically identical;

the only absolute criterion for malignancy is metastasis.

Residual adrenal Tumor

Pheochromocytoma

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Pheochromocytoma

Pheochromocytoma: Clinical aspects

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