PAL4 Adrenal Pathology and Tumors

• Diseases of the Adrenal Glands
• Quiz for Adrenal Pathology and Tumours

  December 2023
• Adrenal cortex

  Consists of 3 layers of distinct cell types: Zona glomerulosa, Zona fasciculata, Zona reticularis

  
• Adrenal cortex

  Produces three major classes of steroids: mineralocorticoids, glucocorticoids, adrenal androgens
• Adrenal medulla

  Chromaffin cells which synthesize and secrete catecholamines
• Zona glomerulosa

  • Outer layer, 10% of the cortex, consists of cords or columns of polyhedral cells
• Zona fasciculata

  • Middle layer, ~70% of the cortex, composed of columns of lipid rich cells
• Zona reticularis

  • Inner layer, consists of cords of more compact cells than those of zona fasciculata
• Adrenocortical Hyperfunction or Hyperadrenalism

  Three distinctive hyper-adrenal clinical syndromes: Hypercortisolism (Cushing syndrome), Hyperaldosteronism, Adrenogenital or virilizing syndromes
• Cushing syndrome

  Condition resulting from long-term exposure to excessive glucocorticoids, most commonly caused by therapeutic administration of exogenous glucocorticoids

  
• Cushing's disease

  Cushing syndrome caused by excessive secretion of adrenocorticotropin hormone (ACTH) by a pituitary tumor, usually an adenoma

  
• Clinical features of Cushing Syndrome

  • Centripetal distribution of fat - truncal obesity, moon facies and buffalo hump, loss of collagen - thin skin, striae, easy bruising, weight gain, hypertension, weakness, glucose intolerance, osteoporosis, infections, mental changes, hirsutism, menstruation changes

  
• Hypercortisolism

  Atrophy of selective fast-twitch or type II myofibers, decrease in muscle mass, proximal limb weakness
• Glucocorticoids

  Induce gluconeogenesis & inhibit uptake of glucose by cells, leading to hyperglycemia and glycosuria
• Glucocorticoids

  Catabolic effect on proteins, leading to loss of collagen and bone resorption
• Glucocorticoids

  Suppress immune response, increased risk of infections
• Pituitary cause or ectopic ACTH

  May give increase in skin pigmentation due to melanocyte-stimulating activity in the ACTH precursor molecule
• Mental disturbances in Cushing syndrome

  Mood swings, depression and frank psychosis
• AMPK enzyme

  5′-adenosine monophosphate (AMP)-activated protein kinase, regulates lipid metabolism, inhibits lipogenesis and activates fatty acid oxidation
• Glucocorticoids

  Decrease AMPK enzyme in visceral adipose tissues, leading to increased lipogenesis, lipid stores and lipolysis, resulting in central and visceral fat deposition
• Causes of Cushing Syndrome

  • Exogenous (iatrogenic, adulterated treatment)
  • Endogenous ACTH dependent (Cushing disease, ectopic ACTH syndrome)
  • Endogenous ACTH independent (adrenal adenoma, adrenal carcinoma, macronodular hyperplasia, primary pigmented nodular adrenal disease, McCune-Albright syndrome)

  
• Cushing's syndrome is most commonly caused by the therapeutic administration of exogenous glucocorticoids

  
• Cushing's disease is Cushing's syndrome caused by excessive secretion of ACTH by a pituitary tumor, usually an adenoma

  
• Ectopic ACTH syndrome is Cushing's syndrome caused by secretion of ACTH by non-pituitary neoplasms

  
• ACTH-dependent Cushing syndrome accounts for 70% of cases, ACTH-independent accounts for 15-20% of cases

  
• McCune-Albright syndrome is a rare genetic disorder that can cause Cushing syndrome

  
• Crooke hyaline changes

  In the pituitary in Cushing syndrome, the normal glandular basophilic cytoplasm of ACTH-producing cells is replaced by homogeneous, lightly basophilic material due to accumulation of intermediate keratin filaments

  
• In Cushing syndrome due to exogenous glucocorticoids, there is bilateral adrenal cortical atrophy due to suppression of endogenous ACTH

  
• Diffuse hyperplasia in ACTH dependent Cushing syndrome

  • Bilateral adrenal enlargement, expanded "lipid-poor" zona reticularis, outer zone of vacuolated "lipid-rich" cells

  
• Nodular hyperplasia in ACTH dependent Cushing syndrome

  • Nodules composed of vacuolated "lipid-rich" cells, accounting for the yellow colour

  
• Primary pigmented nodular adrenocortical disease (PPNAD)

  Rare cause of ACTH-independent Cushing's syndrome, characterized by multiple small, pigmented nodules in the adrenal cortex

  
• Macronodular hyperplasia

  Adrenals almost entirely replaced by prominent nodules of varying sizes containing lipid-poor and lipid rich cells
• Micronodular hyperplasia

  Adrenals contain 1 to 3 mm darkly pigmented nodules containing lipofuscsin pigment

  
• Autonomously functioning hyperplasias resemble adenomas in biochemical testing
• Aberrant adrenal receptor expression

  Ectopic receptors such as GIP, β-adrenergic, vasopressin, serotonin, and angiotensin II receptors can cause ACTH-independent Cushing syndrome

  
• Primary macronodular adrenal hyperplasia is a rare cause of Cushing syndrome characterized by nodular enlargement of both adrenal glands

  
• Lipofuchscin

  Pigment stained positive for PAS and negative for iron stain
• (H and E, X200)
• Canope

  Bolen keluar
• ACTH non-dependent

  Hyperplasia: Macro or micro nodular hyperplasia