Adrenal Gland Disorders

• Cushing syndrome


  Excess production of the adrenal hormones cortisol
• Hyperaldosteronism


  Excess production of the adrenal hormones aldosterone
• Addison disease


  Primary adrenal gland hypofunction
• Cushing syndrome


  • Results from effects of supraphysiologic glucocorticoid levels originating from either exogenous administration or endogenous overproduction by the adrenal gland (adrenocorticotropic hormone [ACTH]-dependent) or by abnormal adrenocortical tissues (ACTH-independent)
• ACTH-dependent Cushing syndrome


  80% of all Cushing syndrome cases, usually caused by overproduction of ACTH by the pituitary gland, causing adrenal hyperplasia
• Ectopic ACTH syndrome


  Excessive ACTH production resulting from an endocrine or nonendocrine tumor, usually of the pancreas, thyroid, or lung (eg, smallcell lung cancer)
• ACTH-independent Cushing syndrome


  Usually caused by adrenal adenomas and carcinomas
• Central obesity and facial rounding


  • Most common findings in Cushing syndrome (90% of patients)
• Peripheral obesity and fat accumulation


  • Occur in 50% of Cushing syndrome patients
• Fat accumulation in the dorsocervical area (buffalo hump)


  • Nonspecific, but increased supraclavicular fat pads are more specific for Cushing syndrome
• Cushing syndrome patients are often described as having moon facies and a buffalo hump
• Establishing hypercortisolism


  1. 24-hour urinary free cortisol (UFC)

  2. Midnight plasma cortisol

  3. Late-night (11 pm) salivary cortisol

  4. Low-dose dexamethasone suppression test (DST)
• Types of Cushing syndrome

  • ACTH-dependent
  • ACTH-independent
  • Ectopic ACTH syndrome
• Types of adrenal insufficiency

  • Primary adrenal insufficiency (Addison's disease)
  • Secondary adrenal insufficiency
• Addison disease


  Primary adrenal insufficiency
• Secondary adrenal insufficiency


  Most commonly results from exogenous corticosteroid use, leading to suppression of the hypothalamic-pituitary-adrenal axis and decreased ACTH release, resulting in impaired androgen and cortisol production
• Symptoms of Addison disease


  • Weight loss
  • Dehydration
  • Hyponatremia
  • Hyperkalemia
  • Elevated blood urea nitrogen
• Hyperpigmentation


  • Common in Addison disease and may involve exposed and nonexposed parts of the body, but not seen in secondary adrenal insufficiency due to low amounts of melanocyte-stimulating hormone
• Short cosyntropin stimulation test


  Can be used to assess patients with suspected hypocortisolism
• Glucocorticoids of choice for adrenal insufficiency


  • Hydrocortisone
  • Cortisone
  • Prednisone
• Acute adrenal insufficiency (also known as adrenal crisis or addisonian crisis)


  Represents a true endocrine emergency
• Metyrapone


  Inhibits 11 β-hydroxylase, thereby inhibiting cortisol synthesis. Initially, patients can demonstrate increased plasma ACTH concentrations because of a sudden drop in cortisol. This can increase androgenic and mineralocorticoid hormones, resulting in hypertension, acne, and hirsutism. Nausea, vomiting, vertigo, headache, dizziness, abdominal discomfort, and allergic rash have been reported after oral administration. Metyrapone is currently available through the manufacturer only for compassionate use.
• Ketoconazole


  Inhibits cytochrome P-450 enzymes, including 11 β-hydroxylase and 17 α-hydroxylase. It is effective in lowering serum cortisol levels after several weeks of therapy. It also has antiandrogenic activity, which may be beneficial in women but can cause gynecomastia and decreased libido in men. The most common adverse effects are reversible elevation of hepatic transaminases, GI discomfort, and dermatologic reactions.
• Etomidate


  Is an imidazole derivative similar to ketoconazole that inhibits 11 βhydroxylase. Because it is only available in a parenteral formulation, use is limited to patients with acute hypercortisolemia requiring emergency treatment.
• Aminoglutethimide


  Inhibits cortisol synthesis by blocking conversion of cholesterol to pregnenolone early in the cortisol pathway. Side effects of severe sedation, nausea, ataxia, and skin rashes limit aminoglutethimide use in many patients.
• Mitotane


  Is a cytotoxic drug that inhibits the 11-hydroxylation of 11-desoxycortisol and 11-desoxycorticosterone in the adrenal cortex, reducing synthesis of cortisol and corticosterone. Degenerates cells within the zona fasciculata and reticularis; the zona glomerulosa is minimally affected during acute therapy but can become damaged after long-term treatment.
• Mifepristone (RU-486)


  Is a progesterone- and glucocorticoid-receptor antagonist that inhibits dexamethasone suppression and increases endogenous cortisol and ACTH levels in normal subjects.
• Surgical resection of offending tumors is the treatment of choice for both ACTH-dependent and ACTH-independent Cushing syndrome
• Pituitary irradiation provides clinical improvement in ~50% of patients within 3 to 5 years, but improvement may not be seen for 6 to 12 months, and pituitary-dependent hormone deficiencies (hypopituitarism) can occur
• Laparoscopic adrenalectomy may be preferred in patients with unilateral adrenal adenomas or for whom transsphenoidal surgery and pituitary radiotherapy have failed or cannot be used