Adrenals

• Adrenal Gland

  A multifunctional organ that produces essential steroid hormones and neuropeptides
• Adrenal Gland

  • Composed of two embryologically distinct tissues: outer adrenal cortex and inner adrenal medulla
  • Adult: pyramid-shaped, located in the superior and medial to the upper pole of the kidneys
• Effects of the adrenal gland

  • Blood pressure
  • Electrolyte imbalance
  • Androgen excess
• Adrenal Cortex

  • G-zone produces aldosterone (mineralocorticoid) which is critical for sodium retention, potassium excretion, acid-base balance, and regulation of blood pressure
  • F-zone produces glucocorticoids: cortisol, cortisone, and corticosterone, crucial for glucose homeostasis and blood pressure
  • R-zone secretes aldosterone, adrenal androgens: DHEA-S, androstenedione and testosterone, and estrogens

  
• Congenital Adrenal Hyperplasia

  Refers to a group of clinical entities that arise from absent or diminished activity of enzymes involved in steroidogenesis
• Congenital Adrenal Hyperplasia


  • 21-hydroxylase is the most common enzyme affected
  • Deficiency results in decreased glucocorticoid
  • 17-hydroxyprogesterone is diagnostic of classic 21-hydroxylase deficiency
  • Infants: failure to thrive, low blood pressure
  • Adult: hirsutism, menstrual irregularities, infertility

  
• Primary Aldosteronism


  Refers to excessive secretion of aldosterone that cannot be suppressed with salt or volume replacement

  
• Primary Aldosteronism


  • Patients present with hypertension, hypokalemia, and metabolic alkalosis
  • Patients have an increased risk of vascular disease such as stroke
  • Most common causes: aldosterone-producing adrenal adenoma, unilateral or bilateral adrenal hyperplasia, familial hyperaldosteronism, adrenocortical carcinomas, ectopic aldosterone secretion
• Diagnosis of Primary Aldosteronism

  1. Plasma aldosterone concentration (PAC) and Plasma renin activity (PRA) - PAC >15ng/dL AND PAC/PRA ratio of ≥30 is suggestive

  2. Patient preparation: morning collection, after patient has been awake for at least 2 hours, seated for 5 to 15 minutes before collection, sodium intake should be restricted

  3. Confirmatory Tests: oral salt loading, IV saline infusion

  4. Adrenal imaging followed after biochemical evaluation

  5. Adrenal venous sampling recommended to distinguish between hyperplasia and aldosterone-secreting adenoma

  
• Treatment of Primary Aldosteronism

  • Surgery - treatment of choice for aldosterone-producing adenoma
  • Mineralocorticoid antagonists - used for adrenal hyperplasia (spironolactone or eplerenone)
  • Prednisone - for familial aldosteronism

  
• Adrenal Insufficiency


  Refers to insufficient hormone secretion from the adrenal cortex
• Types of Adrenal Insufficiency

  • Primary - adrenal
  • Secondary - pituitary
  • Tertiary - hypothalamic
• Adrenal Insufficiency


  • Primary: reduced production of adrenal hormones despite adequate stimulation, most common cause is autoimmune destruction
  • Symptoms: fatigue, decreased appetite, weight loss, nausea
• Diagnosis of Adrenal Insufficiency


  1. Screening Test: ACTH stimulation test - performed at 8am in fasting state, baseline cortisol and ACTH, patient given 250ug cosyntropin IV, detection of cortisol after 30 and 60 mins, >18ug/dL or increase of at least 7ug/dL from baseline is normal

  2. Metyrapone suppression testing - done if secondary adrenal insufficiency suspected, blocks enzymes in steroidogenesis pathway, secondary adrenal insufficiency has near normal response to cosyntropin but abnormal response to metyrapone

  3. Confirmatory Test: Insulin Tolerance Test - gold standard for assessing HPA axis

  
• Treatment of Adrenal Insufficiency

  • Glucocorticoid and mineralocorticoid replacement
  • Secondary adrenal deficiency only requires glucocorticoid replacement
• Isolated Hypoaldosteronism


  • Caused by adrenal gland destruction, chronic heparin therapy, unilateral adrenalectomy, G-zone enzyme deficiencies, may also affect patients with mild renal insufficiency
  • Treated with dietary changes and fludrocortisone (enhances salt retention)
• Hypercortisolism


  Cortisol excess from adrenal tumors (ACTH is low), Cushing's Disease (cortisol excess due to elevated ACTH from pituitary), and other forms of Cushing's syndrome

  
• Diagnosis of Hypercortisolism


  1. Exogenous cortisol use must be ruled out first

  2. Initial screen tests: Urine Free Cortisol (UFC) collected over 24 hours, Midnight salivary cortisol, Dexamethasone suppression testing

  3. Screen tests must produce two positive results for diagnosis

  4. If positive for hypercortisolism, ACTH must be measured to determine cause - ACTH >15ug/dL suggests pituitary, ACTH <5ug/dL suggests adrenal

  5. CT or MRI imaging of adrenal glands

  6. High-dose dexamethasone suppression test - overnight or over 48hrs, used to determine pituitary ACTH production

  7. Gold standard for ACTH production: inferior petrosal sinus sampling (IPSS)

  
• Treatment of Hypercortisolism


  • Cushing's disease - transsphenoidal resection of pituitary tumor
  • Cushing's syndrome - surgical resection first, medical therapy if hypercortisolism persists, bilateral adrenalectomy occasionally necessary if medical therapy unable to suppress cortisol
• Figure 16.9 shows the differential diagnosis of low cortisol states

  
• Figure 16.12 summarizes the diagnostic testing algorithm for Cushing's syndrome