Adrenal function

• Adrenal cortex hormone


  Glucocorticoids: Cortisol
• Adrenal medulla hormone


  Catecholamines: Epinephrine, Norepinephrine, Dopamine
• Glucocorticoid regulation


  Corticotropin Releasing Hormone (CRH) to ACTH
• Mineralocorticoid regulation


  RAA System and to lesser extent ACTH & Potassium level
• Adrenal androgen


  Dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), and androstenedione

  
• Adrenal androgen regulation


  ACTH
• Adrenal cortex


  • Shape like pyramids just above the kidney
  • Pathologic conditions linked to impact on blood pressure and electrolyte balance

  
• 3 zonal layers of adrenal gland

  • Zona glomerulosa
  • Zona fasciculata
  • Zona reticularis

  
• Zona glomerulosa


  • Synthesize mineralocorticoids- ALDOSTERONE
  • Aldosterone plays in Na, K, acid-base homeostasis

  
• Zona fasciculata


  • Synthesize glucocorticoid- CORTISOL
  • Cortisol is responsible for blood glucose homeostasis
  • Also generate androgen precursors-DHEA (dehydroepiandrosterone)

  
• Zona reticularis


  DHEA-S from cholesterol, a precursor for adrenal sex hormone

  
• Cortex steroidogenesis


  1. Corticotropin-releasing hormone (CRH) is secreted from the hypothalamus in response to circadian signals, serum cortisol, and stress, causing release of stored ACTH

  2. Conversion of Cholesterol to pregnenolone is the " first-rate limiting step" in steroid biosynthesis

  
• Aldosterone


  • Major mineralocorticoid
  • Helps regulate water and electrolytes, and blood pressure
  • Regulated primarily by RAAS, also ACTH to some extent

  
• Aldosterone functions


  • Acts on RTE to retain NA+ and Cl-
  • Excretes H+ and K+

  
• Primary hyperaldosteronism (Conn's syndrome)

  • Usually due to benign adrenal adenoma or hyperplasia of adrenal cortex
  • Usually results to hypertension & Potassium depletion
• Sex steroids/weak androgens/adrenal androgens

  • Both men & women secrete adrenal androgens, but much larger amounts are secreted by the gonads
  • Secretion from the adrenal is controlled by ACTH, not by gonadotropins
  • Principal adrenal androgen is DHEA (dehydroepiandosterone)
  • Androgens are metabolized to 17-ketosteroids (17-KS)

  
• Cortisol


  • Principal glucocorticoid
  • Has an anti inflammatory and immunosuppressive actions
  • Exerts negative feedback to ACTH production from pituitary
  • The liver degrades all the glucocorticoids to metabolites excreted in urine, where they are measured as a group called 17-hydroxycorticosteroid (17-OHCS)

  
• Regulation of cortisol


  • Stress: surgical trauma, hypoglycemia, pyrogens, hemorrhage, pregnancy, oral contraceptives
  • Diurnal rhythm: Peak is 8am, a small rise at 4pm (surge after meal), Trough values: 10-11 pm (50% lower than 8am)

  
• Plasma cortisol binding


  • CBG/transcortin 93-90%
  • Albumin 12-20%
  • Free (active) 5-10%
• Plasma ACTH


  Used to differentiate between primary & secondary hypoadrenalism
• Specimen consideration for ACTH: DO NOT USE GLASS when collecting blood; ACTH become adsorbed to the glass
• Specimen consideration for ACTH: Timing is important due to circadian rhythm: PEAK: 8am, TROUGH: 10 pm
• Hormone levels in primary vs secondary hypoadrenalism

  • Cortisol: Low
  • ACTH: High (primary), Low (secondary)

  
• Cushing's syndrome


  • General term used to describe any condition resulting from increased cortisol
  • Pseudo-Cushing's syndrome may exist with chronic alcoholism and/or a high level of cortisol-binding globulin associated with pregnancy or the use of contraception, which can be confused with Cushing's syndrome
  • Noniatrogenic causes include pituitary tumors (60% of all cases), ectopic ACTH (20% of all cases), and adrenal adenoma and adrenal carcinoma (combined 20% of all cases)
• Clinical observations in Cushing's syndrome

  • Truncal obesity w/ thin extremities; purple striae; plethoric face
  • Abnormal glucose tolerance (hyperglycemia)
  • HYPERTENSION (due to aldosterone excess)
  • Hirsutism & menstrual disorders in women (due to androgen excess)
• Lab findings in Cushing's syndrome

  • Elevated urine 17-OHCS & 17 KS
  • Elevated urinary-free cortisol

  
• Cushing's syndrome categories


  • Cushing's disease (ACTH dependent)
  • Cushing's syndrome (ACTH independent)
• Cushing's disease


  • ACTH dependent
  • Caused by an ACTH producing pituitary tumor; the feedback control system is nonfunctional
  • INCREASED cortisol and INCREASED ACTH
  • Increased glucose, sodium, and aldosterone

  
• Cushing's syndrome


  • ACTH independent
  • Caused by adrenal adenoma that produces excess cortisol; the feedback control system is functional
  • INCREASED cortisol and DECREASED ACTH
  • Increased glucose, sodium, and aldosterone

  
• Dexamethasone suppression test


  1. Dexamethasone is a potent analog of cortisol & can be effective in suppressing pituitary secretion of ACTH. It acts like a negative feedback at the level of the pituitary.

  2. Can be used for differential diagnosis of endogenous depression

  
• Metyrapone inhibition test


  1. Metyrapone decreased cortisol by inhibiting enzymatic conversion of 11-deoxycortisol to cortisol

  2. ACTH is stimulated due to decreased cortisol production

  
• Normal dexamethasone suppression test: cortisol <5.0 ug/dL, low 17-OHCS

  
• Positive dexamethasone suppression test: cortisol >5.0 ug/dL (NOT SUPPRESSED)

  
• Addison's disease


  • Deficiency of adrenal corticosteroid (HYPOADRENALISM)
  • Causes by administration of exogenous steroids, tuberculous destruction of adrenal glands, autoantibodies, other idiopathic

  
• Clinical observations in Addison's disease

  • Weight loss & Muscle wasting
  • HYPOTENSION (Due to deficient Aldosterone/ HYPOALDOSTERONISM)
  • Salt craving (due to deficient Aldosterone)
  • HYPERPIGMENTATION OF SKIN
• Lab findings in Addison's disease

  • Decreased plasma cortisol, urine free cortisol, & 17-OHCS
• Determining cause of Addison's disease

  1. Use of synthetic ACTH

  2. ADRENAL CORTEX DISORDER: No change in plasma & urine cortisol

  3. PITUITARY DISORDER: Result is an increase in plasma & urine cortisol

  
• Hyperaldosteronism


  Excessive aldosterone production

  
• Lab findings in hyperaldosteronism

  • Low Serum Potassium
  • High urinary Potassium excretion
  • Moderate Alkalosis
  • HYPERTENSION

  
• Primary hyperaldosteronism (Conn's syndrome)

  • Excessive aldosterone w/ unresponsive RAA System (low renin)
  • Usually due to benign adenoma