The adrenal gland part 2: aldosterone, androgens and adrenal disorders

Adrenal cortex steroid hormones
1. Zona glomerulosa
  1. Mineralocoricoids - aldosterone
    1. Salt
2. Zona fasiculata
  1. Glucocorticoids - cortisol
    1. Sugar
3. Zona reticularis
  1. Androgens - DHEA- sulfate
    1. Sex
Mineralocorticoids - Aldosterone
1. Binds to mineralocorticoid receptor
  1. Cortisol also binds to the MR with similar affinity
    1. Apparent mineralocorticoid excess
      1. Actual mineralocorticoid levels may be normal or low
      2. Symptoms of excessive mineralocorticoid (aldosterone) - causing hypertension and hypervolaemia
        Caused by: inhibition or mutation of the 11-beta hydroxysteroid DH (11-beta HSD) which deactivates cortisol by converting to cortisone
        As cortisol cannot be inactivated by this path its levels remain high and it acts within the kidneys at the MR
        Causes a pseudohyperaldosteronism
        11-beta HSD protects the MR from cortisol (which circulates at a higher concentration to aldosterone)
        -
        Liquorice contains glycyrrhetinic acid (inhibits 11-beta-HSD)
2. Regulated by renin-angiotensin system (RAS)
3. Regulation
  1. Stimulus: decreased blood volume, decreased Na(+), rapid change in posture (postural/orthostatic hypotension), decreased renal perfusion
    1. Detected by specialised cellsin the kidney (macula densa cells - Na(+) drop), baroreceptors and
      1. Kidney: juxtaglomerular cells release renin (enzyme) which clea,ves circulating angiotensinogen into angiotensin-1
        Lungs: angiotensin-1 cleaved to angiotensin-2
        Adrenal gland: angiotensin-2 stimulates the synthesis and release of aldosterone from the zona glomerulosa of the adrenal cortex
        Kidney: Aldosterone stimulates; increased Na(+) reabsorption -> increased water reabsorption -> restoration of normal blood volume
        -
Adrenal androgens - Dihydroepiandrosterone (DHEA), typically slufated (DHEA-S)
1. By weightadrenal androgens are the major adrenal steroid
  1. Main secreted form is DHEA(S)
    1. The sulfated form of DHEA is converted to DHEA (or other steroids) in the peripheral tissues
      1. ACTH stimulates DHEA secretion - however DHEA is not released in diurnal pattern (like cortisol) indicating another level of control
    2. DHEA secretion declines with age and overall people with chronic illness have a reduced level of DHEA
      1. DHEA anti-aging therapy?
        Widely used in the USA as an over-the-conter medication
        Clinical trials do not reveal miraculous effects (in humans) - some benefit to bone and sense of self-being
        In animal models DHEA supplement; increases immunity, cures T2DM and gives a leaner body mass
        Excess causes; acne and greasy hair (also, a potential link with breast cancer)
2. Clinical relevance of adrenal androgens
  1. Can be metabolised to more potent androgens and to oestrogens
    1. Only source of oestrogens in post-menopausal women
  2. In cushing's syndomre there is excess ACTH production and therefore excess glucocorticoid and adrenal androgens
    1. Excess androgens cause; acne and balding in men; and virillization in women (male-sex characteristic development; enlarged clitoris, hirsuitism)
  3. Congenital adrenal hyperplasia
Disorders of adrenal function
1. Cushing's syndrome
  1. Glucocorticoid excess
  2. Signs and symptoms
    1. Acne (androgens)
    2. Buffalo hump and moon face
    3. Hypertension
    4. Oesteoporosis
    5. Skin thickening, with easy bruising and poor healing
    6. Increased abdominal fat with striae (stretch marks)
    7. Muscle weakness
  3. Causes
    1. Iatrogenic (drug induced): excess of prescription glucocorticoids
      1. Commonest
      2. When a patient started on steroid treatment they ae issues with a sterd card indicating that they should not be withdrawn suddenly from the treatment
        Steroids act negatively (feedback) on the hypothalamus and pituitary to supress releasing and tropic hormone release
        No production from the adrenal glands
        Treatment >3wks can cause a long term shutdown of the adrenals and therapy should be gradually reduced
        Instant ceasation of treatment can result in adrenal insufficiency
    2. Less common
      1. Cushing's disease (pituitary tumour secreting ACTH)
      2. Adrenal adenoma
        Oversecretion of cortisol
      3. Ectopic ATCH production from small cell lung carcinoma
2. Adrenal insufficiency
  1. Causes
    1. Primary - destruction of adrenals
      1. TB, HIV, autoimmune
    2. Secondary - failure of ACTH secretion
  2. Slow and insidious condition (up to 90% of adrenal tissue can be lost before symptoms seen)
    1. However 'stress' can cause a hypoadrenal crisis
      1. Severe hoypotension
      2. Dehydration
      3. Coma -> death
      4. Treated with fluid and steroid replacement
3. Congenital adrenal hyperplasia
  1. Signs and symptoms (in babies)
    1. Ambiguous genitalia
      1. Enlarged clitoris, pubic hair, partially fused labia, failure to thrive, salt wasting (enlarged adrenals)
    2. All as a result of...
      1. Excess adrenal androgens
        Males born with early developed pubic gair and growth (advanced sex characteristics)
        Females with ambiguous genitalia (androgens promoting male-sex changes)
        Excess androgens because the body is trying to make mineralo- and glucocorticoids due to stimulation - but lacking enzyme - androgens produced instead
        (i.e. low blood pressure, low Na(+), stresses
      2. Cortisol deficiency - failure to thrive
      3. Aldosterone deficiency - salt wasting
  2. Deficiency of steroid hormone 21-hydroxylase
    1. No aldosterone, cortisol, but excess of DHEA (androgens)

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The adrenal gland part 2: aldosterone, androgens and adrenal disorders

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	Created by maisie_oj about 11 years ago