Hypoadrenalism

Hypoadrenalism

Addison’s Disease

·        Primary adrenal failure: Failure of gluco- and mineralo-corticoids – both have similar hypotensive and electrolyte effects (different mechanisms but additive)

·        Pure glucocorticoid (eg cortisol) deficiency gives:

o  Hypotension (postural and resting BP) due to:

§  Depletion of plasma renin substrate (angiotensinogen): Cortisol is permissive to PRS production and lowers angiotensin levels and hence vascular tone

§  Reduced cardiac contractility and stroke volume due to sodium shift from ECF to ICF (with tendency to hyperkalaemia reciprocal to the Na cell influx)

§  These lead to secondary effects including ¯ renal plasma flow, reduced GFR and mild elevation in urea

o  Hyponatraemia results from:

§  Shift of Na+ from ECF into cells – K shifts out

§  Very high ADH (vasopressin) levels

§  Reduced renal free water clearance (in part from ADH excess and from the reduced GFR)

·        Pure mineralocorticoid (ie aldosterone) deficiency gives: 

o  Reduced Na uptake exchanging for K+ and H+ in renal distal tubule and in other epithelial surfaces (gut, sweat) ® hyponatraemia

o  Secondary effects: hypotension, reduced GFR, clearly raised urea, raised K+

·        With suspected Addison‟s, need to check for features of:

o  Mineralocorticoid deficit (few, but relate to salt depletion)

o  ACTH excess (hyperpigmentation)

o  A pituitary lesion (space occupying effects)

o  Hypopituitarism (gonadal, thyroid, prolactin or GH deficiency, PRL excess, ADH/vasopressin)

o  History of glucocorticoid medication 

·         Symptoms: very non-specific, weakness, abdominal pain, depression, „viral illness‟, anorexia, D&V, nausea, pigmentation in palmar creases and buccal mucosa (takes ­­ACTH), arthralgia, myalgia, weight loss, nocturia, confusion, irritability, constipation, dehydration, dizziness (eg due to Na depletion ® postural hypotension), hypoglycaemia (reduced gluconeogenesis. Lack of cortisol will obscure adrenergic effects of hypoglycaemia), diarrhoea, ¯libido, vitiligo (autoimmune mediated depigmentation of patches of skin). Not constipation or dehydration in pure cortisol deficiency

·        Addisonian Crisis: tachycardia, fever, shock, coma

·        Diagnostic tests:

o  Plasma renin (most sensitive indicator of mineralo-corticoid insufficiency)

o  Short ACTH stimulation test (Synacthen)

§  Better than 24 hr urine Cortisol (midnight cortisol test is equivalent to 24 hour urine).

§  Usually test at 0 and 30 minutes

§  Use long Synacthen test (0, 4, 6 hours) only when in doubt

§  If Cortisol doesn‟t rise then do prolonged ACTH stimulation test over 3 days (eg to differentiate between Addison‟s and prednisone suppression).

o  Basal (8 – 9 am) plasma ACTH will determine gland or origin (if high then primary, if low then secondary)

o  Basal (8 – 9 am) plasma Cortisol little help due to wide normal range

o  Test for adrenal antibodies and check for signs of Tb (eg calcification on Xray) 

·        Also test for: hyperkalaemia, hyponatraemia, hypoglycaemia, uraemia, mild acidosis, hypercalcaemia (?from pre-renal failure), normocytic anaemia, abnormal LFTs, ­eosinophilia, ¯neutropenia

·        Causes: 

o 80% idiopathic (autoimmune).  Associated with Graves, Hashimoto‟s, IDDM, pernicious anaemia

o  Tb, metastases (insufficiency only after 90% of both adrenals destroyed)

Secondary Hypoadrenalism: Pituitary Failure

·        Tests for longstanding (ie > 6 – 8 years)

o   Short Synacthen test: measures adrenal atrophy 

o   Insulin tolerance test: check for ACTH and cortisol release. Little data to judge normal range ® not often used clinically

Adrenal atrophy from glucocorticoid therapy

·        Occasionally short Synacthen test shows a delayed response

·        Long Synacthen less convenient but more reliable

Steroid Medication

·        Replacement doses for Cortisol:

o   Hydrocortisone = 15 mg per day, have to take 3 times a day due to short T½, and to avoid plasma peaks (® side effects, eg osteoporosis)

o   Prednisone: 7 mg per day.  Longer T½

o   Adjust by measuring cortisol (ie 24 hour urine cortisol). Replacement therapy does not usually suppress elevated ACTH

o   No abrupt changes in dose, increase in intercurrent illness. If vomiting then iv dose

o   Use Fludrocortisone for aldosterone replacement

·        Withdrawal:

o   Withdrawal of long term prednisone needs to be done slowly (ie monthly reductions) due to atrophy

o   Signs of CG deficiency imply withdrawal is too fast