Corticosteroids
- Glucocorticosteriods produced in zona fasiculata in supra-renal gland
- Circadian variation.
- Adrenocorticotropic hormone (ACTH) also has melanin releasing hormone (MRH) which may cause pigmentation at higher levels.
- ACTH is stimulated by CRH (Corticotropin-releasing hormone ) and ADH (anti diuretic hormone)
Basal Levels
- Released episodically and to stress response
- Basal levels should be taken between 8-9am
- Suppression and stimulation tests used for diagnosis of deficiency/excess
- inhibit ACTH/CRH release > decrease cortisol levels
- diagnosis for Cushings
ACTH stimulation test
- synthetic ACTH to stimulate cortisol production
- short and 9am stimulation tests are used to differentially diagnosis Addison’s disease from other adrenal insufficiency disorders
Addisons disease – primary hypoadrenalism
- destruction of entire adrenal cortex (all 3 hormones reduced)
- differs from pituitary insufficiency as mineralocorticoid levels are normal
- reduced cortisol levels lead to higher levels of CRH/ACTH
- autoimmune (AI), TB, HIV, surgery, infarction, malignancy, amyloidosis
- associated w/ Other AI diseases
- auto-antibodies against 21a hydroxlase
Clinical features
- vague and non-specific
- Addison crisis – hypotension and dehydration after illness/surgery ( treatment urgent )
- Grey pigmentation in majority of cases (increase in ACTH)
- Postural systolic hypotension (mineralocorticoid deficiency)
Diagnosis
- If suspected take blood samples and treat urgently (saline/hydrocortisone)
- Short ACTH stimulation test
- Impaired cortisol response confirms hypoadrenalism but doesn’t differentiate between Addisons and secondary.
- 9am plasma ACTH levels
- ACTH >80ng/l with low cortisol confirms Addisons
- hyponatremia, hyperkalemia, hypoglycaemia, auto-antibodies
Treatment
- Treatment regime
- fludrocortisone treatment assessed by salt balance, no postural blood pressure drop and renin suppression
- Treat hyperkalemia if necessary
Secondary hypoadrenalism
- hypothalamic-pituitary disease, long term corticosteroid therapy
- Panhypopituitarism is seen in hypothalamic-pituitary disease,
- Hydrocortisone should be given before thyroid medication.
Congenital adrenal hyperplasia
- Autosomal recessive disease, 21-hydroxylase defect (CYP21A2)
- Lack of cortisol causes an increase in ACTH > hyperplasia of adrenal glands
- Build-up of steroid precursors lead to androgen pathways > virilisation
- Clinical features
- Sexual ambiguity, adrenal failure, salt loss, urogenital abnormalities
- Later – precocious puberty, hirsuitism
- Diagnosis
- Serum 17-hydroxyprogesterone – high levels in blood test is diagnostic of classic 21-hydroxylase deficiency
- Treatment
- Dependent upon clinical features and severity