Lecture 7.2 - Adrenal disorders.pdf

Cushing's syndrome: ◦Cushing's syndrome - chronic exposure to increased cortisol levels ‣ Benign pituitary disorder Cushing's syndrome vs Cushing's disease: ◦Cushing's disease is not the same as Cushing's syndrome ◦Cushing's disease is the specific case of a benign ACTH se...

Cushing's syndrome: ◦Cushing's syndrome - chronic exposure to increased cortisol levels ‣ Benign pituitary disorder Cushing's syndrome vs Cushing's disease: ◦Cushing's disease is not the same as Cushing's syndrome ◦Cushing's disease is the specific case of a benign ACTH secreting pituitary adenoma -> pituitary adenoma ◦Cushing's syndrome is the general constellation of symptoms resulting from chronic exposure to increased cortisol levels (broad term) ◦Cushing's syndrome is much more common than Cushing's disease ◦Cushing's syndrome is most commonly secondary to long-term treatment with glucocorticoids Iatrogenic Cushing's syndrome: ◦Iatrogenic Cushing's syndrome -> long-term treatment with glucocorticoid drugs (e.g. hydrocortisone, prednisone, prednisolone, dexamethasone) ◦Anti-inflammatory and immunomodulatory effects of glucocorticoid drugs ‣ Used to treat inflammatory disorders, such as asthma, inflammatory bowel disease, rheumatoid arthritis, and other autoimmune conditions ‣ Also used to suppress immune reaction to organ transplantation ◦Side effects of glucocorticoids are the same as the effects of higher cortisol levels, and can also have mineralocorticoid effects (can bind to the mineralocorticoid receptor) ◦Key point - Glucocorticoids should NOT be stopped suddenly and the glucocorticoid dosage should be reduced gradually Cushing's syndrome - signs and symptoms: ◦Thin arms and legs with muscle weakness due to increased muscle proteolysis which causes wasting of proximal muscles ◦Increased lipogenesis in adipose tissue leading to weight gain and deposition of fat in abdomen (abdominal obesity), neck ("buffalo hump") and face (moon-shaped face, plethoric cheeks, plethoric face) ◦Purple and wide striae (stretch marks) on lower abdomen, upper arms and thighs due to the catabolic effects on skin proteins which leads to easy bruising due to thinning of the skin and subcutaneous tissue ◦"Steroid diabetes" - secondary diabetes due to increased hepatic gluconeogenesis and muscle proteolysis (hyperglycaemia with associated polyuria and polydipsia) ◦Increased susceptibility to bacterial infections, poor wound healing and acne due to immunosuppressive and anti-inflammatory actions of cortisol ◦Osteoporosis caused by calcium metabolism disturbances and loss of bone matrix protein which may lead to back pain, fractures and collapse of ribs ◦Hypertension due to sodium and fluid retention caused by the mineralocorticoid effects of excess cortisol (in excess, cortisol has aldosterone- like effects since it can also bind to the mineralocorticoid receptor due to the steroid hormone receptor homology ◦Psychologic symptoms - mental changes (e.g. symptoms of depression)  ◦Hypogonadism (e.g. menstrual disorders in women) ◦Hirsutism (excessive body hair growth, mostly facial hair) and baldness in women ‣ DHEA and androstenedione from the zona reticularis of the adrenal cortex are weak androgens (much lower affinity for the testosterone receptor than testosterone) and are converted peripherally to testosterone - in females, adrenal androgen hypersecretion results in hirsutism and masculinisation (e.g. adrogenic alopecia, deep voice, clitoromegaly) in large tumours) ◦Clinical effects of Cushing's syndrome and their frequency: ‣ Cushing's syndrome mortality is >50%, if not treated ‣ Death usually results from severe infection ‣ Growth ceases when Cushing's syndrome occurs in children (short stature is permanent if treatment is not started before the epiphyses of the bones have sealed Diagnosis: ◦Always follow the golden rule: ‣ Clinical diagnosis ‣ Biochemical diagnosis (blood test) ‣ Radiological diagnosis to localise the problem Cushing's syndrome - clinical tests: ◦09.00 and 24.00 cortisol levels (plasma/saliva) ‣ Stimulation test ‣ Simple screening tests done before suppression tests (e.g. midnight cortisol levels, saliva samples) Can get false positives with this test ‣ Suppression test ◦24 hour urinary free cortisol ◦Dexamethasone (1mg taken in the evening) suppression of plasma cortisol - normal ‣ Measure cortisol levels before 9am ‣ Patients with Cushing’s syndrome will pose high levels of cortisol in the morning ◦Dexamethasone suppression of plasma cortisol ‣ Dexamethasone is a potent synthetic steroid, so when given orally normally suppresses by feedback inhibition the secretion of ACTH and thus cortisol ◦Screening test: ‣ Overnight dexamethasone suppression test: Low dose (1 mg tablet) of dexamethasone at 11pm and measurement of blood cortisol levels the next monring (8-9 am) -> suppression of cortisol to