The Adrenal Gland Flashcards
What is the structure of the adrenal cortex in terms of what it produces?
Outer:mineralocorticoids (aldosterone) which control Na+ and K+ balance
Middle:glucocorticoids (cortisol) which affect carbs, lipid and protein metabolism
Inner: androgens, have a weak effect until conversion to testosterone and dihydrotestosterones
Salt, Sugar, Sex
How is the adrenal cortex stimulated to realise cortisol and androgens?
Corticotropin-releasing hormone (CrH) is released from hypothalamus. This stimulates release of Adrenocorticotrophic hormone (ACTH) from the pituitary, which stimulates the adrenal cortex
What is Cushing’s syndrome?
Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the HPA axis as well as loss of the circadian rhythm of cortisol secretion
What are some causes of Cushing’s?
- ACTH dependent (raised)
- Cushing’s disease-ACTH secreting pituitary adenoma resulting in bilateral adrenal hyperplasia
- Ectopic ACTH production: small cell lung cancers and carcinoid tumours - ACTH independent (reduced levels due to -ve feedback)
- Iatrogenic: oral steroids (common)
- Adrenal adenoma/cancer
- Adrenal modular hyperplasia
What is a Dexamethasone suppression test?
Dexamethasone is a potent synthetic steroid that, when given orally would normally suppress (by feedback inhibition) the secretion of ACTH and thus cortisol. Dexamethasone suppression of plasma cortisol by >50% is characteristic of Cushing’s disease because for the diseased pituitary, even though it is relatively insensitive to cortisol, it does retain some sensitivity to potent synthetic steroids. Suppression does not normally occur in adrenal tumours or ectopic ACTH production.
What would be the result of a dexamethasone suppression test with an adrenal tumour?
No cortisol suppression because the adrenal gland is unaffected by dexamethasone
What would be the result of a dexamethasone suppression test with a pituitary adenoma (Cushing’s disease)?
A low dose test may lead to no changes in cortisol but a higher dose should reduce cortisol levels
What would be the result of a dexamethasone suppression test with ACTH/CRH secreting ectopic tumour?
No cortisol suppression even at higher doses
What would be the result of a dexamethasone suppression test with adrenal modular hyperplasia?
No cortisol suppression
What are the symptoms of Cushing’s syndrome?
Weight gain
Mood change (depression, lethargy, irritability)
Proximal weakness
Gonadal dysfunction (irregular menses, ED)
Acne
Recurrent Achilles’ tendon rupture
What are the signs of Cushing’s syndrome?
Central obesity Plethora, moon face Buffalo hump Skin and muscle atrophy Bruises Purple abdominal striae HTN hyperglycaemia Infection prone Poor healing
What is the treatment for steroid caused Cushing’s?
Stop medications
What is the treatment for Cushing’s caused by Cushing’s disease?
Selective removal of pituitary adenoma (trans-sphenoidally) and potentially also bilateral adrenalocetomy if source unlocatable
What is the treatment of Cushing’s syndrome caused by an adrenal adenoma
Adrenalectomy (but doesnt resolve cancer- may need radiotherapy and adrenolytic drugs)
What is the treatment for Cushing’s syndrome due to an ectopic ACTH source?
Surgery if tumour can be located and hasn’t spread
Lower cortisol pre-op with metyrapone/ketoconazole/fluconazole
What is the prognosis of untreated Cushing’s?
Increased vascular mortality
Treatment reduces mortality but symptoms largely remain so follow up carefully
How do you investigate suspected Cushing’s syndrome?
- Overnight dexamethasone suppression test (1mg at midnight and a 8am cortisol level)/ 24hr urinary free cortisol is an alternative.
- (If 1. Was abnormal) 48 hr dexamethasone suppression test (measure cortisol at hours 0 and 48)
How do you localise the cause of Cushing’s syndrome once it is confirmed?
- ACTH levels
2. Imaging: CT/MRI (Adrenal glands), MRI (pituitary), IV contrast CT chest,abdo,pelvis +_ MRI (ectopic causes)
What is another word for primary adrenocortical insufficiency?
Addison’s disease
What are the causes of Addison’s disease? (6)
80% autoimmune (in the UK) TB (Commonest world wide) Adrenal metastases (lung, breast and renal primaries) Lymphoma Opportunistic infections in HIV Adrenal haemorrhage
What is secondary adrenal insufficiency?
Suppression of cortisol secretion most commonly due to chronic steroid use which suppresses the HPA axis.
Will become apparent upon withdrawal of steroids
What are the signs and symptoms of Addison’s disease?
Lean Tanned (w/ pigmented palmar creases, and buccal mucosa) Tired Tearful +_ weakness, Dizzy/faints, postural hypotension Flu like aches and pains Low mood NV
What test would you do to confirm/explore Addison’s disease and what results would you be expecting?
Na low, K+ high (due to reduced mineralocorticoids) Glucose low (due to low cortisol)
Short ACTH stimulation test (plasma cortisol level, give tetracosactide, measure cortisol 1/2h after)
Plasma renin and aldosterone (to assess mineralocorticoid levels)
CXR/AXR: for cause ie TB
In what situations would you expect cortisol to be falsely high?
Pregnancy
Oral contraceptive pill
Due to increased cortisol binding globulin
