Cushing's disease Flashcards
Cushing’s disease refers to a primary/secondary hyper-hypo _____
Secondary hyperadrenalism
(or type of primary hyperpituitarism)
What is the pathophysiology behind Cushing’s disease
pituitary adenoma
secretes excessive ACTH
stimulates excessive cortisol release from adrenal glands
How is Cushing’s syndrome different to Cushing’s disease
Cushing’s syndrome means too much cortisol. This could be due to a pituitary adenoma (Cushing’s disease) or other causes like exogenous steroids, ectopic ACTH.
Cushing’s disease refers to a pituitary adenoma causing an excess in cortisol (Cushing’s syndrome)
What are features of Cushing’s disease/syndrome?
Moon face
Central obesity
Buffalo hump
Abdominal striae (stretch marks)
Limb muscle wasting
Hirsutism (male pattern facial hair in women)
Hyperpigmentation of skin (only when excess ACTH)
Easy bruising
Poor skin healing
What are metabolic effects of Cushing’s disease?
Hypertension
Cardiac hypertrophy
Type 2 diabetes
Dyslipidaemia
Osteoporosis
How does Cushing’s disease cause hypertension?
Cortisol promotes reabsorption of sodium in the kidneys
More fluid retention
Increased blood pressure
Cortisol also has vasoconstrictive effects contributing to increased resistance and elevated bp
How does Cushing’s disease cause cardiac hypertrophy?
Chronic hypertension means increased workload for heart leading to hypertrophy.
Also greater volume in blood (reabsorption of sodium and water) means increased pre-load which also contributes to cardiac hypertrophy.
How does Cushing’s disease cause T2DM?
Cortisol affects insulin resistance, impairing glucose metabolism, promoting gluconeogenesis and promotes hyperglycaemia.
Chronic exposure to cortisol affect pancreatic beta cells leading to impaired secretion of insulin.
How does Cushing’s disease cause osteoporosis?
Chronic exposure to high levels of cortisol can inhibit osteoblast activity, reducing formation of new bone tissue.
Cortisol stimulates osteoclasts so increased bone resorption.
Net loss of bone mass.
Cortisol can also increase urinary excretion of calcium and interferes with vitamin D and calcium absorption, furthering bone loss.
Cortisol inhibits the differentiation of mesenchymal stem cells into osteoblasts.
How can you test for Cushing’s disease?
A high-dose 48 hour dexamethasone test.
If have Cushing’s disease then will suppress the cortisol levels (show normal level).
(dexamethasone acts like cortisol to provide negative feedback to hypothalamus and pituitary, preventing it from producing CRH and ACTH so adrenal glands not stimulated to produce cortisol. The high dose is enough to suppress pituitary adenoma but not an adrenal adenoma or ectopic ACTH)
What other investigations can be taken to confirm Cushing’s disease?
MRI showing pituitary adenoma
Full blood count: high WBC count
How do you treat Cushing’s disease?
Trans-sphenoidal removal of the pituitary adenoma
If not possible, remove both adrenal glands and give life-long steroid replacement therapy
True or false: there may be hyperpigmentation of the skin with Cushing’s disease?
True
Excessive ACTH can lead to increased levels of melanocyte-stimulating hormone leading to increased melanin production.
