Cushing's Disease

Question 1

what is cushing’s syndrome?

Answer 1

a hormonal disorder caused by prolonged exposure to high levels of the hormone cortisol, which can lead to various symptoms like weight gain, especially around the face and abdomen

Question 2

what is cushing’s disease?

Answer 2

• a specific form of cushing’s syndrome caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma
• this results in excessive stimulation of the adrenal glands, leading to hypercortisolism

Question 3

what is the aetiology of cushing’s syndrome?

Answer 3

• ACTH-secreting pituitary adenoma
• ACTH-secreting/CRH-secreting non-pituitary tumour (e.g. SCLC, bronchial carcinoid, pancreatic neuroendocrine, thymic)
• cortisol-secreting adrenal adenoma/carcinoma
• primary bilateral macronodular adrenal hyperplasia (PBMAH)
• iatrogenic (e.g. prolonged use of glucocorticoids)

Question 4

what are the functions of cortisol?

Answer 4

• gluconeogenesis
• proteolysis
• lipolysis → lipogenesis
• inhibition of the production of several inflammatory cytokines causing downregulation of the immune response
• reduction in osteogenesis → osteoporosis
• in high concentrations, cortisol exhibits mineralocorticoid effects, increasing sodium and water retention whilst increasing potassium excretion

Question 5

what are the symptoms of cushing’s syndrome?

Answer 5

• weakness
• facial fullness
• weight gain
• low mood
• decreased libido
• polydipsia
• polyuria
• increased frequency of infections

Question 6

what are the signs on examination of cushing’s syndrome?

Answer 6

• truncal obesity
• buffalo hump
• supraclavicular fat pads
• moon facies
• proximal muscle wasting
• hypertension
• oedema
• headache, visual field defect, galactorrhea (e.g. cushing’s disease)

Question 7

what are the investigations for cushing’s syndrome?

Answer 7

• FBC (e.g. ↑ WCC)
• U&Es (e.g. hypokalaemia, hypernatraemia)
• 24-hour urinary free cortisol (e.g. ≥3 X ULN)
• late-night salivary cortisol ↑
• low-dose dexamethasone suppression test
• plasma ACTH (e.g. ↑ ACTH-dependent, - ACTH-independent)
• ? high-dose dexamethasone suppression test
• ? inferior petrosal sinus sampling (IPSS)
• MRI pituitary
• CT chest + abdomen

Question 8

what is involved in the low-dose dexamethasone suppression test?

Answer 8

• 1 mg of dexamethasone is administered at 11 pm, and serum cortisol is measured at 8 am the following morning
• a normal result would be morning cortisol suppression

Question 9

what is involved in the high-dose dexamethasone suppression test?

Answer 9

• is indicated if ACTH levels are detectable
• useful for differentiating between pituitary and ectopic ACTH production
• a reduction of basal urinary-free cortisol of greater than 90% supports a diagnosis of a pituitary adenoma

Question 10

what is inferior petrosal sinus sampling (IPSS)?

Answer 10

• an invasive procedure in which ACTH levels are sampled from veins that drain the pituitary gland
• these ACTH levels are compared with peripheral ACTH levels to determine whether a pituitary tumour is responsible for ACTH-dependent cushing’s syndrome

Question 11

what is the management of exogenous cushing’s syndrome?

Answer 11

involves reviewing the patient’s current glucocorticoid treatments and reducing doses where possible (e.g. often with steroid-sparing immunosuppressive agents)

Question 12

what is the management of endogenous cushing’s syndrome?

Answer 12

• inhibit glucocorticoid synthesis (e.g. ketoconazole, metyrapone, mitotane)
• laparoscopic excision (e.g. adrenal adenoma)
• trans-sphenoidal surgery (e.g. pituitary tumour)

Question 13

what are the long-term complications of cushing’s syndrome?

Answer 13

• hypertension
• diabetes
• obesity
• metabolic syndrome
• osteoporosis