cushing's syndrome

Question 1

what is cushing’s syndrome caused by

Answer 1

Excess gluticorticoids and loss of the negative feed back loop to the hypothalamus leads to excess adrenal cortex activity. So increased production of aldosterone, cortisol, androgens.

Question 2

What is the physiology behind release of adrenal cortex hormones?

Answer 2

1) Hypothalamus sectres corticotropin releasing hormone. (CRH)
2) CRH acts on the anterior pituitary gland. Adrenocorticotropic hormone (ACTH) is secreted.
3) ACTH travels in the blood and stimulates the adrenal cortex to secrete aldosterone, glucocorticoids (cortisol) and androgens.

Question 3

What are the symptoms of cushing’s syndrome?

Answer 3

1) central weight gain
2) mood change (depression)
3) insomnia
4) Oliomenorrhoea / amenorrhoea
5) thin skin
6) hair growth
7) acne
8) muscle weakness
9) decreased growth in children
10) back pain
11) polyuria
12) psychosis
13) recurrent achilles tendon rupture

Question 4

What are the signs of cushing’s syndrome?

Answer 4

FACE:

• moon face
• Red cheeks
• acne
• hirsutism (hairy face)
• frontal balding

SKIN

• thin skin and bruising
• poor wound healing
• skin infections
• Stretch marks

MSK

• osteoporosis
• kyphosis
• buffalo lump
• Proximal myopathy (symmetrical weakness of upper/lowe limbs)
• proximal muscle wasting
• pathalogical fractures of vertebrae and ribs.

Other

• hypertension
• central obesity

Question 5

What are the risk factors / causes of cushing’s syndrome?

Answer 5

1) ACTH dependant
- Cushing’s disease (bilateral adrenal hyperplasia caused by ACTH secreting pituitary adenoma.
- ectopic ACTH production

——–> leads to glucocorticoid excess.

2) ACTH non dependant
primary excess of glucocorticoid due to adrenal tumour or nodular hyperplasia.

Drugs - longterm oral steroid

Question 6

Most cases of obese, hypertensive and hirsute are not cushing’s. So what investigations do we do to confirm diagnosis?

Answer 6

***Random levels of cortisol are useless.

1) Dexamethasone suppression tests to assess adrenal gland function by measuring how cortisol levels change in response to an injection of dexamethasone.
2) 24-hour urinary free cortisol measurement. (not as reliable as DST)
3) Circadian rhythm. Cortisol samples taken at 9am and 12 midnight. Cushing’s have high midnight cortisol levels.

Question 7

What is the treatment for cushing’s?

Answer 7

Treat the cause.

• Iatrogenic - stop drug
• Cushing’s disease, selective removal of pituitary adenoma.
• adrenal adenoma/carcinoma = adrenalectomy.
• cortisol inhibiting medications such as Ketoconazole and metyrapone.

Question 8

What is the prognosis of untreated cushing’s?

Answer 8

Poor prognosis and death from vascular causes due to hypertension.

• MI
• heart failure
• Infection

Question 9

what are the differential diagnoses for cushing’s ?

Answer 9

Nelson’s syndrome - high levels of ACTH lead to pigmentation.