Cushing's syndrome

Question 1

Definition of Cushing’s syndrome

Answer 1

prolonged exposure to glucocorticoids (such as cortisol) and the symptoms which are associated with this

Question 2

The causes of symptoms in Cushing’s syndrome

Answer 2

Can either be ACTH dependent of independent. In some cases it can be “Pseudo-Cushing’s syndrome”

Question 3

ACTH dependent

Answer 3

Most commonly it is Cushing’s disease, the second most common is due to ectopic ACTH syndrome (usually caused by small cell carcinoma).

Question 4

ACTH independent

Answer 4

Most common is adrenal adenoma

Question 5

Pseudo-Cushing’s syndrome

Answer 5

Most commonly occurs in depression

Question 6

Epidemiology of Cushing’s

Answer 6

Can be Iatrogenic in nature, or due to ectopic ACTH syndrome, Cushing’s disease, adrenal tumors

Women are 3-8x more likely to be affected than men. Smoking is linked to it due to the increased incidence of lung cancer.

Prevalence of getting Cushing’s is higher in those above 50. Occurs more often in women around the ages of 25-45

Question 7

Symptoms of Cushing’s syndrome

Answer 7

Central obesity, glucose intolerance, hypertension, hirsutism, abdominal stria, ankle edema, hyper pigmentation, exophthalmus, skin abnormalities, menstrual irregularities, and skeletal abnormalities.

Adrenal incidentilomas can lead to mild hypercortisolism, some ACTH suppression, some symptoms.

Question 8

First line diagnosis

Answer 8

First line: Late night saliva cortisol (preformed at least twice), urinary cortisol (at least twice, should be 3x above normal) and a low dose dexamethasone test (either 1mg over night or 2 days 2 mg)

Question 9

Second line diagnosis

Answer 9

CRH which stimulates the pituitary to secrete ACTH can be used for ectopic and pituitary ACTH tumors. For second line both CRH and dexamethasone can be used together (4mg).

Method: 1mg/kg of CRH is administered intravenously. ACTH and cortisol levels are measured before CRH injection and at 15, 30, 45, 60, 90 and 120 minutes after injection. A rise in the cortisol value of 20% or more above the basal level or a rise in ACTH value at least 50% above basal level is considered evidence for an ACTH-dependent lesion (such as a pituitary ACTH secreting tumor)

Question 10

Other ways of diagnosis

Answer 10

MRI, CT, PET scans

Question 11

Treatment

Answer 11

Ectopic and CRH syndromes are treated with surgery
Non-resectable tumors: adrenal enzyme inhibitors or bilateral adrenalectomy
Primary adrenal diseases: adrenalectomy, mitotane (an antineoplastic drug for adrenocortical carcinoma)