Cushing's disease

Syndrome of glucocorticoid steroid excess, secondary to corticotroph adenoma of the pituitary gland. The diagnosis is confirmed with failure of cortisol suppression on a low dose dexamethasone suppression test, elevated ACTH and with an elevated midnight cortisol.

Does the patient have muscle weakness and wasting? Can they climb the stairs or rise from a chair easily? Can they brush or dry their hair easily? 

These questions are specifically seeking evidence of proximal myopathy.

Has the patient gained or lost weight? What is the pattern of the weight distribution? What is the timing of the weight gain? 

Weight gain is typically new onset, central, with relative wasting of the limbs (apple on a stick appearance).

Simple weight gain in childhood tends to be associated with tall stature, while the onset of paediatric Cushing’s with loss of growth velocity. Hence a Cushingoid child may turn from the tallest to the shortest in their class, whereas a child with simple obesity will tend to be one of the tallest.

Weight gain in puberty and pregnancies is common and not necessarily indicative of Cushing’s.

Weight loss may be associated with ectopic ACTH or malignant disease.

Have associated medical conditions been detected? 

Hypertension, type 2 diabetes mellitus, osteoporosis (new back pain or low fragility fractures), and depression are all common, and hypertension and glucose intolerance may form part of the metabolic syndrome in association with obesity.

However, in combination these are suggestive of Cushing’s syndrome as is osteoporosis which is frequently undiagnosed.

Have there been any skin changes: acne, hirsuitism, bruising, or redness of the face?

Plethora, acne, hirsuitism and easy bruising are all supportive of a diagnosis of Cushing’s. Overt virilisation is suggestive of adrenal aetiology.

Has the patient developed swollen ankles or puffy extremities? 

Fluid retention is suggestive of very high levels of cortisol gaining access to the mineralocorticoid receptors in the kidney.

Has the patient noticed a change in mood, for example depression or emotional lability? 

Depression is common in Cushing’s.

Has the patient noticed change in their libido or in their sexual characteristics? 

Women with adrenal tumours may develop an increase in well being and in libido, as well as overt virilisation: acne, hirsuitism, clitoromegaly associated with increased androgens.

Male patients may notice a loss of libido and erectile dysfunction with Cushing’s syndrome.

What is the patient's menstrual history? Has this changed? Have periods become irregular? 

Oligomenorrhoea or secondary amenorrhoea may be associated with either PCOS or Cushing’s syndrome and needs careful investigation.

Has the patient noticed changes in their voice? 

New deepening of the voice is suggestive of an adrenal virilising tumour.

Has the patient noticed increased muscle bulk, for example broadening of the shoulders? 

Increased muscle bulk is suggestive of an adrenal virilising tumour rather than pituitary dependent disease.

Could the patient be taking any steroid containing medications?

Multiple medications interfere with the hypothalamic pituitary adrenal axis. Patients taking long term prednisolone >7.5mg will almost inevitably have adrenal suppression. However, many patients may not realise that other medications contain steroids.

For example asthma inhalers, multiple skin creams taken for medical and cosmetic purposes, joint injections, and even some alternative remedies have been found to contain steroids and so make interpretation of serum cortisol levels difficult.

Estrogen containing medications such as the contraceptive pill and hormone replacement therapy also make interpretation difficult due to a rise in serum cortisol binding globulin.