Cushing's syndrome

The clinical syndrome of glucocorticoid excess. This may be caused by exogenous steroid use, ACTH independent adrenal disease, or ectopic ACTH. The diagnosis Cushing's disease specifically refers to Cushing's caused by ACTH secreting tumours of the pituitary gland.

Has the patient gained or lost weight? 

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 there been any skin changes: acne, redness, bruising or new hair growth? 

Acne, hirsutism and easy bruising are all supportive of a diagnosis of Cushing’s, particularly of recent onset. Overt virilisation is suggestive of adrenal aetiology. Ask whether the patient or their family have noticed increased redness of their face or a change in their appearance.

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 developed a change in their menstrual cycle?

Oligomenorrhoea and secondary amenorrhoea may be associated with either polycystic ovarian syndrome or Cushing’s syndrome. Both require careful investigation.

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.

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? 

It's suggestive of an adrenal virilising tumour.

Does the patient have hypertension?

Though hypertension is common, it supports a clinical suspicion of Cushing's, especially when associated with mild hypokalaemia.

Have they developed diabetes, or a worsening of their glycaemic control?

Type 2 diabetes mellitus and glucose intolerance have an increased incidence in Cushing's. Existing diabetes is exacerbated by glucocorticoid excess.

Are they known or suspected to have osteoporosis?

Osteoporosis is frequently undiagnosed. A patient may have lost height or developed back pain rather than having an obvious low fragility fracture.

What is the patient's detailed drug history?

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.