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.
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.
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.
These questions are specifically seeking evidence of proximal myopathy.
Oligomenorrhoea and secondary amenorrhoea may be associated with either polycystic ovarian syndrome or Cushing’s syndrome. Both require careful investigation.
Fluid retention is suggestive of very high levels of cortisol gaining access to the mineralocorticoid receptors in the kidney.
Depression is common in Cushing’s.
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.
New deepening of the voice is suggestive of an adrenal virilising tumour.
It's suggestive of an adrenal virilising tumour.
Though hypertension is common, it supports a clinical suspicion of Cushing's, especially when associated with mild hypokalaemia.
Type 2 diabetes mellitus and glucose intolerance have an increased incidence in Cushing's. Existing diabetes is exacerbated by glucocorticoid excess.
Osteoporosis is frequently undiagnosed. A patient may have lost height or developed back pain rather than having an obvious low fragility fracture.
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.