Glucocorticoid receptors are present in virtually all cells, reflecting the diverse actions of cortisol, and hence the symptoms and signs of hypercortisolaemia encompass all organ systems. Many of the symptoms associated with hypercortisolaemia are common and of little specificity, such as weight gain, lethargy, weakness, menstrual irregularities, loss of libido, hirsutism, acne, depression, and psychosis (Table 1). While each symptom itself may be mild, the presence of a greater number of features in any given patient increases the likelihood of Cushing’s syndrome. The signs most useful in differentiating Cushing’s syndrome include the presence of proximal myopathy, and easy bruising, purplish striae, thinness, and fragility of the skin. The sign of proximal weakness is most easily demonstrated by asking the patient to stand from sitting position without the use hands; an initial backwards movement of the but tocks is present in early myopathy, while in more severe cases rising from a chair may not be possible.
Table1. Clinical features of Cushing’s syndrome
Presentation differs between genders, with purple striae, muscle atrophy, osteoporosis, and kidney stones being more common in men [26]. Gonadal dysfunction is common in both sexes. The ad verse effects of glucocorticoids on bone metabolism are evidenced by decreased bone mineral density, especially of the axial skeleton. Over 70% of patients with Cushing’s syndrome may present with psychiatric symptoms ranging from anxiety to frank psychosis; if present, depression is often agitated in nature, and some degree of psychiatric disturbance often persists following remission of Cushing’s syndrome. Impairment in short- term memory and cognition is common and can persist for at least a year following treatment. Cortisol excess predisposes to hypertension and glucose intolerance.
Classically, the ectopic ACTH syndrome due to small cell lung cancer may have a rapid onset with severe features: profound weakness, myopathy, hyperpigmentation, diabetes mellitus, and hypokalaemic alkalosis, while there is often neither weight gain nor the classical cushingoid appearance. In contrast, the clinical phenotype and biochemical features of neuroendocrine tumours (of any tissue origin) may be indistinguishable from that of Cushing’s disease, causing diagnostic difficulty.
Clinical and biochemical features may commonly vary in a ‘cyclical fashion’, causing diagnostic difficulty. Signs and symptoms fluctuate with circulating cortisol, such as facial plethora, myopathy, mood, blood pressure, and blood glucose, and all investigations may be normal when hypercortisolaemia is absent. Great care is needed to seek for evidence of ‘cyclicity’ in the clinical history.
