A 56yr old woman with vitiligo becomes hypotensive and generally unwell and is diagnosed with primary adrenocortical insufficiency (Addison’s disease). Which one of the following statements is true of this condition?
a. cortisol is released from the chromaffin cells of the adrenal medulla
b. adrenocorticotropic hormone (ACTH) is suppressed
c. the diurnal variation in cortisol secretion is exaggerated
d. hyperkalaemia is a feature
e. hyperpigmentation is a feature





Cortisol (a glucocorticoid) is released from endocrine cells of the middle (zona fasciculata) layer of the adrenal cortex. Its plays a major role in the body’s response to physiological stress through modulating metabolic, immune and cardiovascular activity.

Cortisol secretion is stimulated by adrenocorticotropic hormone (ACTH) from the pituitary gland, which in turn, is controlled by corticotropin releasing hormone (CRH) from the hypothalamus (the hypothalamo-pituitary-adrenal axis). It is the hypothalamus which integrates physiological, central and environmental signals with diurnal patterns to generate the appropriate level of glucocorticoid activation.

Plasma cortisol concentration varies throughout the day (diurnal variation) with peaks in the early morning (06.00-10.00hrs) – to prepare the body for a stressful day – and troughs during sleep.

Primary adrenocortical insufficiency means failure of the adrenal gland itself to secrete mineralocorticoid and glucocorticoid hormone. Autoimmune destruction of the adrenal cortex (idiopathic autoimmune Addison’s disease) is the most common cause. In this condition, serum cortisol will therefore be low but ACTH high as the pituitary tries to stimulate an unresponsive adrenal cortex. Clinical features are hypotension and hypoglycaemia (from cortisol deficiency) together with hyponatraemia and hyperkalaemia (from lack of mineralocorticoid). Hyperpigmentation (particularly of skin creases) results from high levels of circulating ACTH stimulating melanocortin receptors on dermal melanocytes. There is a strong association between Addison’s disease and other autoimmune conditions, particularly vitiligo.

Figure 1a (left). Loss of pigmentation on dorsum hand caused by vitiligo (autoimmune condition often associated with Addison’s disease). Figure 1b (right). Hyperpigmentation of palmar creases in Addison’s disease.

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