Adrenal gland Pathophysiology
Adrenocortical insufficiency occurs as primary adrenal failure when the pathology lies in the adrenal gland, rather than secondary to failure of ACTH secretion. The symptoms may be vague, such as in the case of AD, a 22-year-old woman who presented with lethargy and fatigue. She was known to have autoimmune hypothyroidism and had been on thyroxine replacement therapy for 2 years. She now complained of increasing lethargy and intermittent abdominal pain. She became extremely unwell one day following an episode of food poisoning and was admitted to hospital as an emergency with diarrhoea, vomiting and hypotension.
Examination revealed evidence of increased pigmentation of the palmar creases, over the knees and in the mouth, and hypotension with a postural fall in blood pressure of 30 mmHg. Blood tests showed her to have a blood sugar of 2.6 mmol/L, Na 131 mmol/L, K 5.6 mmol/ L and urea 12.6 mmol/L. A blood sample was saved for cortisol and ACTH estimation and she was treated with intravenous and subsequently oral hydrocortisone replacement therapy. Later results showed the plasma cortisol to be 95 nmol/Lin combination with anACTH concentration of 205 ng/L. A diagnosis of Addison’s disease was made and she received advice from the endocrinology team about emergency hydrocortisone therapy, ‘sick day rules’ covering what to do in the event of intercurrent illness, and how to obtain a Medic-alert bracelet to wear continuously.
Addison’s disease. First described by Addison in 1855, the disease is caused by the destruction of adrenal tissue. The disease is usually autoimmune in origin, with the detection of adrenal autoantibodies in the plasma of 75–80% of patients, but there are numerous other causes (Table 21.1). The disease may present first as an Addisonian crisis, with fever, abdominal pain and hypotensive collapse and pigmentation of skin (Fig. 21a) and mucous membranes, due to very high circulating concentrations of adrenocorticotrophic hormone (ACTH). Areas often affected early include the skin under the fingernails, scars and buccal mucosa. The diagnosis is confirmed by measuring paired cortisol and ACTH (Fig. 21b). The presence of adrenal autoantibodies is a helpful diagnostic indicator. There is hyperkalaemia, hyponatraemia, hypoglycaemia and high urine Na+. Initial treatment, if the patient is in crisis, is intravenous saline solution to correct low blood volume, and hydrocortisone. Thereafter, the patient is maintained on oral glucocorticoids, for example hydrocortisone and the synthetic mineralocorticoid fludrocortisone.
Approximately 50% of patients with autoimmune Addison’s disease have positive thyroid antibodies and/or other autoimmune endocrine phenomena (see Chapter 22).
In the Western world, autoimmune disease accounts for the majority of cases of adrenal insufficiency although worldwide tuberculosis, which causes infection and subsequent fibrosis of the adrenal glands, remains the most likely diagnosis. More recently, other infections such as cytomegalovirus and fungal infections are increasingly common in the context of HIV/ AIDS. Malignant infiltration is also seen; the adrenals are a recognized site for metastatic spread from a number of malignancies and patients with AIDS may develop adrenal Kaposi’s sarcoma.
Hypoaldosteronism, which is a deficiency of aldosterone release resulting in sodium loss, occurs in the following:
1. Addison’s disease (see above) or specific enzyme deficiencies.
2. Diabetes, and may be secondary to deficient renin release. This may occur due to neuropathy which affects the β-adrenergic stimulation of renin release from the kidney.
3. Very rarely, some patients are insensitive to endogenous aldosterone because of an aldosterone receptor defect in the target cell.