medwireNews: The Endocrine Society has released updated guidelines for the management of primary adrenal insufficiency (PAI) in adults and children.

The guidelines, which appear in The Journal of Clinical Endocrinology & Metabolism, cover diagnosis and treatment of PAI, management of adrenal crisis, and outline additional monitoring needs of PAI patients.

Among the diagnostic recommendations is that unexplained hypoglycaemia should trigger investigation especially in children. Guideline authors Stefan Bornstein (Universitätsklinikum Dresden, Germany) and colleagues advise use of the corticotropin stimulation test where possible, but also stress that patients with severe symptoms or adrenal crisis should receive immediate hydrocortisone, prior to test results being known.

The guidelines advise that the diagnostic procedure should also include measurement of plasma adrenocorticotropic hormone, to help confirm PAI, and simultaneous measurement of plasma renin and aldosterone to test for mineralocorticoid deficiency.

For treating children, the authors recommend hydrocortisone, given three or four times a day at a starting dose of 8 mg/m2 body surface area per day. They advise against the use of synthetic, long-acting glucocorticoids, noting that “hydrocortisone has a short half-life and is easier to titrate in children.”

They add: “Overtreatment must be avoided, and daily dose should be adjusted depending on clinical status and growth.”

The guidelines also recommend fludrocortisone in children with aldosterone deficiency and sodium chloride supplements for newborns and up to the age of 12 months. Children need monitoring at least annually by an endocrinologist, they state, while infants should be seen at least every 3 to 4 months.

Based on published data, the authors anticipate one in every 12 PAI patients (adults and children) having a life-threatening adrenal crisis in the coming year. Education is key to preventing these events, but when they occur, children should receive an immediate injection of 50 to 100 mg/m2 hydrocortisone followed by a further 50 to 100 mg/m2 over the next 24 hours.

However, the team stresses that “there are no systematic dose-response-studies, and therefore the glucocorticoid doses recommended for the treatment of adrenal crisis are largely on an empiric basis.”

They advise adjusting the dose in line with the “severity of illness or magnitude of the stressor”, and say that doctors should avoid under-dosing, even at the expense of short-term overdosing.

Summarising, Bornstein and team note that “diagnostic procedures and treatment strategies for PAI are still far from being optimal”, highlighting, for example, the consequences of being unable to mimic normal circadian and pulsatile hormone secretion.

But there are promising new treatment avenues, they say, including autoimmune treatment in newly diagnosed patients, stem cell treatment, and, potentially, gene therapy for patients with monogenic forms of PAI.

By Eleanor McDermid, Senior medwireNews Reporter

J Clin Endocrinol Metab 2016; Advance online publication

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