SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook.

The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often necessary for primary adrenal insufficiency but not for corticotroph deficiency. Androgen replacement by DHEA may be offered in certain conditions. Monitoring is based on the detection of signs of under- and over-dosage and on the diagnosis of associated auto-immune disorders.

Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis.

A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms (fatigue, anorexia, weight loss, hypotension, hyponatremia and hyperkalemia amongst adrenal causes of insufficiency). The diagnosis should be considered in case of pituitary disease or a state of shock. Treatment should be commenced immediately without waiting for confirmation from biochemical tests, which rely on cortisol level at 8am (expected to be low) and on ACTH level (expected to be high in the case of primary adrenal insufficiency). If these tests are inconclusive, a Synacthen test should be carried out. The threshold limits are provided as a guide. Low plasma cortisol and normal to low plasma ACTH indicates a pituitary origin for the deficiency. In this situation, the Synacthen test can give a false normal result, and if this adrenal insufficiency is strongly suspected, an insulin hypoglycemia test or metyrapone (Metopirone®) test should be carried out. In children younger than 2yr, hypoglycemia, dehydration and convulsions are frequently observed and in young girls, virilization is suspect of congenital adrenal hyperplasia . The circadian rhythm of cortisol is not present until after 4months of age and the Synacthen test is the only one that is feasible. In children older than 2yrs, the signs and diagnostic methods are the same as in the adult. Cessation of corticosteroid treatment is a frequent circumstance however there is little published data and no evidence for definitive guidelines. After ceasing a short period of corticosteroid treatment, patient education is all that is required. After longer treatment, consensus leaves the choice up to the physician, between educating the patient and prescribing hydrocortisone in case of stress, or prescribing low daily dose hydrocortisone and evaluating the ACTH axis over time until normal function is recovered.