Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone

Abstract

The rapid ACTH injection test is an indirect screening test for adrenocortical insufficiency. As a supplement to this test, we evaluated the practicability of single measurements of plasma cortisol, ACTH, aldosterone, and PRA as a definitive diagnostic test of primary adrenocortical insufficiency (PAI). We also tested the value of PRA measurements during treatment with hydro- and fludrocortisone (HC and FC) as a guide for correct mineralocorticoid substitution. In 45 patients with PAI, results of the rapid ACTH test and single measurements of the four hormones (all tests between 0800-0900 h) were compared. Single hormone measurements were also made in 55 normal subjects and 46 patients with pituitary disease (cortisol and ACTH only), most of them with mild to severe secondary adrenocortical insufficiency (SAI). The rapid ACTH test was abnormal in 100% of 41 patients with PAI tested. Plasma ACTH, PRA, and the ratios of ACTH/cortisol and PRA/plasma or urinary aldosterone were clearly elevated in 100% of the patients with PAI. The ACTH/cortisol ratio also distinguished 100% of patients with PAI from those with SAI, but not always control subjects from those with SAI. Thus, dynamic tests (CRH or insulin tests) are indicated if SAI is suspected. PAI and involvement of zona fasciculata and glomerulosa function can be diagnosed with high reliability by measuring cortisol, ACTH, aldosterone, and PRA either together with the rapid ACTH test or later, after a short interval of steroid substitution. PRA measurements during treatment with HC and FC correlated better with the mineralocorticoid dose than plasma potassium and sodium levels. PRA measurement is a valuable guide for FC replacement therapy. It should be titrated into the upper normal range to avoid under- and overtreatment.

Basal Serum Cortisol Levels are not Predictive of Response to Corticotropin but Have Prognostic Significance in Patients with Septic Shock

“…The short corticotropin stimulation test is the most commonly performed test for the diagnosis of primary adrenal insufficiency (18, 19). However, it is limited when hypoadrenalism occurs secondary to recent hypothalamic or pituitary insults and caution is necessary when interpreting the test results (17).…”

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing's Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

“…Tiredness and lassitude, without clear-cut hypotension, also may reflect underreplacement, and the adequacy of mineralocorticoid dosage should be assessed before increasing the glucocorticoid dose. Measurement of plasma renin activity also can be useful, especially in newly diagnosed patients until they are on a stable dose of fludrocortisone, with the goal to keep levels in the upper normal range (182, 183). It is important to note that mineralocorticoid replacement may need to be increased in hot weather due to increased salt loss in perspiration, especially in patients who are exposed to ambient temperatures (10).…”

Management of hypertension and heart failure in patients with Addison's disease

“…Most expert reviews recommend monitoring renin during the routine treatment of Addison's disease with the goal being either plasma renin activity or renin in the upper part of the normal range . Occasional patients develop hypokalaemia and oedema on fludrocortisone despite a normal renin.…”