Mineralocorticoids in the management of primary adrenocortical insufficiency

Abstract

Plasma renin activity (PRA) and plasma volume (PV) were determined in 22 adult patients treated for Addison's disease (AD) and reporting at the clinic for follow-up. Mean PRA was thrice the upper limit of normal (9.1 +/- 7.1 ng/ml/h (SD)) and mean PV was decreased (87% +/- 11 (SD)), consistent with residual hypovolemia in most patients, despite conventional treatment with both fluorocortisol (FF) and cortisone acetate. There was an inverse relationship between PRA and PV. Both PRA and PV were significantly correlated with FF dosage. On the other hand, no correlation was found between PV and either systolic or diastolic blood pressure (BP), while PRA was significantly correlated with systolic but not diastolic BP. Four patients were persistently hypertensive (diastolic BP greater than 100 mmHg) with elevated PRA in 3, associated with a definitely low PV in two cases. Two of these patients were progressively taken off FF, so as to control BP. Thus, in view of the not infrequent occurrence of arterial hypertension in AD patient on conventional treatment, we would warn against attempts at normalizing PV and PRA by means of FF, irrespective of BP in asymptomatic cases. In fact, when hypertension develops, reduction or sometimes withdrawal of FF may be recommended as a first therapeutic step.

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

“…In the presence of a normal hypothalamic‐pituitary‐adrenal axis, essential hypertension is often managed with drugs affecting sodium balance and the RAA axis, but there have not been any studies in patients with Addison's disease to guide specific antihypertensive therapy. In 1991, Jadoul et al . recommended that a reduction in the fludrocortisone dose or even withdrawal was the first therapeutic step when a patient with Addison's disease develops hypertension.…”

“…However, if the renin is at the upper end of normal or elevated, renovascular causes should be considered and excluded by appropriate radiological investigation if necessary. Plasma volume correlates inversely with plasma renin activity and decreases upon dose reduction or withdrawal of fludrocortisone, while AII, a potent vasoconstrictor, increases up to 10‐fold after fludrocortisone is withdrawn . Therefore, if euvolaemic hypertension in Addison's disease is managed by an inappropriate decrease or cessation in fludrocortisone dose, a pathologically reduced plasma volume is offsetting the high vasoconstrictor effects of elevated AII.…”

Clinical approach to adrenal insufficiency in hospitalised patients

“…Patients with primary adrenal insufficiency may require adjuvant mineralocorticoid therapy despite glucocorticoid replacement, to prevent sodium losses and hyperkalaemia. Fludrocortisone is given in smaller doses (0.05–0.1 mg) when patients are receiving hydrocortisone and larger doses (0.2 mg) may be required in patients receiving longer acting preparations with little mineralocorticoid activity (24). Hypertension, oedema and hypokalaemia are signs of excessive mineralocorticoid replacement.…”

Adrenal Insufficiency Overview

“…cases showed adrenal calcification. While all cases of idiopathic Addison disease showed small or even undetectable adrenals and no calcification [73,74].…”