Hyponatremia and hyperkalemia in adrenal insufficiency
- David B Mount, MD
David B Mount, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor Emeritus
- University of Rochester School of Medicine and Dentistry
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
The electrolyte disturbances in primary adrenal insufficiency are due to diminished secretion of cortisol and aldosterone (see "Causes of primary adrenal insufficiency (Addison's disease)"). A major function of aldosterone is to increase urinary potassium secretion. As a result, hypoaldosteronism can be associated with hyperkalemia and mild metabolic acidosis [1,2]. Sodium wasting is a variable feature of this disorder. It is not prominent in adults with isolated hypoaldosteronism, probably because aldosterone secretion is only modestly reduced. (See "Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)".)
Although aldosterone normally enhances sodium reabsorption, other sodium-retaining factors (such as angiotensin II and norepinephrine) are able to compensate for the decreased availability of aldosterone . However, patients with primary adrenal insufficiency may have severe hypoaldosteronism, leading to salt wasting and possibly hypotension and adrenal crisis. (See "Clinical manifestations of adrenal insufficiency in adults".)
Other causes of hyponatremia and hyperkalemia, as well as the evaluation of patients with hyponatremia or hyperkalemia, are discussed elsewhere. (See "Causes of hyponatremia in adults" and "Causes and evaluation of hyperkalemia in adults" and "Diagnostic evaluation of adults with hyponatremia".)
HYPONATREMIA AND HYPERKALEMIA
Hyponatremia and hyperkalemia are the two major electrolyte abnormalities of primary adrenal insufficiency. Hyponatremia is mediated by increased release of antidiuretic hormone (ADH) which results in water retention and a reduction in the plasma sodium concentration [3,4]. Both cortisol and aldosterone deficiency contribute to this problem:
●The hypersecretion of ADH seen in cortisol deficiency may be due in part to the reductions in systemic blood pressure and cardiac output induced (via an unknown mechanism) by the lack of cortisol. However, a more important mechanism may be that cortisol deficiency results in increased hypothalamic secretion of corticotropin releasing hormone (CRH), an ADH secretagogue [5-8]. Cortisol feeds back negatively on CRH and ACTH, an inhibitory effect that is removed with adrenal insufficiency [5,9]. In addition, cortisol appears to directly suppress ADH secretion [10-12]. Thus, ADH levels increase when plasma cortisol levels are low.
- DeFronzo RA. Hyperkalemia and hyporeninemic hypoaldosteronism. Kidney Int 1980; 17:118.
- Szylman P, Better OS, Chaimowitz C, Rosler A. Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. N Engl J Med 1976; 294:361.
- Oelkers W. Hyponatremia and inappropriate secretion of vasopressin (antidiuretic hormone) in patients with hypopituitarism. N Engl J Med 1989; 321:492.
- Ishikawa S, Schrier RW. Effect of arginine vasopressin antagonist on renal water excretion in glucocorticoid and mineralocorticoid deficient rats. Kidney Int 1982; 22:587.
- Wolfson B, Manning RW, Davis LG, et al. Co-localization of corticotropin releasing factor and vasopressin mRNA in neurones after adrenalectomy. Nature 1985; 315:59.
- Kalogeras KT, Nieman LK, Friedman TC, et al. Inferior petrosal sinus sampling in healthy subjects reveals a unilateral corticotropin-releasing hormone-induced arginine vasopressin release associated with ipsilateral adrenocorticotropin secretion. J Clin Invest 1996; 97:2045.
- Papanek PE, Raff H. Physiological increases in cortisol inhibit basal vasopressin release in conscious dogs. Am J Physiol 1994; 266:R1744.
- Schrier RW. Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol 2006; 17:1820.
- Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol 1987; 252:R635.
- Watts AG, Tanimura S, Sanchez-Watts G. Corticotropin-releasing hormone and arginine vasopressin gene transcription in the hypothalamic paraventricular nucleus of unstressed rats: daily rhythms and their interactions with corticosterone. Endocrinology 2004; 145:529.
- Kovács KJ, Földes A, Sawchenko PE. Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. J Neurosci 2000; 20:3843.
- Ma XM, Aguilera G. Differential regulation of corticotropin-releasing hormone and vasopressin transcription by glucocorticoids. Endocrinology 1999; 140:5642.
- Robertson GL, Aycinena P, Zerbe RL. Neurogenic disorders of osmoregulation. Am J Med 1982; 72:339.
- Mount DB. The brain in hyponatremia: both culprit and victim. Semin Nephrol 2009; 29:196.
- Diederich S, Franzen NF, Bähr V, Oelkers W. Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases. Eur J Endocrinol 2003; 148:609.
- Olchovsky D, Ezra D, Vered I, et al. Symptomatic hyponatremia as a presenting sign of hypothalamic-pituitary disease: a syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-like glucocorticosteroid responsive condition. J Endocrinol Invest 2005; 28:151.
- Males JL, Spitler AL, Townsend JL. Addison's disease. A review of thirty-two cases. J Okla State Med Assoc 1971; 64:298.
- Nerup J. Addison's disease--clinical studies. A report fo 108 cases. Acta Endocrinol (Copenh) 1974; 76:127.
- De Rosa G, Corsello SM, Cecchini L, et al. A clinical study of Addison's disease. Exp Clin Endocrinol 1987; 90:232.
- Chiang WF, Cheng CJ, Wu ST, et al. Incidence and factors of post-adrenalectomy hyperkalemia in patients with aldosterone producing adenoma. Clin Chim Acta 2013; 424:114.
- Fischer E, Hanslik G, Pallauf A, et al. Prolonged zona glomerulosa insufficiency causing hyperkalemia in primary aldosteronism after adrenalectomy. J Clin Endocrinol Metab 2012; 97:3965.
- Ahmed AB, George BC, Gonzalez-Auvert C, Dingman JF. Increased plasma arginine vasopressin in clinical adrenocortical insufficeincy and its inhibition by glucosteroids. J Clin Invest 1967; 46:111.
- van Buren M, Rabelink TJ, Koppeschaar HP, Koomans HA. Role of glucocorticoid in excretion of an acute potassium load in patients with Addison's disease and panhypopituitarism. Kidney Int 1993; 44:1130.
- Oelkers W, Diederich S, Bähr V. Diagnosis and therapy surveillance in Addison's disease: rapid adrenocorticotropin (ACTH) test and measurement of plasma ACTH, renin activity, and aldosterone. J Clin Endocrinol Metab 1992; 75:259.
- Quinkler M, Oelkers W, Remde H, Allolio B. Mineralocorticoid substitution and monitoring in primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab 2015; 29:17.