Isolated Hypoaldosteronism: an Overlooked Cause of Hyponatraemia ⁎ I

European Journal of Internal Medicine 18 (2007) 246–248 www.elsevier.com/locate/ejim

Brief report Isolated hypoaldosteronism: An overlooked cause of hyponatraemia ⁎ I. Talapatra , S. Kalavalapalli, D.J. Tymms

Royal Albert Edward Infirmary, Wigan Lane, Wigan, WN1 2NN United Kingdom Received 14 April 2006; received in revised form 20 August 2006; accepted 19 September 2006

Abstract

We report three patients with hyponatraemia due to isolated hypoaldosteronism. Addison's disease was ruled out in each of these patients by a normal short synacthen test. Two patients had severe hyponatraemia and fluid restriction helped improve the sodium level only marginally. One was treated with demeclocycline, which did not prove to be effective. Subsequently, all three patients were found to have aldosterone deficiency and treatment with fludrocortisone caused their sodium levels to return to normal. © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Keywords: Hyponatraemia; Hypoaldosteronism; Renin; Fludrocortisone

1. Introduction plasma sodium had ranged from 124 to 130 mmol/l (normal 135–145 mmol/l) for the past 2 years. The patient had Isolated hypoaldosteronism is often overlooked as a cause postural hypotension causing his dizziness. Investigations of hyponatraemia. A patient with hyponatraemia is assessed undertaken showed the following results: plasma osmolality for plasma volume depletion or overloading, Addison's 280 mosmol/kg H2O (normal 280–298 mosmol/kg H2O), disease, SIADH (syndrome of inappropriate ADH secretion) urine osmolality 370 mosmol/kg H2O, urine sodium and urinary or gastric loss of sodium and is then treated 30 mmol/l, random cortisol 546 nmol/l, plasma sodium accordingly. There have not been many case reports of 128 mmol/l, potassium 5.2 mmol/l (normal 3.5–5.3 mmol/l), isolated hypoaldosteronism as a cause of hyponatraemia urea 7 mmol/l (normal 2.5–7 mmol/l) and creatinine with a normal potassium level. Treatment with fludrocorti- 100 μmol/l (normal 95–140 μmol/l). Chest X-ray was sone was found to be highly effective in all of our patients, unremarkable. with restoration of plasma sodium level to normal. Hence, An aldosterone short synacthen test was performed that estimation of plasma aldosterone constitutes an important showed normal results for baseline cortisol (416 nmol/l) and investigation for hyponatraemia. its response (761 nmol/l) to ACTH injection. However, the aldosterone (80 pmol/l) and renin levels (b0.2) were low, 2. Case reports suggesting an isolated form of secondary hypoaldosteronism (hyporeninaemic hypoaldosteronism), which was treated Our first patient was an 82-year-old gentleman referred with fludrocortisone 50 μg daily. Plasma sodium improved for persistent hyponatraemia and dizziness. The patient's to 138 mmol/l with potassium of 3.8 mmol/l with correction of postural hypotension. Our second patient was a 64-year-old lady, a known hypertensive and type 2 diabetic, who presented with col- ⁎ Corresponding author. Diabetes centre, Royal Albert Edward Infirmary, Wigan Lane, Wigan WN1 2NN United Kingdom. Tel.: +44 1942264713; lapse with a capillary blood glucose of 3 mmol/l and se- fax: +44 1942822191. vere hyponatraemia. Investigations undertaken showed the E-mail address: [email protected] (I. Talapatra). following results: plasma sodium 116 mmol/l, potassium

0953-6205/$ - see front matter © 2007 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejim.2006.09.026 I. Talapatra et al. / European Journal of Internal Medicine 18 (2007) 246–248 247

Table 1 Various findings in the three patients with hyponatraemia Patient 1 Patient 2 Patient 2 Patient 3 (test repeated) Cortisol: baseline 416 nmol/l (normal: 220–720); Cortisol: baseline 635 nmol/l and Cortisol: baseline 385 nmol/l and 761 nmol 30 min after ACTH(synacthen) 981 nmol/l after synacthen injection 780 nmol/l after synacthen injection injection (normal: N580 nmol/l) Aldosterone: baseline: 80 pmol/l and 190 pmol/l Aldosterone: baseline: 100 pmol/l and Aldosterone: Aldosterone: baseline: 60 pmol/l after synacthen injection (normal: 250 pmol/l after synacthen injection baseline: 85 pmol/l baseline 110–450 pmol/l and a rise of N150 pmol/l after synacthen injection) Renin: baselineb0.2 pmol/ml/h (normal: 1.1–2.7) Renin: baseline 2.9 pmol/ml/h (raised) Urea: 7 mmol/l on presentation Urea: 4 mmol/l on presentation Urea: 3.8 mmol/l on presentation and and 6.5 nmol/l after correction and 5.1 nmol/l after correction 4.2 mmol/l after correction of of hyponatraemia of hyponatraemia hyponatraemia Creatinine: 100 μmol/l on presentation and Creatinine: 95 μmol on presentation Creatinine: 89 μmol/l on presentation 103 μmol/l after correction and 102 μmol/l after correction and 80 μmol/l after correction of of hyponatraemia (normal values) of hyponatraemia (normal values) hyponatraemia.(normal values) Sodium: 128 mmol/l on presentation and Sodium: 116 mmol/l on presentation Sodium: 117 mmol/l on presentation 138 mmol/l after correction of hyponatraemia and 135 mmol/l after correction and 136 mmol/l after correction of hyponatraemia of hyponatraemia Potassium: 5.2 mmol/l Potassium: 5.0 mmol/l on presentation Potassium: 5.1 mmol/l on presentation on presentation and 3.8 mmol/l after and 4.4 mmol/l after correction and 4.2 mmol/l after correction correction of hyponatraemia of hyponatraemia of hyponatraemia Albumin: 36 mmol/l on presentation and Albumin: 35 mmol/l on presentation and Albumin: 36 mmol/l on presentation 37 mmol/l (normal) after correction of 36 mmol/l after presentation and 37 mmol/l after correction hyponatraemia of hyponatraemia of hyponatraemia Haemoglobin: 14.2 g/dl Haemoglobin: 11.7 g/dl on presentation and Haemoglobin: 10.7 g/dl on on presentation and 13.7 g/dl after 12.3 g/dl after correction of hyponatraemia presentation and 11 g/dl on correction of hyponatraemia correction of hyponatraemia BP: on presentation: 150/90 (lying) and BP: on presentation: BP 130/80 (lying) and BP: on presentation 140/70 (lying) 120/70 (standing); BP 155/90 on correction 110/70 (standing); BP 135/90 on correction and 130/70 (standing); BP 150/80 of hyponatraemia with no postural drop of hyponatraemia with no postural drop on correction of hyponatraemia with no postural drop Pulse rate: on presentation 80/min (lying) Pulse rate: 100/min on presentation Pulse rate: 96/min (lying) and and 90/min (standing); pulse 76/min (lying down) and 112/min (standing); 102/min (on standing); pulse rate on correction of hyponatraemia with not pulse rate 72/min (lying) after correction 64/min on correction of hyponatraemia much change with posture of hyponatraemia with not much change with not much change with posture with posture. Body weight: 62.6 kg initially; 64.4 kg after Body weight: 63.4 kg initially; 65 kg after Body weight 53.4 kg initially; 56 kg correction of hyponatraemia correction of hyponatraemia on recovery from hyponatraemia

5 mmol/l, urea 4 mmol/l, normal creatinine, plasma os- shadow. A short synacthen test was normal for cortisol, with the molality 249, urine osmolality 658 and urine sodium levels being 385 and 780 nmol/l, respectively, before and 128 mmol/l. Chest X-ray was unremarkable. BP was 130/ after synacthen injection. Fluid restriction and treatment 80 (on lying) and 110/70 mmHg (on standing). Fluid intake with demeclocycline caused the sodium to improve to restriction to 1 l/day caused the sodium to improve to 124 mmol/l. Early morning aldosterone was 60 pmol/l (↓) 122 mmol/l. A short synacthen test was normal for cortisol. and the patient was treated with fludrocortisone 100 μg/day Plasma cortisol levels were 635 and 981 nmol/l, respective- with an improvement of plasma sodium to 136 mmol/l. ly, before and after the synacthen injection. However, early morning plasma aldosterone was 85 pmol/l (low) and PRA 3. Discussion 2.9 pmol/ml/h (high). The patient was diagnosed with aldosterone deficiency and treated with fludrocortisone 100 μg/ Aldosterone causes reabsorption of sodium and chloride day. Plasma sodium improved to 135 mmol/l. and excretion of potassium and hydrogen ion in the distal The third patient, a 73-year-old lady who was on convulated tubule. In aldosterone deficiency, renal sodium loss amiodarone for hypertrophic cardiomyopathy, presented with occurs, resulting in hyponatraemia. With volume depletion, a blackout. BP was 140/70 (on lying) and 130/70 mmHg (on ADH (anti-diuretic hormone) release is expected by a reflex standing). Investigations undertaken showed: plasma sodium mechanism via the carotid sinus baroreceptors. This was 117 mmol/l, potassium 5.1 mmol/l, urea 3.8 mmol/l, plasma possibly responsible for a SIADH-like biochemical picture in osmolality 256, urine osmolality 455 and urine sodium our second and third patients. However, aldosterone deficien- 170 mmol/24 h. Chest X-ray showed an enlarged cardiac cy, as the cause for it, needed to be treated with fludrocortisone 248 I. Talapatra et al. / European Journal of Internal Medicine 18 (2007) 246–248 for the plasma sodium level to normalise. These patients did an early morning aldosterone level be measured in all not respond well to water restriction. patients with hyponatraemia. Isolated hypoaldosteronism Idiopathic SIADH with low aldosterone and postural may be present despite the patient's having a normal cortisol hypotension can occur in elderly subjects. Chronic mild level, contributing to the patient's hyponatraemia, and it may hyponatraemia can occur with idiopathic SIADH in be easily overlooked. Treatment with fludrocortisone in individuals above 80 years of age; it is usually asymptomatic small doses is very effective [6]. and does not require fludrocortisone therapy [1]. In most elderly patients, intravascular volume contracts as arterial 4. Learning points pressure and total peripheral resistance increase. Plasma renin activity and angiotensin II levels are normal or usually • Cortisol needs to be estimated in all patients with reduced, suggesting an attenuated relationship between hyponatraemia. intravascular volume and the renin–angiotensin system [2]. • If the cortisol level is normal or if a short synacthen test Fludrocortisone, in high doses, may sometimes be helpful in for cortisol excludes Addison's disease, plasma aldoste- hyponatraemia in SIADH [3], but our patients required small rone needs to be estimated. doses of it, suggesting mineralocorticoid-responsive hypo- • Simple treatment with fludrocortisone in aldosterone natraemia rather than SIADH. deficiency is highly effective. There are two types of isolated hypoaldosteronism [4]. Isolated primary hypoaldosteronism occurs in primary defect References in zona glomerulosa, chronic idiopathic hypoaldosteronism, familial corticosterone methyloxidase deficiency types 1 and [1] Anpalahan M. Chronic idiopathic hyponatraemia in older people dueto 2, persistent hypotension and prolonged heparin administra- syndrome of inappropriate anti-diuretic hormone secretion (SIADH) possibly related to ageing. J Am Geriatr Soc 2001;49(6):788–92. tion. Renin level is high in primary hypoaldosteronism. Also, [2] Beers MH, et al, editors. Hypertension. 3rd ed. Merck Manual of ACE-I therapy can cause mild hypoaldosteronism with Geriatics; July 2005. 834 [Section II, Chapter 85]. raised renin levels and could have contributed to the second [3] Fichman MP, Bethune JE. The role of adrenocorticoids in the patient's aldosterone deficiency (she was receiving lisino- inappropriate anti-diuretic hormone syndrome. Ann Intern Med – pril). Hyporeninaemic hypoaldosteronism [5] occurs with 1968;68(4):806 20. [4] Arai K, Shibasaki T, Chrousos GP. Aldosterone deficiency and type 2 diabetes, tubulo-interstitial nephritis, type IV renal resistance; 2002 [Endotext.com; chapter 24, March 1]. tubular acidosis, beta blockers and non-steroidal anti- [5] Schambelan M, Sebastian A. Hyporeninaemic hypoaldosteronism. Adv inflammatory drugs. Hyponatraemia with hyperkalaemia Intern Med 1979;24:385–405. generally occurs in hypoaldosteronism, together with urinary [6] Sebastian A, Schambelan M, Lindenfield S, Morris RC. Amelioration sodium above 20 mmol/l. However, all three of our patients of metabolic acidosis with fludrocortisone therapy in hyporeninaemic hypoaldosteronism. N Engl J Med 1977;297:576–83. had hyponatraemia with normal potassium levels (Table 1). We recommend that an aldosterone-synacthen test be done or