Figure 1: Pathogenetic mechanism of hyponatremia in primary adrenal insufficiency.
CRH: Corticotropin-Releasing Hormone; BP: Blood Pressure; ADH: Antidiuretic Hormone
Filippatos TD Liamis G Liontos A Elisaf MS*Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
*Corresponding author: Moses S Elisaf, Professor, Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece, Tel: +302651007509; Fax: +302651007016; E-mail: email@example.com, firstname.lastname@example.org
Primary adrenal insufficiency (Addison’s disease) is a rather common etiology of decreased sodium levels (serum sodium <135 mmol/L). Aim of the short review is to present the current evidence of the pathogenetic mechanisms, diagnosis and treatment of hyponatremia in patients with primary adrenal insufficiency. The pathogenesis of hyponatremia in patients with primary adrenal insufficiency is mainly attributed to increased secretion of antidiuretic hormone (ADH). Certain clues may aid clinicians to differentiate primary adrenal insufficiency and the syndrome of inappropriate ADH secretion (SIADH). Treatment of hyponatremia in patients with primary adrenal insufficiency includes cortisol administration and volume repletion. Clinicians should be vigilant for the exclusion of primary adrenal insufficiency in patients with hyponatremia.
Hyponatremia; Sodium; Primary adrenal insufficiency; Syndrome of inappropriate antidiuretic hormone secretion; Cortisol
Primary adrenal insufficiency (Addison’s disease), which is usually caused by autoimmune adrenalitis (often associated with autoimmune disorders) and less frequently by infections (e.g. tuberculosis, human immunodeficiency virus, fungal infections) metastatic carcinoma, hemorrhage and medications, is a rather common etiology of decreased sodium levels (serum sodium <135 mmol/L) [1-30]. However, the true incidence of primary adrenal insufficiency in patients with hyponatremia is not clear, since evidence from prospective and retrospective clinical trials indicates that basal serum cortisol levels are not measured routinely even in patients with unexplained decreased serum sodium levels. Moreover, despite the association between adrenal insufficiency and hyponatremia, a more detailed investigation of the hypothalamic, pituitary and adrenal function is rarely performed [31-37].
The pathogenesis of hyponatremia in patients with primary adrenal insufficiency is mainly attributed to increased secretion of antidiuretic hormone (ADH), which in turn results in water retention and dilutional decrease of serum sodium levels. The increased secretion of ADH in this case is caused by cortisol deficiency, which is a physiologic tonic inhibitor of ADH secretion and exerts negative feedback on corticotropin-releasing hormone (CRH) and ADH; hence, cortisol deficiency leads to increased CRH and ADH secretion [38-41]. Additionally, ADH is secreted in parallel with CRH by the paraventricular nuclei cells in the hypothalamus, since it is an important ACTH secretagogue . The increased ADH secretion in patients with adrenal insufficiency is also attributed to alterations in systemic hemodynamics (reduction of blood pressure and cardiac output), which in turn stimulate the baroreceptor-mediated ADH secretion [28,40,41,43]. Finally, it has been shown that the administration of glucocorticoids can directly suppress pituitary ADH secretion and their discontinuation may be followed by an increased secretion of ADH [44- 48] (Figure 1).
Figure 1: Pathogenetic mechanism of hyponatremia in primary adrenal insufficiency.
Experimental data support the etiological correlation of increased ADH secretion and hyponatremia in primary adrenal insufficiency. The administration of vaptans, which act as ADH V2 receptor antagonists in the kidney, normalizes the urinary dilution ability in adrenalectomized mineralcorticoid–replaced rats . Additionally, an increase in renal sensitivity to ADH, shown as up-regulation of renal aquaporin-2 water channels, is implicated in the development of hyponatremia in glucocorticoid-resistant rats .
It is also possible that ADH-independent mechanisms may play a role in the pathogenesis of hyponatremia in primary adrenal insufficiency. In this context, factors such as impaired renal hemodynamics and decreased distal fluid delivery to the diluting segments of the nephron may provoke hyponatremia [41,45]. Experimental data supports this concept, since it has been shown that glucocorticoid deficiency is associated with upregulation of the Na+-K+-2Cl- co-transporter, the Na+-H+ exchanger isoform 3 and the cortical β and γ subunits of epithelial sodium channel, which promotes sodium retention and reduces fluid delivery to the distal nephron diluting segments and finally results in decreased free-water excretion. However, this ADH-independent mechanism on water excretion capacity becomes significant only in cases of increased water intake .
Primary adrenal insufficiency also results in aldosterone deficiency, which significantly contributes to the pathogenesis of hyponatremia. Aldosterone deficiency promotes renal sodium wasting, hypovolemia and baroreceptor-mediated increased secretion of ADH [3,6,51,52]. Thus, aldosterone deficiency causes hyponatremia through two mechanisms: i) the increased levels of ADH and subsequent upregulation of aquaporin-2 water channels in the renal tubules, and ii) the extracellular volume depletion-induced reduction in GFR inducing increased proximal tubular sodium reabsorption and reduced fluid delivery to the distal diluting segment of the nephron [38,53].
In some cases of autoimmune polyendocrinopathy, primary adrenal insufficiency is accompanied by hypothyroidism that, if severe and especially if causing myxedema, may contribute to the pathogenesis of hyponatremia .
It should be mentioned that the most causes of primary adrenal insufficiency impair the adrenal cortex as a whole and may result in concurrent deficiencies of cortisol, aldosterone and adrenal androgen. Thus, acute adrenocortical insufficiency (adrenal crisis) is mandatory to be included in the differential diagnosis of a hyponatremic patient who has weakness, abdominal pain, nausea, vomiting, diarrhea, fever, lethargy, confusion or coma . Chronic adrenocortical insufficiency (Addison’s disease) is usually characterized by the pattern of hyponatremia, hyperkalemia and hypovolemia (Table 1). Certain clinical (hypotension, skin hyperpigmentation of the sun-exposed surfaces or even oral mucosa) and laboratory findings (hyperkalemia, raised blood urea, hypoglycemia, hypercalcemia, eosinophilia) may aid the diagnosis.
Table 1: Differential diagnosis between primary adrenal insufficiency and syndrome of inappropriate antidiuretic hormone secretion (SIADH) FE: Fractional Excretion
However, in some case the diagnosis of Addison’s disease is difficult, since primary adrenal insufficiency can present without hypovolemia, orthostatic hypotension or hyperkalemia. For example, the presence of hyponatremia in patients with hypoaldosteronism and renal salt wasting may cause red blood swelling resulting in increased plasma volume and elevated interstitial pressure that promotes shift of water from the interstitial to the intravascular volume. Additionally, the hypovolemiainduced increased symphathetic nervous system activity promotes venous vasoconstriction and subsequently reduces the volume of the vascular compartment leading to increase of filling pressures [55-57].
Furthermore, hyperkalemia is evident only in approximately 50- 60% of patients with primary adrenal insufficiency [58,59]. The absence of hyperkalemia may be due to isolated hypocortisolism (for example due to autoantibodies with a high affinity for the zona fasciculata) or to aldosterone-independent regulation of potassium metabolism (for example decreased potassium intake or extrarenal potassium losses). Additionally, patients with autoimmune disorders or cancer may have circulating cation proteins that activate the calcium sensing receptor in the thick ascending limb of Henle, resulting in inhibition of the K+-Na+- Cl- cotransporter and subsequently promoting natriuresis and kaliuresis [29,55,60-62].
Patients with primary adrenal insufficiency without significant hypoaldosteronism may have euvolemic hyponatremia with a ‘SIADHlike picture that is characterized by increased urinary osmolality and urine sodium concentration . SIADH is one of the most common causes of hyponatremia in the clinical practice. Its diagnosis is based on clinicolaboratory criteria after the exclusion of other commonly causes of hyponatremia, including thiazides administration, salt-wasting nephropathy, cancer, and endocrinopathies, such as primary and secondary adrenal insufficiency and severe hypothyroidism [6,64-72]. In patients with a ‘SIADH-like’ picture, certain clues may aid clinicians to differentiate between hyponatremia due to primary adrenal insufficiency and hyponatremia due to SIADH (Table 1) . These differences are mainly attributed to the fact that primary adrenal insufficiency is associated with hypoaldosteronism-related hypovolemia causing low fractional excretion rate of uric acid and urea, whereas SIADH is associated with high values of these parameters [1,69,73]. Additionally, a useful and easy test to differentiate between SIADH and adrenal insufficiency is the presence of ketonuria, which is detected in patients with hyponatremia associated with adrenal insufficiency due to increased fatty acid oxidation and subsequent production of ketones .
The diagnosis of primary adrenal insufficiency is established if ACTH levels are elevated (>2-fold the upper limit of the reference range) and in the standard dose ACTH stimulation test (250 µg corticotropin iv) serum cortisol concentrations 30-60 minutes after the administration of synthetic ACTH are <18 µg/dl (<500 nmol/L) . Patients taking glucocorticoid supplements or spironolactone should not take them on the day of the test. If the ACTH stimulation test is not available, the diagnosis of adrenal insufficiency is based on serum cortisol and ACTH levels, which should be measured at 8 to 9 am to avoid influences of their circadian rhythm. Elevated ACTH levels (>2-fold the upper limit of the reference range) with low cortisol [<5 µg/dL (<140 nmol/L)] are highly suggestive, especially in patients who are in stress. Even ACTH levels within the normal range are rather inappropriate when cortisol levels are very low. The simultaneous measurement of plasma renin and aldosterone to determine mineralcorticoid deficiency is also recommended .
Cortisol administration and volume repletion result in decrease of ADH secretion and increase of serum sodium levels in hyponatremic patients with primary adrenal insufficiency. It should be mentioned that volume repletion should be established with careful administration of isotonic saline solutions and with repeated measurements of serum sodium levels in order to prevent inappropriate overcorrection of serum sodium concentration that may result in the osmotic demyelination syndrome with its devastating consequences [75-80]. Additionally, mineralocorticoid replacement is needed especially in patients who have primary adrenal insufficiency with clinical or laboratory findings suggesting hypovolemia. In these cases careful monitoring and adjustment of treatment are mandatory [10,74,81].
It should be mentioned that in patients who have both primary adrenal insufficiency and hypothyroidism, hydrocortisone replacement should be given first, before thyroid hormone replacement, because treatment of hypothyroidism in patients with untreated adrenal insufficiency may result in addisonian crisis due to profound reduction of circulating cortisol levels owing to thyroxin-induced cortisol clearance and to increased cortisol requirements owing to thyroxin-induced restoration of basal metabolic rate .
- Filippatos TD, Liamis G, Christopoulou F, Elisaf MS (2016) Ten common pitfalls in the evaluation of patients with hyponatremia. Eur J Intern Med 29: 22-25. [Ref.]
- Oelkers W (1996) Adrenal insufficiency. N Engl J Med 335: 1206- 1212. [Ref.]
- Arlt W, Allolio B (2003) Adrenal insufficiency. Lancet 361: 1881-1893. [Ref.]
- Betterle C, Volpato M (1998) Adrenal and ovarian autoimmunity. Eur J Endocrinol 138: 16-25. [Ref.]
- Bornstein SR (2009) Predisposing factors for adrenal insufficiency. N Engl J Med 360: 2328-2339. [Ref.]
- Liamis G, Milionis HJ, Elisaf M (2011) Endocrine disorders: Causes of hyponatremia not to neglect. Ann Med 43: 179-187. [Ref.]
- Takahashi K, Kagami S, Kawashima H, Kashiwakuma D, Suzuki Y, et al. (2016) Sarcoidosis presenting Addison’s disease. Intern Med 55: 1223-1228. [Ref.]
- Correia F, Fernandes A, Mota TC, Garcia M, Castro-Correia C, et al. (2015) Hyponatremia in a Teenager: A Rare Diagnosis. Pediatr Emerg Care 31: 860-863. [Ref.]
- Sahin M, Oguz A, Tuzun D, Boysan SN, Mese B, et al. (2015) Primary adrenal failure due to antiphospholipid syndrome. Case Rep Endocrinol 2015: 161497. [Ref.]
- Quinkler M, Oelkers W, Remde H, Allolio B (2015) Mineralocorticoid substitution and monitoring in primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab 29: 17-24. [Ref.]
- Liamis G, Milionis HJ, Elisaf M (2011) Hyponatremia in patients with infectious diseases. J Infect 63: 327-335. [Ref.]
- Ekpebegh CO, Ogbera AO, Longo-Mbenza B, Blanco-Blanco E, Awotedu A, et al. (2011) Basal cortisol levels and correlates of hypoadrenalism in patients with human immunodeficiency virus infection. Med Princ Pract 20: 525-529. [Ref.]
- Choudhary S, Alam A, Dewan V, Yadav D, Dubey NK (2011) An unusual presentation of Addison’s disease-A case report. Clin Pediatr Endocrinol 20: 57-60.
- Hsieh S, White PC (2011) Presentation of primary adrenal insufficiency in childhood. J Clin Endocrinol Metab 96: E925-E928. [Ref.]
- Ebeling F, Rahkonen L, Saastamoinen KP, Matikainen N, Laitinen K (2011) Addison’s disease presenting as hyperemesis, hyponatremia and pancytopenia in early pregnancy. Acta Obstet Gynecol Scand 90: 121-122. [Ref.]
- Smith JP, Burren C, Cherinet Y (2011) Extreme hyponatraemia with intact neurological outcome in a young child with Addison’s disease. BMJ Case Rep. [Ref.]
- Allolio B, Lang K, Hahner S (2011) Addisonian crisis in a young man with atypical anorexia nervosa. Nat Rev Endocrinol 7: 115-121. [Ref.]
- Lewandowski K, Hincz P, Grzesiak M, Cajdler-Luba A, Salata I, et al. (2010) New onset Addison’s disease presenting as prolonged hyperemesis in early pregnancy. Ginekol Pol 81: 537-540. [Ref.]
- Hung ZS, Lai YH, Hsu YH, Wang CH, Fang TC, et al. (2010) Disseminated cryptococcosis causes adrenal insufficiency in an immunocompetent individual. Intern Med 49: 1023-1026. [Ref.]
- Triantafyllou P, Mavrides P, Katzos G, Printza N, Papachristou F (2010) A girl with progressive fatigue and hyponatremia. Addison’s disease. Pediatr Nephrol 25: 2269, 2271-2263. [Ref.]
- Jacobi J, Schnellhardt S, Kulschewski A, Amann KU, Kuefner MA, et al. (2010) An unusual case of hyponatraemia. Nephrol Dial Transplant 25: 998-1001. [Ref.]
- Gujjar A, Al-Mamari A, Jacob PC, Jain R, Balkhair A, et al. (2010) Extrapontine myelinolysis as presenting manifestation of adrenal failure: a case report. J Neurol Sci 290: 169-171. [Ref.]
- Al-Mamari A, Balkhair A, Gujjar A, Ben Abid F, Al-Farqani A, et al. (2009) A case of disseminated tuberculosis with adrenal insufficiency. Sultan Qaboos Univ Med J 9: 324-327. [Ref.]
- Cassar C, Procter R, Davidson F, Collier A, Malik IA, et al. (2009) An unusual case of profound hyponatraemia and bilateral adrenal calcifications. Ann Clin Biochem 46: 523-526. [Ref.]
- Yokoyama T, Toda R, Kimura Y, Mikagi M, Aizawa H (2009) Addison’s disease induced by miliary tuberculosis and the administration of rifampicin. Intern Med 48: 1297-1300. [Ref.]
- Nishiuchi T, Imachi H, Fujiwara M, Murao K, Onishi H, et al. (2009) A case of non-Hodgkin’s lymphoma primary arising in both adrenal glands associated with adrenal failure. Endocrine 35: 34-37. [Ref.]
- Donckier JE, Lacrosse M, Michel L (2007) Bilateral adrenal lymphoma with Addison’s disease : a surgical pitfall. Acta Chir Belg 107: 219-221. [Ref.]
- Mascarenhas JV, Jude EB (2014) Delayed diagnosis of Addison’s disease: an approach to management. BMJ Case Rep. [Ref.]
- Thompson MD, Kalmar E, Bowden SA (2015) Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison’s disease. BMJ Case Rep. [Ref.]
- Li W, Okwuwa I, Toledo-Frazzini K, Alhomosh A (2013) Adrenal crisis in a patient with acute myeloid leukaemia. BMJ Case Rep. [Ref.]
- Tzoulis P, Bouloux PM (2015) Inpatient hyponatraemia: adequacy of investigation and prevalence of endocrine causes. Clin Med (Lond) 15: 20-24. [Ref.]
- Clayton JA, Le Jeune IR, Hall IP (2006) Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM 99: 505-511. [Ref.]
- Huda MS, Boyd A, Skagen K, Wile D, van Heyningen C, et al. (2006) Investigation and management of severe hyponatraemia in a hospital setting. Postgrad Med J 82: 216-219. [Ref.]
- Whyte M, Down C, Miell J, Crook M (2009) Lack of laboratory assessment of severe hyponatraemia is associated with detrimental clinical outcomes in hospitalised patients. Int J Clin Pract 63: 1451-1455. [Ref.]
- Verbalis JG, Greenberg A, Burst V, Haymann JP, Johannsson G, et al. (2016) Diagnosing and treating the syndrome of inappropriate antidiuretic hormone secretion. Am J Med 129: 537.
- Diederich S, Franzen NF, Bahr V, Oelkers W (2003) Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases. Eur J Endocrinol 148: 609-617. [Ref.]
- Winchester Behr T, Sonnenblick M, Nesher G, Munter G (2012) Hyponatraemia in older people as a sign of adrenal insufficiency: a case-control study. Intern Med J 42: 306-310. [Ref.]
- Ishikawa S, Schrier RW (1982) Effect of arginine vasopressin antagonist on renal water excretion in glucocorticoid and mineralocorticoid deficient rats. Kidney Int 22: 587-593. [Ref.]
- Wolfson B, Manning RW, Davis LG, Arentzen R, Baldino F Jr (1985) Co-localization of corticotropin releasing factor and vasopressin mRNA in neurones after adrenalectomy. Nature 315: 59-61. [Ref.]
- Schrier RW (2006) Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol 17: 1820-1832. [Ref.]
- Raff H (1987) Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol 252: R635-R644. [Ref.]
- Salata RA, Jarrett DB, Verbalis JG, Robinson AG (1988) Vasopressin stimulation of adrenocorticotropin hormone (ACTH) in humans. In vivo bioassay of corticotropin-releasing factor (CRF) which provides evidence for CRF mediation of the diurnal rhythm of ACTH. J Clin Invest 81: 766-774. [Ref.]
- Chen YC, Cadnapaphornchai MA, Summer SN, Falk S, Li C, et al. (2005) Molecular mechanisms of impaired urinary concentrating ability in glucocorticoid-deficient rats. J Am Soc Nephrol 16: 2864-2871. [Ref.]
- Kuwahara S, Arima H, Banno R, Sato I, Kondo N, et al. (2003) Regulation of vasopressin gene expression by cAMP and glucocorticoids in parvocellular neurons of the paraventricular nucleus in rat hypothalamic organotypic cultures. J Neurosci 23: 10231-10237. [Ref.]
- Linas SL, Berl T, Robertson GL, Aisenbrey GA, Schrier RW, et al. (1980) Role of vasopressin in the impaired water excretion of glucocorticoid deficiency. Kidney Int 18: 58-67. [Ref.]
- Kovacs KJ, Foldes A, Sawchenko PE (2000) Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. J Neurosci 20: 3843-3852. [Ref.]
- Ma XM, Aguilera G (1999) Differential regulation of corticotropinreleasing hormone and vasopressin transcription by glucocorticoids. Endocrinology 140: 5642-5650. [Ref.]
- Kim JK, Summer SN, Wood WM, Schrier RW (2001) Role of glucocorticoid hormones in arginine vasopressin gene regulation. Biochem Biophys Res Commun 289: 1252-1256. [Ref.]
- Wang W, Li C, Summer SN, Falk S, Cadnapaphornchai MA et al. (2006) Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency. Am J Physiol Renal Physiol 290: F1135-F1142. [Ref.]
- Saito T, Ishikawa SE, Ando F, Higashiyama M, Nagasaka S, et al. (2000) Vasopressin-dependent upregulation of aquaporin-2 gene expression in glucocorticoid-deficient rats. Am J Physiol Renal Physiol 279: F502-F508. [Ref.]
- Robertson GL, Aycinena P, Zerbe RL (1982) Neurogenic disorders of osmoregulation. Am J Med 72: 339-353. [Ref.]
- Mount DB (2009) The brain in hyponatremia: both culprit and victim. Semin Nephrol 29: 196-215. [Ref.]
- Ohara M, Cadnapaphornchai MA, Summer SN, Falk S, Yang J, et al. (2002) Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat. Biochem Biophys Res Commun 299: 285-290. [Ref.]
- Michels AW, Eisenbarth GS (2010) Immunologic endocrine disorders. J Allergy Clin Immunol 125: 226-237. [Ref.]
- van der Hoek J, Hoorn EJ, de Jong GM, Janssens EN, de Herder WW (2009) Severe hyponatremia with high urine sodium and osmolality. Clin Chem 55: 1905-1908. [Ref.]
- Chung HM, Kluge R, Schrier RW, Anderson RJ (1987) Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 83: 905-908. [Ref.]
- Cherney DZ, Davids MR, Halperin ML (2002) Acute hyponatraemia and ‘ecstasy’: insights from a quantitative and integrative analysis. QJM 95: 475-483. [Ref.]
- DeFronzo RA (1980) Hyperkalemia and hyporeninemic hypoaldosteronism. Kidney Int 17: 118-134. [Ref.]
- Szylman P, Better OS, Chaimowitz C, Rosler A (1976) Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. N Engl J Med 294: 361-365. [Ref.]
- Shah SS, Oh CH, Coffin SE, Yan AC (2005) Addisonian pigmentation of the oral mucosa. Cutis 76: 97-99. [Ref.]
- Soule S (1999) Addison’s disease in Africa-a teaching hospital experience. Clin Endocrinol (Oxf) 50: 115-120. [Ref.]
- Gagnon RF, Halperin ML (2001) Possible mechanisms to explain the absence of hyperkalaemia in Addison’s disease. Nephrol Dial Transplant 16: 1280-1284. [Ref.]
- Kinjo T, Higuchi D, Oshiro Y, Nakamatsu Y, Fujita K, et al. (2009) Addison’s disease due to tuberculosis that required differentiation from SIADH. J Infect Chemother 15: 239-242. [Ref.]
- Liamis G, Filippatos TD, Elisaf MS (2016) Thiazide-associated hyponatremia in the elderly: what the clinician needs to know. J Geriatr Cardiol 13: 175-182. [Ref.]
- Liamis G, Filippatos TD, Elisaf MS (2016) Electrolyte disorders associated with the use of anticancer drugs. Eur J Pharmacol 777: 78-87. [Ref.]
- Liamis G, Elisaf M (2000) Syndrome of inappropriate antidiuresis associated with multiple sclerosis. J Neurol Sci 172: 38-40. [Ref.]
- Liamis G, Milionis H, Elisaf M (2008) A review of drug-induced hyponatremia. Am J Kidney Dis 52: 144-153. [Ref.]
- Liamis G, Milionis H, Elisaf M (2008) Blood pressure drug therapy and electrolyte disturbances. Int J Clin Pract 62: 1572-1580. [Ref.]
- Milionis HJ, Liamis GL, Elisaf MS (2002) The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ 166: 1056-1062. [Ref.]
- Rizos E, Liamis G, Elisaf M (2002) Multiple metabolic abnormalities in a patient with the syndrome of inappropriate antidiuresis. Nephron 91: 339-340. [Ref.]
- Filippatos TD, Elisaf MS (2013) Hyponatremia in patients with heart failure. World J Cardiol 5: 317-328. [Ref.]
- Filippatos TD, Milionis HJ, Elisaf MS (2005) Alterations in electrolyte equilibrium in patients with acute leukemia. Eur J Haematol 75: 449-460. [Ref.]
- Decaux G, Musch W (2008) Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 3: 1175-1184. [Ref.]
- Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, et al. (2016) Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 101: 364-389. [Ref.]
- Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, et al. (2014) Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 29. [Ref.]
- Liamis G, Filippatos TD, Elisaf MS (2015) Correction of hypovolemia with crystalloid fluids: Individualizing infusion therapy. Postgrad Med 127: 405-412. [Ref.]
- Filippatos TD, Liamis G, Elisaf MS (2016) Ten pitfalls in the proper management of patients with hyponatremia. Postgrad Med 24: 1-7. [Ref.]
- Wu JW, Wang PN, Lirng JF, Hsu RW, Chen WT (2014) Extrapontine myelinolysis in a patient with primary adrenal insufficiency. Acta Neurol Taiwan 23: 146-152. [Ref.]
- Liamis G, Filippatos TD, Elisaf MS (2014) Treatment of hyponatremia: the role of lixivaptan. Expert Rev Clin Pharmacol 7: 431-441. [Ref.]
- Liamis G, Kalogirou M, Saugos V, Elisaf M (2006) Therapeutic approach in patients with dysnatraemias. Nephrol Dial Transplant 21: 1564-1569. [Ref.]
- Oelkers W, Diederich S, Bahr V (1992) 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 75: 259-264. [Ref.]
- Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, et al. (2012) Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 18: 988-1028. [Ref.]
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Citation: Filippatos TD, Liamis G, Liontos A, Elisaf MS (2016) Hyponatremia in Primary Adrenal Insufficiency: An Often Overlooked Cause of Decreased Sodium Levels. Int J Nephrol Kidney Failure 2(3): doi http://dx.doi.org/10.16966/2380-5498.130
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