Severe Hyponatremia Unveiling Isolated ACTH Deficiency in Chronic Alcohol Abuse: A Diagnostic Challenge
Main Article Content
Abstract
Isolated adrenocorticotropic hormone deficiency (IAD) secondary to chronic alcohol abuse is an extremely rare condition, often underdiagnosed due to nonspecific clinical features overlapping with complications of alcoholism. A 42-year-old Brazilian male with chronic alcohol abuse was admitted for hematemesis and severe hyponatremia refractory to conventional therapy. Biochemical evaluation revealed profound hypocortisolism with inappropriately low adrenocorticotropic hormone (ACTH) levels and normal pituitary function and imaging. A comprehensive workup ruled out other potential causes of hyponatremia. Diagnosis of IAD was hypothesized. Hydrocortisone replacement therapy led to rapid clinical improvement and normalization of sodium levels. This case highlights the importance of considering IAD in chronic alcoholics with unexplained hyponatremia. Early diagnosis and corticosteroid replacement therapy are essential to prevent life-threatening complications.
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Scaroni C, Albiger NM, Palmieri S, Iacuaniello D, Graziadio C, Damiani L, Zilio M, Stigliano A, Colao A, Pivonello R; Al-together to Beat Cushing’s Syndrome (ABC) study group. Approach to patients with pseudo-Cushing's states. Endocrine Connections. 2020 Jan;9(1):R1-R13. doi: 10.1530/EC-19-0435
Rachdaoui N, Sarkar DK. Effects of alcohol on the endocrine system. Endocrinol Metab Clin North Am. 2013 Sep;42(3):593-615.
Woeber KA, Arky R. Hypoglycaemia as the result of isolated corticotrophin-deficiency. Br Med J. 1965 Oct 9;2(5466):857-8. doi: 10.1136/bmj.2.5466.857.
Baba S, Takase S, Uenoyama R, Morita S, Mizoi Y, Hishida S. Isolated corticotrophin-deficiency found through alcohol-induced hypoglycemic coma. Horm Metab Res. 1976; 8(4): 274–278, doi: 10.1055/s-0028-1093634, indexed in Pubmed: 182631. 14.
Steer P, Marnell R, Werk EE. Clinical alcohol hypoglycemia and isolated adrenocorticotrophic hormone deficiency. Ann Intern Med. 1969; 71(2): 343–348, doi: 10.7326/0003-4819-71-2-343, indexed in Pubmed: 4184388
Kearney T, Robinson S, Johnston DG. Isolated corticotropin deficiency in chronic alcoholism. J R Soc Med. 2000; 93(1): 15–17, doi: 10.1177/014 107680009300105, indexed in Pubmed: 10700840. 15.
Skowrońska-Jóźwiak E, Orzechowski S, Piętak W, Lewiński A. Rare clinical problem — isolated ACTH deficiency associated with chronic alcohol abuse. Endokrynologia Polska. 2022;73(4):778-783. doi: 10.5603/EP.a2022.0056
Ohara N, Hirota N, Takada T, Tani T, Terajima K, Ozawa T, Seki Y, Akiyama K, Yoneoka Y.An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report. Am J Case Rep . 2023 Jul 3:24:e939840. doi: 10.12659/AJCR.939840.
Heather N. Richardson, Soon Y. Lee, Laura E. O’Dell, George F. Koob and Catherine L. Rivier Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state. European Journal of Neuroscience, Vol. 28, pp. 1641–1653, 2008 doi:10.1111/j.1460-9568.2008.06455.x
Nadia Rachdaoui, & Dipak K. Sarkar. Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. Alcohol Research. 2017;38(2):255-276
Brian J Wentworth, Helmy M Siragy, Adrenal Insufficiency in Cirrhosis, Journal of the Endocrine Society, Volume 6, Issue 10, October 2022, bvac115, https://doi.org/10.1210/jendso/bvac115.
Andrioli M, Pecori Giraldi F, Cavagnini F. Isolated corticotrophin deficiency. Pituitary. 2006; 9(4): 289–295, doi: 10.1007/s11102-006-0408-5, indexed in Pubmed: 17077949
Heiko Krude and Annette Grüters. Implications of Proopiomelanocortin (POMC) Mutations in Humans: The POMC Defi-ciency Syndrome. Trends Endocrinol Metab. 2000 Jan-Feb;11(1):15-22. doi: 10.1016/s1043-2760(99)00213-1
Kasperlik-Załuska AA, Czarnocka B, Czech W. Autoimmunity as the most frequent cause of idiopathic secondary adrenal insufficiency: report of 111 cases. Autoimmunity. 2003; 36(3): 155–159, doi: 10.1080/0891693031 000095871, indexed in Pubmed: 12911282
Iglesias P, Peiró I, Biagetti B, Paja-Fano M, Cobo DA, García Gómez C, Mateu-Salat M, Genua I, Majem M, Riudavets M, Gavira J, Lamas C, Fernández Pombo A, Guerrero-Pérez F, Villabona C, Cabezas Agrícola JM, Webb SM, Díez JJ. Immunothera-py-induced isolated ACTH deficiency in cancer therapy. Endocr Relat Cancer. 2021; 28(12): 783–792, doi: 10.1530/ERC-21-0228, indexed in Pubmed: 34609950
Bando H, Iguchi G, Kanie K, Nishizawa H, Matsumoto R, Fujita Y, Odake Y, Yoshida K, Suda K, Fukuoka H, Tanaka K, Ogawa W, Takahashi Y. Isolated adrenocorticotropic hormone deficiency as a form of paraneoplastic syndrome. Pituitary. 2018; 21(5): 480–489, doi: 10.1007/s11102-018-0901-7, indexed in Pubmed: 30008158
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(6): 609–617, doi: 10.1530/eje.0.1480609, indexed in Pubmed: 12773132
Grossman A. The Diagnosis and Management of Central Hypoadrenalism. J Clin Endocrinol Metab. 2010; 95(11): 4855–4863, doi: 10.1210/jc.2010- 0982, indexed in Pubmed: 20719838
Rondon-Berrios H, Velez J, Hyponatremia in Chirrosis. Clin Liver Dis. 2022 May; 26(2): 149–164. doi: 10.1016/j.cld.2022.01.001
Rivier C. Alcohol stimulates ACTH secretion in the rat: mechanisms of action and interactions with other stimuli. Alcohol Clin Exp Res. 1996 Apr;20(2):240-54. doi: 10.1111/j.1530-0277.1996.tb01636.x
Vengeliene V, Bilbao A, Molander A, Spanagel R. Neuropharmacology of alcohol addiction. Br J Pharmacol. 2008 May;154(2):299-315. doi: 10.1038/bjp.2008.30. Epub 2008 Mar 3.
Rainer Spanagel. Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev. 2009 Apr;89(2):649-705. doi: 10.1152/physrev.00013.2008
Grossman A. Brain opiates and neuroendocrine function. Clin Endocrinol Metab. 1983 Nov;12(3):725-46. doi: 10.1016/s0300-595x(83)80062-0.
Jezova D, Guillaume V, Jurankova E, Carayon P, Oliver C. Studies on the physiological role of ANF in ACTH regulation. Endocr Regul. 1994 Dec;28(4):163-9.
Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science. 1989 Mar 31;243(4899):1721-4. doi: 10.1126/science.2467382.
Raff H. Glucocorticoid inhibition of neurohypophysial vasopressin secretion. Am J Physiol. 1987; 252(4 Pt 2): R635–R644, doi: 10.1152/ajpregu.1987.252.4.R635, indexed in Pubmed: 3032001.
Adinoff B, Martin PR, Bone GH, Eckardt MJ, Roehrich L, George DT, Moss HB, Eskay R, Linnoila M, Gold PW. Hypothala-mic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence. Arch Gen Psychiatry. 1990 Apr;47(4):325-30. doi: 10.1001/archpsyc.1990.01810160025004. PMID: 2157379.
Ray LA, Mackillop J, Leggio L, Morgan M, Hutchison KE. Effects of naltrexone on cortisol levels in heavy drinkers. Pharmacol Biochem Behav. 2009 Feb;91(4):489-94. doi: 10.1016/j.pbb.2008.09.004. Epub 2008 Sep 13. PMID: 18824022; PMCID: PMC3660224.