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2014 | 9 | 3 | 495-499

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Gitelman syndrome DD thiazide diuretics abuse


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Introduction. Gitelman syndrome (GS) is a rare inherited disorder. Mutations in SLC12A3 gene that encode tubular Na+Cl-cotransporter (NCCT) cause hypokalemic metabolic alkalosis, salt loss, hypomagnesaemia and hypocalciuria. The symptoms include weakness, vertigo, hypotension, tetany, paresthesia and nausea. Diagnostic criteria are a normal urine concentrating ability, normal glomerular filtration rate (GFR), hypomagnesaemia (<0,65mmol/l), hypokalemia (<3,6mmol/l) and hypocalciuria (<0,1mmol/mmol creatinine). Previously, the diagnosis was made by exclusion. Today, genetic analysis can ensure diagnosis. Thiazide diuretics (TD) abuse with similar abnormalities can make the differential diagnosis difficult. Causal therapy of GS does not exist. The substitution of potassium and magnesium are therapeutic strategies. Case presentation. A 41-year-old obese woman presented at the emergency department with recurrent episodes of hypokalemia with concomitant weakness, muscle cramps, polyuria and collapse. The results of laboratory testing of blood and urine led to the suspected diagnosis of GS. In the follow-up examinations, the results were inconsistent. Therefore, a transient thiazide diuretics abuse was assumed. Discussion. This case demonstrates the difficulties in making the diagnosis of GS on the basis of only clinical and laboratory tests, without the use of genetic analysis. The differentiation between GS and thiazide diuretic abuse is especially difficult.










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1 - 6 - 2014
8 - 7 - 2014


  • Department of Medicine II, University Medical Center Mainz, Johannes Gutenberg-University Mainz, 55131, Mainz, Germany
  • Department of internal medicine, St. Vincenz and Elisabeth Hospital Mainz (KKM), 55131, Mainz, Germany
  • Department of internal medicine, St. Vincenz and Elisabeth Hospital Mainz (KKM), 55131, Mainz, Germany


  • [1] Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Transactions of the Association of American Physicians 1966;79:221–235
  • [2] Colussi G, Rombola G, Brunati C, De Ferrari ME. Abnormal reabsorption of Na+/CI-by the thiazideinhibitable transporter of the distal convoluted tubule in Gitelman’s syndrome. American journal of nephrology 1997;17:103–111 http://dx.doi.org/10.1159/000169082[Crossref]
  • [3] Bettinelli A, Tedeschi S. Hypokalemia and hypomagnesemia of hereditary renal tubular origin. Bartter and Gitelman syndromes. Acta bio-medica: Atenei Parmensis 2003;74:163–167 [PubMed]
  • [4] Gross PR, D. Das Gitelman-Syndrom. Nephro-News 2002;3:1–4
  • [5] Galli-Tsinopoulou A, Patseadou M, Hatzidimitriou A, et al. Gitelman syndrome: first report of genetically established diagnosis in Greece. Hippokratia 2010;14:42–44
  • [6] Konrad M, Weber S. Recent advances in molecular genetics of hereditary magnesium-losing disorders. Journal of the American Society of Nephrology: JASN 2003;14:249–260 http://dx.doi.org/10.1097/01.ASN.0000049161.60740.CE[Crossref]
  • [7] Aoi N, Nakayama T, Sato N, et al. Case-control study of the role of the Gitelman’s syndrome gene in essential hypertension. Endocrine journal 2008;55:305–310 http://dx.doi.org/10.1507/endocrj.K07E-021[WoS][Crossref]
  • [8] Fremont OT, Chan JC. Understanding Bartter syndrome and Gitelman syndrome. World journal of pediatrics: WJP 2012;8:25–30 http://dx.doi.org/10.1007/s12519-012-0333-9[WoS][Crossref]
  • [9] Cole DE, Quamme GA. Inherited disorders of renal magnesium handling. Journal of the American Society of Nephrology: JASN 2000;11:1937–1947 [WoS]
  • [10] Hashida T, Yamada M, Hashimoto K, et al. Loss of consciousness and hypokalemia in an elderly man with a mutation of the thiazide-sensitive Na-Cl cotransporter gene. Endocrine journal 2006;53:859–863 http://dx.doi.org/10.1507/endocrj.K06-076[Crossref]
  • [11] de Jong JC, Willems PH, Mooren FJ, van den Heuvel LP, Knoers NV, Bindels RJ. The structural unit of the thiazide-sensitive NaCl cotransporter is a homodimer. The Journal of biological chemistry 2003;278:24302–24307 http://dx.doi.org/10.1074/jbc.M303101200[Crossref]
  • [12] Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet journal of rare diseases 2008;3:22 http://dx.doi.org/10.1186/1750-1172-3-22[Crossref][WoS]
  • [13] Lemmink HH, Knoers NV, Karolyi L, et al. Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain. Kidney international 1998;54:720–730 http://dx.doi.org/10.1046/j.1523-1755.1998.00070.x[Crossref]
  • [14] Mastroianni N, Bettinelli A, Bianchetti M, et al. Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome. American journal of human genetics 1996;59:1019–1026
  • [15] Nijenhuis T, Vallon V, van der Kemp AW, Loffing J, Hoenderop JG, Bindels RJ. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. The Journal of clinical investigation 2005;115:1651–1658 http://dx.doi.org/10.1172/JCI24134[Crossref]
  • [16] Riveira-Munoz E, Chang Q, Godefroid N, et al. Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome. Journal of the American Society of Nephrology: JASN 2007;18:1271–1283 http://dx.doi.org/10.1681/ASN.2006101095[Crossref][WoS]
  • [17] Roser M, Eibl N, Eisenhaber B, et al. Gitelman syndrome. Hypertension 2009;53:893–897 http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.127993[Crossref][WoS]
  • [18] San-Cristobal P, de los Heros P, Ponce-Coria J, Moreno E, Gamba G. WNK kinases, renal ion transport and hypertension. American journal of nephrology 2008;28:860–870 http://dx.doi.org/10.1159/000139639[WoS][Crossref]
  • [19] Fava C, Montagnana M, Rosberg L, et al. Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure. Human molecular genetics 2008;17:413–418 http://dx.doi.org/10.1093/hmg/ddm318[WoS][Crossref]
  • [20] Ferrari P, Frey FJ. [Pharmacologic action of diuretics in the kidney]. Therapeutische Umschau Revue therapeutique 2000;57:345–350 http://dx.doi.org/10.1024/0040-5930.57.6.345[Crossref]
  • [21] Riancho JA, Saro G, Sanudo C, Izquierdo MJ, Zarrabeitia MT. Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association 2006;21:217–220 http://dx.doi.org/10.1093/ndt/gfi093[Crossref]
  • [22] Kurtz AW, C. Niere und Salz-/Wasser-Haushalt. Stuttgart, Germany: Georg Thieme Verlag; 2010
  • [23] Bettinelli A, Bianchetti MG, Borella P, et al. Genetic heterogeneity in tubular hypomagnesemia-hypokalemia with hypocalcuria (Gitelman’s syndrome). Kidney international 1995;47:547–551 http://dx.doi.org/10.1038/ki.1995.68[Crossref]
  • [24] Colussi G, Bettinelli A, Tedeschi S, et al. A thiazide test for the diagnosis of renal tubular hypokalemic disorders. Clinical journal of the American Society of Nephrology: CJASN 2007;2:454–460 http://dx.doi.org/10.2215/CJN.02950906[Crossref]
  • [25] Warnock DG. Nitric oxide and Bartter and Gitelman syndromes. Kidney international 2001;60:1197–1198 http://dx.doi.org/10.1046/j.1523-1755.2001.0600031197.x[Crossref]
  • [26] Kurschat C, Heering P, Grabensee B. [Gitelman’s syndrome: an important differential diagnosis of hypokalemia]. Dtsch Med Wochenschr 2003;128:1225–1228 http://dx.doi.org/10.1055/s-2003-39456[Crossref]
  • [27] Scognamiglio R, Negut C, Calo LA. Aborted sudden cardiac death in two patients with Bartter’s/Gitelman’s syndromes. Clinical nephrology 2007;67:193–197 http://dx.doi.org/10.5414/CNP67193[Crossref]
  • [28] Pachulski RT, Lopez F, Sharaf R. Gitelman’s notso-benign syndrome. The New England journal of medicine 2005;353:850–851 http://dx.doi.org/10.1056/NEJMc051040[Crossref]
  • [29] Scognamiglio R, Calo LA, Negut C, Coccato M, Mormino P, Pessina AC. Myocardial perfusion defects in Bartter and Gitelman syndromes. European journal of clinical investigation 2008;38:888–895 http://dx.doi.org/10.1111/j.1365-2362.2008.02034.x[Crossref]
  • [30] Haller E. Eating disorders. A review and update. The Western journal of medicine 1992;157:658–662
  • [31] Mascolo M, Chu ES, Mehler PS. Abuse and clinical value of diuretics in eating disorders therapeutic applications. The International journal of eating disorders 2011;44:200–202 http://dx.doi.org/10.1002/eat.20814[Crossref][WoS]
  • [32] Waller G, Babbs M, Wright F, Potterton C, Meyer C, Leung N. Somatoform dissociation in eating-disordered patients. Behaviour research and therapy 2003;41:619–627 http://dx.doi.org/10.1016/S0005-7967(03)00019-6[Crossref]
  • [33] Winston AP. The clinical biochemistry of anorexia nervosa. Annals of clinical biochemistry 2012;49:132–143 http://dx.doi.org/10.1258/acb.2011.011185[Crossref]
  • [34] Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C. Gitelman syndrome: pathophysiological and clinical aspects. QJM: monthly journal of the Association of Physicians 2010;103:741–748 http://dx.doi.org/10.1093/qjmed/hcq123[Crossref]
  • [35] Thomas L. Labor und Diagnose. Frankfurt, Germany: TH-Books Verlagsgesellschaft; 2000
  • [36] Cadwallader AB, de la Torre X, Tieri A, Botre F. The abuse of diuretics as performance-enhancing drugs and masking agents in sport doping: pharmacology, toxicology and analysis. British journal of pharmacology 2010;161:1–16 http://dx.doi.org/10.1111/j.1476-5381.2010.00789.x[WoS][Crossref]

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