Correspondence

Cure of Apparent Mineralocorticoid Excess by Kidney Transplantation

N Engl J Med 1998; 339:1787-1788December 10, 1998

Article

To the Editor:

Kidney 11β-hydroxysteroid dehydrogenase 2 protects against mineralocorticoid excess by oxidatively converting cortisol, which binds to mineralocorticoid receptors as well as does aldosterone, to cortisone. Loss-of-function mutations in the gene for this enzyme cause the syndrome of apparent mineralocorticoid excess, with severe hypertension and hypokalemia.1,2 Most patients with the syndrome can be treated effectively with mineralocorticoid-receptor antagonists, potassium-sparing diuretics, and dexamethasone. We describe a woman with apparent mineralocorticoid excess who was cured by renal transplantation.

Hypertension was diagnosed in a woman at 19 years of age, and apparent mineralocorticoid excess at 28 years of age because of a prolonged half-life of 11β[³H]cortisol and decreased excretion of A-ring–reduced metabolites of cortisol. A point mutation in exon 5 of the 11β-hydroxysteroid dehydrogenase 2 gene resulting in the replacement of arginine by cysteine at codon 279 (R279C) was identified.3 The patient was treated successfully with atenolol, enalapril, and dexamethasone. When she was 31 years of age end-stage renal failure developed as a result of nephrosclerosis, and hemodialysis was begun. She subsequently underwent kidney transplantation; her own kidneys were not removed. Since then, while she has been receiving only immunosuppressive therapy (cyclosporine and 6 mg of methylprednisolone per day), her blood pressure, serum potassium concentration, and plasma renin activity have been normal.

Before the onset of renal failure, the patient had unequivocal manifestations of mineralocorticoid excess (Table 1Table 1Results of Laboratory Tests before and after Renal Transplantation.). The diagnosis of apparent mineralocorticoid excess was established by the findings of a high ratio of urinary metabolites of cortisol (tetrahydrocortisol and 5α-tetrahydrocortisol) to a metabolite of cortisone (tetrahydrocortisone) and a high ratio of urinary cortisol to cortisone.4 After transplantation, while receiving dexamethasone to suppress endogenous cortisol secretion, the patient had a normal ratio of urinary cortisol to cortisone (0.61) after the administration of 15 mg of cortisol, documenting that cortisol was normally oxidized but that the urinary ratio of tetrahydrocortisol and 5α-tetrahydrocortisol to tetrahydrocortisone was not normal. The urinary ratio of cortisol to cortisone most likely improved because of the 11β-hydroxysteroid dehydrogenase 2 activity of the new kidney, whereas the urinary ratio of tetrahydrocortisol and 5α-tetrahydrocortisol to tetrahydrocortisone did not because the defective enzyme was still present at other sites and the activity of 11β-hydroxysteroid dehydrogenase 1 favors 11-oxo-steroid reduction.

In summary, the curative effect of renal transplantation in this patient demonstrates that the syndrome of apparent mineralocorticoid excess is a renal disorder.

Mario Palermo, M.D.
University of Sassari

Maria Cossu, M.D.
SS. Annunziata Hospital, Sassari, Italy

Cedric H.L. Shackleton, Ph.D., D.Sc.
Children's Hospital Oakland Research Institute, Oakland, CA 94609

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Citing Articles (16)

Citing Articles

1. 1

   Zaki Hassan-Smith, Paul M Stewart. (2011) Inherited forms of mineralocorticoid hypertension. Current Opinion in Endocrinology, Diabetes and Obesity 18:3, 177-185
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2. 2

   Paolo Ferrari. (2010) The role of 11β-hydroxysteroid dehydrogenase type 2 in human hypertension. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1802:12, 1178-1187
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3. 3

   Kyu Bok Choi. (2007) Hypertensive Hypokalemic Disorders. Electrolyte & Blood Pressure 5:1, 34
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4. 4

   Neenoo Khosla, Donn Hogan. (2006) Mineralocorticoid Hypertension and Hypokalemia. Seminars in Nephrology 26:6, 434-440
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5. 5

   Fabian Hammer, Paul M. Stewart. (2006) Cortisol metabolism in hypertension. Best Practice & Research Clinical Endocrinology & Metabolism 20:3, 337-353
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6. 6

   Paolo Ferrari. (2003) Cortisol and the renal handling of electrolytes: role in glucocorticoid-induced hypertension and bone disease. Best Practice & Research Clinical Endocrinology & Metabolism 17:4, 575-589
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   Yoshiyu Takeda, Takashi Yoneda, Masashi Demura, Kenji Furukawa, Mikiya Usukura, Hiroshi Mabuchi. (2002) 19-Noraldosterone in pregnancy-induced hypertension. Steroids 67:7, 605-610
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   Thekkepat C Sandeep, Brian R Walker. (2001) Pathophysiology of modulation of local glucocorticoid levels by 11β-hydroxysteroid dehydrogenases. Trends in Endocrinology & Metabolism 12:10, 446-453
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   David G. Warnock. (2001) Genetic forms of human hypertension. Current Opinion in Nephrology and Hypertension 10:4, 493-499
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    Robert C Wilson, Saroj Nimkarn, Maria I New. (2001) Apparent mineralocorticoid excess. Trends in Endocrinology & Metabolism 12:3, 104-111
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    Seth L. Alper. (2001) Sporadic cases of Liddle's syndrome: Clues to essential hypertension?. American Journal of Kidney Diseases 37:3, 632-635
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12. 12

    Tanja Zaehner, Valmai Plueshke, Brigitte M. Frey, Felix J. Frey, Paolo Ferrari. (2000) Structural analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene in end-stage renal disease. Kidney International 58:4, 1413-1419
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13. 13

    Paolo Ferrari. (2000) Authorʼs reply. Journal of Hypertension 18:7, 971-972
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    David G. Warnock. (2000) Aldosterone-related genetic effects in hypertension. Current Hypertension Reports 2:3, 295-301
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15. 15

    Paolo Ferrari, Zygmunt Krozowski. (2000) Role of the 11β-hydroxysteroid dehydrogenase type 2 in blood pressure regulation. Kidney International 57:4, 1374-1381
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16. 16

    Paolo Ferrari, Emanuela Lovati, Felix J. Frey. (2000) The role of the 11β-hydroxysteroid dehydrogenase type 2 in human hypertension. Journal of Hypertension 18:3, 241-248
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