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Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency

Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11β-Hydroxysteroid Dehydrogenase... BACKGROUNDPathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects.METHODSWe studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses.RESULTSThe normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21–3.69] and 2.54 [2.35–2.88], and in adults were 4.42 [3.70–4.90] and 2.23 [1.92–2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls.CONCLUSIONSerum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Hypertension Oxford University Press

Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11β-Hydroxysteroid Dehydrogenase Type 2 Deficiency

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
ISSN
0895-7061
eISSN
1941-7225
DOI
10.1093/ajh/hpy051
Publisher site
See Article on Publisher Site

Abstract

BACKGROUNDPathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11βHSD2 deficiency in those heterozygous subjects.METHODSWe studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses.RESULTSThe normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21–3.69] and 2.54 [2.35–2.88], and in adults were 4.42 [3.70–4.90] and 2.23 [1.92–2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls.CONCLUSIONSerum F/E ratio and cortisone allow to identify partial 11βHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.

Journal

American Journal of Hypertension – Oxford University Press

Published: Jul 16, 2018

Keywords: 11βHSD2 deficiency; AME syndrome; blood pressure; cortisol; cortisone; HSD11B2 mutation; hypertension

References

  • Inherited forms of mineralocorticoid hypertension
    Hassan-Smith, Z; Stewart, PM
  • Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess
    Carvajal, CA; Gonzalez, AA; Romero, DG; González, A; Mosso, LM; Lagos, ET; Hevia, Mdel P; Rosati, MP; Perez-Acle, TO; Gomez-Sanchez, CE; Montero, JA; Fardella, CE
  • Overexpression of 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue and portal hypercortisolism in non-alcoholic fatty liver disease
    Candia, R; Riquelme, A; Baudrand, R; Carvajal, CA; Morales, M; Solís, N; Pizarro, M; Escalona, A; Carrasco, G; Boza, C; Pérez, G; Padilla, O; Cerda, J; Fardella, CE; Arrese, M
  • A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern
    Carvajal, CA; Campino, C; Martinez-Aguayo, A; Tichauer, JE; Bancalari, R; Valdivia, C; Trejo, P; Aglony, M; Baudrand, R; Lagos, CF; Mellado, C; Garcia, H; Fardella, CE
  • Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction
    Baudrand, R; Campino, C; Carvajal, CA; Olivieri, O; Guidi, G; Faccini, G; Sateler, J; Cornejo, J; Martin, BS; Dominguez, JM; Cerda, J; Mosso, LM; Owen, GI; Kalergis, AM; Fardella, CE
  • Aldosterone as a modulator of immunity: implications in the organ damage
    Herrada, AA; Campino, C; Amador, CA; Michea, LF; Fardella, CE; Kalergis, AM
  • Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients
    Baudrand, R; Domínguez, JM; Carvajal, CA; Riquelme, A; Campino, C; Macchiavello, S; Bozinovic, M; Morales, M; Pizarro, M; Solis, N; Escalona, A; Boza, C; Arrese, M; Fardella, CE
  • Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation
    Aglony, M; Martínez-Aguayo, A; Carvajal, CA; Campino, C; García, H; Bancalari, R; Bolte, L; Avalos, C; Loureiro, C; Trejo, P; Brinkmann, K; Giadrosich, V; Mericq, V; Rocha, A; Avila, A; Perez, V; Inostroza, A; Fardella, CE
  • Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor
    Arriza, JL; Weinberger, C; Cerelli, G; Glaser, TM; Handelin, BL; Housman, DE; Evans, RM
  • Type I (mineralocorticoid) receptors in the guinea pig
    Myles, K; Funder, JW
  • Molecular biology of mineralocorticoid metabolism
    Fardella, CE; Miller, WL
  • 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response
    Tomlinson, JW; Walker, EA; Bujalska, IJ; Draper, N; Lavery, GG; Cooper, MS; Hewison, M; Stewart, PM
  • 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action
    Draper, N; Stewart, PM
  • Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase
    Mune, T; Rogerson, FM; Nikkilä, H; Agarwal, AK; White, PC
  • A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess
    Wilson, RC; Krozowski, ZS; Li, K; Obeyesekere, VR; Razzaghy-Azar, M; Harbison, MD; Wei, JQ; Shackleton, CH; Funder, JW; New, MI
  • Evidence for an unidentified steroid in a child with apparent mineralocorticoid hypertension
    New, MI; Levine, LS; Biglieri, EG; Pareira, J; Ulick, S
  • A syndrome of apparent mineralocorticoid excess associated with defects in the peripheral metabolism of cortisol
    Ulick, S; Levine, LS; Gunczler, P; Zanconato, G; Ramirez, LC; Rauh, W; Rösler, A; Bradlow, HL; New, MI
  • Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess
    Dave-Sharma, S; Wilson, RC; Harbison, MD; Newfield, R; Azar, MR; Krozowski, ZS; Funder, JW; Shackleton, CH; Bradlow, HL; Wei, JQ; Hertecant, J; Moran, A; Neiberger, RE; Balfe, JW; Fattah, A; Daneman, D; Akkurt, HI; De Santis, C; New, MI
  • 11β-hydroxysteroid dehydrogenase type 2 polymorphisms and activity in a Chilean essential hypertensive and normotensive cohort
    Campino, C; Quinteros, H; Owen, GI; Carvajal, CA; Morales, M; Olivieri, O; Guidi, G; Faccini, G; Pasini, F; Baudrand, R; Padilla, O; Valdivia, C; Thichauer, J; Lagos, CF; Kalergis, AM; Fardella, CE
  • Citosine-adenine-repeat microsatellite of 11β-hydroxysteroid dehydrogenase 2 gene in hypertensive children
    Valdivia, C; Carvajal, CA; Campino, C; Allende, F; Martinez-Aguayo, A; Baudrand, R; Vecchiola, A; Lagos, CF; Tapia-Castillo, A; Fuentes, CA; Aglony, M; Solari, S; Kalergis, AM; García, H; Owen, GI; Fardella, CE
  • Apparent mineralocorticoid excess by a novel mutation and epigenetic modulation by HSD11B2 promoter methylation
    Pizzolo, F; Friso, S; Morandini, F; Antoniazzi, F; Zaltron, C; Udali, S; Gandini, A; Cavarzere, P; Salvagno, G; Giorgetti, A; Speziali, G; Choi, SW; Olivieri, O
  • Epigenetics and arterial hypertension: the challenge of emerging evidence
    Friso, S; Carvajal, CA; Fardella, CE; Olivieri, O
  • HSD11B2 haploinsufficiency in mice causes salt sensitivity of blood pressure
    Bailey, MA; Craigie, E; Livingstone, DEW; Kotelevtsev, YV; Al-Dujaili, EAS; Kenyon, CJ; Mullins, JJ
  • Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure
    Chobanian, AV; Bakris, GL; Black, HR; Cushman, WC; Green, LA; Izzo, JL; Jones, DW; Materson, BJ; Oparil, S; Wright, JT; Roccella, EJ
  • Aldosterone, plasma Renin activity, and aldosterone/renin ratio in a normotensive healthy pediatric population
    Martinez-Aguayo, A; Aglony, M; Campino, C; Garcia, H; Bancalari, R; Bolte, L; Avalos, C; Loureiro, C; Carvajal, CA; Avila, A; Perez, V; Inostroza, A; Fardella, CE
  • Measurement of low levels of plasma renin activity. A methodological improvement
    Montero, J; Soto, J; Fardella, C; Foradori, A; Valdés, G
  • Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency
    Yau, M; Haider, S; Khattab, A; Ling, C; Mathew, M; Zaidi, S; Bloch, M; Patel, M; Ewert, S; Abdullah, W; Toygar, A; Mudryi, V; Al Badi, M; Alzubdi, M; Wilson, RC; Al Azkawi, HS; Ozdemir, HN; Abu-Amer, W; Hertecant, J; Razzaghy-Azar, M; Funder, JW; Al Senani, A; Sun, L; Kim, SM; Yuen, T; Zaidi, M; New, MI
  • In silico structure-function analysis of pathological variation in the HSD11B2 gene sequence
    Manning, JR; Bailey, MA; Soares, DC; Dunbar, DR; Mullins, JJ
  • Apparent mineralocorticoid excess: genotype is correlated with biochemical phenotype
    Mune, T; White, PC
  • Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients
    Henschkowski, J; Stuck, AE; Frey, BM; Gillmann, G; Dick, B; Frey, FJ; Mohaupt, MG
  • Age-related changes in 11β-hydroxysteroid dehydrogenase type 2 activity in normotensive subjects
    Campino, C; Martinez-Aguayo, A; Baudrand, R; Carvajal, CA; Aglony, M; Garcia, H; Padilla, O; Kalergis, AM; Fardella, CE
  • 11-Beta dehydrogenase type 2 activity is not reduced in treatment resistant hypertension
    Ghazi, L; Dudenbostel, T; Hachem, ME; Siddiqui, M; Lin, CP; Oparil, S; Calhoun, DA
  • Screening for endocrine hypertension: an endocrine society scientific statement
    Young, JWF; Calhoun, DA; Lenders, JWM; Stowasser, M; Textor, SC
  • Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2
    Lovati, E; Ferrari, P; Dick, B; Jostarndt, K; Frey, BM; Frey, FJ; Schorr, U; Sharma, AM
  • Chapter 7—epigenetics and arterial hypertension: evidences and perspectives A2—laurence, jeffrey
    Friso, S; Carvajal, CA; Pizzolo, F; Fardella, CE; Olivieri, O; Beusekom, MV
  • Syndrome of apparent mineralocorticoid excess. A defect in the cortisol-cortisone shuttle
    Stewart, PM; Corrie, JE; Shackleton, CH; Edwards, CR
  • Apparent mineralocorticoid excess in a Brazilian kindred: hypertension in the heterozygote state
    Li, A; Li, KX; Marui, S; Krozowski, ZS; Batista, MC; Whorwood, CB; Arnhold, IJ; Shackleton, CH; Mendonca, BB; Stewart, PM
  • Conditional deletion of HSD11B2 in the brain causes salt appetite and hypertension
    Evans, LC; Ivy, JR; Wyrwoll, C; McNairn, JA; Menzies, RI; Christensen, TH; Al-Dujaili, EA; Kenyon, CJ; Mullins, JJ; Seckl, JR; Holmes, MC; Bailey, MA
  • Requirement for mass spectrometry sex steroid assays in the journal of clinical endocrinology and metabolism
    Handelsman, DJ; Wartofsky, L
  • Case for the wider adoption of mass spectrometry-based adrenal steroid testing, and beyond
    Monaghan, PJ; Keevil, BG; Stewart, PM; Trainer, PJ