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Monogenic Forms of Hypertension

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Secondary Hypertension

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

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Abstract

Essential hypertension is a high-prevalent disease in general population, and its incidence increases with aging. Nevertheless, secondary hypertension is characterized by a specific and potentially reversible cause of increased blood pressure levels. Among them, secondary endocrine forms of hypertension due to an excessive secretion of adrenal hormones (cortisol, aldosterone, or catecholamines) are relatively common.

In this chapter, we will describe a subset of more rare monogenic forms of secondary hypertension, characterized by electrolyte disorders (especially potassium levels), hypertension (often resistant), and suppressed renin–aldosterone axis. They represent simple models for the physiology of the renal control of sodium or potassium levels, as well as plasma volume. Furthermore, in some cases, these rare forms of hypertension could explain some of the features closer to the essential phenotype of hypertension, thus suggesting some common pathophysiological mechanism and a personalized treatment.

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References

  1. Grasso M, Boscaro M, Scaroni C, Ceccato F. Secondary arterial hypertension: from routine clinical practice to evidence in patients with adrenal tumor. High Blood Press Cardiovasc Prev. 2018;25:345–54.

    Google Scholar 

  2. Barbot M, Ceccato F, Scaroni C. The pathophysiology and treatment of hypertension in patients with Cushing’s syndrome. Front Endocrinol (Lausanne). 2019;10:321.

    Google Scholar 

  3. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32:81–151.

    Google Scholar 

  4. Peter M. Congenital adrenal hyperplasia: 11β-hydroxylase deficiency. Semin Reprod Med. 2002;20:249–54.

    Article  CAS  Google Scholar 

  5. Bulsari K, Falhammar H. Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Endocrine. 2017;55:19–36.

    Article  CAS  Google Scholar 

  6. Valadares LP, Pfeilsticker ACV, de Brito Sousa SM, Cardoso SC, de Moraes OL, Gonçalves de Castro LC, et al. Insights on the phenotypic heterogenity of 11β-hydroxylase deficiency: clinical and genetic studies in two novel families. Endocrine. 2018;62:326–32.

    Article  CAS  Google Scholar 

  7. Nimkarn S, New MI. Steroid 11β- hydroxylase deficiency congenital adrenal hyperplasia. Trends Endocrinol Metab. 2008;19:96–9.

    Article  CAS  Google Scholar 

  8. Biason-Lauber A, Boscaro M, Mantero F, Balercia G. Defects of steroidogenesis. J Endocrinol Invest. 2010;33:756–66.

    Article  CAS  Google Scholar 

  9. Nordenskjöld A, Holmdahl G, Frisén L, Falhammar H, Filipsson H, Thorén M, et al. Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2008;93:380–6.

    Article  Google Scholar 

  10. Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J Clin Endocrinol Metab. 1983;56:222–9.

    Article  CAS  Google Scholar 

  11. Rösler A, Leiberman E, Sack J, Landau H, Benderly A, Moses SW, et al. Clinical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Horm Res. 1982;16:133–41.

    Article  Google Scholar 

  12. Curnow KM, Slutsker L, Vitek J, Cole T, Speiser PW, New MI, et al. Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. Proc Natl Acad Sci U S A. 1993;90:4552–6.

    Article  CAS  Google Scholar 

  13. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:364–89.

    Article  CAS  Google Scholar 

  14. Auchus RJ. Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol. 2017;165:71–8.

    Article  CAS  Google Scholar 

  15. Biason A, Mantero F, Scaroni C, Simpson ER, Waterman MR. Deletion within the CYP17 gene together with insertion of foreign DNA is the cause of combined complete 17 alpha-hydroxylase/17,20-lyase deficiency in an Italian patient. Mol Endocrinol. 1991;5:2037–45.

    Article  CAS  Google Scholar 

  16. Zuber MX, Simpson ER, Waterman MR. Expression of bovine 17 alpha-hydroxylase cytochrome P-450 cDNA in nonsteroidogenic (COS 1) cells. Science. 1986;234:1258–61.

    Article  CAS  Google Scholar 

  17. Sherbet DP, Tiosano D, Kwist KM, Hochberg Z, Auchus RJ. CYP17 mutation E305G causes isolated 17,20-lyase deficiency by selectively altering substrate binding. J Biol Chem. 2003;278:48563–9.

    Article  CAS  Google Scholar 

  18. Biglieri EG, Kater CE. 17 alpha-hydroxylation deficiency. Endocrinol Metab Clin North Am. 1991;20:257–68.

    Article  CAS  Google Scholar 

  19. New MI, Geller DS, Fallo F, Wilson RC. Monogenic low renin hypertension. Trends Endocrinol Metab. 2005;16:92–7.

    Article  CAS  Google Scholar 

  20. Mantero F, Opocher G, Rocco S, Carpenè G, Armanini D. Long-term treatment of mineralocorticoid excess syndromes. Steroids. 1995;60:81–6.

    Article  CAS  Google Scholar 

  21. Funder JW. Apparent mineralocorticoid excess. J Steroid Biochem Mol Biol. 2017;165:151–3.

    Article  CAS  Google Scholar 

  22. Limumpornpetch P, Stewart PM. Apparent mineralocorticoid excess. In: Encyclopedia of endocrine diseases. Elsevier; 2019. p. 638–43.

    Google Scholar 

  23. Mantero F, Palermo M, Petrelli MD, Tedde R, Stewart PM, Shackleton CH. Apparent mineralocorticoid excess: type I and type II. Steroids. 1996;61:193–6.

    Article  CAS  Google Scholar 

  24. Mariniello B, Ronconi V, Sardu C, Pagliericcio A, Galletti F, Strazzullo P, et al. Analysis of the 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension. Am J Hypertens. 2005;18:1091–8.

    Article  CAS  Google Scholar 

  25. Ceccato F, Trementino L, Barbot M, Antonelli G, Plebani M, Denaro L, et al. Diagnostic accuracy of increased urinary cortisol/cortisone ratio to differentiate ACTH-dependent Cushing’s syndrome. Clin Endocrinol (Oxf). 2017;87.

    Google Scholar 

  26. Liddle GW, Bledsoe T, Coppage WS Jr. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Phys. 1963;76:199–213.

    CAS  Google Scholar 

  27. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger J, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature. 1994;367:463–7.

    Article  CAS  Google Scholar 

  28. Rossi E, Rossi GM. Liddle syndrome. In: Encyclopedia of endocrine diseases. Elsevier; 2019. p. 652–63.

    Google Scholar 

  29. Cui Y, Tong A, Jiang J, Wang F, Li C. Liddle syndrome: clinical and genetic profiles. J Clin Hypertens. 2017;19:524–9.

    Article  CAS  Google Scholar 

  30. Pagani L, Diekmann Y, Sazzini M, De Fanti S, Rondinelli M, Farnetti E, et al. Three reportedly unrelated families with Liddle syndrome inherited from a common ancestor. Hypertens (Dallas, Tex 1979). 2018;71:273–9.

    Article  CAS  Google Scholar 

  31. Hanukoglu I. ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters. FEBS J. 2017;284:525–45.

    Article  CAS  Google Scholar 

  32. Kurtz TW, Dominiczak AF, DiCarlo SE, Pravenec M, Morris RC. Molecular-based mechanisms of mendelian forms of salt-dependent hypertension. Hypertension. 2015;65:932–41.

    Article  CAS  Google Scholar 

  33. Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky DA, Hummler E, Ryba NJP, et al. The cells and peripheral representation of sodium taste in mice. Nature. 2010;464:297–301.

    Article  CAS  Google Scholar 

  34. Geller DS. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000;289:119–23.

    Article  CAS  Google Scholar 

  35. Rafestin-Oblin M-E, Souque A, Bocchi B, Pinon G, Fagart J, Vandewalle A. The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related. Endocrinology. 2003;144:528–33.

    Article  CAS  Google Scholar 

  36. Zennaro M-C, Boulkroun S, Fernandes-Rosa F. Inherited forms of mineralocorticoid hypertension. Best Pract Res Clin Endocrinol Metab. 2015;29:633–45.

    Article  CAS  Google Scholar 

  37. O’Shaughnessy KM. Gordon syndrome: a continuing story. Pediatr Nephrol. 2015;30:1903–8.

    Article  Google Scholar 

  38. Gordon RD, Hodsman GP. The syndrome of hypertension and hyperkalaemia without renal failure: long term correction by thiazide diuretic. Scott Med J. 1986;31:43–4.

    Article  CAS  Google Scholar 

  39. Mayan H, Vered I, Mouallem M, Tzadok-Witkon M, Pauzner R, Farfel Z. Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J Clin Endocrinol Metab. 2002;87:3248–54.

    Article  CAS  Google Scholar 

  40. Pelham CJ, Ketsawatsomkron P, Groh S, Grobe JL, de Lange WJ, Ibeawuchi S-RC, et al. Cullin-3 regulates vascular smooth muscle function and arterial blood pressure via PPARγ and RhoA/Rho-kinase. Cell Metab. 2012;16:462–72.

    Article  CAS  Google Scholar 

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Conflict of Interest

Disclosure of Potential Conflicts of Interest: All authors declare that they have no conflicts of interest that might be perceived as influencing the impartiality of the reported research.

Funding: This study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Research Involving Human Participants and Patient Consent: Informed consent to describe patients’ history has been obtained.

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Authors and Affiliations

  1. Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy

    Filippo Ceccato & Franco Mantero

Authors
  1. Filippo Ceccato
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  2. Franco Mantero
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Correspondence to Filippo Ceccato .

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Editors and Affiliations

  1. Center of Clinical Physiology and Hypertension, Policlinic Hospital, University of Milan, Milan, Italy

    Alberto Morganti

  2. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Enrico Agabiti Rosei

  3. Department of Medicine, Endocrine Unit, University of Padua, Padova, Italy

    Franco Mantero

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Ceccato, F., Mantero, F. (2020). Monogenic Forms of Hypertension. In: Morganti, A., Agabiti Rosei, E., Mantero, F. (eds) Secondary Hypertension . Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-030-45562-0_6

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  • DOI: https://doi.org/10.1007/978-3-030-45562-0_6

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-45561-3

  • Online ISBN: 978-3-030-45562-0

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