Ewha Med J.  2023 Dec;46(S1):e30. 10.12771/emj.2023.e30.

Pediatric Endocrine Hypertension Related to the Adrenal Glands

Affiliations
  • 1Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
  • 2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea

Abstract

Endocrine causes of pediatric hypertension are relatively rare but important because of their distinct treatment options. Adrenal diseases accompanied by an excess of mineralocorticoids, glucocorticoids, and catecholamines are major causes of endocrine hypertension. Typical causes of mineralocorticoidrelated hypertension include primary aldosteronism, congenital adrenal hyperplasia (11β- and 17 α-hydroxylase deficiencies), and apparent mineralocorticoid excess. Cushing syndrome and pheochromocytoma/paraganglioma are the primary causes of glucocorticoid- and catecholaminerelated hypertension, respectively. This review provides an overview of the diagnostic evaluations, including hormonal assays and imaging studies, used to identify the underlying causes of pediatric endocrine hypertension, focusing on adrenal disorders. It presents details regarding the major adrenal disorders and recommended therapeutic approaches, emphasizing the importance of early detection and disease-specific management to prevent cardiovascular and metabolic complications in affected children.

Keyword

Cushing syndrome; Hypertension; Endocrine system diseases; Hyperaldosteronism; Pediatrics; Pheochromocytoma

Reference

References

1. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017; 140(3):e20171904. DOI: 10.1542/peds.2017-3035. PMID: 29192011.
2. Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K, et al. Global prevalence of hypertension in children: a systematic review and meta-analysis. JAMA Pediatr. 2019; 173(12):1154–1163. DOI: 10.1001/jamapediatrics.2019.3310. PMID: 31589252. PMCID: PMC6784751.
3. Gupta-Malhotra M, Banker A, Shete S, Hashmi SS, Tyson JE, Barratt MS, et al. Essential hypertension vs. secondary hypertension among children. Am J Hypertens. 2015; 28(1):73–80. DOI: 10.1093/ajh/hpu083. PMID: 24842390. PMCID: PMC4318949.
4. Fernandes-Rosa FL, Boulkroun S, Fedlaoui B, Hureaux M, Travers-Allard S, Drossart T, et al. New advances in endocrine hypertension: from genes to biomarkers. Kidney Int. 2023; 103(3):485–500. DOI: 10.1016/j.kint.2022.12.021. PMID: 36646167.
5. Kim S, Tsao H, Kang Y, Young DA, Sen M, Wenke JC, et al. In vitro evaluation of an injectable chitosan gel for sustained local delivery of BMP-2 for osteoblastic differentiation. J Biomed Mater Res B Appl Biomater. 2011; 99B(2):380–390. DOI: 10.1002/jbm.b.31909. PMID: 21905214.
6. Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011; 32(1):81–151. DOI: 10.1210/er.2010-0013. PMID: 21051590. PMCID: PMC3365799.
7. Stockand JD. New ideas about aldosterone signaling in epithelia. Am J Physiol Renal Physiol. 2002; 282(4):F559–F576. DOI: 10.1152/ajprenal.00320.2001. PMID: 11880316.
8. Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. 2013; 34(9):518–530. DOI: 10.1016/j.tips.2013.07.003. PMID: 23953592. PMCID: PMC3951203.
9. Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004; 56(3):331–349. DOI: 10.1124/pr.56.3.1. PMID: 15317907.
10. Curtis BM, O'Keefe JH Jr. Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clin Proc. 2002; 77(1):45–54. DOI: 10.4065/77.1.45. PMID: 11794458.
11. Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann Intern Med. 2020; 173(1):10–20. DOI: 10.7326/M20-0065. PMID: 32449886. PMCID: PMC7459427.
12. Vaidya A, Mulatero P, Baudrand R, Adler GK. The expanding spectrum of primary aldosteronism: implications for diagnosis, pathogenesis, and treatment. Endocr Rev. 2018; 39(6):1057–1088. DOI: 10.1210/er.2018-00139. PMID: 30124805. PMCID: PMC6260247.
13. Reznik Y, Amar L, Tabarin A. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 3: confirmatory testing. Ann Endocrinol. 2016; 77(3):202–207. DOI: 10.1016/j.ando.2016.01.007. PMID: 27318644.
14. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016; 101(5):1889–1916. DOI: 10.1210/jc.2015-4061. PMID: 26934393.
15. Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S, et al. A chimaeric llβ-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 1992; 355(6357):262–265. DOI: 10.1038/355262a0. PMID: 1731223.
16. Scholl UI, Stölting G, Schewe J, Thiel A, Tan H, Nelson-Williams C, et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet. 2018; 50(3):349–354. DOI: 10.1038/s41588-018-0048-5. PMID: 29403011. PMCID: PMC5862758.
17. Geller DS, Zhang J, Wisgerhof MV, Shackleton C, Kashgarian M, Lifton RP. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 2008; 93(8):3117–3123. DOI: 10.1210/jc.2008-0594. PMID: 18505761. PMCID: PMC2515083.
18. Scholl UI, Stölting G, Nelson-Williams C, Vichot AA, Choi M, Loring E, et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. eLife. 2015; 4:e06315. DOI: 10.7554/eLife.06315. PMID: 25907736. PMCID: PMC4408447.
19. Yoo HW. Diverse etiologies, diagnostic approach, and management of primary adrenal insufficiency in pediatric age. Ann Pediatr Endocrinol Metab. 2021; 26(3):149–157. DOI: 10.6065/apem.2142150.075. PMID: 34610702. PMCID: PMC8505038.
20. Hinz L, Pacaud D, Kline G. Congenital adrenal hyperplasia causing hypertension: an illustrative review. J Hum Hypertens. 2018; 32(2):150–157. DOI: 10.1038/s41371-017-0002-5. PMID: 29255217.
21. Auchus RJ. The genetics, pathophysiology, and management of human deficiencies of P450c17. Endocrinol Metab Clin North Am. 2001; 30(1):101–119. vii. DOI: 10.1016/S0889-8529(08)70021-5. PMID: 11344930.
22. Lee HI, Kwon A, Suh JH, Choi HS, Song KC, Chae HW, et al. Two cases of 17α-hydroxylase/17,20-lyase deficiency caused by the CYP17A1 mutation. Ann Pediatr Endocrinol Metab. 2021; 26(1):66–70. DOI: 10.6065/apem.2040184.092. PMID: 33819959. PMCID: PMC8026339.
23. El-Maouche D, Arlt W, Merke DP. Congenital adrenal hyperplasia. Lancet. 2017; 390(10108):2194–2210. DOI: 10.1016/S0140-6736(17)31431-9. PMID: 28576284.
24. Auchus RJ. Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol. 2017; 165((Pt A)):71–78. DOI: 10.1016/j.jsbmb.2016.02.002. PMID: 26862015. PMCID: PMC4976049.
25. Lu Y, Zhang D, Zhang Q, Zhou Z, Yang K, Zhou X, et al. Apparent mineralocorticoid excess: comprehensive overview of molecular genetics. J Transl Med. 2022; 20(1):500. DOI: 10.1186/s12967-022-03698-9. PMID: 36329487. PMCID: PMC9632093.
26. Yau M, Haider S, Khattab A, Ling C, Mathew M, Zaidi S, et al. Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency. Proc Natl Acad Sci USA. 2017; 114(52):E11248–E11256. DOI: 10.1073/pnas.1716621115. PMID: 29229831. PMCID: PMC5748222.
27. Kotanidou EP, Giza S, Tsinopoulou VR, Vogiatzi M, Galli-Tsinopoulou A. Diagnosis and management of endocrine hypertension in children and adolescents. Curr Pharm Des. 2020; 26(43):5591–5608. DOI: 10.2174/1381612826666201113103614. PMID: 33185153.
28. Stratakis CA. Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am. 2012; 41(4):793–803. DOI: 10.1016/j.ecl.2012.08.002. PMID: 23099271. PMCID: PMC3594781.
29. Storr HL, Chan LF, Grossman AB, Savage MO. Paediatric Cushing's syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol Metab. 2007; 18(4):167–174. DOI: 10.1016/j.tem.2007.03.005. PMID: 17412607.
30. Kim SE, Lee NY, Cho WK, Yim J, Lee JW, Kim M, et al. Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report. Ann Pediatr Endocrinol Metab. 2022; 27(4):315–319. DOI: 10.6065/apem.2142100.050. PMID: 35038837. PMCID: PMC9816470.
31. Shah NS, Lila A. Childhood Cushing disease: a challenge in diagnosis and management. Horm Res Paediatr. 2011; 76((Suppl 1)):65–70. DOI: 10.1159/000329173. PMID: 21778752.
32. Devoe DJ, Miller WL, Conte FA, Kaplan SL, Grumbach MM, Rosenthal SM, et al. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab. 1997; 82(10):3196–3202. DOI: 10.1210/jc.82.10.3196. PMID: 9329338.
33. Lodish MB, Keil MF, Stratakis CA. Cushing's syndrome in pediatrics: an update. Endocrinol Metab Clin North Am. 2018; 47(2):451–462. DOI: 10.1016/j.ecl.2018.02.008. PMID: 29754644. PMCID: PMC5962291.
34. Magiakou MA, Smyrnaki P, Chrousos GP. Hypertension in Cushing's syndrome. Best Pract Res Clin Endocrinol Metab. 2006; 20(3):467–482. DOI: 10.1016/j.beem.2006.07.006. PMID: 16980206.
35. Cicala MV, Mantero F. Hypertension in Cushing's syndrome: from pathogenesis to treatment. Neuroendocrinology. 2010; 92((Suppl 1)):44–49. DOI: 10.1159/000314315. PMID: 20829617.
36. Havekes B, Romijn JA, Eisenhofer G, Adams K, Pacak K. Update on pediatric pheochromocytoma. Pediatr Nephrol. 2009; 24(5):943–950. DOI: 10.1007/s00467-008-0888-9. PMID: 18566838.
37. Neumann HP, Young WF Jr, Krauss T, Bayley JP, Schiavi F, Opocher G, et al. 65 Years of the double helix: genetics informs precision practice in the diagnosis and management of pheochromocytoma. Endocr Relat Cancer. 2018; 25(8):T201–T219. DOI: 10.1530/ERC-18-0085. PMID: 29794110.
38. Lenders JWM, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SKG, Murad MH, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(6):1915–1942. DOI: 10.1210/jc.2014-1498. PMID: 24893135.
39. Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, et al. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010; 95(5):2023–2037. DOI: 10.1210/jc.2009-2830. PMID: 20215394.
40. Bholah R, Bunchman TE. Review of pediatric pheochromocytoma and paraganglioma. Front Pediatr. 2017; 5:155. DOI: 10.3389/fped.2017.00155. PMID: 28752085. PMCID: PMC5508015.
41. Eisenhofer G, Lenders JWM, Timmers H, Mannelli M, Grebe SK, Hofbauer LC, et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem. 2011; 57(3):411–420. DOI: 10.1373/clinchem.2010.153320. PMID: 21262951. PMCID: PMC3164998.
42. Bílek R, Vlček P, Šafařik L, Michalský D, Novák K, Dušková J, et al. Chromogranin A in the laboratory diagnosis of pheochromocytoma and paraganglioma. Cancers. 2019; 11(4):586. DOI: 10.3390/cancers11040586. PMID: 31027285. PMCID: PMC6521298.
43. Pacak K, Eisenhofer G, Ahlman H, Bornstein SR, Gimenez-Roqueplo AP, Grossman AB, et al. Pheochromocytoma: recommendations for clinical practice from the first international symposium. Nat Clin Pract Endocrinol Metab. 2007; 3(2):92–102. DOI: 10.1038/ncpendmet0396. PMID: 17237836.
44. Babic B, Patel D, Aufforth R, Assadipour Y, Sadowski SM, Quezado M, et al. Pediatric patients with pheochromocytoma and paraganglioma should have routine preoperative genetic testing for common susceptibility genes in addition to imaging to detect extra-adrenal and metastatic tumors. Surgery. 2017; 161(1):220–227. DOI: 10.1016/j.surg.2016.05.059. PMID: 27865588. PMCID: PMC5164949.
45. Brito JP, Asi N, Gionfriddo MR, Norman C, Leppin AL, Zeballos-Palacios C, et al. The incremental benefit of functional imaging in pheochromocytoma/paraganglioma: a systematic review. Endocrine. 2015; 50(1):176–186. DOI: 10.1007/s12020-015-0544-7. PMID: 25663601.
46. Jha A, Ling A, Millo C, Gupta G, Viana B, Lin FI, et al. Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx)-related pheochromocytoma and paraganglioma in the pediatric population. Eur J Nucl Med Mol Imaging. 2018; 45(5):787–797. DOI: 10.1007/s00259-017-3896-9. PMID: 29204718. PMCID: PMC6707509.
47. Dias Pereira B, Nunes da Silva T, Bernardo AT, César R, Vara Luiz H, Pacak K, et al. A clinical roadmap to investigate the genetic basis of pediatric pheochromocytoma: which genes should physicians think about? Int J Endocrinol. 2018; 2018:8470642. DOI: 10.1155/2018/8470642. PMID: 29755524. PMCID: PMC5884154.
48. Buffet A, Ben Aim L, Leboulleux S, Drui D, Vezzosi D, Libé R, et al. Positive impact of genetic test on the management and outcome of patients with paraganglioma and/or pheochromocytoma. J Clin Endocrinol Metab. 2019; 104(4):1109–1118. DOI: 10.1210/jc.2018-02411. PMID: 30698717.
49. Nagaraja V, Eslick GD, Edirimanne S. Recurrence and functional outcomes of partial adrenalectomy: a systematic review and meta-analysis. Int J Surg. 2015; 16((Pt A)):7–13. DOI: 10.1016/j.ijsu.2015.01.015. PMID: 25681039.
50. Romero M, Kapur G, Baracco R, Valentini RP, Mattoo TK, Jain A. Treatment of hypertension in children with catecholamine-secreting tumors: a systematic approach. J Clin Hypertens. 2015; 17(9):720–725. DOI: 10.1111/jch.12571. PMID: 26010736. PMCID: PMC8031986.
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