A rare case of juvenile hypertension: coexistence of type 2 multiple endocrine neoplasia -related bilateral pheochromocytoma and reninoma in a young patient with ACE gene polymorphism

BMC Endocrine Disorders

Salvatore Maria Corsello²  Alfredo Pontecorvi²  Alessandro Prete²  Giulia Canu³  Angelo Minucci³  Francesco Torino¹  Ettore Capoluongo³  Rosa Maria Paragliola² 

[1] Department of Systems Medicine, Università degli Studi Tor Vergata, Rome, Italy;Endocrinology Unit, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, Rome, 00168, Italy;Biochemistry and Clinical Biochemistry Unit, Università Cattolica del Sacro Cuore, Rome, Italy

关键词: Hypertension;    ACE polymorphism;    MEN2B;    Reninoma;    Pheochromocytoma;   

Others  :  1215936
DOI  :  10.1186/s12902-015-0022-5

 received in 2015-03-04, accepted in 2015-06-01,  发布年份 2015

【 摘 要 】

Background

Pheochromocytoma and reninoma represent two rare diseases causing hypertension. We here reported a rare case of association between type 2 multiple endocrine neoplasia related bilateral pheochromocytoma and reninoma. Moreover, polymorphism of ACE gene, which is known to be related to an increase of cardiovascular risk, has been found in the same patient.

Case presentation

A 24 year old Caucasian man came to our attention for severe hypertension, resistant to anti-hypertensive polytherapy. At the age of twenty he had undergone total thyroidectomy with lymphadenectomy for medullary carcinoma. Genetic testing showed a RET mutation of codon 918 (exon 16) not documented in other family members. During the follow-up, a progressive increase of urinary metanephrines and catecholamines was recorded. Our evaluation confirmed the presence of severe hypertension (220/140 mmHg) and a severe increase of urinary catecholamines and metanephrines. Due to the presence of hypokalemia, other causes of hypertension were researched leading to the discovery of hyperreninemia (236 μUI/ml) with mild hyperaldosteronism, and a mild increase of the renal artery resistance at ultrasound. An abdominal MRI showed multiple adrenal masses and a right kidney nodular lesion of about 2 cm.

The patient underwent bilateral adrenalectomy and right nephrectomy, and histology confirmed the presence of bilateral pheochromocytoma and right reninoma. The post-surgery laboratory evaluation showed a rapid reduction of the urinary metanephrines while plasma renin level remained low in spite of the bilateral adrenalectomy without any mineralocorticoid supplementation. To further investigate these unusual feature, we performed genetic testing for the ACE gene, which revealed the presence of ACE I/D polymorphism.

Conclusion

This unique report describes the association between two rare causes of hypertension in the same patient. Furthermore, the absence of requirement of mineralocorticoid supplementation in spite of bilateral adrenalectomy, represent an uncommon and interest finding.

【 授权许可】

   
2015 Paragliola et al.

【 参考文献 】

• [1]Plouin PF, Amar L, Lepoutre C. Phaeochromocytomas and functional paragangliomas: clinical management. Best Pract Res Clin Endocrinol Metab. 2010; 24:933-41.
• [2]Pacak K, Linehan WM, Eisenhofer G, Walther MM, Goldstein DS. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med. 2001; 134:315-29.
• [3]Torino F, Paragliola RM, Barnabei A, Corsello SM. Medullary thyroid cancer: a promising model for targeted therapy. Curr Mol Med. 2010; 10:608-25.
• [4]Trnka P, Orellana L, Walsh M, Pool L, Borzi P. Reninoma: an uncommon cause of renin-mediated hypertension. Front Pediatr. 2014; 2:89.
• [5]Minucci A, Canu G, Concolino P, Guarino D, Boccia S, Ficarra S et al.. DNA from buccal swab is suitable for rapid genotyping of angiotensin-converting enzyme insertion/deletion (I/D) polymorphism. Clin Chim Acta. 2014; 431:125-30.
• [6]Kota SK, Kota SK, Meher LK, Tripathy PR, Sruti J, Modi KD. Pheochromocytoma with renal artery stenosis: a case-based review of literature. J Cardiovasc Dis Res. 2012; 3:36-9.
• [7]Sizemore GW, Carney JA, Gharib H, Capen CC. Multiple endocrine neoplasia type 2B: eighteen-year follow-up of a four-generation family. Henry Ford Hosp Med J. 1992; 40:236-44.
• [8]DeLellis RA, Lloyd RV, Heitz PU, Eng C. World health organization classification of tumours. Pathology and genetics of tumours of endocrine organs. IARC Press, Lyon, France; 2004.
• [9]Mannelli M, Castellano M, Schiavi F, Filetti S, Giacchè M, Mori L et al.. Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. J Clin Endocrinolol Metab. 2009; 94:1541-7.
• [10]Martins R, Bugalho MJ. Paragangliomas/pheochromocytomas: clinically oriented genetic testing. Int J Endocrinol. 2014; 2014:794187.
• [11]Machens A, Ukkat J, Brauckhoff M, Gimm O, Dralle H. Advances in the management of hereditary medullary thyroid cancer. J Intern Med. 2005; 257:50-9.
• [12]Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones. 2009; 8:23-8.
• [13]Gujral TS, Singh VK, Jia Z, Mulligan LM. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B. Cancer Res. 2006; 66:10741-9.
• [14]Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996; 276:1575-9.
• [15]Zelinka T, Eisenhofer G, Pacak K. Pheochromocytoma as a catecholamine producing tumor: implications for clinical practice. Stress. 2007; 10:195-203.
• [16]Vaidyanathan G. Meta-iodobenzylguanidine and analogues: chemistry and biology. Q J Nucl Med Mol Imaging. 2008; 52:351-68.
• [17]Erdos EG, Skidgel RA. The angiotensin I-converting enzyme. Lab Invest. 1987; 56:345-8.
• [18]Alhenc-Gelas F, Baussant T, Hubert C, Soubrier F, Corvol P. The angiotensin converting enzyme in the kidney. J Hypertens Suppl. 1989; 7:S9–S13 (discussion S14).
• [19]Esther CR, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE. Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest. 1996; 74:953-65.
• [20]Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990; 86:1343-6.
• [21]Danser AH, Deinum J, Osterop AP, Admiraal PJ, Schalekamp MA. Angiotensin I to angiotensin II conversion in the human forearm and leg. Effect of the angiotensin converting enzyme gene insertion/deletion polymorphism. J Hypertens. 1999; 17:1867-72.
• [22]Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D et al.. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992; 359:641-4.
• [23]Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol. 2000; 20:484-92.
• [24]Inanir A, Basol N, Karakus N, Yigit S. The importance of association between angiotensin-converting enzyme (ACE) I/D polymorphism and diabetic peripheral neuropathy. Gene. 2013; 530:253-6.
• [25]Wang Z, Wang P, Wang X, He X, Wang Z, Xu D et al.. Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: A systematic review and meta-analysis. Metabolism. 2013; 62:1227-38.
• [26]MacKenzie SM, Connell JM, Davies E. Non-adrenal synthesis of aldosterone: a reality check. Mol Cell Endocrinol. 2012; 350:163-7.
• [27]Freel EM, Bernhardt R, Ingram M, Wallace AM, Fraser R, Davies E et al.. Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy. Clin Endocrinol (Oxf). 2007; 66:659-65.
• [28]Essick EE, Sam F. Cardiac hypertrophy and fibrosis in the metabolic syndrome: a role for aldosterone and the mineralocorticoid receptor. Int J Hypertens. 2011;346985.
• [29]Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A. Cardiovascular manifestations of phaeochromocytoma. J Hypertens. 2011; 29:2049-60.
• [30]MacKenzie SM, Fraser R, Connell JM, Davies E. Local renin-angiotensin systems and their interactions with extra-adrenal corticosteroid production. J Renin Angiotensin Aldosterone Syst. 2002; 3:214-21.