Phaeochromocytoma and endocrine hypertension

The single idea that organises the whole topic is that endocrine hypertension in children splits into two mechanistic families: catecholamine-driven disease (phaeochromocytoma and paraganglioma) and mineralocorticoid-driven disease (the monogenic low-renin causes). The first is caught by metanephrines and fixed by alpha-blockade then surgery; the second is caught by a renin–aldosterone–potassium panel and fixed by matching the drug to the gene. [1] [11]

This page covers the recognition and management of phaeochromocytoma and paraganglioma in children, then turns to the broader endocrine causes of hypertension: the monogenic mineralocorticoid syndromes (Liddle, apparent mineralocorticoid excess, eleven- and seventeen-hydroxylase deficiency, Gordon syndrome), primary aldosteronism, and cortisol and thyroid excess. It links to the Cushing and congenital adrenal hyperplasia leaves for their dedicated pathways rather than repeating them. [2] [12]

Overview & Definition

Phaeochromocytoma and paraganglioma are tumours of the chromaffin cell, the neuroendocrine cell that stores and releases catecholamines. An adrenal medullary lesion is a phaeochromocytoma; an identical lesion arising in the extra-adrenal paraganglia — the organ of Zückerkandl, the head and neck, the thorax — is a paraganglioma. Both leak metanephrines and both can cause the same catecholamine storm. [1]

What sets the paediatric disease apart is its hereditary burden and its behaviour. Children more often present with sustained hypertension rather than the classic adult episodic spells, their tumours are more often bilateral, multifocal and extra-adrenal, and roughly four in ten carry a germline mutation. The old teaching that phaeochromocytomas follow a "rule of tens" — ten percent bilateral, malignant, extra-adrenal and familial — describes adult disease and badly undercalls the heritable fraction in children. [2] [5]

Endocrine hypertension is the broader umbrella for any hormone-driven rise in blood pressure. It includes the catecholamine tumours, the mineralocorticoid-excess syndromes (whether monogenic, aldosterone-driven or cortisol-driven), and hypertension from thyroid or parathyroid excess. The first step in any hypertensive child is therefore endocrine: measure metanephrines for the catecholamine family, and renin with aldosterone for the mineralocorticoid family. [10] [12]

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1. [1]Lenders JW; Duh QY; Eisenhofer G; et al Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2014.PMID 24893135
2. [2]Casey RT; Hendriks E; Deal C; et al International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents. Nat Rev Endocrinol, 2024.PMID 39147856
3. [3]Lenders JW; Pacak K; Walther MM; et al Biochemical diagnosis of pheochromocytoma: which test is best? JAMA, 2002.PMID 11903030
4. [4]Barontini M; Levin G; Sanso G Characteristics of pheochromocytoma in a 4- to 20-year-old population. Ann N Y Acad Sci, 2006.PMID 17102069
5. [5]Havekes B; Romijn JA; Eisenhofer G; et al Update on pediatric pheochromocytoma. Pediatr Nephrol, 2009.PMID 18566838
6. [6]Ganesh HK; Acharya SV; Goerge J; et al Pheochromocytoma in children and adolescents. Indian J Pediatr, 2009.PMID 20072855
7. [7]Muth A; Crona J; Gimm O; et al Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. J Intern Med, 2019.PMID 30536464
8. [8]Castinetti F; Waguespack SG; Machens A; et al Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study. Lancet Diabetes Endocrinol, 2019.PMID 30660595
9. [9]Funder JW; Carey RM; Mantero F; et al The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2016.PMID 26934393
10. [10]Kapur G; Baracco R Evaluation of hypertension in children. Curr Hypertens Rep, 2013.PMID 23904150
11. [11]New MI; Geller DS; Fallo F; et al Monogenic low renin hypertension. Trends Endocrinol Metab, 2005.PMID 15808805
12. [12]Garovic VD; Hilliard AA; Turner ST Monogenic forms of low-renin hypertension. Nat Clin Pract Nephrol, 2006.PMID 17066054