Rejected by the New England Journal of Medicine in June 2017.

To the Editor:

West (*) describes angiogenesis, erythropoiesis, and vasoconstriction as clinical sequelae arising from chronically hypoxic tissues at altitude. Another, similar, effect is solid-organ hyperplasia.

In the late 1960s a Peruvian medical student observed several-fold enlargement of the carotid bodies in Andean altitude dwellers (1,2). The degree of enlargment increased with time spent at altitude and, in animal models, reversed after restoration of normoxia (3). Interestingly, this hyperplasia is mediated via endothelin signalling, not by hypoxia-inducible-factors (4).

Tissue hyperplasia may also occur in hypoxic patients at sea level. For example, even before the Peruvian discovery, hyperplasia – and sometimes malignancy – of adrenal chromaffin cells, i.e. pheochromocytomas, were described in adults having uncorrected cyanotic congenital heart disease (5). Carotid body cells and adrenal chromaffin cells have similar lineage (from the neural crest) and similar function (oxygen sensing).

(*) West, John B. Physiological effects of chronic hypoxia. New England Journal of Medicine. 2017; 376: 1965-1971.

(1) Arias-Stella J. Human carotid body at high altitudes. (Abstract). American Journal of Pathology. 1969; 55: 82a.

(2) Heath D. The carotid bodies in chronic respiratory disease. Histopathology. 1991; 18: 281-283.

(3) Kay JM, Laidler P. Hypoxia and the carotid body. J Clin Pathol Suppl (R Coll Pathol). 1977; 11: 30-44.

(4) Platero-Luengo A, González-Granero S, Durán R, Díaz-Castro B, Piruat J, García-Verdugo JM, Pardal R, López-Barneo J. An O2-Sensitive Glomus Cell-Stem Cell Synapse Induces Carotid Body Growth in Chronic Hypoxia. Cell. 2014; 156, 291–303.

(5) Folger GM, Roberts WC, Mehrizi A, Shah KD, Glancy DL, Carpenter CCJ, Esterly JR. Cyanotic Malformations of the Heart with Pheochromocytoma: A Report of Five Cases. Circulation. 1964; 29: 750-757.

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Published on January 29, 2018