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Endocrine dysfunction in hereditary hemochromatosis

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Abstract

Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

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  1. Division of Endocrinology, Department of Medical and Surgical Sciences, University Alma Mater Studiorum, S. Orsola-Malpighi Hospital, Via Massarenti 9, Bologna, Italy

    C. Pelusi, D. I. Gasparini, N. Bianchi & R. Pasquali

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  1. C. Pelusi
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Pelusi, C., Gasparini, D.I., Bianchi, N. et al. Endocrine dysfunction in hereditary hemochromatosis. J Endocrinol Invest 39, 837–847 (2016). https://doi.org/10.1007/s40618-016-0451-7

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