Keywords
Metabolic Diseases
Iron Overload
Hemochromatosis
Endocrine System Diseases
Hypogonadism
Thyroid Diseases
How to Cite
Abstract
Background: Hyperferritinemia is common in endocrinology consultations, mainly due to metabolic causes. However, hemochromatosis, a genetic disorder that alters iron metabolism, is essential to identify as it is a treatable cause of endocrine-metabolic alterations.
Purpose: To describe the endocrinological manifestations from the metabolic or hormonal point of view of patients with hyperferritinemia differentiated between those with a confirmed or unconfirmed diagnosis of hemochromatosis.
Methodology: Observational, analytical, retrospective study that included patients evaluated in the Endocrinology unit of the outpatient clinic of a tertiary clinic in Medellín - Colombia, with elevated ferritin levels.
Results: A total of 28 patients were included, with a median age of 54.5 years, and a male predominance in 75% of the cases. The predominant comorbidity was overweight, present in 17 patients (60.71%). Among the hormonal alterations, the primary one was primary hypothyroidism, observed in 10 patients (35.7%). When patients were categorized by a diagnosis of hemochromatosis, there were no statistically significant differences in terms of gender, age, BMI, metabolic comorbidities, hormonal alterations, levels of ALT, AST, HbA1c, total testosterone, lipid profile, thyroid, or transferrin saturation. However, ferritin levels in the confirmed hemochromatosis and H63D heterozygosity groups were statistically significantly higher.
Conclusions: In the presence of hyperferritinemia, it is essential to consider differential diagnoses such as hemochromatosis, given its association, if left untreated, with multiple endocrine diseases, including osteoporosis.
References
Sandnes M, Ulvik RJ, Vorland M, Reikvam H. Hyperferritinemia-a clinical overview. J Clin Med. 2021;10(9):2008. https://doi.org/10.3390/jcm10092008
Piperno A, Pelucchi S, Mariani R. Hereditary hyperferritinemia. Int J Mol Sci. 2023;24(3):2560. https://doi.org/10.3390/ijms24032560
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol. 2022;77(2):479-502. https://doi.org/10.1016/j.jhep.2022.03.033
Brissot P, Pietrangelo A, Adams PC, de Graaff B, McLaren CE, Loreál O. Haemochromatosis. Nat Rev Dis Primers. 2018;4:18016. https://doi.org/10.1038/nrdp.2018.16
Adams PC, Jeffrey G, Ryan J. Haemochromatosis. Lancet. 2023;401(10390):1811-21. https://doi.org/10.1016/s0140-6736(23)00287-8
American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(supl. 1):S20-42. https://doi.org/10.2337/dc24-s002
Rauber MR, Pilger DA, Cecconello DK, Falcetta FS, Marcondes NA, Faulhaber GAM. Hepcidin is a useful biomarker to evaluate hyperferritinemia associated with metabolic syndrome. An Acad Bras Cienc. 2019;91(2):e20180286. https://doi.org/10.1590/0001-3765201920180286
Kersting N, Fontana JC, de Athayde FP, Marcante Carlotto F, Accorsi Machado B, da Silva Rodrigues de Araújo C, et al. Hereditary hemochromatosis beyond hyperferritinemia: Clinical and laboratory investigation of the patient’s profile submitted to phlebotomy in two reference centers in southern Brazil. Genet Mol Biol. 2023;46(2):e20220230. https://doi.org/10.1590/1678-4685-gmb-2022-0230
Espinoza-Herrera YP, Muñoz-Maya OG, Chacón-Cardona JA. Hiperferritinemia y sospecha de sobrecarga de hierro en pacientes del Hospital Pablo Tobón Uribe, entre los años 2010 a 2020. Hepatología. 2023;4(1):60-74. https://doi.org/10.52784/27112330.167
Lommaert E, Verlinden W, Duysburgh I, Holvoet T, Schouten J. Hyperferritinemia and non-HFE hemochromatosis: differential diagnosis and workup. Acta Gastroenterol Belg. 2023;86(2):356-9. https://doi.org/10.51821/86.2.11249
Bhattad PB, Goyal A, Hamati AN, Madhok A, Venkatachalam S, Madhuramthakam DS, et al. Hemochromatosis arthropathy in heterozygous HFE H63D mutation without iron overload- an entity less commonly touched. J Med Res. 2021;7(1):27-9. https://doi.org/10.31254/jmr.2021.7108
Barbara KH, Marcin L, Jedrzej A, Wieslaw Z, Elzbieta AD, Malgorzata M, et al. The impact of H63D HFE gene carriage on hemoglobin and iron status in children. Ann Hematol. 2016;95(12):2043-8. https://doi.org/10.1007/s00277-016-2792-x
Ropero P, Briceño O, López Alonso G, Agúndez JAG, González Fernández FA, García Hoz F, et al. La mutación H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular. Rev Esp Enferm Dig. 2007;99(7):376-81. https://doi.org/10.4321/S1130-01082007000700002
Valenti L, Corradini E, Adams LA, Aigner E, Alqahtani S, Arrese M, et al. Consensus Statement on the definition and classification of metabolic hyperferritinaemia. Nat Rev Endocrinol. 2023;19(5):299-310. https://doi.org/10.1038/s41574-023-00807-6
Krygier A, Szczepanek-Parulska E, Filipowicz D, Rucha?a M. Changes in serum hepcidin according to thyrometabolic status in patients with Graves’ disease. Endocr Connect. 2020;9(3):234-42. https://doi.org/10.1530/ec-20-0017
Fischli S, von Wyl V, Trummler M, Konrad D, Wueest S, Ruefer A, et al. Iron metabolism in patients with Graves’ hyperthyroidism. Clin Endocrinol. 2017;87(5):609-16. https://doi.org/10.1111/cen.13450
Corradini E, Buzzetti E, Pietrangelo A. Genetic iron overload disorders. Mol Aspects Med. 2020;75:100896. https://doi.org/10.1016/j.mam.2020.100896
Pelusi C, Gasparini DI, Bianchi N, Pasquali R. Endocrine dysfunction in hereditary hemochromatosis. J Endocrinol Invest. 2016;39(8):837-47. https://doi.org/10.1007/s40618-016-0451-7
Barton JC, Acton RT. Diabetes in HFE Hemochromatosis. J Diabetes Res. 2017;2017:9826930. https://doi.org/10.1155/2017/9826930
Wu H, Yu M, Xiao C, Zhang Q, Xiao X. Clinical characteristics of endocrinopathies in Chinese patients with hereditary haemochromatosis. Diabetes Metab Res Rev. 2021;37(4):e3448. https://doi.org/10.1002/dmrr.3448
Muñoz Moreno D, Miguélez González M, González Fernández L, Percovich Hualpa JC. A review of systemic infiltrative diseases and associated endocrine diseases. Endocrinol Diabetes Nutr. 2021;68(5):312-20. https://doi.org/10.1016/j.endinu.2020.06.006
Liu Yin J, Cussen C, Harrington C, Foskett P, Raja K, Ala A. Guideline review: European Association for the Study of Liver (EASL) Clinical Practice Guidelines on Haemochromatosis. J Clin Exp Hepatol. 2023;13(4):649-55. https://doi.org/10.1016/j.jceh.2022.11.003
Crawford DHG, Ramm GA, Bridle KR, Nicoll AJ, Delatycki MB, Olynyk JK. Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver. Hepatol Int. 2023;17(3):522-41. https://doi.org/10.1007/s12072-023-10510-3
Olynyk JK, Ramm GA. Hemochromatosis. N Engl J Med. 2022;387(23):2159-70. https://doi.org/10.1056/nejmra2119758
Cabrera E, Crespo G, VanWagner LB. Diagnosis and management of hereditary hemochromatosis. JAMA. 2022;328(18):1862-3. https://doi.org/10.1001/jama.2022.17727
El Osta R, Grandpre N, Monnin N, Hubert J, Koscinski I. Hypogonadotropic hypogonadism in men with hereditary hemochromatosis. Basic Clin Androl. 2017;27:13. https://doi.org/10.1186/s12610-017-0057-8
Uitz PM, Hartleb S, Schaefer S, Al-Fakhri N, Kann PH. Pituitary function in patients with hereditary haemochromatosis. Horm Metab Res. 2013;45(1):54-61. https://doi.org/10.1055/s-0032-1323702
Maghnie M, Uga E, Temporini F, di Iorgi N, Secco A, Tinelli C, et al. Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. Eur J Endocrinol. 2005;152(5):735-41. https://doi.org/10.1530/eje.1.01911
Birtolo MF, Antonini S, Saladino A, Zampetti B, Lavezzi E, Chiodini I, et al. ACTH stimulation test for the diagnosis of secondary adrenal insufficiency: light and shadow. Biomedicines. 2023;11(3):904. https://doi.org/10.3390/biomedicines11030904
Javorsky BR, Raff H, Carroll TB, Algeciras-Schimnich A, Singh RJ, Colón-Franco JM, et al. New cutoffs for the biochemical diagnosis of adrenal insufficiency after ACTH stimulation using specific cortisol assays. J Endocr Soc. 2021;5(4):bvab022. https://doi.org/10.1210/jendso/bvab022
Francucci CM, Gatti C, Camilletti A, Fiscaletti P, Caudarella R, Boscaro M. Hypogonadism and reduced bone mineral density in heterozygous H63D mutation in the HFE gene: an unusual presentation of hereditary hemochromatosis. J Androl. 2007;28(1):21-6. https://doi.org/10.2164/jandrol.106.000786
Kelley M, Joshi N, Xie Y, Borgaonkar M. Iron overload is rare in patients homozygous for the H63D mutation. Can J Gastroenterol Hepatol. 2014;28(4):198-202. https://doi.org/10.1155/2014/468521
Hasan SMM, Farrell J, Borgaonkar M. C282Y/H63D compound heterozygosity is a low penetrance genotype for iron overload-related disease. J Can Assoc Gastroenterol. 2022;5(5):240-7. https://doi.org/10.1093/jcag/gwac025
Baschant U, Altamura S, Steele-Perkins P, Muckenthaler MU, Spasi? MV, Hofbauer LC, et al. Iron effects versus metabolic alterations in hereditary hemochromatosis driven bone loss. Trends Endocrinol Metab. 2022;33(9):652-63. https://doi.org/10.1016/j.tem.2022.06.004
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