Hypoparathyroidism in a Case of Transfusion Dependent Thalassemia
Repeated blood transfusions in transfusion dependent thalassemia (TDT) leads to iron overload-related endocrine complications. Hypoparathyroidism (HPT) with severe signs of hypocalcemia is a recognized complication among these patients.
A 14-year-old thalassaemic boy, on regular transfusion and on anticonvulsant therapy with a presumptive diagnosis of epilepsy for the last 1 year, was admitted with high fever and severe muscle cramps with positive Trousseau’s sign. He was diagnosed as a case of primary HPT and magnesium deficiency on the basis of low serum calcium, high phosphate, normal alkaline phosphates, very low intact parathyroid hormone (iPTH), normal serum vitamin D and very low serum magnesium level. His calcium, magnesium and phosphate level normalised following treatment with intravenous magnesium and calcium. His iPTH improved but remained at low normal. He was discharged from hospital with oral calcium, calcitriol, and magnesium supplementation. The anticonvulsant (Phenobarbitone) was successfully withdrawn gradually over the next six months without any recurrence of seizure in the subsequent 3 years of follow up.
Acquired HPT (apparently from hemosiderosis) is a common cause of hypocalcemia; and magnesium depletion further complicated the situation leading to severe hypocalcemia with recurrent episodes of convulsion. Magnesium replacement improved the parathyroid hormone (PTH) value proving its role in acquired HPT. Very high phosphate level on admission and poor PTH response with respect to the low serum calcium, indicates intrinsic parathyroid pathology. Metabolic abnormalities should always be evaluated in thalassaemic subject with seizure disorder and it appears that the initial convulsive episodes were due to hypocalcemia.
Muscle pain, cramps or convulsion may occur from HPT and simultaneous magnesium deficiency in transfusion dependent thalassaemic subjects. Metabolic correction is more important than anticonvulsant medication. Calcium and
magnesium should both be assessed routinely in transfusion dependent thalassemic patients.
Hamed EM, Meabed MH, Aly U, Hussein RRS. Recent progress in gene therapy and other targeted therapeutic approaches for beta thalassemia. Current Drug Targets. 2019;20(16):1603-23. https://www.ncbi.nlm.nih.gov/pubmed/31362654. https://doi.org/10.2174/1389450120666190726155733.
Galanello R,Origa R. Beta-thalassemia.Orphanet J Rare Dis. 2010;5:1-11. https://www.ncbi.nlm.nih.gov/pubmed/20492708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893117. https://doi.org/10.1186/1750-1172-5-11.
De Sanctis V, Vullo C, Bagni B, Chiccoli L. Hypoparathyroidismin beta- thalassemia major clinical and laboratory observations in 24 patients. Acta Haematol.1992;88(2-3):105-8. https://www.ncbi.nlm.nih.gov/pubmed/1466190.
De Sanctis V, Elsedfy H, Soliman AT, et al. Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocrinol Metab. 2016;20(4):451-9. https://www.ncbi.nlm.nih.gov/pubmed/27366710. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911833. https:/doi.org/10.4103/2230-8210.183456.
Mariani R, Trombini P, Pozzi M, Piperno A. Iron metabolism in thalassemia and sickle cell disease. Mediterr J Hematol Infect Dis. 2009;1(1):e2009006. https://www.ncbi.nlm.nih.gov/pubmed/21415988. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033158. https://doi.org/10.4084/MJHID.2009.006.
Fuhrmann DC, Brüne B. Mitochondrial composition and function under the control of hypoxia. Redox Biol. 2017;12:208-15. https://www.ncbi.nlm.nih.gov/pubmed/28259101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333533. https://doi.org/10.1016/j.redox.2017.02.012.
Chern JP, Lin KH. Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. J Pediatr Hematol Oncol. 2002;24(4):291-3. https://www.ncbi.nlm.nih.gov/pubmed/11972098. https://doi.org/10.1097/00043426-200205000-00014.
Angelopoulos NG, Goula A, Rombopoulos G, et al. Hypoparathyroidism in transfusion-dependent patients with betathalassemia. J Bone Miner Metab. 2006;24(2):138–45. https://www.ncbi.nlm.nih.gov/pubmed/16502121. https://doi.org/10.1007/s00774-005-0660-1.
Chern JP, Lin KH, Tsai WY,et al. Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia. J Pediatr Hematol Oncol. 2003;25(11):880-4. https://www.ncbi.nlm.nih.gov/pubmed/14608198. https://doi.org/10.1097/00043426-200311000-00011.
Filosa A, Di Maio S, Vocca S, Saviano A, Esposito G, Pagano L. Longitudinal monitoring of bone mineral density in thalassemic patients: Genetic structure and osteoporosis. Acta Paediatr. 1997;86(4):342–6. https://www.ncbi.nlm.nih.gov/pubmed/9174216. https://doi.org/10.1111/j.1651-2227.1997.tb09019.x.
Hyman CB, Ortega JA, Costin G, Takahashi M. The clinical significance of magnesium depletion in thalassemia. Ann N Y Acad Sci.1980;344:436-43. https://www.ncbi.nlm.nih.gov/pubmed/6930882. https://doi.org/10.1111/j.1749-6632.1980.tb33683.x.
Hirtz D, Ashwal S, Berg A, et al. Practice parameter: Evaluating a first nonfebrile seizure in children: Report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology. 2000;55(5):616-23. https://www.ncbi.nlm.nih.gov/pubmed/10980722. https://doi.org/10.1212/wnl.55.5.616.
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