Abstract
Introduction
Patients with Chronic hypoparathyroidism (CHPT) receiving conventional treatment are exposed to several long-term complications including basal ganglia calcifications, posterior subcapsular cataract, kidney stones, and renal insufficiency. The aim of this study was to assess the prevalence and the associated factors of these complications in patients with CHPT.
Methods
We conducted a cross-sectional study including 58 patients with CHPT. All participants underwent physical examination, biochemical assessment (total serum calcium, serum phosphorus, serum albumin, intact-PTH, serum magnesium, 25-hydroxy-vitamin D, serum creatinine, thyroid stimulating hormone (TSH), and 24-hour urinary calcium), slit lamp examination, brain computed tomography scan (CT-scan), and renal ultrasound.
Results
Participants had a mean age of 52.6 ± 16.4 years and a gender ratio (women/men) of 3.5. Fahr syndrome, cataract, urolithiasis, and renal failure were found in 55%, 62%, 12%, and 17% of cases, respectively. CHPT duration >15 years (Adjusted-OR = 43.1, 95-CI: 2.63–703.06, p = 0.008) and poor adherence to treatment (Adjusted-OR = 8.04, 95%-CI: 1.52–42.42, p = 0.014) were independently associated with the risk of Fahr syndrome. Age >55 years (adjusted-OR = 5.07, 95-CI: 1.10–23.42, p = 0.037), disease duration >15 years (adjusted-OR = 20.21, 95-CI: 1.54–265.84, p = 0.022), and magnesium level <0.8 mmol/l (adjusted-OR = 36.46, 95-CI: 3.75–354.08, p = 0.002) were independently associated with the risk of subcapsular cataract. Only hypercalciuria (Adjusted-OR = 21.27, 95-CI: 2.31–195.91, p = 0.007) was an independent risk factor for kidney stones. Renal failure was not associated with kidney stones (p = 1). However, creatinine clearance was negatively correlated with age (r = −0.784; p < 10−3) and disease duration (r = −0.352; p = 0.007).
Conclusion
Our results revealed high prevalences of neurological, ocular, and renal complications in patients with CHPT and emphasized the importance of regular biological monitoring, therapeutic adjustments, screening, and adherence to treatment in the prevention of these complications.
Similar content being viewed by others
Data availability
Data are available from the authors upon reasonable request.
References
B.L. Clarke, E.M. Brown, M.T. Collins, H. Jüppner, P. Lakatos, M.A. Levine et al. Epidemiology and Diagnosis of Hypoparathyroidism. J. Clin. Endocrinol. Metab. 101, 2284–2299 (2016)
J. Bilezikian, A. Khan, J. Potts, M. Brandi, B. Clarke, D. Shoback et al. Hypoparathyroidism in the Adult: Epidemiology, Diagnosis, Pathophysiology, Target Organ Involvement, Treatment, and Challenges for Future Research. J. Bone Min. Res. 26, 2317–2337 (2011)
D.M. Shoback, J.P. Bilezikian, A.G. Costa, D. Dempster, H. Dralle, A.A. Khan et al. Presentation of Hypoparathyroidism: Etiologies and Clinical Features. J. Clin. Endocrinol. Metab. 101, 2300–2312 (2016). https://doi.org/10.1210/jc.2015-3909
F. Tecilazich, A.M. Formenti, S. Frara, R. Giubbini, A. Giustina, Treatment of hypoparathyroidism. Best. Pr. Res. Clin. Endocrinol. Metab. 32, 955–964 (2018)
A.A. Khan, J.P. Bilezikian, M.L. Brandi, B.L. Clarke, N.J. Gittoes, J.L. Pasieka et al. Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop. J. Bone Min. Res. 37, 2568–2585 (2022)
E.G. Abate, B.L. Clarke, Review of Hypoparathyroidism. Front. Endocrinol. 7, 172 (2017)
K. David, C. Moyson, D. Vanderschueren, B. Decallonne, Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study. Eur. J. Endocrinol. 180, 71–78 (2019)
X. Girerd, O. Hanon, K. Anagnostopoulos, C. Ciupek, J.J. Mourad, S. Consoli, Assessment of antihypertensive compliance using a self-administered questionnaire: development and use in a hypertension clinic. Presse Med. 30, 1044–1048 (2001)
M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 96, 1911–1930 (2011)
F. Livio, J. Biollaz, M. Burnier. Renal function estimation by MDRD equation: interest and limitations for drug dosing. Rev. Med. Suisse 4, 2596–2600 (2008)
A.C. Webster, E.V. Nagler, R.L. Morton, P. Masson, Chronic Kidney Disease. Lancet Lond. Engl. 389, 1238–1252 (2017)
J. Bollerslev, L. Rejnmark, C. Marcocci, D.M. Shoback, A. Sitges-Serra, W. van Biesen et al. European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults. Eur. J. Endocrinol. 173, G1–G20 (2015)
G. Donzuso, G. Mostile, A. Nicoletti, M. Zappia, Basal ganglia calcifications (Fahr’s syndrome): related conditions and clinical features. Neurol. Sci. 40, 2251–2263 (2019)
K. Jaworski, M. Styczyńska, M. Mandecka, J. Walecki, D.A. Kosior, Fahr Syndrome – an Important Piece of a Puzzle in the Differential Diagnosis of Many Diseases. Pol. J. Radio. 82, 490–493 (2017)
A. el Maghraoui, N. Birouk, A. Zaim, I. Slassi, M. Yahyaoui, T. Chkili, Fahr syndrome and dysparathyroidism. 3 cases. Presse Med. 24, 1301–1304 (1995)
M.R. Rubin, D.W. Dempster, H. Zhou, E. Shane, T. Nickolas, J. Sliney et al. Dynamic and structural properties of the skeleton in hypoparathyroidism. J. Bone Min. Res. J. Am. Soc. Bone Min. Res. 23, 2018–2024 (2008)
A.A. Khan, H. AbuAlrob, Z. Punthakee, M. Shrayyef, R.E. Werfalli, H.A. Kassem et al. Canadian national hypoparathyroidism registry: an overview of hypoparathyroidism in Canada. Endocrine 72, 553–561 (2021)
R. Goswami, R. Sharma, V. Sreenivas, N. Gupta, A. Ganapathy, S. Das, Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin. Endocrinol. 77, 200–206 (2012)
F. Illum, E. Dupont, Prevalences of CT-detected calcification in the basal ganglia in idiopathic hypoparathyroidism and pseudohypoparathyroidism. Neuroradiology 27, 32–37 (1985)
D.M. Mitchell, S. Regan, M.R. Cooley, K.B. Lauter, M.C. Vrla, C.B. Becker et al. Long-term follow-up of patients with hypoparathyroidism. J. Clin. Endocrinol. Metab. 97, 4507–4514 (2012)
C. Konca Degertekin, D. Gogas Yavuz, Z. Pekkolay, E. Saygili, K. Ugur, A. Or Koca et al. Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study. Calcif. Tissue Int. 110, 204–214 (2022)
C. Sachs, H.E. Sjöberg, K. Ericson, Basal ganglia calcifications on CT: relation to hypoparathyroidism. Neurology 32, 779–782 (1982)
T. Neumayer, N. Hirnschall, M. Georgopoulos, O. Findl, Natural course of posterior subcapsular cataract over a short time period. Curr. Eye Res. 42, 1604–1607 (2017)
H. Takahashi, [Ca(2+)-ATPase activity in the hypocalcemic cataract]. Nippon Ganka Gakkai Zasshi 98, 142–149 (1994)
L. Underbjerg, T. Sikjaer, L. Mosekilde, L. Rejnmark, Postsurgical hypoparathyroidism-risk of fractures, psychiatric diseases, cancer, cataract, and infections. J. Bone Min. Res J. Am. Soc. Bone Min. Res. 29, 2504–2510 (2014)
T. Vadiveloo, P.T. Donnan, C.J. Leese, K.J. Abraham, G.P. Leese, Increased mortality and morbidity in patients with chronic hypoparathyroidism: A population-based study. Clin. Endocrinol. 90(2), 285–292 (2019)
S.H. Kim, Y. Rhee, Y.M. Kim, Y.J. Won, J. Noh, H. Moon et al. Prevalence and complications of nonsurgical hypoparathyroidism in Korea: A nationwide cohort study. PloS One 15, e0232842 (2020)
A.M. Koçer, M.A. Şekeroğlu, Ç.E. Önder, S. Çevik, F.E. Söğüt, Ş.M. Kuşkonmaz et al. Quantitative investigation of the effect of surgically induced hypoparathyroidism on cataract development. J. Bone Min. Metab. 40, 92–100 (2022)
R. Agarwal, I. Iezhitsa, P. Agarwal, A. Spasov, Magnesium deficiency: does it have a role to play in cataractogenesis? Exp. Eye Res. 101, 82–89 (2012)
R. Agarwal, L. Iezhitsa, P. Agarwal, Pathogenetic role of magnesium deficiency in ophthalmic diseases. Bio Met. 27, 5–18 (2014)
I. Levy, C. Licht, A. Daneman, E. Sochett, J. Harrington, The Impact of Hypoparathyroidism Treatment on the Kidney in Children: Long-Term Retrospective Follow. J. Clin. Endocrinol. Metab. 100, 4106–4113 (2015)
E.O. Gosmanova, P. Houillier, L. Rejnmark, C. Marelli, J.P. Bilezikian, Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review. Rev. Endocr. Metab. Disord. 22, 297–316 (2021)
E.O. Gosmanova, K. Chen, L. Rejnmark, F. Mu, E. Swallow, A. Briggs et al. Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study. Adv. Ther. 38, 1876–1888 (2021)
L. Underbjerg, T. Sikjaer, L. Mosekilde, L. Rejnmark, Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J. Bone Min. Res. 28, 2277–2285 (2013)
W. Arlt, C. Fremerey, F. Callies, M. Reincke, P. Schneider, W. Timmermann et al. Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Eur. J. Endocrinol. 146, 215–222 (2002)
M. Ketteler, K. Chen, E.O. Gosmanova, J. Signorovitch, F. Mu, J.A. Young et al. Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study. Adv. Ther. 38, 1946–1957 (2021)
M.P. Lopes, B.S. Kliemann, I.B. Bini, R. Kulchetscki, V. Borsani, L. Savi et al. Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications. Arch. Endocrinol. Metab. 60, 532–536 (2016)
G. Leidig-Bruckner, T. Bruckner, F. Raue, K. Frank-Raue, Long-Term Follow-Up and Treatment of Postoperative Permanent Hypoparathyroidism in Patients with Medullary Thyroid Carcinoma: Differences in Complete and Partial Disease. Horm. Metab. Res. 48, 806–813 (2016)
A. Meola, E. Vignali, A. Matrone, F. Cetani, C. Marcocci, Efficacy and safety of long-term management of patients with chronic post-surgical hypoparathyroidism. J. Endocrinol. Invest. 41, 1221–1226 (2018)
L. Underbjerg, T. Sikjaer, L. Rejnmark, Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study. J. Bone Min. Res. 33, 822–831 (2018)
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Ethics approval and consent to participate
This study was approved by the ethics committee of La Rabta university hospital (CEBM.EPS.HR/06/2020). All enrolled patients provided written informed consent before starting the study.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cherchir, F., Oueslati, I., Yazidi, M. et al. Long-term complications of permanent hypoparathyroidism in adults: prevalence and associated factors. Endocrine (2024). https://doi.org/10.1007/s12020-024-03765-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12020-024-03765-9