FGF23 Reveals Mineral Imbalance in Hypoparathyroidism

FGF23 Reveals Mineral Imbalance in Hypoparathyroidism – Hypoparathyroidism (HypoPT) is a rare endocrine condition marked by inadequate or absent production of parathyroid hormone (PTH), leading to low calcium levels (hypocalcemia), elevated phosphate levels (hyperphosphatemia), and disturbed calcium-phosphate balance (1, 2). When this deficiency persists over the long term, it is referred to as chronic hypoparathyroidism, which is characterized by a sustained lack of PTH that results in ongoing hypocalcemia and often hyperphosphatemia.

Patients with chronic hypoparathyroidism may experience symptoms such as muscle cramps, fatigue, difficulty thinking clearly (“brain fog”), anxiety, depression, and reduced physical ability, and in severe cases, seizures or cardiac issues. The most common cause is surgery on the neck, like thyroid or parathyroid surgery. Less often, causes include autoimmune conditions, inherited syndromes, or genetic issues affecting the parathyroid glands (2). Chronic hypoparathyroidism is also associated with cardiovascular complications and an increased risk of developing kidney disease (3, 4).

FGF23 Reveals Mineral Imbalance in Hypoparathyroidism

In a recent study, researchers examined FGF23 levels in patients with chronic hypoparathyroidism (5). The results showed that, despite maintaining normal serum calcium and other biochemical markers, these patients often exhibited elevated FGF23 levels. This finding indicates the presence of subclinical disturbances in mineral metabolism that are not detected through standard biochemical assessments. Elevated FGF23 may reflect underlying dysregulation of mineral homeostasis, which could have implications for bone health and long-term mineral balance. The study underscores the potential value of monitoring FGF23 as a biomarker for ongoing mineral disturbances in the management of chronic hypoparathyroidism.

The BIOMEDICA FGF23 intact and FGF23 C-terminal ELISA kits were used in this study (5).

 FGF23 intact ELISA (cat. no.BI-20700) and FGF23 (C-terminal) (cat. no. BI-20702)   

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Elevated FGF23 Despite Biochemical Control Reveals Hidden Mineral Dysregulation in Chronic Hypoparathyroidism. Malagrinò M, Piazza A, Bisceglia N, Capra S, Cantone C, Pagotto U, Zavatta G. J Endocr Soc. 2025 Dec 20;10(2):bvaf217. doi: 10.1210/jendso/bvaf217. PMID: 41623900; PMCID: PMC12853065.

Abstract

Background: Fibroblast growth factor (FGF23) is a phosphate-regulating hormone and might be a biomarker of cardiorenal comorbidities in the general population. Its role in hypoparathyroidism is unclear.

Objective: To assess the prevalence of abnormal FGF23 concentrations in patients with chronic hypoparathyroidism and explore their associations with mineral metabolism and renal phosphate handling.

Design: Cross-sectional, observational study complemented by a retrospective longitudinal analysis of biochemical parameters over a median follow-up of 5 years.

Patients: Forty-eight consecutive patients with chronic hypoparathyroidism (mean age 60.6 ± 16.3 years; 85% women; 87.5% postsurgical) evaluated at an academic medical center between January 2023 and December 2024.

Measurements: Serum intact FGF23 levels, serum calcium (Ca) and phosphate (P), Ca × P product, PTH, 1,25-dihydroxyvitamin D [1,25(OH)₂D], estimated glomerular filtration rate (eGFR), and renal phosphate reabsorption [maximum rate of renal tubular reabsorption of phosphate/glomerular filtration rate (TmPO₄/GFR)].

Results: Elevated FGF23 levels were found in 71% of patients (mean 157.9 ± 92.4 pg/mL; reference range 23.2-95.4), despite adequate biochemical control (calcium 8.7 ± 0.8 mg/dL; phosphate 4.5 ± 0.8 mg/dL; Ca × P product 39.2 ± 6.8 mg²/dL²). FGF23 was associated with longer disease duration (P = .004), lower eGFR (P = .008), lower PTH (P = .03), reduced 1,25(OH)₂D (P = .016), and elevated Ca × P product (P = .036). Despite elevated FGF23, TmPO₄/GFR was paradoxically increased, suggesting impaired renal responsiveness. Female sex and Ca × P product were independent predictors of FGF23 levels.

Conclusion: FGF23 is frequently elevated in chronic hypoparathyroidism, indicating a disrupted phosphate metabolism, and its increase seems to be ineffective in promoting phosphate excretion, probably due to renal resistance mechanisms. Further studies are needed to clarify the role of FGF23 as a clinical biomarker, risk factor, and potential therapeutic target in this population.

Literature

1. Chronic Hypoparathyroidism-Current and Emerging Therapies. Khan S, Khan AA.Endocr Pract. 2025 Nov;31(11):1478-1487. doi: 10.1016/j.eprac.2025.07.011. Epub 2025 Jul 16. PMID: 40680836.
2. Unveiling the complexities of hypoparathyroidism: a comprehensive review of clinical manifestations, diagnosis, and novel therapies. Cetani F, Bertoldo F, Bononi M, Tarallo M, Camozzi V, Cipriani C, Palermo A, Pasquali D, Zavatta G. J Endocrinol Invest. 2026 Apr;49(4):725-746. doi: 10.1007/s40618-025-02760-9. Epub 2025 Dec 3. PMID: 41335198; PMCID: PMC13053346.
3. Skeletal and nonskeletal consequences of hypoparathyroidism. Silva BC. Arch Endocrinol Metab. 2022 Nov 11;66(5):642-650. doi: 10.20945/2359-3997000000553. PMID: 36382753; PMCID: PMC10118831.
4. Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review : Renal disease in chronic hypoparathyroidism. Gosmanova EO, Houillier P, Rejnmark L, Marelli C, Bilezikian JP.Rev Endocr Metab Disord. 2021 Jun;22(2):297-316. doi: 10.1007/s11154-020-09613-1. Epub 2021 Feb 18. PMID: 33599907; PMCID: PMC8087595.
5. Elevated FGF23 Despite Biochemical Control Reveals Hidden Mineral Dysregulation in Chronic Hypoparathyroidism. Malagrinò M, Piazza A, Bisceglia N, Capra S, Cantone C, Pagotto U, Zavatta G. J Endocr Soc. 2025 Dec 20;10(2):bvaf217. doi: 10.1210/jendso/bvaf217. PMID: 41623900; PMCID: PMC12853065.

 

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