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Primer hiperparatiroidizmde klorür/fosfor ve klorür/magnezyum oranı

Yıl 2025, Cilt: 8 Sayı: 4, 731 - 738, 30.07.2025
https://doi.org/10.32322/jhsm.1721141

Öz

Arka Plan:
Giderek daha fazla tanınan bir endokrin bozukluk olan primer hiperparatiroidizm (PHPT), hiperkalsemik ve normokalsemik olmak üzere iki alt tipe ayrılmaktadır. Son dönem çalışmalarda, klorür/fosfor (Cl/P) ve klorür/magnezyum (Cl/Mg) oranları gibi biyokimyasal parametrelerin, PHPT’ye bağlı komplikasyonların tanısal değerlendirilmesi ve risk sınıflandırmasında yardımcı olabileceği öne sürülmektedir. Bu çalışmada, Cl/P ve Cl/Mg oranlarının PHPT alt tiplerini ayırt etmedeki tanısal ve öngörücü değerinin yanı sıra osteoporoz ve nefrolitiazis riskinin değerlendirilmesindeki potansiyel rolü araştırılmıştır.

Yöntem:
Bu retrospektif çalışmaya, 2019–2022 yılları arasında Ankara Bilkent Şehir Hastanesi’nde PHPT nedeniyle paratiroidektomi uygulanan 116 hasta dahil edilmiştir. Tüm hastalar, uluslararası kılavuzlara göre cerrahi endikasyonları karşılamaktaydı. Normokalsemik PHPT olguları, tekrarlayan normal kalsiyum düzeyleri ile birlikte sekonder nedenlerin dışlanmasıyla tanımlanmıştır. Hastaların preoperatif biyokimyasal parametreleri, görüntüleme bulguları ve komplikasyon profilleri analiz edilmiştir. Cl/P ve Cl/Mg oranları hesaplanarak Mann-Whitney U testi, Spearman korelasyon analizi ve ROC eğrisi analizi ile değerlendirilmiştir.

Bulgular:
Cl/P oranı, hiperkalsemik PHPT olgularında normokalsemik olgulara göre anlamlı düzeyde daha yüksek bulunmuştur (medyan 42,4 vs. 38,3; p = 0,0125) ve kemik mineral yoğunluğu ile pozitif korelasyon göstermiştir. Cl/P için belirlenen >43,6 eşik değeri, PHPT alt tiplerini ayırt etmede %80 özgüllük sağlamıştır (AUC: %64,1). Cl/Mg oranı alt tipler arasında anlamlı fark göstermemekle birlikte, nefrolitiazis riski ile anlamlı ilişki göstermiştir. ≤55 eşik değeri bu riski öngörmede %82,4 duyarlılık ve %66,7 özgüllük sunmuştur (AUC: %70,5; p = 0,0002).

Sonuç:
Cl/P ve Cl/Mg oranları, PHPT tanısal sürecini ve komplikasyon risk sınıflamasını destekleyen, düşük maliyetli ve kolay erişilebilir biyobelirteçler olarak umut vadetmektedir. Cl/P oranı, normokalsemik ve hiperkalsemik alt tiplerin ayrımında fayda sağlarken; Cl/Mg oranı, nefrolitiazis riski yüksek bireylerin belirlenmesinde etkili olmuştur. Bulgular, önceki çalışmalarla uyumludur ve bu oranların PHPT’nin klinik değerlendirme algoritmalarına entegre edilebileceğini düşündürmektedir.

Kaynakça

  • Bilezikian JP, Marcocci C, Khan AA, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-3569. doi:10.1210/jc.2014-1413
  • Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115-125. doi:10.1038/nrendo.2017.104
  • Maruani G, Hertig A, Paillard M, Houillier P. Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to calcium. Clin J Am Soc Nephrol. 2010;5(12):2174-2182.
  • Cusano NE, Bilezikian JP. Updates on the skeletal impact of hyperparathyroidism. Curr Opin Endocrinol Diabetes Obes. 2016;23(6):410-416.
  • Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99(10):3570-3579. doi:10.1210/jc.2014-1414
  • Chang R, Delgado A, Morales B, et al. The utility of chloride-to-phosphorus ratio in distinguishing normocalcemic from hypercalcemic primary hyperparathyroidism. Endocr Pract. 2023;29(5):559-566.
  • Cetani F, Pardi E, Marcocci C. Update on the clinical and therapeutic management of primary hyperparathyroidism. Endocr Pract. 2017; 23(10):1153-1166.
  • Johnson TM, He X, Wan J, et al. Elevated Cl/P ratio as a predictor of bone density decline in primary hyperparathyroidism. J Endocr Soc. 2024;8(2):122-129.
  • Smith TA, Gupta V, Luo J. Exploring the role of magnesium in primary hyperparathyroidism: a prospective cohort study. Clin Endocrinol (Oxf). 2024;91(1):72–80.
  • Filippiadis DK, Reisinger I, Ezziddin S, et al. Imaging and biochemical pitfalls in the diagnosis and follow-up of primary hyperparathyroidism. Eur Radiol. 2023;33(3):1920-1927.
  • Bollerslev J, Rejnmark L, Zahn A, et al. European Expert Consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE educational program of parathyroid disorders. Eur J Endocrinol. 2022;186(2): R33-R63. doi:10.1530/EJE-21-1044
  • Shariq MA, Inabnet WB, Valderamma S, Shifrin A. Impact of preoperative hypercalciuria on bone mineral density and renal function after parathyroidectomy in primary hyperparathyroidism. Surgery. 2020;168(1):149-154. doi:10.1016/j.surg.2020.02.004
  • Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99(10):3570-3579. doi:10.1210/jc.2014-1413
  • Kearns AE, Thompson GB. Medical and surgical management of hyperparathyroidism. Mayo Clin Proc. 2002;77(1):87-91. doi:10.4065/ 77.1.87
  • Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Mineral Res. 2022;37(11):2293-2314. doi:10.1002/jbmr.4677
  • Khan AA, Hanley DA, Rizzoli R, et al. Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int. 2017;28(1):1-19. doi:10.1007/s00198-016-3716-2
  • Kiriakopoulos A, Petralias A, Linos D. Classic primary hyperparathyroidism versus normocalcemic and normohormonal variants: do they really differ? World J Surg. 2018;42(4):992-997. doi:10. 1007/s00268-018-4512-2
  • Yu Y, Qiu J, Chuan F, Feng Z, Long J, Zhou B. The Ca-Cl/P ratio: a novel and more appropriate screening tool for normocalcaemic or overt primary hyperparathyroidism. Endocr Pract. 2024;30(3):231-238. doi: 10.1016/j.eprac.2023.12.004
  • Wright C, King D, Small M, Gibson C, Gardner R, Stack BC Jr. The utility of the Cl:PO4 ratio in patients with variant versions of primary hyperparathyroidism. Otolaryngol Head Neck Surg. 2021;164(2):308-314. doi:10.1177/0194599820947009
  • Wright C, King D, Silva-Nas J, et al. Post-operative chloride phosphate and calcium phosphate ratios in hyperparathyroidism patients. J Surgical Endocrinol. 2022;4(1):129-135.
  • Wang Q, Li X, Chen H, et al. The chloride/phosphate ratio combined with alkaline phosphatase as a valuable predictive marker for primary hyperparathyroidism in Chinese individuals. Sci Rep. 2017;7(1):4868. doi:10.1038/s41598-017-05183-6
  • Saponaro F, Marcocci C, Apicella M, et al. Hypomagnesuria is associated with nephrolithiasis in patients with asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab. 2020;105(8):dgaa233. doi:10.1210/clinem/dgaa233
  • Yin M, Liu Q, Wang Q, et al. Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China. Endocr Connect. 2021;10(11):1387-1392. doi:10.1530/EC-21-0267
  • Na D, Tao G, Shu-Ying L, et al. Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study. BMC Endocr Disord. 2021;21(1):170. doi:10.1186/s12902-021-00838-y
  • Ong GS, Walsh JP, Stuckey BG, et al. The importance of measuring ionized calcium in characterizing calcium status and diagnosing primary hyperparathyroidism. J Clin Endocrinol Metab. 2012;97(9):3138-3145. doi:10.1210/jc.2012-1429

Clinical significance of chloride-to-phosphorus and chloride-to-magnesium ratios in primary hyperparathyroidism

Yıl 2025, Cilt: 8 Sayı: 4, 731 - 738, 30.07.2025
https://doi.org/10.32322/jhsm.1721141

Öz

Aims: Primary hyperparathyroidism (PHPT), a well-recognized endocrine disorder, is subclassified into hypercalcemic and normocalcemic forms. Recent studies suggest that biochemical ratios such as the chloride-to-phosphorus (Cl/P) and chloride-to-magnesium (Cl/Mg) ratios may aid in the diagnostic evaluation and risk stratification of PHPT-related complications. This study aimed to investigate the diagnostic and predictive utility of the Cl/P and Cl/Mg ratios in differentiating PHPT subtypes and assessing the risk of osteoporosis and nephrolithiasis.
Methods: This retrospective study included 116 patients who underwent parathyroidectomy for PHPT at Ankara Bilkent City Hospital between 2019 and 2022. All patients met surgical criteria based on international guidelines, and normocalcemic PHPT (N-PHPT) cases were defined by repeatedly normal calcium measurements and exclusion of secondary causes. Preoperative biochemical parameters, imaging findings, and complication profiles were analyzed. Cl/P and Cl/Mg ratios were calculated and evaluated using the Mann-Whitney U test, Spearman correlation, and receiver operating characteristic (ROC) analysis.
Results: The Cl/P ratio was significantly higher in hypercalcemic PHPT than in normocalcemic patients (median 42.4 vs. 38.3, p=0.0125) and was positively associated with bone mineral density. A Cl/P threshold of >43.6 yielded 80.0% specificity in distinguishing PHPT subtypes [area under the curve (AUC): 64.1%]. The Cl/Mg ratio, although not differing between subtypes, was significantly associated with nephrolithiasis risk, with a cut-off value of ≤55 providing 82.4% sensitivity and 66.7% specificity (AUC: 70.5%, p<0.001).
Conclusion: The Cl/P and Cl/Mg ratios show promise as low-cost, accessible biomarkers for enhancing diagnostic evaluation and risk stratification in PHPT. The Cl/P ratio demonstrated utility in distinguishing normocalcemic from hypercalcemic subtypes, while the Cl/Mg ratio effectively identified patients at increased risk of nephrolithiasis. These results are consistent with previous studies and support the potential integration of these indices into clinical assessment algorithms for PHPT.

Kaynakça

  • Bilezikian JP, Marcocci C, Khan AA, Potts JT Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561-3569. doi:10.1210/jc.2014-1413
  • Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115-125. doi:10.1038/nrendo.2017.104
  • Maruani G, Hertig A, Paillard M, Houillier P. Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to calcium. Clin J Am Soc Nephrol. 2010;5(12):2174-2182.
  • Cusano NE, Bilezikian JP. Updates on the skeletal impact of hyperparathyroidism. Curr Opin Endocrinol Diabetes Obes. 2016;23(6):410-416.
  • Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99(10):3570-3579. doi:10.1210/jc.2014-1414
  • Chang R, Delgado A, Morales B, et al. The utility of chloride-to-phosphorus ratio in distinguishing normocalcemic from hypercalcemic primary hyperparathyroidism. Endocr Pract. 2023;29(5):559-566.
  • Cetani F, Pardi E, Marcocci C. Update on the clinical and therapeutic management of primary hyperparathyroidism. Endocr Pract. 2017; 23(10):1153-1166.
  • Johnson TM, He X, Wan J, et al. Elevated Cl/P ratio as a predictor of bone density decline in primary hyperparathyroidism. J Endocr Soc. 2024;8(2):122-129.
  • Smith TA, Gupta V, Luo J. Exploring the role of magnesium in primary hyperparathyroidism: a prospective cohort study. Clin Endocrinol (Oxf). 2024;91(1):72–80.
  • Filippiadis DK, Reisinger I, Ezziddin S, et al. Imaging and biochemical pitfalls in the diagnosis and follow-up of primary hyperparathyroidism. Eur Radiol. 2023;33(3):1920-1927.
  • Bollerslev J, Rejnmark L, Zahn A, et al. European Expert Consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE educational program of parathyroid disorders. Eur J Endocrinol. 2022;186(2): R33-R63. doi:10.1530/EJE-21-1044
  • Shariq MA, Inabnet WB, Valderamma S, Shifrin A. Impact of preoperative hypercalciuria on bone mineral density and renal function after parathyroidectomy in primary hyperparathyroidism. Surgery. 2020;168(1):149-154. doi:10.1016/j.surg.2020.02.004
  • Eastell R, Brandi ML, Costa AG, D’Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014; 99(10):3570-3579. doi:10.1210/jc.2014-1413
  • Kearns AE, Thompson GB. Medical and surgical management of hyperparathyroidism. Mayo Clin Proc. 2002;77(1):87-91. doi:10.4065/ 77.1.87
  • Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Mineral Res. 2022;37(11):2293-2314. doi:10.1002/jbmr.4677
  • Khan AA, Hanley DA, Rizzoli R, et al. Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int. 2017;28(1):1-19. doi:10.1007/s00198-016-3716-2
  • Kiriakopoulos A, Petralias A, Linos D. Classic primary hyperparathyroidism versus normocalcemic and normohormonal variants: do they really differ? World J Surg. 2018;42(4):992-997. doi:10. 1007/s00268-018-4512-2
  • Yu Y, Qiu J, Chuan F, Feng Z, Long J, Zhou B. The Ca-Cl/P ratio: a novel and more appropriate screening tool for normocalcaemic or overt primary hyperparathyroidism. Endocr Pract. 2024;30(3):231-238. doi: 10.1016/j.eprac.2023.12.004
  • Wright C, King D, Small M, Gibson C, Gardner R, Stack BC Jr. The utility of the Cl:PO4 ratio in patients with variant versions of primary hyperparathyroidism. Otolaryngol Head Neck Surg. 2021;164(2):308-314. doi:10.1177/0194599820947009
  • Wright C, King D, Silva-Nas J, et al. Post-operative chloride phosphate and calcium phosphate ratios in hyperparathyroidism patients. J Surgical Endocrinol. 2022;4(1):129-135.
  • Wang Q, Li X, Chen H, et al. The chloride/phosphate ratio combined with alkaline phosphatase as a valuable predictive marker for primary hyperparathyroidism in Chinese individuals. Sci Rep. 2017;7(1):4868. doi:10.1038/s41598-017-05183-6
  • Saponaro F, Marcocci C, Apicella M, et al. Hypomagnesuria is associated with nephrolithiasis in patients with asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab. 2020;105(8):dgaa233. doi:10.1210/clinem/dgaa233
  • Yin M, Liu Q, Wang Q, et al. Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China. Endocr Connect. 2021;10(11):1387-1392. doi:10.1530/EC-21-0267
  • Na D, Tao G, Shu-Ying L, et al. Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study. BMC Endocr Disord. 2021;21(1):170. doi:10.1186/s12902-021-00838-y
  • Ong GS, Walsh JP, Stuckey BG, et al. The importance of measuring ionized calcium in characterizing calcium status and diagnosing primary hyperparathyroidism. J Clin Endocrinol Metab. 2012;97(9):3138-3145. doi:10.1210/jc.2012-1429
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Endokrinoloji
Bölüm Orijinal Makale
Yazarlar

Beril Turan Erdoğan 0000-0003-1391-0647

Esra Çopuroğlu 0000-0003-1615-3266

Gülsüm Karaahmetli 0000-0002-5883-3545

Fatma Dilek Dellal Kahramanca 0000-0003-0755-4543

Fatma Neslihan Çuhacı Seyrek 0000-0003-1042-3640

Hüsniye Başer 0000-0002-6371-2959

Oya Topaloğlu 0000-0003-2501-935X

Reyhan Ersoy 0000-0002-7437-1176

Bekir Çakır 0000-0001-7526-8827

Yayımlanma Tarihi 30 Temmuz 2025
Gönderilme Tarihi 17 Haziran 2025
Kabul Tarihi 14 Temmuz 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 8 Sayı: 4

Kaynak Göster

AMA Turan Erdoğan B, Çopuroğlu E, Karaahmetli G, vd. Clinical significance of chloride-to-phosphorus and chloride-to-magnesium ratios in primary hyperparathyroidism. J Health Sci Med /JHSM /jhsm. Temmuz 2025;8(4):731-738. doi:10.32322/jhsm.1721141

Üniversitelerarası Kurul (ÜAK) Eşdeğerliği:  Ulakbim TR Dizin'de olan dergilerde yayımlanan makale [10 PUAN] ve 1a, b, c hariç  uluslararası indekslerde (1d) olan dergilerde yayımlanan makale [5 PUAN]

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