Primary hyperparathyroidism: clinical forms and their features. Retrospective study

Background: Primary hyperparathyroidism (PHPT) is a disease characterized by autonomous production of parathyroid hormone (PTH) from one or more parathyroid glands. Over the past 50 years asymptomatic form of the disease have become more prevalent in developed countries.

Aims: To evaluate the clinical forms of PHPT presented in recent years and to specify the clinical and laboratory features in patients with symptomatic and asymptomatic forms of the disease.

Materials and methods: We reviewed medical records of 449 patients admitted to three Medical Centers (Saint-Petersburg, Russia) between 2011–2018. Anamnesis, anthropometric data, laboratory (PTH, serum total calcium and ionized calcium, phosphorus, alkaline phosphatase, 24-h calciuria level, 25(OH)D) and instrumental (ultrasonography, scintigraphy, CT/MRI scan, DXA) tests were analyzed.

Results: Patients’ average age was 59 years, with 93.1% women, and an F:M ratio of 13.5:1. Symptomatic form of PHPT was identified in 310 patients (69%), while 139 were asymptomatic. 4.2% of patients had PHPT as part of MEN syndrome. Almost half of the male population had urolithiasis and 45% of women had osteoporosis. Cardiovascular diseases were present in 64.4% of cases. 25(OH)D level was determined only in 20% of cases and was higher in asymptomatic patients (32.2 & 18.6 ng/ml, p = 0.003). Normocalcemic form of PHPT was diagnosed in 37 patients (8.2%) and was characterized not only by normocalcemia and lower PHT level, but also by smaller adenoma size (p = 0.01) and hypocalcemic syndrome after surgery.

Conclusions: Study results showed that symptomatic PHPT is more prevalent in the Russian population, that there are gender distinctions affecting the clinical presentation, and that the frequency of cardiovascular disease is high in this patient population. PHPT as part of MEN syndrome was detected in 4.2% of cases and required molecular genetic testing. Normocalcemic form of PHPT with postoperative hypocalcemia was present in every fourth patient. Rare determination of 25(OH)D level imposes the need of mandatory assessment of vitamin D supplementation and the reduction of its deficiency as part of the preoperative preparation of PHPT patients.

primary hyperparathyroidism, parathyroid neoplasms, parathyroid hormone, vitamin D, hypercalcemia

1. Bilezikian JP, Cusano NE, Khan AA, et al. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;2:16033. doi: https://doi.org/10.1038/nrdp.2016.33.

2. Дедов И.И., Мельниченко Г.А., Мокрышева Н.Г., и др. Первичный гиперпаратиреоз: клиника, диагностика, дифференциальная диагностика, методы лечения // Проблемы эндокринологии. – 2016. – Т. 62. – №6. – С. 40-77. [Dedov II, Melnichenko GA, Mokrysheva NG, et al. Primary hyperparathyroidism: the clinical picture, diagnostics, differential diagnostics, and methods of treatment. Problems of Endocrinology. 2016;62(6):40-77. (In Russ.)] doi: https://doi.org/10.14341/probl201662640-77.

3. Fraser WD. Hyperparathyroidism. Lancet. 2009;374(9684):145-158. doi: https://doi.org/10.1016/s0140-6736(09)60507-9.

4. AACE/AAES Task Force on Primary Hyperparathyroidism. The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. Endocr Pract. 2005;11(1):49-54. doi: https://doi.org/10.4158/EP.11.1.49.

5. Roizen J, Levine MA. Primary hyperparathyroidism in children and adolescents. J Chin Med Assoc. 2012;75(9):425-434. doi: https://doi.org/10.1016/j.jcma.2012.06.012.

6. Gasser RW. Clinical aspects of primary hyperparathyroidism: clinical manifestations, diagnosis, and therapy. Wiener Medizinische Wochenschrift. 2013;163(17-18):397-402. doi: https://doi.org/10.1007/s10354-013-0235-z.

7. Ferraz-de-Souza B. The evolution of primary hyperparathyroidism. Arch Endocrinol Metab. 2015;59(5):381-382. doi: https://doi.org/10.1590/2359-3997000000124.

8. Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168-178. doi: https://doi.org/10.1016/S0140-6736(17)31430-7.

9. Мокрышева Н.Г., Рожинская Л.Я., Перетокина Е.В., и др. Анализ основных эпидемиологических характеристик первичного гиперпаратиреоза в России (по данным регистра) // Проблемы эндокринологии. – 2012. – Т. 58. – №5. – С. 16-20. [Mokrysheva NG, Rozhinskaia LIa, Peretokina EV, et al. The results of analysis of the major epidemiological characteristics of primary hyperparathyroidism in Russia based on the registry data. Problems of Endocrinology. 2012;58(5):16-20. (In Russ.)] doi: https://doi.org/10.14341/Probl201258516-20.

10. Bilezikian JP, Brandi ML, Eastell R, et al. 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: https://doi.org/10.1210/jc.2014-1413.

11. Chiodini I, Cairoli E, Palmieri S, et al. Non classical complications of primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018;32(6):805-820. doi: https://doi.org/10.1016/j.beem.2018.06.006.

12. Ejlsmark-Svensson H, Rolighed L, Rejnmark L. Effect of parathyroidectomy on cardiovascular risk factors in primary hyperparathyroidism: a randomized clinical trial. J Clin Endocrinol Metab. 2019; 104(8):3223-3232. doi: https://doi.org/10.1210/jc.2018-02456.

13. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons Guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959-968. doi: https://doi.org/10.1001/jamasurg.2016.2310.

14. Pepe J, Cipriani C, Sonato C, et al. Cardiovascular manifestations of primary hyperparathyroidism: a narrative review. Eur J Endocrinol. 2017;177(6):297-308. doi: https://doi.org/10.1530/EJE-17-0485.

15. Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115-125. doi: https://doi.org/10.1038/nrendo.2017.104.

16. McMahon DJ, Carrelli A, Palmeri N, et al. Effect of parathyroidectomy upon left ventricular mass in primary hyperparathyroidism: a meta-analysis. J Clin Endocrinol Metab. 2015;100(12):4399-4407. doi: https://doi.org/10.1210/jc.2015-3202.

17. Lotito A, Teramoto M, Cheung M, et al. Serum parathyroid hormone responses to vitamin D supplementation in overweight/obese adults: a systematic review and meta-analysis of randomized clinical trials. Nutrients. 2017;9(3):241. doi: https://doi.org/10.3390/nu9030241.

18. Cusano NE, Cipriani C, Bilezikian JP. Management of normocalcemic primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018;32(6):837-845. doi: 10.1016/j.beem.2018.09.009.