Primary hyperparathyroidism in Russia according to the registry

BACKGROUND: There are no large-scale epidemiological studies on primary hyperparathyroidism (PHPT) in Russia. The high prevalence of the disease, the high risk of disability and death in this cohort of patients requires the study of the epidemiological and clinical structure of PHPT to determine the extent of medical care.

AIM: Evaluate the frequency of PHPT detection and characterize its clinical forms in Russia using an online registry.

METHODS: The object of the study is the database of the State Register of Patients with PHPT – 1914 patients from 71 regions of the Russian Federation. New cases of the disease, as well as dynamic indicators are recorded when patients visit outpatient clinics or medical institutions. The analysis of data made at the end of December 2017 was carried out. The following parameters were evaluated: demographic and clinical indicators; indicators of phosphorus-calcium metabolism, the main forms of PHPT and its course, the primary characteristic of PHPT in hereditary syndromes and parathyroid carcinoma. Results are presented as mean and standard deviations, or medians and quartiles; descriptive statistics of qualitative attributes – absolute and relative frequencies.

RESULTS: the total number of patients with PHPT in the registry on 31 of December 2017 was 1914 cases (0.001% of the population of the Russian Federation). Identification of PHPT was 1.3 cases per 100 thousand of the population in Russia, 7.6 cases in Moscow, 6.1 cases per 100 thousand in the Moscow region. The average age of patients at the time of diagnosis was 55.6 ± 10 years. The active phase of the disease was registered in 84.6% of patients (1620/1914), most of whom had a symptomatic PHPT – 67.1% (1087/1620), and 32.9% – a asymptomatic disease (533/1620). Symptomatic disease with visceral complications was detected in 15.8% cases (172/1087), with bone complications in 48.4% (526/1087). The mixed form of the disease was detected in 35.8% of patients with manifest form (389/1087). Normocalcemic variant PHPT (nPHPT) was registered in 14.5% cases (234/1620). Sporadic PHPT occurs in 83% of cases (1592/1914). 326 patients (17%) had a suspicion for hereditary form of the disease: average age was 31.2 ± 12.3 years. A genetic analysis was conducted in 61 patients (3.2%): showed the mutation in the MEN1 gene in 2.9% of cases (55/1914) and the mutation in the CDC73 gene – in 0.3% of cases (6/1914) (HPT-JT syndrome). Parathyroid carcinoma was confirmed in 1.8% of all patients (35/1914). Surgical treatment was performed in 64.5% of patients (1234/1914). Remission was achieved in 94% of cases (1160/1234), in 6% of cases relapse after surgical treatment or persistence of PHPT was recorded.

CONCLUSION: detection of PHPT in the Russian Federation raised in comparison to 2016, which is associated with an active start of registration of patients in the regions. At this stage, it is necessary to modify the principles of registration and control, to make a platform for gathering information and calculating the necessary volumes of medical care for PHPT patients.

primary hyperparathyroidism, detection of primary hyperparathyroidism, registry of patients with primary hyperparathyroidism, normocalcemic primary hyperparathyroidism, mild primary hyperparathyroidism, parathyroid cancer

1. Mokrysheva NG. The primary hyperparathyroidism: the actual conception of the issue. Treatment and prevention. 2013; (2):143-152.

2. Mokrysheva NG, Gulyaeva SS, Rozhinskaya LYa, et al. The severe course of hyperparathyroidism in the elderly: clinical cases. Problems of endocrinology. 2009;55(1);33-35.

3. Castellano E, Tassone F, Attanasio R, et al. Mild primary hyperparathyroidism as defined in the Italian Society of Endocrinology’s Consensus Statement: prevalence and clinical features. J Endocrinol Invest. 2016; 39(3):349-354. doi: https://doi.org/10.1007/s40618-015-0412-6

4. Bollerslev J, Marcocci C, Sosa M, et al. Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism. Eur J Endocrinol. 2011; 165(6):851-864. doi: https://doi.org/10.1530/EJE-11-0589

5. Silverberg SJ, Bilezikian JP. Evaluation and management of primary hyperparathyroidism. J Clin Endocrinol Metab. 1996; 81(6):2036-2040. doi: https://doi.org/10.1210/jcem.81.6.8964825

6. Allerheiligen DA, Schoeber J, Houston RE, et al. Hyperparathyroidism. Am Fam Physician. 1998; 57(8):1795-1802.

7. 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

8. Potts JT, Ackerman IP, Barker CF, et al. Diagnosis and management of asymptomatic primary hyperparathyroidism. National Institutes of Health Consensus Development Conference. October 29-31, 1990. Consens Statement. 1990; 8(7):1-18.

9. Bilezikian JP, Potts JT Jr, Fuleihan Gel-H, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st Century. J Clin Endocrinol Metab. 2002;87(12):5353–5361. doi: https://doi.org/10.1210/jc.2002-021370.

10. Eastell R, Arnold A, Brandi ML, et al. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009;94(2):340–350. doi: https://doi.org/10.1210/jc.2008-1758

11. 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

12. Dedov II, Vasil’eva TO, Rozhinskaia LIa, Mokrysheva NG. Epidemiology of primary hyperparathyroidism. Problems of endocrinology. 2010;56(5):3-7. doi: https://doi.org/10.14341/probl20105653-7

13. Silverberg SJ. Vitamin D deficiency and primary hyperparathyroidism. J Bone Miner Res. 2007;22 Suppl 2:V100-V104. doi: https://doi.org/10.1359/jbmr.07s202

14. Silverberg SJ, Clarke BL, Peacock M, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3580-3594. doi: https://doi.org/10.1210/jc.2014-1415

15. Dedov II, Melnichenko GYa, Rozhinskaya LYa, et al. Clinical recommendations. Primary hyperparathyroidism (PHPT): clinic, diagnostics, differential diagnostics, methods of treatment. Manual for doctors. Moscow: Print; 2017.

16. Yeh MW, Ituarte PH, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013; 98(3):1122-1129. doi: 10.1210/jc.2012-4022

17. Yu N, Donnan PT, Murphy MJ, Leese GP. Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK. Clin Endocrinol (Oxf). 2009; 71(4):485-493. doi: https://doi.org/10.1111/j.1365-2265.2008.03520.x

18. Mokrysheva NG. Primary hyperparathyroidism: epidemiology, clinic, modern principles of diagnosis and treatment. [dissertation abstract] Moscow; 2011. 44 p. http://medical-diss.com/medicina/pervichnyy-giperparatireoz-epidemiologiya-klinika-sovremennye-printsipy-diagnostiki-i-lecheniya

19. De Geronimo S, Romagnoli E, Diacinti D, et al. The risk of fractures in postmenopausal women with primary hyperparathyroidism. Eur J Endocrinol. 2006;155(3):415-420 doi: https://doi.org/10.1530/eje.1.02225

20. Castellano E, Attanasio R, Boriano A, et al. Sex difference in the clinical presentation of primary hyperparathyroidism: influence of menopausal status. J Clin Endocrinol Metab. 2017; 102(11):4148-4152. doi: https://doi.org/10.1210/jc.2017-01080

21. Mamedova EO, Mokrysheva NG, Rozhinskaya LYa. Characteristics of primary hyperparathyroidism in young patients. Problems of endocrinology. 2018; 64(3):163-169. doi: 10.14341/probl9399

22. Eller-Vainicher C, Chiodini I, Battista C, et al. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res., 2009; 24(8):1404-1410. doi: https://doi.org/10.1359/jbmr.090304

23. Pardi E, Borsari S, Saponaro F, et al. Mutational and large deletion study of genes implicated in hereditary forms of primary hyperparathyroidism and correlation with clinical features. PLoS One. 2017;12(10):e0186485. doi: 10.1371/journal.pone.0186485

24. Van Leeuwaarde RS, de Laat JM, Pieterman CR, et al. The future: medical advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer, 2017;2 4(10):T179-T193. doi: https://doi.org/10.1530/ERC-17-0225

25. Busaidy N, Jimenez C, Habra M, et al. Parathyroid carcinoma: a 22-year experience. Head Neck, 2004; 26(8):716-726 doi: https://doi.org/10.1002/hed.20049