Primary hyperparathyroidism (PHT) is the third most common endocrine disorder in men and women after diabetes mellitus and thyroid disease and one of the most frequent causes of osteoporosis and fractures among the secondary osteopathy. PHT refers to socially significant problems in connection with involvement in the pathological process of the majority of organs and system In recent years, the conception of epidemiology, clinic and tactics of management of patients with PHT has changed due to significant increase of morbidity at the expense of identification of mild forms of disease. The modern management concept tactics depends on clinical manifestations. Bearing in mind the importance of the problem under consideration, the working group was set up for the development of federal recommendations on the treatment of PHT based on the principles of evidence-based medicine. The experience accumulated by the domestic and international experts was summarized in the federal clinical guidelines on PHT.

SummaryParathyroid carcinoma is an extremely rare disorder with little treatment options. It could be misdiagnosed in medical centers with little experience in management of such cases. Our clinical case shows that the initial misdiagnosis of a parathyroid carcinoma in a young woman has led to the development of multiple lung metastases, thus making its treatment hardly possible. Initiation of treatment with sorafenib – a multi-kinase inhibitor approved for treatment of different types of cancer but not parathyroid carcinoma – has led to a significant decrease in the size of lung metastases and has prevented the progression of hyperparathyroidism, which is usually severe in cases of parathyroid carcinoma. The detection of a germline CDC73 mutation in this patient has raised additional concerns about the necessity of periodic screening for early detection of renal, jaw and uterine lesions.Learning points:Diagnosis of parathyroid carcinoma may be challenging due to the absence of reliable diagnostic criteria. Thus, thorough histological examination is needed using immunohistochemical staining of resected tissue in suspicious cases. CDC73 genetic testing should be considered in patients with parathyroid carcinoma.Sorafenib may be a promising treatment of patients with parathyroid carcinoma with distant metastases.

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BackgroundPrimary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.ObjectiveTo identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.DesignWe enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.MethodsThe other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed.ResultsNGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8.ConclusionsHereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.