Cardiovascular and metabolic status in patients with primary hyperparathyroidism: a single-center experience.

Introduction: Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies. Methods: 838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688). Results: There were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2. Discussion: The present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT.

The Russian registry of primary hyperparathyroidism, latest update.

Introduction: Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation. Materials and methods: The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/). Results: The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1, CDC73, RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol. Conclusion: The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.

Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study.

BACKGROUND: Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT. METHODS: One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers. RESULTS: 45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery. CONCLUSION: PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.

Multiple Metastases of Parathyroid and Papillary Thyroid Carcinoma in a Female Patient Treated with Long-Term Hemodialysis.

Parathyroid cancer is a rare, clinically aggressive malignancy with a prevalence of approximately 0.005% relative to all carcinoma cases and 1-5% among patients with primary hyperparathyroidism. Prognosis largely depends on the extent of the primary surgery. Non-radical surgical treatment increases the risk of local and distant metastases of the parathyroid cancer associated with limited treatment options. The combination of thyroid and parathyroid disorders has been described rather well for the general population; however, cases of parathyroid and thyroid carcinoma in the same patient are extremely rare (1 case per 3000 patients with parathyroid disorders). We present a rare clinical case of combination of parathyroid and thyroid cancers with metastases of both tumors to the neck lymph nodes in a woman with a mutation in the MEN1 gene (NM_130799.2): c.658T > C p.Trp220Arg (W220R), who has been exposed to radiation for 20 years before diagnosis of thyroid cancer and received renal replacement therapy with long-term hemodialysis before the diagnosis of parathyroid cancer. The patient underwent several surgeries because of metastases of the parathyroid cancer in the neck lymph nodes. Surgeons used intraoperative navigation methods (single-channel gamma detection probe, Gamma Probe 2, and fluorescence angiography with indocyanine green (ICG)) to clarify the volume of surgery. Currently, the patient is still in laboratory remission, despite the structural recurrence of tumors.

The Russian Registry of Chronic Hypoparathyroidism.

INTRODUCTION: Chronic hypoparathyroidism is a relatively rare disease associated with multicomponent medical therapy and various complications. The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool to enhance quality of medical care, as well as to determine the optimal clinical and therapeutic approaches, and prognostic markers of the disease. THE AIM: of this study is to estimate the clinical and biochemical profile, long-term complications, medical therapy and disease control of the patients with chronic postsurgical and non-surgical hypoparathyroidism. MATERIALS AND METHODS: the cross-sectional, observational, continuous study was based on the Russian Registry of patients with hypoparathyroidism. 544 patients from 63 regions of the Russian Federation were included in this study. RESULTS: The majority of cases had postsurgical etiology (88.4%). Postsurgical hypoparathyroidism prevailed in females (р<0.001). About a half of patients had blood calcium and phosphorus targets, 56 and 52% respectively. Nephrolithiasis was confirmed in 32.5%, nephrocalcinosis - in 12.3% of cases. The risk of nephrocalcinosis/nephrolithiasis increased by 1.85 times with disease duration more than 4.5 years. The cataract was found in 9.4%. The cut-off point for the development of cataracts was 9.5 years, with a 6.96-fold increased risk. The longer duration of hypoparathyroidism of any etiology was associated with more frequent cataract (p=0.0018).We found brain calcification in 4%, arrhythmias in 7.2% and neuropsychiatric symptoms in 5.15% of cases. Generally, the BMD in the studied group corresponded to age values, and there was no evidence for the phenomenon of high bone density. TBS was consistent with normal bone microarchitectonics. In our study, the majority of patients (83.5%) was treated with standard therapy of calcium and vitamin D supplements. 5 patients with severe disease course were treated with rhPTH (1-34). CONCLUSIONS: Analysis of the presented database indicates insufficient diagnosis of the complications associated with chronic hypoparathyroidism. Overall, hypoparathyroidism is associated with higher risks of renal stone formation, decreased GFR, cataract especially in patients with longer duration of disease.

Serum circulating miRNA-342-3p as a potential diagnostic biomarker in parathyroid carcinomas: A pilot study.

OBJECTIVE: To compare the serum miRNA expression profiles between patients with benign and malignant parathyroid tumours. BACKGROUND: Despite recent advances in molecular biology, a histological tissue biopsy is still the method of choice used to diagnose most cancers. The preoperative cytology is not an applicable method for diagnosis of parathyroid cancer (PC); therefore, huge interest exists in terms of finding alternative methodologies to seek specific cancer biomarkers. DESIGN: A retrospective cross-sectional study. PATIENTS AND METHODS: Serum samples of patients with PC (n = 13) and parathyroid adenoma (PA) (n = 11), age (p = .999) and sex (p = .999) were matched and examined via the simultaneous comparative expression analysis of 754 microRNAs (miRNAs). The «TaqMan OpenArray Human MicroRNA Panel¼ (Applied Biosystems) was used to conduct real-time PCRs using the «QuantStudio 12К Flex¼ station (Life Technologies). RESULTS: According to the results of a pilot study, significant changes in expression levels between the PC group and the PA group (control) (p < .05) were observed for 17 miRNAs. Among them, the downregulation of miRNA-342-3p met the Benjamini-Hochberg adjustment criteria for multiple comparisons (p = .02). CONCLUSIONS: Serum miRNA-342-3p could be a promising biomarker for PC to improve diagnosis and prognosis.

Denosumab for management of severe hypercalcemia in primary hyperparathyroidism.

Hypercalcemic crisis is a severe but rare complication of primary hyperparathyroidism (PHPT), and data on denosumab treatment of patients with this disease is still very limited. The aim of this paper is to investigate the hypocalcemic effect of denosumab in PHPT patients with severe hypercalcemia when surgery should be delayed or is impossible for some reasons. We performed a retrospective study of 10 patients. The analysis included the use of biochemical markers of calcium-phosphorus metabolism, which were followed after the administration of 60 mg of denosumab. The trend to calcium reduction was already determined on the 3rd day after denosumab administration. In most cases the decrease in serum calcium level to the range of 2.8 mmol/L on average or lower was observed on the 7th day (P = 0.002). In addition to a significant increase in calcium levels we confirmed a significant increase in the estimated glomerular filtration rate on 7th day (P = 0.012). After that, seven patients underwent successful parathyroidectomy and achieved eucalcemia or hypocalcemia, one patient developed the recurrence of parathyroid cancer after initial surgery, while two patients with severe cardiovascular pathology refused surgery. Our study shows that denosumab is a useful tool in PHPT-associated hypercalcemia before surgery or if surgery is contraindicated.

Adrenocorticotropic hormone-producing pheochromocytoma: A case report.

INTRODUCTION: Cases of ectopic production of adrenocorticotropic hormone are considerably rare, but persistent in clinical practice. Extremely rare cases of ectopic production, such as via pheochromocytoma secretion, require special clinical attention and prior knowledge. It is important to understand the diagnostic algorithm for identifying ectopic sources of adrenocorticotropic hormone production. PRESENTATION OF CASE: In this clinical vignette we report a patient with a complex variety of clinical symptoms and no discernable cause for hypercriticism. Our clinical case outlines the diagnostic struggles, treatment challenges and surgical tactic for management of a rare ectopic ACTH producing pheochromocytoma. DISCUSSION: Highly variable clinical manifestations of ectopic ACTH producing pheochromocytoma, with typical signs of Cushing's syndrome and pheochromocytoma account for significant diagnostic difficulties and low incidence of verification of this pathology. Correction of symptoms and patient stabilization are of utmost importance throughout treatment. CONCLUSION: ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma is extremely rare, but should be considered as a possible source for ACTH production. The diagnostic challenges of this condition can be met with confidence when a strict search protocol is conducted for detection of ACTH source.