The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study

Background Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. Methods Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9–15 months after PTX (PTX group) or 9–15 months after diagnosis (non-PTX group). Results At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median − 4% vs. − 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80–89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. Conclusion Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Assessment of the prevalence of anemia in patients with primary hyperparathyroidism: a single-center observational study

BACKGROUND: The combination of primary hyperparathyroidism (PHPT) with anemia was first described in 1931. It remains unclear whether PHPT is the direct cause of anemia, or it develops due to PHPT’s complications. The frequency of PHPT-­associated anemia in the Russian population is unknown.AIM: To assess the prevalence of anemia in patients with PHPT admitted to the Department of Parathyroid Glands Pathology in the Endocrinology Research Centre from January 2017 to August 2020.MATERIALS AND METHODS: The study included patients with PHPT over 18 years old. A single-center observational one-stage one-sample uncontrolled study was carried out. We analyzed laboratory and instrumental data obtained during inpatient examination in accordance with the standards of medical care. Statistical analysis was performed using Statistica 13 (StatSoft, USA) and SPSS (IBM, USA) software packages.RESULTS: The study included 327 patients with PHPT, 28 (9%) men and 299 (91%) women. The median age was 59 years [51; 66]. 26 patients (8%) with anemia were identified. Statistically significant differences between patients with and without anemia were found only in the GFR. Comparison of patients with and without anemia didn’t reveal any significant differences in the incidence of PHPT’s complications.Significant differences in serum hemoglobin concentration and average hemoglobin concentration in erythrocytes were revealed between patients with and without vertebrae fractures. In the group of patients without compression fractures these parameters were higher.In the subgroup of patients with total calcium concentration above 3 mmol/L and PTH above 3 normal values, the incidence of anemia reached 21% (95% CI: 10%; 35%). Within this group we revealed tendencies to higher levels of PTH, ionized calcium and osteocalcin in patients with anemia.CONCLUSION: In general, there was no correlation between hypercalcemia, the degree of PTH elevation and the presence of anemia in patients with PHPT. However, in the subgroup of patients with severe hypercalcemia, there was a relationship between the concentration of PTH, ionized calcium and the presence of anemia. In patients with PHPT and vertebral fractures, significantly lower concentrations of blood hemoglobin and hemoglobin in erythrocytes were observed.

Vitamin D Supplementation in Sarcoidosis: A Double-Edged Sword

Sarcoidosis is complicated by disordered vitamin D and calcium metabolism, which has important implications on disease activity and bone health. Although the majority of the patients with sarcoidosis are typically deficient in 25-hydroxyvitamin D, repletion of vitamin D is controversial in light of the hypercalcemia risk. Presently, there are no clear guidelines regarding vitamin D supplementation as a part of osteoporosis prevention in patients with vitamin D deficiency and sarcoidosis. We report a patient with sarcoidosis who presented with severe hypercalcemia following vitamin D supplementation and review the debated role of vitamin D supplementation in vitamin D-deficient sarcoid patients.

Concomitant familial hypocalciuric hypercalcemia and single parathyroid adenoma: a case report

Background Primary hyperparathyroidism (PHPT) is a common endocrine disorder and the most frequent benign cause of hypercalcemia. PHPT is characterized by autonomous hypersecretion of parathyroid hormone (PTH), regardless of serum calcium levels. Familial hypocalciuric hypercalcemia (FHH) is a rare, benign syndrome only affecting the regulation of calcium metabolism. FHH is an autosomal-dominant genetic disease with high penetrance, caused by an inactivating variant in the CASR gene encoding the calcium-sensing receptor (CaSR). We present a unique case of concomitant PHPT and FHH without clinically actionable variants in MEN1. Case presentation A 47-year-old Caucasian man with severe hypercalcemia, genetic FHH, and initially normal parathyroid scintigraphy was referred for endocrine evaluation due to nonspecific symptoms. Biochemical evaluation showed elevated serum ionized calcium and PTH. The calcium–creatinine clearance ratio was low. All other biochemical measures were normal, including kidney function. Genetic evaluation was redone and confirmed FHH. A new parathyroid scintigraphy showed a significant single adenoma corresponding to the lower left gland. The patient underwent parathyroidectomy, and a parathyroid adenoma was removed. A reduced level of hypercalcemia persisted due to FHH. Conclusions The correct diagnosis of the underlying cause of hypercalcemia is important to ensure the right treatment. Patients with FHH should avoid operative treatment, and PHPT should be differentiated from MEN1 to determine whether surgery should include parathyroidectomy with removal of one adenoma or 3.5 hyperplastic parathyroid glands.

Parathyroid hormone-independent hypercalcemia and hypercalciuria of a patient with nephrolithiasis and nephrocalcinosis and impaired vitamin D metabolism due to a defect in the CYP24A1 gene

Hypercalcemia associated with impaired vitamin D metabolism is a rare autosomal recessive disorder. The mechanism of this pathology is the impairment of inactivation of active metabolites of vitamin D because of mutations in the CYP24A1 gene, which leads to an increase of calcium absorption and the development of hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. The phenotype of the disease ranges from severe forms which are diagnosed in early infancy (severe hypercalcemia associated with dehydration, vomiting, nephrocalcinosis, and sometimes death) to milder forms, that often are diagnosed in adulthood and manifested with recurrent nephrolithiasis and nephrocalcinosis. Differential diagnosis is carried out with the most common causes of hypercalcemia: primary hyperparathyroidism and malignant neoplasms. To diagnose, the determination of vitamin D metabolites and genetic research are used. As a treatment for mild forms, it is recommended to limit dairy products, to keep a drinking regimen, to refuse taking vitamin D and calcium preparations, and use of sunscreens. The article presents a clinical case of parathyroid hormone-independent hypercalcemia due to mutation of the CYP24A1 gene of a 20-year-old patient suffering from nephrolithiasis and nephrocalcinosis since the age of 16 with a confirmed violation of vitamin D metabolism.