Meta-analysis on the effect of mild primary hyperparathyroidism and parathyroidectomy upon arterial stiffness

Context current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold-standard method for assessing aortic stiffness, which predicts cardiovascular morbidity and mortality. Objective Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. Data sources PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library Study selection Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Data extraction Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Data synthesis Nine observational studies and one RCT were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT as compared to controls (MD=1.18, 0.67 to 1.68, p<0.0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD= -0.48, -0.88 to -0.07, p=0.022). Conclusion Aortic stiffness is increased in patients with mild pHPT, supporting the notion that also mild pHPT is associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

Hereditary Cushing’s syndrome caused by primary bilateral macronodular adrenal hyperplasia due to ARMC5 mutation with concomitant primary hyperparathyroidism: the first known case in Russia

Primary bilateral macronodular adrenal hyperplasia (PBMAH), a genetically heterogeneous disease, is a rare cause of Cushings syndrome. Until recently, few cases were attributed to mutations in known genes. However, in 2013, ARMC5, a newly discovered tumor suppressor gene, was identified. Further studies have shown that mutations in the ARMC5 gene are found in 2555% of all PBMAH cases. This article describes a clinical case of hereditary Cushings syndrome caused by PBMAH in a 37-year old patient. The patients family history is remarkable for the presence of Cushings syndrome and PBMAH in the patients mother. Bilateral adrenalectomy was performed as the treatment of choice. Genetic analysis using whole-exome sequencing confirmed the hereditary cause of the disease, revealing a germline heterozygous mutation in the ARMC5 gene. The patient also had concomitant mild primary hyperparathyroidism, which had not been observed before in genetic carriers with the ARMC5 mutation.

Hypercalcaemia during pregnancy: Review of maternal and fetal complications, investigations, and management

Introduction Asymptomatic mild primary hyperparathyroidism is increasingly being identified during pregnancy. Recent studies have demonstrated inconsistent findings with regard to pregnancy complications and the need for surgical intervention during pregnancy. Method A retrospective audit of outcomes of pregnancies complicated by hypercalcaemia over a 15-year period was performed. Results Twenty-nine pregnancies to 26 women with hypercalcaemia were identified, corresponding to 37 cases per 100,000 deliveries. Hypercalcaemia was due to primary hyperparathyroidism in 90% of cases, with mean serum calcium of 2.89 mmol/l and mean ionised calcium 1.43 mmol/l. Four women underwent successful neck exploration during pregnancy. Pregnancy complications were limited to three cases of pre-eclampsia and one case of symptomatic neonatal hypoparathyroidism. Conclusion Close observation without surgical intervention would seem reasonable in women with mild hypercalcaemia during pregnancy.

The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism

Context Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.