Explore the vast range of titles available.

The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of \"Hyperparathyroidism. Primary\" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized.

Hyperparathyroidism is due to increased activity of the parathyroid glands, either from an intrinsic abnormal change altering excretion of parathyroid hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal change affecting calcium homoeostasis stimulating production of parathyroid hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third most common endocrine disorder, with the highest incidence in postmenopausal women. Asymptomatic disease is common, and severe disease with renal stones and metabolic bone disease arises less frequently now than it did 20–30 years ago. Primary hyperparathyroidism can be cured by surgical removal of an adenoma, increasingly by minimally invasive parathyroidectomy. Medical management of mild disease is possible with bisphosphonates, hormone replacement therapy, and calcimimetics. Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. However, the biochemical definition of vitamin D deficiency and its treatment are subject to much debate. Secondary hyperparathyroidism as the result of chronic kidney disease is important in the genesis of renal bone disease, and several new treatments could help achieve the guidelines set out by the kidney disease outcomes quality initiative.

Key Words: primary hyperparathyroidism, epidemiology, incidence, prevalence

An increased risk of fractures in primary hyperparathyroidism (PHPT) has been reported in a number of relatively small studies. Performing a systematic literature search, we identified available studies and calculated common estimates by pooling results from the individual studies in a meta-analysis. Searching EMBASE and PubMed, we identified published studies reporting the risk of fractures in PHPT compared to a control group. We calculated odds ratio (OR) with 95% confidence interval (CI). A total of 804 studies were identified of which 12 studies were included. Risk of any fracture was increased compared to controls (OR 2.01; 95% CI, 1.61-2.50; I2 46%, 5 studies). Analysis of fracture risk at specific sites showed an increased risk of fracture at the forearm (OR 2.36; 95% CI, 1.64-3.38; I2 0%, 4 studies) and spine (OR 3.00; 95% CI, 1.41, 6.37, I2 88%, 9 studies). Risk estimate for hip fractures was non-significantly increased (OR 1.27; 95% CI, 0.97-1.66; I2 0%, 3 studies). Risk of vertebral fractures (VFx) was also increased if analyses were restricted to only studies with a healthy control group (OR 5.76; 95% CI, 3.86-8.60; I2 29%, 6 studies), studies including patients with mild PHPT (OR 4.22; 95% CI, 2.20-8.12; I2 57%, 4 studies) or studies including postmenopausal women (OR 8.07; 95% CI, 4.79-13.59; I2 0%, 3 studies). PHPT is associated with an increased risk of fractures. Although a number of studies are limited—it seems that the risk is increased across different skeletal sites including patients with mild PHPT and postmenopausal women.

Abstract Context Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with an impact on fracture incidence and bone mineral density after surgery have not been firmly established. Objective To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT). Design Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register. Setting Tertiary referral center. Patients or other participants Seven hundred nine patients with successful parathyroidectomy for pHPT and 2112 controls matched on sex, age, and municipality were included in the study. Main outcome measures Fracture incidence, absolute change, and ≥2.77% increase in bone mineral density of femoral neck, L2–L4, and distal third of radius at 1-year follow-up. Results Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (incidence rate ratio for the highest tertile 220– mg/d 0.29, 95% confidence interval 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin, and adenoma weight were all associated with bone mineral density recovery after surgery. Conclusion Twenty-four-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT.

Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association. This work aimed to compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT. A retrospective matched-cohort study (2005-2020) was conducted at an integrated health-care delivery system in Southern California. Women aged 18 to 44 years were included. Patients with a biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). Main outcome measures included achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care). The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI, 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with coexisting PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (P = .023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n = 22), during (n = 5), or after pregnancy/never (n = 24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium less than 11.5 mg/dL (2.9 mmol/L). We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).

This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for “Primary hyperparathyroidism” and “Malignant neoplasm”. Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13–0.25; I2 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06–0.08; I2 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03–0.07; I2 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23–1.33; I2 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy.

Primary hyperparathyroidism (PHPT) caused by double adenoma may carry a higher risk of failure to cure. We compared outcomes in single adenoma (SA), double adenoma (DA) and four-gland hyperplasia (HP). Patients undergoing initial parathyroidectomy for PHPT were categorized by diagnosis. The primary outcome was persistent/recurrent disease postoperatively. Of 3408 patients, 81.3% had SA, 9.5% had DA, and 9.3% had HP. Rates of persistence/recurrence were 2.9%, 5.3%, and 4.5% in SA, DA, and HP, respectively (p = 0.281). Patients with persistence/recurrence had higher preoperative calcium (11.0 vs 10.7 mg/dl, p = 0.028) and PTH (96 vs 77 pg/ml, p = 0.015), and lower rates of IOPTH normalization (77% vs 96%, p < 0.001). On multivariable analysis, DA was associated with increased risk of persistent/recurrent disease (OR 3.0, p = 0.017). Most patients with DA are cured with removal of two glands, but approximately 5% experience disease persistence/recurrence. Low-normal final IOPTH was associated with lower risk of persistent/recurrent disease. •Double adenoma occurs in almost 10% of patients undergoing initial surgery for PHPT.•Rates of recurrent/persistent disease are similar in DA and four-gland hyperplasia.•In a multivariate model, DA is associated with higher risk of failure to cure.•Low-normal IOPTH is associated with decreased risk of persistence/recurrence.•Careful use of IOPTH may minimize the risk of failure to cure in DA.

Purpose This study aims to investigate the clinical and genetic features and change of clinical spectrum of primary hyperparathyroidism (PHPT) in children and adolescents. Methods The clinical and follow-up data of 74 pediatric patients (onset age ≤ 18 years) with PHPT during 1975–2022 were retrospectively analyzed. For comparison, patients were divided into four subgroups according to their time of diagnosis. Genetic analysis was conducted in 40 patients. Results Pediatric PHPT cases increased largely over time [34 cases (45.9%) in 2015–2022]. The rate of asymptomatic PHPT increased by time (14.7% in 2015–2022 vs. 0% before 2015), in accordance with routine screening of serum calcium becoming a more frequent reason for clinic visit (17.6% in 2015–2022 vs. 0% before 2015). Skeletal manifestation significantly decreased in recent years (64.7% in 2015–2022 vs. 100.0% in 1975–1994, P  < 0.05). Sixty-seven patients (90.5%) of the whole cohort underwent parathyroidectomy. Atypical parathyroid adenoma and parathyroid carcinoma occurred in 13.4% and 4.5% of the surgical cases, respectively. Recurrence and persistence of PHPT were observed in 17.9% of postsurgical patients. Germline rare variations (RVs) of PHPT-related genes were found in 42.5% (17/40) of all cases with genetic testing. Compared with no-variation group, the variation group had higher incidence of multiple parathyroid lesions (42.8% vs. 4.3%, P  = 0.014), and lower rate of benign lesions and higher rate of recurrence and persistence. Conclusion Milder cases of Pediatric PHPT are coming to clinical attention probably due to routine lab testing. Genetic testing is recommended for pediatric PHPT patients.

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development.