Hungry bone syndrome (HBS) characterised by prolonged hypocalcemia, occurs commonly following parathyroidectomy in patients with primary hyperparathyroidism (PHPT). Although this complication is common, research in this field is very scarce. This study aimed to determine the incidence, characteristics of patients with HBS, and the effect of preoperative biochemical parameters on HBS.

In this retrospective study we enroled 144 patients with PHPT who underwent successful parathyroidectomy from January 2010 to January 2020. Preoperative and postoperative laboratory parameters were assessed. Logistic regression analysis was used to identify factors affecting the incidence of HBS.

One hundred six patients (73.6%) were women and the female-to-male ratio was 2.8-1. The median (IQR) age of all patients was 54 (19) years. HBS developed in 25 (17.36%) patients (5 men and 20 women, p = 0.425). Total calcium and parathyroid hormone preoperatively were significantly higher in patients with HBS, while serum phosphorus and magnesium levels did not differ statistically between the two groups. The resected parathyroid gland volume was higher in those with HBS compared to those without. Postoperatively, patients with HBS had longer hospital stays and lower serum phosphorus levels. However, these variables could not predict the occurrence of HBS after surgery in the performed regression model.

The patients with HBS had higher levels of calcium and parathyroid hormone preoperatively, along with larger resected parathyroid glands. Nevertheless, preoperative parameters were unable to predict HBS. Therefore, biochemical monitoring after surgery seems necessary to detect HBS and protect patients from severe hypocalcemia.

During 2024, there were many practice-changing innovations in the field of endocrinology, particularly related to the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs). From the substantial new evidence published in 2024, 10 studies are highlighted that offer critical information for clinicians who manage or comanage patients with endocrine disorders including prediabetes, diabetes, obesity, and hyperparathyroidism. Two of the 10 articles are focused on use of GLP-1RAs in multiple clinical settings not studied in the original GLP-1RA trials, including after bariatric surgery and before endoscopy. Two additional studies focused on GLP-1RA explore the risk for thyroid cancer in patients prescribed GLP-1RA and the effect of a GLP-1RA on chronic kidney disease in patients with type 2 diabetes. Three articles investigate opportunities for deintensification of insulin frequency or an alternate method of insulin delivery in patients with type 2 diabetes. One article explores the cardiometabolic effects of intermittent fasting in persons with prediabetes and type 2 diabetes. The last 2 articles explore the incidence of diabetes after SARS-CoV-2 infection and the skeletal effects of parathyroidectomy as a treatment of hyperparathyroidism. The results of each study have a direct effect on the delivery of care for patients with prediabetes, type 2 diabetes, and hyperparathyroidism.

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]).

SPECT/CT has been well established as a valuable technique in nuclear medicine parathyroid imaging, but most previous studies were done in patients with primary hyperparathyroidism. In this retrospective study, we examined the diagnostic performance of [99mTc]NaTcO4 / [99mTc]Tc-MIBI planar subtraction parathyroid scintigraphy (PS), SPECT/CT, and a combination of the two in a patient cohort consisting of mostly end-stage renal disease (ESRD) patients with secondary or tertiary hyperparathyroidism, using histopathological results as the reference standard.

Among 116 patients included, 98 (84.5%) had ESRD. The overall sensitivity of subtraction PS, SPECT/CT and combined interpretation was 69% (95% confidence interval: 64-73%), 67% (61-72%), and 79% (74-84%), while the specificity was 68% (59-76%), 71% (61-80%), and 60% (50-70%), respectively. For patients without ESRD with predominantly primary hyperparathyroidism, the sensitivity was 93% (70-99%), 89% (57-98%), and 100% (70-100%), and the specificity was 88% (76-94%), 87% (71-95%), and 84% (67-93%), respectively. For those with ESRD with predominantly tertiary and secondary hyperparathyroidism, the sensitivity was 67% (62-72%), 66% (60-71%), 78% (73-83%), and the specificity was 55% (42-67%), 57% (43-70%), and 43% (30-58%), respectively.

SPECT/CT was not superior to subtraction PS in ESRD patients with hyperparathyroidism. Combining these two techniques improves sensitivity, but likely with the expense of reduction in specificity. Both planar subtraction PS and SPECT/CT have suboptimal diagnostic performance in ESRD patients compared with non-ESRD patients where these techniques provide impressive sensitivity and specificity.

A giant parathyroid adenoma (GPTA) is a rare type of primary hyperparathyroidism (PHPT) characterized by a weight of at least 3.5 g. We report a case of a 24-year-old male patient who presented with generalized fatigue and pathological left humeral fracture, found to have a serum calcium level of 16.9 mg/dL and a parathyroid hormone (PTH) level of 3,164 pg/mL. A 5.4 g right inferior type E parathyroid adenoma was excised with normalization of PTH levels. His clinical course was complicated by hungry bone syndrome and required management by a multidisciplinary team involving internal medicine, endocrinology, endocrine surgery, orthopedic surgery, nephrology, thoracic surgery, and genetics.

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia. It is secondary to hypersecretion of parathyroid hormone (PTH) by the parathyroid glands. Today, PHTP is asymptomatic in 80-90% of cases. Its repercussions are mainly renal (nephrolithiasis, nephrocalcinosis, decline in renal function) and skeletal (osteoporosis, fractures), and should be systematically investigated. Diagnosis is only biological, and in its classic form relies on the association of hypercalcemia, inappropriate PTH (normal or elevated) and hypercalciuria. Diagnosis of normocalcemic forms, where only PTH is elevated, requires elimination of secondary hyperparathyroidism and confirmation of elevated PTH on two consecutive samples, over a 3 to 6 months period. Imaging evaluation, which combines neck ultrasound with scintigraphy or 18F-choline PET/CT, is of interest only if surgery is indicated. Surgical management of the hyperfunctioning parathyroid gland(s) is the only curative treatment for HPTP. Medical management concerns patients for whom surgery is not indicated, who present a surgical contraindication or who refuse surgery. The diagnosis of HPTP warrants contact with an endocrinologist to ensure its management.

Parathyroidectomy (PT) is commonly performed for hyperparathyroidism. We investigated the association between surgical subspecialty and adverse outcomes in patients undergoing PT.

This retrospective cohort analysis utilized the 2005-2018 National Surgery Quality Improvement Program (NSQIP) database. Current Procedural Terminology (CPT) codes were used to identify cases with a primary procedure of PT. Demographics, comorbidities, and complication incidences were compared between patients undergoing surgery by general surgeons or otolaryngologists using chi-square analyses. The independent effect of surgical subspecialty on adverse outcomes was analyzed using binary logistic regression.

49,667 (86.7%) PT performed by general surgeons and 7,595 (13.3%) by otolaryngologists were identified from 2005 to 2018. Chi-square analysis indicated that general surgery patients had lower incidences of obesity (42.0% vs. 44.6%; p < 0.001) and higher incidences of diabetes mellitus (8.1% vs. 5.8%; p < 0.001). Demographic characteristics that significantly differed between cohorts included race (p < 0.001) and age (p < 0.001). Unadjusted analyses indicated that otolaryngologist-performed PT had lower incidences of unplanned reoperation (0.9% vs. 1.1%; p = 0.048) and unplanned readmission (2.9% vs. 3.6%; p = 0.009). After adjusting for confounders, logistic regression analyses indicated that otolaryngologist-performed PT had increased odds of prolonged operation time (OR 1.605; 95% CI 1.475-1.746; p < 0.001). Significant differences in mortality, medical complications, and surgical complications were not found.

Surgical subspecialty is associated with PT operative time but is not associated with perioperative complications.

The online version contains supplementary material available at 10.1007/s12070-025-05436-1.

Primary hyperparathyroidism (PHPT) is a common endocrine disease especially in postmenopausal women and in older adults, with elevated parathyroid hormone (PTH) levels by parathyroid glands. The main symptoms of PHPT are hypercalcemia, often associated with hypercalciuria, urolithiasis and bone demineralization that results in osteopenia or osteoporosis and increases overall fracture risk. Parathyroidectomy is today the only definitive treatment for patients to prevent worsening of symptoms. Minimally invasive targeted approach for parathyroidectomy can be offered to patients with well-localized disease, and combined with intraoperative PTH monitoring, the success rate reaches 95-97%; with short operative time, low complications rates and decreased hospital costs. To date, minimally invasive parathyroidectomy (MIP) can be performed under local anesthesia and most patients can be discharged on the same day of surgery or the following morning. The aim of this article is to summarize the current evidence of MIP under local anesthesia and its clinical outcomes to assess the effectiveness and safety of this procedure.

We searched PubMed, Embase, Cochrane and Web of Science databases from their date of inception until 30th May 2024. Inclusion criteria consisted in articles from any country written in English reporting MIP under local anesthesia related clinical outcomes in humans. RCTs, quasi-RCTs, cross-sectional studies, retrospective and prospective cohort studies, case-control studies were included.

We identified 23 eligible studies that included 2470 adults (mostly female asymptomatic) with PHPT; follow-up duration varied from six months to 24 months. All studies were screened for assessments of quality based on Newcastle-Ottawa Scale and the risk of bias based on ROBIN-I of the included studies. The operative time, number of conversions to general anesthesia, hospital stay and complications was respectively: 43.86 minutes, with 114 conversions to general anesthesia, mean hospitalization time was 16.83±8.62 hours and complications reported in 71 patients. Previously of surgery, the abnormal parathyroid gland is localized using multiplexed ion beam imaging (MIBI) plus ultrasound (US) in 12 studies, only MIBI in three studies, thallium-technetium scan plus US in three studies, single-photon-emission computed tomography (SPECT) plus US in one study and a combination of MIBI, US, SPECT, CT and magnet resonance in one study. The mean preoperative value of PTH and serum calcium was 277.44 pg/mL and 11.49 mg/dL respectively; while the mean postoperative value of PTH and serum calcium was 46.18 pg/mL and 9.11 mg/dL respectively. At the definitive histology the most of pathology is adenoma with 542 cases reported, followed by hyperplasia with 35 cases and only 20 cases of carcinoma.

Focused mini-invasive parathyroidectomy under local anesthesia, guided by positive preoperative localization exams and accurate laboratory data, could be a feasible and effective surgical technique to cure primary hyperparathyroidism, with reduced operative time, a small surgical incision, shorter hospitalization stay and a lower occurrence of postoperative complications.

This study aims to investigate the clinical and genetic features and change of clinical spectrum of primary hyperparathyroidism (PHPT) in children and adolescents.

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.

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.

Milder cases of Pediatric PHPT are coming to clinical attention probably due to routine lab testing. Genetic testing is recommended for pediatric PHPT patients.

Parathyroid cancer (PC) presents clinically as a case of hyperparathyroidism associated with local compression symptoms. The definitive diagnosis of PC is complex as it requires unequivocal criteria of invasion in postoperative biopsy. Given the difficulty in confirming the diagnosis of PC, attempts have been made to address this problem through the search for biomarkers, mainly using immunohistochemistry. Within this theme, the phenomenon of epithelial-mesenchymal transition and cancer stem cell markers have been scarcely studied; this could eventually help discriminate between a diagnosis of parathyroid adenoma or carcinoma. On the other hand, identification of oncogenes and tumor suppressing genes, as well as epigenetic markers such as miRNAs, lncRNAs, and circRNAs all play a crucial role in tumorigenesis and have enormous potential as diagnostic tools. Furthermore, proteomic-based and inflammatory markers have also been described as diagnostic aids for this uncommon neoplasm. This review presents a clinical approach to the disease, as well as providing a state-of-the-art analysis of basic biomarkers in diagnosis and future projections in this field.

Persistent and recurrent primary hyperparathyroidism (PHPT) represent significant challenges in the management of PHPT. Persistent PHPT is defined as persistence of hypercalcemia following parathyroidectomy (PTX) or the recurrence of hypercalcemia within the first 6 months following surgery. Recurrent PHPT is defined as recurrence of hypercalcemia after 6 months following PTX and requires normalization of serum calcium prior to the recurrence. These conditions are often attributed to missed or ectopic glands, multiglandular disease, surgeon inexperience, or rare causes such as parathyromatosis and parathyroid carcinoma. Diagnosis requires a detailed biochemical evaluation, imaging studies, and exclusion of other causes of hypercalcemia as well as secondary causes of hyperparathyroidism. Preoperative imaging modalities, including neck ultrasound, SPECT-CT with 99m Tc-sestamibi scan, 4D-CT, 18F-Fluorocholine PET/CT, and PET/MRI are helpful in localizing abnormal parathyroid glands in cases requiring repeat surgery. Repeat surgery is associated with higher risk and requires an experienced surgeon. When surgery is not indicated or possible, medical management with cinacalcet and antiresorptive therapies may be considered. This review highlights the etiology, diagnostic approaches, and management strategies for persistent and recurrent PHPT, emphasizing the importance of multidisciplinary care in order to optimize outcomes.

Primary hyperparathyroidism (PHPT) is underdiagnosed. Opportunistic assessment for enlarged parathyroid glands on routine CT examinations is a proposed approach to improve diagnosis. However, the proportion of at-risk patients with a relevant CT is unknown. We aimed to determine the proportion of individuals with hypercalcemia untested for PHPT who had CT examinations on which opportunistic screening could have been performed and to assess characteristics associated with imaging availability.

This retrospective study included adults with hypercalcemia untested for PHPT within our health system between January 2018 and December 2022. Each patient was classified as imaging available versus unavailable based on the presence of contrast-enhanced CTs including the parathyroid region performed between January 2013 and December 2022. Characteristics of these groups were compared.

The sample comprised 10,702 patients (mean age, 57 years; 6,422 female and 4,280 male patients) with CTs available in 1,318 (12.3%). Characteristics associated with the greatest odds of available CT were Charlson Comorbidity Index ≥ 5 (odds ratio [OR] 5.29, P < .0001), death during the study period (OR 2.31, P < .0001), fatigue (OR 1.90, P < .0001), weakness (OR 1.60, P < .0001), and calcium > 12.0 mg/dL (OR 1.44, P < .0001). Characteristics associated with the lowest odds of available CT were age ≥ 85 years (OR 0.27, P < .0001), age < 35 years (OR 0.58, P < .0001), and chronic kidney disease (OR 0.64, P < .0001).

More than 12% of patients with hypercalcemia who were untested for PHPT had at least one CT that could have been used to opportunistically assess the parathyroid glands. Patients with imaging tended to have more comorbidities than those without.

Primary hyperparathyroidism (PHPT) with mild hypercalcemia (Ca <12 mg/dL) often remains asymptomatic. However, PHPT may induce various psychiatric symptoms, including depression, cognitive dysfunction, and infrequently, psychotic symptoms, predominantly in older adults rather than in middle-aged or younger individuals.

A 48-year-old man, with no history of physical or mental illness, experienced delusions about a suspicious car in his neighborhood, believing it was linked to criminal activity. This led to his being taken into custody after harming himself and his family. He was admitted for psychiatric evaluation and diagnosed with PHPT after mild hypercalcemia was discovered. He was initially treated medically for the mild hypercalcemia; however, only his disorientation showed improvement, and his broader psychiatric symptoms persisted. His delusions ceased only after surgical intervention. Following discharge, he remained symptom-free without requiring antipsychotic medication.

This case highlights the importance of considering PHPT in patients of any age presenting with psychosis, even with mild hypercalcemia. Surgical options for patients with PHPT should be considered when medical interventions fail.

Current clinical practice guidelines were established by several organizations to guide the diagnosis and treatment of hypertension in men and women in a similar manner despite data demonstrating differences in underlying mechanisms. Few publications have provided a contemporary and comprehensive review focused on characteristics of hypertension that are unique to women across their life spectrum. We performed a computerized search using PubMed, OVID, EMBASE, and Cochrane library databases between 1995 and 2023 that highlighted relevant clinical studies, challenges to the management of hypertension in women, and multidisciplinary approaches to hypertension control in women, including issues unique to racial and ethnic minority groups. Despite our current understanding of underlying mechanisms and strategies to manage hypertension in women, numerous challenges remain. Here, we discuss potential factors contributing to hypertension in women, differences related to effects of lifestyle modifications and drug therapy between men and women, the impact of sleep, and the importance of recognizing disparities in socioeconomic conditions and access to care. This review outlines several opportunities for future studies to fill gaps in knowledge to achieve optimal control of hypertension in women using a multidisciplinary approach, particularly related to sex-specific treatment approaches while considering socioeconomic conditions and life stages from premenopause through the transition to menopause.

In this manuscript, we provide critical commentary on the systematic review by Augustin et al, which investigated acute pancreatitis induced by primary hyperparathyroidism during pregnancy. Although this is an infrequent complication, it poses severe risks to both maternal and fetal health. Due to its infrequent occurrence in clinical practice, this review is based on an analysis of individual case reports over the past 55 years. While this is not the first study to utilize this sampling method for primary hyperparathyroidism-induced acute pancreatitis, it is unique in that it has a sufficiently large sample size with statistically significant results. Our discussion focuses on the diagnostic challenges associated with this condition, which are grounded in the mechanisms of parathyroid hormone secretion and variations in serum calcium levels. We also address the limitations of the current review and suggest potential strategies to increase diagnostic accuracy and improve health outcomes for both mothers and fetuses during pregnancy.

Treatment of primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism due to idiopathic hypercalciuria (SHPT-IH) is markedly different. Robust diagnostic tools to differentiate between both entities are however lacking.

Evaluate the thiazide challenge test (TCT) in clinical practice, its aid in clinical decision making, and evaluate the accuracy (sensitivity, specificity) and potentially useful parameters of the TCT.

Monocentric observational retrospective cohort study from January 2017 to November 2023 in an outpatient Endocrinology department, Ghent University Hospital (Belgium). Twenty-five adult patients with hypercalciuria, elevated parathyroid hormone (PTH), and high-normal or elevated serum calcium underwent a TCT. Outcome measures were serum, urinary biochemical parameters before and after testing, clinical and imaging outcomes, treatment, and follow-up.

Patients with a TCT-based working diagnosis of PHPT show greater increases in albumin-adjusted calcium and total serum calcium concentration than patients with SHPT-IH (+0.11 ± 0.10 vs +0.0071 ± 0.10 mmol/L; P = .025 and +0.14 ± 0.12 vs +0.012 ± 0.15 mmol/L; P = .024, respectively). The TCT-based working diagnosis of PHPT has a sensitivity of 81.8%, a specificity of 77.8%, and a likelihood ratio of 3.68 of estimating a correct final diagnosis. Urinary calcium excretion, PTH, calcium-phosphorous ratio, PTH inhibition rate, and the parathyroid function index do not differ significantly in patients with PHPT compared with those with SHPT-IH.

The TCT aids in discriminating patients with PHPT from those with SHPT-IH based on a rise in serum calcium. Other parameters are not different between both groups. Larger prospective trials are necessary to further define the diagnostic potential of the TCT, its most appropriate biochemical outcome variables, and decision cut-offs.

Parathyroidectomy has been shown to reduce cardiovascular risk factors in some studies, although findings on these parameters remain inconsistent.

This study aimed to evaluate inflammatory and cardiovascular risk markers in patients with Primary Hyperparathyroidism (PHPT) before and one month after successful parathyroidectomy (PTX).

We retrospectively analyzed PHPT patients who visited the outpatient clinic between 2015 and 2020. Patient demographics, hemogram data, calcium, parathormone (PTH), vitamin D, high-density lipoprotein (HDL), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-HDL ratio (MHR) were recorded and compared pre- and postoperatively.

The analysis revealed significant postoperative increases in platelet, MPV, HDL, PLR, and vitamin D levels (p = 0.001, p = 0.001, p = 0.001, p = 0.024, p = 0.001, respectively). Conversely, PTH, calcium, NLR, and MHR levels significantly decreased (p = 0.001, p = 0.001, p = 0.011, p = 0.019, respective-ly). Correlation analysis demonstrated a negative association between postoperative PTH and vitamin D (p = 0.010, r = -0.292**) and a positive association between postoperative PTH and both calcium (p = 0.008, r = 0.309**) and NLR (p = 0.046, r = 0.227**). Multivariable regression analysis demonstrated that postoperative PTH levels were significantly associated with calcium (B = 39.82, Beta = 0.321, p = 0.0469), NLR (B = 110.02, Beta = 0.428, p = 0.0384), baseline comorbidity scores (B = -30.54, Beta = -0.287, p = 0.0361), and preoperative inflammation levels (B = 25.69, Beta = 0.311, p = 0.0386).

Our findings highlight a potential link between PHPT and inflammatory-cardiovascular risk, with parathyroidectomy exerting a beneficial effect within the first month post-surgery. The study also suggests that these risk factors may be modifiable with timely surgical intervention.

Not applicable.

Surgery is the preferred treatment for primary hyperparathyroidism (PHPT), but the presence of MIBI-avid thyroid nodules can complicate the localization of parathyroid adenoma (PA). In this case report, we discuss the role of imaging in localizing PA in a patient with concurrent thyroid nodules. A 49-year-old female presented with hypercalcemia and elevated parathyroid hormone levels. Technetium-99m-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) showed MIBI-avid enhancement in the left thyroid lobe. Neck ultrasonography revealed 3 thyroid nodules in the left lobe, categorized as Thyroid Imaging Reporting and Data System (TI-RADS) 4. Fine-needle aspiration cytology yielded indeterminate results, and iPTH washout concentration was not elevated. Parathyroid 4-dimensional computed tomography (4D CT) was performed, which revealed an extra thyroid lesion on the left side, favoring PA. Left thyroid lobectomy and parathyroidectomy were performed, and the pathology report confirmed PA and follicular thyroid carcinoma. In cases where MIBI-avid thyroid nodules mimic PA, a combination of imaging modalities including technetium-99m-sestamibi SPECT/CT, neck ultrasonography, and parathyroid 4D CT can aid in differentiating between intrathyroid PA and extrathyroidal locations. Accurate preoperative localization is crucial for successful surgical management of PHPT. These imaging techniques play a pivotal role in guiding surgical decisions and ensuring optimal patient outcomes.

Primary hyperparathyroidism (PHPT) is a frequent disease. Prevalence continues to rise in Europe, long after the advent of automated calcemia meters, while incidence has stabilized. The disease is much more common in women, at around 75% of cases, and is more prevalent with advancing age, and particularly post-menopause.

BACKGROUND. Primary hyperparathyroidism (PHPT) is underdiagnosed. Opportunistic imaging-based parathyroid gland assessment is a proposed strategy for identifying patients at increased risk of undiagnosed PHPT. However, whether this approach is likely to identify individuals with clinically significant disease is unknown. OBJECTIVE. This study's objective was to assess for associations of the presence of an enlarged parathyroid gland on contrast-enhanced CT with clinical outcomes causally related to PHPT. METHODS. This retrospective cohort study included patients 18 years old or older with at least one contrast-enhanced chest or neck CT examination performed from January 2012 to December 2012, at least one noncontrast CT examination covering the chest or neck region without a date restriction, and at least one clinical encounter in the health system from January 2022 to December 2022. A neuroradiologist reviewed the CT examinations to determine the presence versus absence of an enlarged parathyroid gland on the 2012 study. Patient demographics, serum calcium results, and diagnosis codes for clinical outcomes causally related to PHPT were extracted from the EHR. Calcium results and diagnosis codes were classified as preexisting if documented before and as incident if documented after the 2012 contrast-enhanced CT examination. RESULTS. The cohort included 1198 patients (593 men and 605 women; mean age, 51.6 years), of whom 43 (3.6%) were assessed as having an enlarged parathyroid gland on the 2012 contrast-enhanced CT examination. PHPT was diagnosed in 16.3% of patients with, versus 0.3% of patients without, an enlarged parathyroid gland (p < .001). After adjustment for age, sex, race, and ethnicity, the presence of an enlarged parathyroid gland on contrast-enhanced CT was associated with significantly increased odds of preexisting nephrolithiasis (OR = 2.71; p = .03), hypercalcemia (OR = 5.30; p < .001), and PHPT (OR = 12.59; p = .008) as well as increased odds of incident osteopenia or osteoporosis (OR = 2.78; p = .008), nephrolithiasis (OR = 4.95; p < .001), hypercalcemia (OR = 7.58; p < .001), and PHPT (OR = 148.01; p < .001). CONCLUSION. An enlarged parathyroid gland indicated increased risk of PHPT as well as increased risk of preexisting and incident clinical conditions causally related to PHPT. CLINICAL IMPACT. Opportunistic CT-based assessment is a promising strategy for identifying patients at increased risk of undiagnosed PHPT; such assessment could potentially prevent some PHPT-related complications through earlier diagnosis and treatment.

Primary hyperparathyroidism (PHPT), a common endocrine disorder, is often diagnosed in its asymptomatic stage. We report the case of a 79-year-old woman with Guillain-Barré syndrome (GBS) who developed progressive hypercalcemia, initially suspected to be immobilization hypercalcemia (IH). However, the detection of elevated intact parathyroid hormone (PTH) confirmed that the hypercalcemia was not solely due to prolonged immobilization associated with GBS but rather due to previously latent PHPT becoming clinically apparent. Treatment with elcatonin and zoledronate inhibited bone resorption, while cinacalcet suppressed PTH secretion, collectively normalizing serum calcium levels and alleviating symptoms. This case illustrates how prolonged immobilization in GBS can enhance bone resorption, leading to IH and unmasking latent PHPT. Recognizing this mechanism underscores the importance of routine calcium monitoring, PTH screening in high-risk patients, and timely intervention to prevent complications, particularly in immobilized or ageing populations.

Parathyroid cancer has been linked to germline mutations of the Cell Division Cycle 73 (CDC73) gene. However, carriers harboring cancer-associated germline CDC73 mutations may develop only parathyroid adenoma or no parathyroid disease. This incomplete penetrance indicates that additional genomic events are required for parathyroid tumorigenesis.

(1) Determine the status of the second CDC73 allele in parathyroid tumors harboring germline CDC73 mutations and (2) compare the genomic landscapes between parathyroid carcinomas and adenomas.

Whole-exome and RNA sequencing of 12 parathyroid tumors harboring germline CDC73 mutations (6 adenomas and 6 carcinomas) and their matched normal tissues.

All 12 parathyroid tumors had gained 1 somatic event predicted to cause a complete inactivation of the second CDC73 allele. Several distinctive genomic features were identified in parathyroid carcinomas compared to adenomas, including more single nucleotide variants bearing the C > G transversion and APOBEC deamination signatures, frequent mutations of the genes involved in the PI-3K/mTOR signaling, a greater number of copy number variations, and substantially more genes with altered expression. Parathyroid carcinomas also share some genomic features with adenomas. For instance, both have recurrent somatic mutations and copy number loss that impact the genes involved in T-cell receptor signaling and tumor antigen presentation, suggesting a shared strategy to evade immune surveillance.

Biallelic inactivation of CDC73 is essential for parathyroid tumorigenesis in carriers harboring germline mutations of this gene. Despite sharing some genomic features with adenomas, parathyroid carcinomas have more distinctive alterations in the genome, some of which may be critical for cancer formation.

To describe diagnostic approaches and management strategies for patients with primary hyperparathyroidism (PHPT) and recent fracture in England.

We developed a survey based on a patient at high fracture risk and a new diagnosis of probable PHPT. The survey was circulated among 50 secondary care professionals identified by the Society for Endocrinology Calcium and Bone special interest group. Descriptive statistics, combinatorial, and thematic analyses were employed.

In the patient with hyperparathyroidism and a recent fracture, 54% of respondents favoured a 24-hour urinary calcium: creatinine clearance ratio, with 85% opting to do so after correcting vitamin D levels. Thirty-two percent (16/50) preferred the spot urinary calcium:creatinine clearance ratio, as a random test (56%, n = 9/16). Ninety-six percent of the respondents agreed they would include a fracture risk assessment in their management plan. Eighty-five percent of the respondents selected dual-energy X-ray absorptiometry scans of the lumbar spine, total hip, and femoral neck as the most popular choice. Before initiating antiosteoporotic medications (AOMs), 94% of the respondents preferred correcting vitamin D levels with diverse regimens. IV zoledronate acid was the preferred AOM, and 58% (n = 29/50) supported cinacalcet usage if the patient was ineligible for parathyroid surgery, while 26% (n = 13/50) opposed cinacalcet use entirely. No significant correlation was found between status as an endocrinology consultant or working in a tertiary care hospital and these management preferences.

This study of National Health Service medical staff identified highly-varied clinical practices in managing PHPT in the setting of high fracture risk, highlighting the need for pragmatic guidelines and wider education.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder with variable clinical presentation. We intend to describe the clinical, biochemical, and radio-pathological profiles of PHPT patients managed over 13 years from South India.

We analysed all patients who underwent evaluation and surgery for PHPT from July 2011 to April 2024.

A total of 862 PHPT patients underwent parathyroidectomy, with female preponderance (61.2%). Analysis was done on 804 patients (>20 years of age) excluding adolescent and paediatric age groups. The mean age was 43.8 years. The presentation in decreasing order of frequency was weakness and fatigue (84.2%); bone pain (35%); renal disease (20.8%) in the form of nephrolithiasis, nephrocalcinosis, or renal dysfunction; and neuropsychiatric manifestations (23.8%). Pathological fractures were observed in 4.5%, hypercalcaemic crisis in 2.6% of patients, and 1% had MEN I (Multiple Endocrine Neoplasia) syndrome. The mean albumin adjusted serum calcium level was 12.3 ± 1.01 mg/dl, and the median serum PTH level was 338 (80-3864) pg/ml. The sensitivity of the ultrasound neck and 99mTc Sestamibi scan was 97.5% and 98.3%, respectively, with a concordance of 93.4%. 25% underwent bilateral neck exploration and parathyroidectomy. Lesions were ectopic in 20 (2.4%) patients. The mean parathyroid gland weight was 1.45 ± 0.75 g. Histopathology revealed parathyroid adenoma (93.5%), parathyroid hyperplasia (1.6%), and parathyroid carcinoma (2.2%). The cure rate was 99.3%, while three patients had persistent disease. Hungry bone syndrome was observed in 12.1%.

There is a changing trend in the clinical and biochemical profiles of PHPT patients in India to a milder form of the disease. The incidence of parathyroid carcinoma was slightly higher compared to a few other centres in India.

Endocrine surgery is a core component of general surgery training. The landscape of endocrine surgery education in surgical residency and association with entrance into endocrine surgery fellowships is unknown.

In total, 353 Accreditation Council for Graduate Medical Education-accredited general surgery program websites were identified and categorized by US region, program type and size, and endocrine surgery educational experience type. Self-identified endocrine surgeons were defined as American Association of Endocrine Surgeons members or fellowship graduates (American Association of Endocrine Surgeons surgeons) or having a thyroid/parathyroid/adrenal practice. Programs that graduated an American Association of Endocrine Surgeons fellow from 2012 onwards were identified, and characteristics associated with endocrine surgery-experience type, self-identified endocrine or American Association of Endocrine Surgeons faculty, and entrance into endocrine surgery fellowship were assessed.

In total, 353 programs were studied. The median number of general surgery residents per program was 25, with 165 (46.7%) small programs (<25 residents) and 188 (53.3%) large (≥25) programs. There were 122 (34.6%) university-based programs, 82 (23.2%) community-based, 139 (39.4%) community-based/university-affiliated, and 10 (2.8%) military. A total 665 self-identified endocrine surgeons were identified at 303 (85.8%) programs; 15 (14.2%) programs had no self-identified endocrine surgeon. There were 361 American Association of Endocrine Surgeons surgeons located at 163 (46.2%) residency programs. In total, 323 (91.5%) programs had information on curriculum/rotations available, 58 (17.9%) with dedicated endocrine surgery educational experiences, 226 (70%) with rotations mixed with other subspecialties, and 39 (12.1%) with none reported. A total 113 (35%) general surgery programs produced a future endocrine surgery fellow and were most likely to be large (81%, P < .001), university-based (64%, P < .001) programs and were more likely to have a self-identified endocrine (102, 90.3%, P = .016) or an American Association of Endocrine Surgeons surgeon (82, 72.6%, P = .004).

Program size and type were strongly associated with endocrine surgery exposure, presence of a self-identified endocrine surgeon, and same-site American Association of Endocrine Surgeons fellowship. Endocrine surgery educational experiences are inconsistent across residencies, and efforts are needed to ensure that surgical residents receive comprehensive, equitable endocrine surgery education.

Although many parathyroid and thyroid operations are performed by nonfellowship-trained general surgeons in the United States, there is growing uncertainty of whether graduating residents can perform these procedures competently. This study investigates trends in competency and autonomy among general surgery residents performing parathyroid and thyroid operations using a national survey-based dataset.

A retrospective analysis of the Society for Improving Medical Professional Learning database was performed. Case data from categorical general surgery residents performing parathyroidectomy or thyroidectomy between 2015 and 2023 were included. Competent performance and meaningful autonomy were dichotomized on the basis of faculty surgeon responses. Agreement between resident and faculty evaluations were assessed. Logistic regression was used to examine resident performance and autonomy using postgraduate year level and case complexity as covariates.

The study included 907 parathyroidectomies and 1,555 thyroidectomies from 724 residents at 77 residency programs. Competent performance was observed in 34.0% of parathyroidectomies and 38.6% of thyroidectomies. Meaningful autonomy was observed in 31.6% of parathyroidectomies and 32.3% of thyroidectomies. Residents and faculty agreed on performance (50.3%) and autonomy (59.1%) in most cases, however when discordant residents often underestimated their performance (44.7%) or autonomy (25.3%). The likelihood of postgraduate year 5 residents demonstrating competent performance or meaningful autonomy was 65.9% and 51.6%, respectively for parathyroidectomy and 77.2% and 58.4%, respectively for thyroidectomy.

Many graduating residents do not demonstrate competent performance or meaningful autonomy in parathyroidectomy and thyroidectomy. Further initiatives are needed to improve graduating general surgeons' competence for these operations, given access disparities to high-volume endocrine surgeons.

The American Association of Endocrine Surgeons suggests screening for familial hypocalciuric hypercalcemia for 24-hour urine calcium <100 mg and for calcium to creatinine clearance ratio <1%. We explored the biochemical and clinical profiles of genetically tested patients to determine the usefulness of these recommendations.

This was a retrospective review of patients who underwent analysis of the calcium-sensing receptor gene.

In total, 401 patients were identified between 2005 and 2024; 332 (83%) were negative for a mutation, 44 (11%) were positive, and 25 (6%) had variants of unknown significance. Median serum calcium was lower in patients who were negative (negative 10.1 mg/dL, variants of unknown significance 10.6 mg/dL, positive 10.9 mg/dL). Median urine calcium was lower in patients who were positive (negative 110 mg, variants of unknown significance 149 mg, positive 82 mg). Median parathyroid hormone levels were comparable between groups (negative 65 pg/mL, variants of unknown significance 58 pg/mL, positive 60 pg/mL). Eight of 21 (38%) patients who tested positive had urine calcium >100 mg and 5 of 21 (24%) had urine calcium >200 mg. Eight of 35 (23%) patients who were positive had a calcium to creatinine clearance ratio >1%. Urine calcium and calcium to creatinine clearance ratio receiver operating characteristic curves showed poor performance in identifying patients with familial hypocalciuric hypercalcemia (area under the curve [95% confidence interval]): 0.55 [0.45-0.65] and 0.63 [0.57-0.7], respectively. For positive patients with imaging, sestamibi was inconclusive or nonlocalizing for 13 of 23 and showed multiglandular disease for localizing scans in 7 of 10. Ultrasound was nonlocalizing or equivocal for 11 of 13. In total, 212 of 401 patients (53%) underwent surgery; 100 of 212 were tested preoperatively (0/100 positive, 5/100 variants of unknown significance) and 112 of 212 patients were tested postoperatively (15/112 positive, 10/112 variants of unknown significance).

Familial hypocalciuric hypercalcemia demonstrates non-negligible biochemical overlap with primary hyperparathyroidism, with many patients having a urine calcium value greater than the American Association of Endocrine Surgeons suggested threshold for considering genetic evaluation. More frequent genetic testing beyond urine measurements may help identify more patients with familial hypocalciuric hypercalcemia.

Currently, parathyroidectomy is the standard treatment for Primary Hyperparathyroidism (PHPT). Surgical treatment is often effective, although not free of complications and relapses. Minimally invasive techniques, such as Microwave Ablation (MWA) and Radiofrequency Ablation (RFA), are an alternative to surgery in selected patients. We have, herein, reported on the successful use of RFA in a patient with post-surgical persistent hyperparathyroidism.

A 54-year-old woman was referred to our Center for mild hypercalcemia with exams revealing Primary Hyperparathyroidism (PHPT). Neck ultrasound and Technetium- 99 Methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy scanning revealed a suspicious right parathyroid hyperplasia/adenoma. She underwent parathyroidectomy and histological examination showed a parathyroid nodular hyperplasia. During the follow-up, she suffered from persistent hyperparathyroidism due to a left parathyroid hyperplasia. Thus she was treated with RFA. Blood tests after the procedure showed the remission of the disease 7 months post-treatment.

A minimally invasive technique for PHPT may represent a valid alternative to surgery, especially in patients with an elevated surgery-related risk. More studies are necessary to investigate the benefit of RFA as a first-line treatment in PHPT.

Primary hyperparathyroidism predominately affects women who are postmenopausal and causes complications, including fragility fractures. Its treatment is parathyroidectomy, which is associated with low complication and >95% cure rates. Considering fractures are associated with premature death, we aimed to determine whether the surgical management of individuals with biochemical diagnosis of primary hyperparathyroidism was associated with a reduction in fracture risk.

In this population-based cohort study, we used administrative health databases to identify adults ≥18 year old who were biochemically diagnosed with primary hyperparathyroidism between 2007 and 2016 in Ontario. Patients were included if their calcium was ≥2.6 mmol/L (≥10.42 mg/dL) with a concurrent parathyroid hormone of ≥2.2 pmol/L (≥20.75 pg/mL). We followed patients and compared the incidence of fractures between those with and without parathyroidectomy. To control for potential confounding, we used inverse probability of treatment weighting to estimate the average treatment effect in the treated. Fine-Gray competing risk regression models were used to determine the association between surgery and time to fracture.

In a cohort of 28,059 with a biochemical diagnosis of primary hyperparathyroidism, the mean age (standard deviation) was 65 years (14.2 years), and 75% (n = 21,139) were female. Only 12.6% (n = 3,523) underwent parathyroidectomy. Weighted fracture cumulative incidence at 12 years postdiagnosis was 10.17% (n = 182) in surgical patients and 14.04% (n = 2,004) in nonsurgical patients. Parathyroidectomy prevented 1 fracture for every 26 surgeries performed (weighted risk difference, 3.87%, 95% confidence interval, 0.96%-6.62%) and reduced the hazard of fracture by 22% (weighted hazard ratio, 0.78; 95% confidence interval, 0.64-0.95).

In a large, publicly funded health system, parathyroidectomy significantly reduced the short- and long-term risk of fragility fractures in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a prevalent clinical condition characterized by an inappropriate secretion of parathyroid hormone (PTH). It is most often caused by one or more parathyroid adenomas, which can, in rare cases, be ectopically located. Ectopic adenomas can pose a diagnostic challenge, lead to treatment delay, and be a common cause of recurrent hypercalcemia after parathyroidectomy. We present the case of a 73-year-old woman referred to our Endocrinology Department for hypercalcemia, with initial blood tests confirming primary hyperparathyroidism. Following a negative cervical ultrasound, a parathyroid sestamibi scan was performed, which identified an MIBI (technetium (Tc)-99m methoxyisobutylisonitrile)-avid focus in the midline posterior cervical region suggestive of an ectopic parathyroid adenoma. Subsequently, a four-dimensional neck CT scan revealed a retro-esophageal nodular lesion. The diagnosis was confirmed through esophageal endoscopic ultrasound-guided fine needle aspiration. The patient underwent minimally invasive parathyroidectomy with a significant intraoperative decrease in PTH levels and a postoperative normalization of calcium levels. Six months after surgery the patient shows no signs of recurrence. This clinical case highlights the importance of a thorough diagnostic workup and the use of multiple imaging modalities to accurately locate parathyroid adenomas. This approach helps prevent incorrect surgical procedures and improves treatment outcomes.

The success of parathyroidectomy depends on accurate intraoperative localization and identification of all diseased glands in parathyroid exploration based on surgeon expertise to prevent persistent hyperparathyroidism. Near-infrared autofluorescence (NIRAF) imaging has recently emerged as a promising adjunctive intraoperative tool for localizing parathyroid glands; however, its potential utility in the assessment of parathyroid glands has yet to be established.

To analyze the differences in NIRAF signatures of parathyroid glands in single vs multiple glands in primary hyperparathyroidism (pHPT).

This prospective diagnostic study analyzed in vivo NIRAF images of parathyroid glands obtained during parathyroidectomies between November 18, 2019, and December 31, 2023, at a single tertiary referral center. Pixel intensities of the images were measured using third-party software. Patients who underwent parathyroidectomy for sporadic pHPT using a second-generation NIRAF imaging device were included. Patients with multiple endocrine neoplasm disorders were excluded. In vivo NIRAF images obtained during the procedures were analyzed.

Near-infrared autofluorescence imaging during parathyroidectomy.

The primary outcomes were the autofluorescence intensity and heterogeneity of single adenomas and multigland disease (ie, double adenomas and 3- or 4-gland hyperplasia) in sporadic pHPT. Normalized autofluorescence intensity was calculated by dividing the mean pixel intensity of the parathyroid gland by the background tissue. A heterogeneity index was calculated by dividing the standard deviation by the mean pixel intensity of the gland. The secondary outcome was the visibility of each parathyroid gland on NIRAF imaging before it became apparent to the naked eye during exploration.

A total of 1287 in vivo NIRAF images obtained from 377 patients (median [IQR] age, 66 [56-73] years; 299 female [79.3%]) were analyzed. Of all patients, 230 (61.0%) had a single adenoma, 91 (24.1%) had double adenomas, and 56 (14.9%) had 3- or 4-gland hyperplasia. A mean (SD) of 3.4 (1.1) parathyroid glands were identified in the procedures. A comparison of 581 diseased glands (45.1%) and 706 normal glands (54.9%) showed a lower median normalized autofluorescence intensity of 2.09 (95% CI, 1.07-4.01) vs 2.66 (95% CI, 1.43-4.20; effect size = 0.36) and higher heterogeneity index of 0.18 (95% CI, 0.07-0.41) vs 0.11 (95% CI, 0.01-0.27; effect size = 0.45), respectively. Of diseased glands, single adenomas (233 [40.1%]) vs double adenomas (187 [32.2%]) and 3- or 4-gland hyperplasia (161 [27.7%]) had a lower median autofluorescence intensity of 1.92 (95% CI, 1.02-4.44) vs 2.22 (95% CI, 1.10-3.97; effect size = 0.21), respectively. On receiver operating characteristic analysis, the optimal autofluorescence intensity threshold to differentiate between single adenomas vs multigland disease was 2.14, with a sensitivity of 64.4%, specificity of 58.1%, and area under the curve of 0.626.

These findings suggest that parathyroid glands in single- vs multigland disease may exhibit different autofluorescence characteristics. Although the effect size was modest, the differences identified should be kept in mind when assessing the parathyroid glands during surgical exploration.

Hypercalcemia can result from either hyperparathyroidism or non-parathyroid conditions. When hypercalcemia is accompanied by undetectable parathyroid hormone (PTH) levels, hyperparathyroidism is rarely considered the diagnosis. Herein, we report the case of a 65-year-old Caucasian woman referred to our hospital for further evaluation of hypercalcemia. Her symptoms included fatigue and brain fog, with undetectable PTH levels. A comprehensive workup, including a series of laboratory and imaging tests, excluded common non-parathyroid causes such as malignancy and familial hypocalciuric hypercalcemia. Ultrasound identified a likely enlarged parathyroid gland, which was further confirmed by a sestamibi scan. After 2 weeks of cinacalcet treatment, the patient's calcium levels decreased, indicating the parathyroid gland as the likely source of hypercalcemia. Parathyroidectomy was subsequently performed, revealing a 1927 mg adenoma. Postoperatively, the patient's calcium levels normalized, PTH levels became detectable within the normal range, and her symptoms resolved, with a marked improvement in energy. This case demonstrates that primary hyperparathyroidism can present with hypercalcemia and undetectable PTH. A genetic mutation in the PTH gene within the adenoma may explain the undetectable PTH levels preoperatively.

Parathyroidectomy for primary hyperparathyroidism (PHPT) could have poor outcomes, even with accurate preoperative localization of the adenomas, because their intraoperative localization can be challenging. Freehand single photon emission computed tomography (fhSPECT) is a new technique for radio-guided intraoperative navigation. Its use during parathyroidectomy could be useful and such data are limited. We herein present our experience on the feasibility of fhSPECT for intraoperative detection of abnormal parathyroid glands. We retrospectively reviewed the clinical data of 55 patients (30-77 years old) with PHPT due to parathyroid adenomas, that were subjected to parathyroidectomy from 12/2017 to 7/2022. In average, 111 ± 74 MBq of Tc-99 m Sestamibi were injected intravenously, approximately 2 h before the operation and fhSPECT was used to generate 3D images during parathyroidectomy. Measurements of PTH and calcium levels were performed preoperatively, postoperatively and 4-6 months after the procedure. FhSPECT successfully identified the parathyroid adenoma in all the patients. It took 3 min (median time) for fhSPECT to detect at least one radioactive spot in all patients. The mean duration of the operation was 66.6 ± 7.3 min. Forty-nine patients out of 55 had solitary and 6/55 had multiple adenomas, whereas 6/55 had ectopic abnormal parathyroid glands. None of the patients had persistent hyperparathyroidism during follow-up. To the best of our knowledge, this is the largest series of patients with PHPT that underwent fhSPECT assisted parathyroidectomy. Our data suggest that this navigation system is helpful in identifying parathyroid adenomas intraoperatively.

Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.

The management of primary hyperparathyroidism (PHPT) during pregnancy may be surgical or conservative. This study compared adverse outcomes between surgical and non-surgical treatments. Additionally, the study investigated the correlation between serum calcium values and complication rates.

A systematic review of retrospective studies, case series, and case reports. Biochemical parameters, interventions, and outcomes of each pregnancy were recorded. The study population comprised two groups: the non-surgical and surgical groups. Adverse outcomes were categorized as maternal, obstetric, or neonatal.

The surgical and non-surgical groups consisted of 163 and 185 patients, respectively. A positive correlation was observed between the mean maternal gestational calcium value and both maternal and obstetric complication. Neonatal complications were more prevalent in patients treated conservatively across all maternal calcium values (p < 0.001). No significant differences were observed in maternal outcomes and overall obstetric outcomes between the study groups, albeit a higher mean serum calcium value in the surgical group (12.3 mg/dL) compared with the non-surgical group (11.1 mg/dL).

Given the significantly lower neonatal adverse outcomes in the surgical group compared to the non-surgical group, along with non-inferior maternal and obstetric outcomes in the surgical group, the overall data of this study suggest that parathyroidectomy is favorable to non-surgical management even in cases of mild hypercalcemia.

Primary hyperparathyroidism (PHPT) is an endocrine disorder marked by elevated secretion of parathyroid hormone (PTH), which results in hypercalcemia and may cause complications in the kidneys and bones. Diagnosing this condition involves ruling out secondary causes and understanding the complexities of the laboratory values associated with PHPT. The disease has become more recognizable to clinicians in an earlier phase thanks to updated screening guidelines. At present, patients can be diagnosed with "classic," "normocalcemic," "normohormonal," or "asymptomatic" PHPT. Many patients are diagnosed through incidental findings of elevated calcium levels or PTH levels during routine blood tests rather than through the presentation of classic symptoms. If asked, patients will invariably harbor subtle or subclinical manifestations despite the absence of overt symptoms. There is debate on whether truly asymptomatic hyperparathyroidism exists.1 We explore the definition and clinical patterns of asymptomatic hyperparathyroidism and propose concise recommendations for recognizing these patients.

Preoperative and intraoperative diagnostic tools influence the surgical management of primary hyperparathyroidism (PHPT), whereby their performance of classification varies considerably for the two common causes of PHPT: solitary adenomas and multiglandular disease. A consensus on the use of such diagnostic tools for optimal perioperative management of all PHPT patients has not been reached.

A decision tree model was constructed to estimate and compare the clinical outcomes and the cost-effectiveness of preoperative imaging modalities and intraoperative parathyroid hormone (ioPTH) monitoring criteria in a 21-year time horizon with a 3% discount rate. The robustness of the model was assessed by conducting a one-way sensitivity analysis and probabilistic uncertainty analysis.

The US healthcare system.

A hypothetical population consisting of 5000 patients with sporadic, symptomatic or asymptomatic PHPT.

Preoperative and intraoperative diagnostic modalities for parathyroidectomy.

Costs, quality-adjusted life-years (QALYs), net monetary benefits (NMBs) and clinical outcomes.

In the base-case analysis, four-dimensional (4D) CT was the least expensive strategy with US$10 276 and 15.333 QALYs. Ultrasound and 99mTc-Sestamibi single-photon-emission CT/CT were both dominated strategies while 18F-fluorocholine positron emission tomography was cost-effective with an NMB of US$416 considering a willingness to pay a threshold of US$95 958. The application of ioPTH monitoring with the Vienna criterion decreased the rate of reoperations from 10.50 to 0.58 per 1000 patients compared to not using ioPTH monitoring. Due to an increased rate of bilateral neck explorations from 257.45 to 347.45 per 1000 patients, it was not cost-effective.

4D-CT is the most cost-effective modality for the preoperative localisation of solitary parathyroid adenomas and multiglandular disease. The use of ioPTH monitoring is not cost-effective, but to minimise clinical complications, the Miami criterion should be applied for suspected solitary adenomas and the Vienna criterion for multiglandular disease.

Typically, primary hyperparathyroidism (PHPT) develops as a result of multiglandular hyperplasia, parathyroid cancer, or parathyroid adenoma. Patients usually present with skeletal manifestations such as low-trauma fractures. Osteitis fibrosa cystica (OFC) is a classic yet rare skeletal manifestation of advanced PHPT currently reported in less than 2% of patients. We present a case of a 29-year-old Indian female who presented with a femur fracture and mandibular OFC 20 days after delivery. The painless mandibular swelling gradually progressed from the third month of pregnancy. The biochemical and radiological investigations were indicative of PHPT-associated OFC. After the excision of the three-and-a-half parathyroid gland, histology revealed benign cystic adenomas and hyperplasia. Based on the associated clinical manifestations, OFC was suspected. Clinical exome sequencing revealed CDC73(+) c.687_688dupAG heterogenous pathogenic autosomal dominant mutation. Undiagnosed PHPT in mothers during pregnancy led to neonatal hypocalcaemic convulsions. With adequate supplementation, the infant recovered completely from transient congenital hypoparathyroidism. OFC is an important diagnosis to consider in a young patient with swelling of the neck and jaw. Simultaneous high levels of PTH and serum calcium should raise a high index of suspicion for OFC. Parathyroidectomy helps manage the biochemical abnormalities and causes regression of the jaw mass that causes facial disfigurement and attenuates the declining BMD. Children born to mothers with PHPT should be evaluated for neonatal hypoparathyroidism and supplemented appropriately to reduce the risk of hypocalcaemic manifestations that can be life-threatening. If the CDC73 mutation is detected, the offspring should be monitored for signs of PHPT due to the high probability of inheritance and parathyroid malignancy.

Ectopic parathyroid adenomas pose significant diagnostic and therapeutic challenges due to their atypical locations outside the usual anatomical boundaries of the parathyroid glands. These adenomas, which represent a small percentage of primary hyperparathyroidism cases, are often found in areas such as the mediastinum, thymus, or retroesophageal space. Their ectopic nature complicates diagnosis, as traditional neck imaging techniques may fail to localize these glands. We present the case of a 27-year-old female who initially presented with nausea, vomiting, severe hypercalcemia, and elevated parathyroid hormone (PTH) levels. Despite being advised to consult an endocrinologist, she experienced difficulty scheduling an appointment. Due to persistent symptoms and laboratory abnormalities, she was subsequently admitted to the hospital. Initial neck imaging failed to identify the parathyroid adenoma. However, subsequent imaging, including parathyroid scintigraphy, revealed an ectopic parathyroid adenoma located in the mediastinum. The patient underwent a successful robotically assisted thymectomy, guided by intraoperative PTH monitoring, which resulted in the resolution of hypercalcemia and normalization of PTH levels. This case underscores the importance of a comprehensive diagnostic approach when dealing with ectopic parathyroid adenomas. Parathyroid scintigraphy, in particular, proves to be a critical tool due to its high sensitivity in detecting ectopic glands. Moreover, our findings emphasize the need for a high index of suspicion for ectopic parathyroid adenomas, especially when conventional neck imaging is inconclusive in cases of hyperparathyroidism. Timely and accurate diagnosis is essential for facilitating precise surgical intervention, ultimately leading to improved patient outcomes.

In previous studies, magnesium (Mg) was found to be lower in cases with more severe primary hyperparathyroidism (PHPT) and higher calcium (Ca) levels. This study evaluated the relationship between serum Mg and serum Ca and phosphorus (P) levels in PHPT and their utility in determining the presence of osteoporosis and nephrolithiasis.

Patients who were followed up with PHPT between March 2019 and March 2023 were analyzed retrospectively. Biochemical data, renal ultrasonography results, dual-energy x-ray absorptiometry (DEXA) reports, and technetium 99 m sestamibi parathyroid scintigraphy reports were obtained. MgxP, Mg/P, Ca/P, and corrected Ca (cCa)/P values were calculated. The relationships between biochemical parameters and clinical outcomes were evaluated statistically.

A total of 543 patients were included in the study. Patients with nephrolithiasis had higher cCa/Mg or Ca/Mg than those without nephrolithiasis. Additionally, ROC analysis revealed that cCa/Mg greater than 5.24 could identify the presence of nephrolithiasis with a sensitivity of 73.3% and a specificity of 73%. No statistically significant correlation existed between the results of the Mg/P, MgxP, cCa/Mg, Ca/Mg values, and DEXA-bone mineral densitometry(BMD).

Ca/Mg and cCa/Mg ratios in particular seem more valuable in determining the presence of nephrolithiasis than the currently used 24-h urine Ca measurement. Compared to urinary Ca measurements, they are cheaper, more practical, and more accessible.

While there has been great progress in the past few decades in the management of endocrine surgery disorders, with adoption of new technologies and approaches, standardization of practice patterns, and guideline recommendations, unequal implementation of these improvement has led to differences in access and outcomes. Health disparities are well documented in this population; however, literature lacks discussion of strategies to decrease disparities. In this article, the authors will describe the current status of health care-related disparities in endocrine surgical care, and discuss opportunities for future investigation and issue an urgent call to action items.

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.

Excess parathyroid hormone (PTH) is associated with an increased risk of cardiovascular disease (CVD).

We aimed to evaluate the correlation between primary hyperparathyroidism (PHPT) and CVD or cardiovascular (CV) death.

Comprehensive searches of PubMed, Embase and ClinicalTrials.gov until May 20, 2023 with the following keywords: "primary hyperparathyroidism," "cardiovascular disease," and "mortality."

Cohort studies and randomized controlled trials comparing PHPT patients to the general population and those who had received parathyroidectomy (PTX) to those who did not.

Three investigators independently extracted data and assessed study quality.

Eleven cohort studies and one randomized controlled trial were identified, including 264,227 PHPT patients with or without PTX, and the average age reported in the studies was 62 years. PHPT was associated with a higher risk of total death (RR 1.39 [95 % confidence interval (CI) 1.23-1.57) and CV death (RR 1.61 [95 % CI 1.47-1.78]) than the general population. However, there was no significant difference in CVD risk between patients with PHPT and the general population (RR 1.73 [95 % CI 0.87-3.47]). When compared to patients without PTX, PTX had a lower risk of CV death (RR 0.75 [95 % CI 0.71-0.80]), total death (RR 0.64 [95 % CI 0.60-0.70]) and CVD (RR 0.92 [95 % CI 0.90-0.94]).

High heterogeneity among the included articles, and most of them were retrospective and older studies.

PHPT was associated with higher risk of total death and CV death while PTX was associated with lower risk of total death, CV death, and CVD.