Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g are called "large" or "giant" adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm³ (control group). In both groups, the majority were women (81.5% - study group, 90.5% - control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3-0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>.

Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. METHODS: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. RESULTS: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity. CONCLUSION: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

Primary Hyperparathyroidism during Pregnancy: Two Tales with Different Outcomes.

Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that are safe during pregnancy. If not diagnosed and managed in a timely manner, serious maternal and foetal complications may occur. We report two cases, one with surgical intervention and one without, to show the importance of timely surgical intervention and discuss the challenges in the management of PHPT in pregnancy.

Risk of Malignant Neoplasm in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

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.

Association between primary hyperparathyroidism and cardiovascular outcomes: A systematic review and meta-analysis.

BACKGROUND: Excess parathyroid hormone (PTH) is associated with an increased risk of cardiovascular disease (CVD). PURPOSE: We aimed to evaluate the correlation between primary hyperparathyroidism (PHPT) and CVD or cardiovascular (CV) death. DATA SOURCES: Comprehensive searches of PubMed, Embase and ClinicalTrials.gov until May 20, 2023 with the following keywords: "primary hyperparathyroidism," "cardiovascular disease," and "mortality." STUDY SELECTIONS: 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. DATA EXTRACTION: Three investigators independently extracted data and assessed study quality. DATA SYNTHESIS: 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]). LIMITATION: High heterogeneity among the included articles, and most of them were retrospective and older studies. CONCLUSIONS: 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.

Actigraphy measures show sleep improvement after parathyroidectomy for primary hyperparathyroidism.

IMPORTANCE: The symptoms of primary hyperparathyroidism are often subtle, such as fatigue, mood changes, and sleep disturbances. After parathyroidectomy, patients often report improvement in sleep and mood; however, objective data supporting these improvements is lacking. OBJECTIVE: This prospective study uses standard measures to objectively and subjectively assess sleep in patients with primary hyperparathyroidism before and after parathyroidectomy. DESIGN: A longitudinal prospective study was conducted over three one-week-long periods: pre-parathyroidectomy, 1-week post-parathyroidectomy, and three months post-parathyroidectomy. During each time point, patients wore an actigraphy device, recorded a sleep diary, and completed the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Depression Anxiety Stress Scale (DASS). Statistical analysis was performed using repeated measures models to compare the average measures among the three time points and test for trends over time. SETTING: Single institution, tertiary care center. PARTICIPANTS: Patients with primary hyperparathyroidism from ages 18 to 89 years old. EXPOSURE: Parathyroidectomy between September 2020 and January 2024. MAIN OUTCOMES AND MEASURES: Actigraphy data, consensus sleep diary, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Depression Anxiety Stress Scales - 21 Items (DASS). RESULTS: Thirty-six patients were enrolled, and 34 patients completed the study. Actigraphy data showed a significant negative trend in average sleep latency (p = 0.045) and average time in bed (p = 0.046). Sleep diary data showed additional differences in the number of awakenings (p = 0.002), wake after sleep onset (p < 0.001), sleep quality (p < 0.001), and sleep efficiency (p = 0.02) among the three time points and/or as a significant negative trend. PSQI and ISI scores were significantly different among the three time points (p = 0.002 and p < 0.001, respectively) and also declined significantly over time (p = 0.008 and p = 0.007, respectively). DASS depression, anxiety, and stress scores were significantly different among the three time points (p < 0.001, p = 0.01, and p < 0.001, respectively), and stress also declined significantly over time (p = 0.005). CONCLUSION AND RELEVANCE: This study represents the most extensive prospective study demonstrating objective and subjective sleep and mood improvement in patients with primary hyperparathyroidism after parathyroidectomy.

Primary hyperparathyroidism in pregnancy: a case report highlighting uncommon complication.

Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After localization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid adenoma. During follow-up, intrauterine growth restriction and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncommon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.

El hiperparatiroidismo primario (HPTP) se caracteriza por niveles elevados de calcio y hormona paratiroidea (PTH). Sin embargo, la interpretación de pruebas diagnósticas, como los niveles de calcio sérico y PTH, es compleja en mujeres embarazadas. El objetivo de este reporte es presentar un caso de HPTP en una adolescente embarazada, con especial hincapié en una complicación infrecuente, así como en las estrategias diagnósticas y de tratamiento. Una mujer embarazada de 17 años presentó hiperémesis gravídica y síntomas neurológicos, lo que llevó al diagnóstico de trombosis venosa cerebral. Posteriores investigaciones revelaron hipercalcemia y niveles persistentemente elevados de PTH, consistentes con HPTP. Tras la realización de estudios de localización, la paciente fue sometida a una paratiroidectomía de emergencia con diagnóstico de adenoma de paratiroides. Durante el seguimiento, se desarrolló restricción del crecimiento intrauterino y preeclampsia grave, lo que resultó en la necesidad de realizar una cesárea de emergencia. Tanto la madre como el neonato evolucionaron favorablemente. El HPTP es una condición infrecuente en la población embarazada y su diagnóstico puede ser desafiante por la superposición de síntomas con los cambios fisiológicos normales del embarazo. La aparición de complicaciones infrecuentes, como fenómenos trombóticos, resalta la necesidad de un abordaje integral para garantizar la detección y el manejo temprano. En la mayoría de los casos, la paratiroidectomía es el tratamiento de elección.

A Rare Ectopic Parathyroid Adenoma in the Prevertebral Space.

Ectopic parathyroid adenomas are an uncommon etiology of primary hyperparathyroidism. We present a case of a patient admitted to the hospital with severe hypercalcemia and elevated parathyroid hormone levels, in whom imaging revealed two distinct parathyroid masses in the prevertebral space, representing a rare and atypical location for parathyroid tissue. This case highlights the importance of considering ectopic parathyroid adenomas as a potential cause of hyperparathyroidism and discusses the diagnostic challenges and management strategies associated with such cases.

Primary Hyperparathyroidism due to Parathyroid Adenoma in Children and Adolescents.

OBJECTIVE: In contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder. METHODS: A retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications. RESULTS: Ten children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results. CONCLUSIONS: PHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up.

Screening for asymptomatic nephrolithiasis in primary hyperparathyroidism patients is warranted.

BACKGROUND: We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients. METHODS: Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis. RESULT: Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 â€‹h urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones. CONCLUSIONS: This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients.

Unveiling the Hidden Stroke Threat in Patients With Atrial Fibrillation and Primary Hyperparathyroidism.

Recent American College of Cardiology (ACC), American Heart Association (AHA), American College of Clinical Pharmacy (ACCP), and Heart Rhythm Society (HRS) guidelines suggest that patients with atrial fibrillation (AF) at intermediate to low annual risk of ischemic stroke can benefit from consideration of factors that might modify their risk of stroke. The role of nontraditional risk factors, such as primary hyperparathyroidism (PHPT), remains unexplored. In our study, we investigated the potential association between PHPT and the risk of ischemic stroke in patients with AF. Using data from the Nationwide Inpatient Sample Database, a retrospective cohort study focused on the adult population with AF, we stratified the participants based on PHPT presence. Demographic information, co-morbidities, and hospitalization details were extracted using International Classification of Diseases, Tenth revision codes. Propensity score matching was applied, encompassing over 20 confounding variables, including the risk factors outlined in the CHA2DS2-VASc (Congestive heart failure (C), Hypertension (H), Age ≥75 years (A2), Diabetes Mellitus (D), Stroke/Transient Ischemic Attack (TIA)/Thromboembolism (S2), Vascular disease (V), Age 65-74 years (A), Sex category [female] (Sc)) score. Multivariate logistic regression analysis was performed after matching to assess the independent impact of PHPT as an ischemic stroke risk factor. A total of 2,051 of the identified 395,249 patients with AF had PHPT. The PHPT group had an average age of 74 years and consisted of more women (66.1% vs 53.0%). After matching, it was observed that the PHPT group had longer hospital stays (5 vs 4 days) and higher hospitalization charges ($45,126 vs $36,644). This group exhibited higher rates of ischemic stroke (6.0% vs 4.4%) and mortality (6.3% vs 4.9%). The adjusted outcomes showed a 1.4-fold increased risk for ischemic stroke and a 1.32-fold increased risk for mortality in the PHPT cohort. The subgroup analysis showed a higher incidence of mortality in men with a high CHA2DS2-VASc score. In conclusion, this study highlights a marked association between PHPT and ischemic stroke in patients with AF, independent of the conventional CHA2DS2-VASc score. The potential mechanisms implicated include vascular changes, cardiac dysfunction, and coagulation cascade alterations. The presence of PHPT should be taken into consideration when deciding the assessment of thromboembolic risk.

[Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism].

BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,¼ resulting in severe and persistent postoperative hypocalcemia. AIM: To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. MATERIALS AND METHODS: The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. RESULTS: There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). CONCLUSION: Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

[Comparative analysis of bone complications/manifestations in sporadic and MEN1-related primary hyperparathyroidism].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) - is a rare syndrome with an autosomal dominant inheritance pattern caused by a mutation in the tumor suppressor gene (MEN1). Parathyroid involvement is the most common MEN1 manifestation resulting in primary hyperparathyroidism (mPHPT). Data on the prevalence and structure of bone disease in mPHPT compared to sporadic one (sPHPT) are often incomplete and contradictory. AIM: The purpose of this study was to compare the severity of bone involvement between mPHPT and sPHPT. MATERIALS AND METHODS: A single-center retrospective study was conducted among young patients in the active phase of PHPT and without prior parathyroidectomy in anamnesis. The analysis included the main parameters of calcium-phosphorus metabolism, bone remodeling markers, as well as an assessment of disease complications. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at sites of lumbar spine, femur and radius. Trabecular bone score (TBS) was applied to estimate trabecular microarchitecture. All patients included in the study underwent genetic testing. RESULTS: Group 1 (mPHPT) included 26 patients, and group 2 (sSHPT) included 30 age-matched patients: the median age in group 1 was 34.5 years [25; 39], in group 2 - 30.5 years [28; 36], (p=0.439, U-test). Within group 1, the subgroup 1A (n=21) was formed with patients without other hormone-produced neuroendocrine neoplasms (NEN) in the gastrointestinal tract (GI) and the anterior pituitary gland. The duration of PHPT was comparable in both groups: mPHPT - 1 year [0; 3] versus sPHPT - 1 year [0; 1], (p=0.533, U-test). There were no differences in the main parameters of calcium-phosphorus metabolism, as well as in the prevalence of kidney complications. In the mPHPT group, bone abnormalities were observed significantly more often compared to sPHPT: 54 vs 10% (p=<0.001; F-test). Statistically significant differences were revealed both in BMD and in Z-score values of the femoral neck and total hip, which were lower in the mPHPT group. These differences remained significant when comparing subgroup 1A with sPHPT. CONCLUSION: MEN1-associated PHPT may be accompanied by a more severe decrease in BMD in the femoral neck and total hip compared to sPHPT regardless of the other hormone-producing NEN. Clarifying the role of mutation in the MEN1 gene in these processes requires further study.

Assessment of left ventricular dysfunction by strain echo in primary hyperparathyroidism and its reversal after parathyroidectomy.

BACKGROUND: Strain echocardiography is a highly sensitive modality for detecting myocardial disease at an early stage. Therefore, we aim to evaluate subclinical left ventricular dysfunction in primary hyperparathyroidism (PHPT) patients with myocardial strain imaging in addition to conventional echocardiography and to look for its reversal after parathyroidectomy (PTx). METHODS: Thirty patients who underwent curative parathyroidectomy for PHPT were included. All patients were evaluated with M mode echo, 2D echo and strain imaging before and 6 months after PTx. Left ventricular ejection fraction, left ventricular diastolic dysfunction, left ventricular hypertrophy (LVH), Global Longitudinal Strain (GLS) and global circumferential strain (GCS) were recorded. RESULTS: On M mode echo, LVH was present in 15 patients and 8 of them improved completely after PTx (p < 0.038). Incidence of systolic and diastolic dysfunction on 2D echo was 10% and 13.3% respectively; while myocardial strain imaging showed impaired systolic function in 46.7% patients. Hence, compared to conventional 2D echo, strain imaging showed 36.7% high detection rate of subnormal cardiac function. There was improvement in left ventricle dysfunction (p = 0.083), GLS and GCS (p = 0.034) after PTx. Serum parathormone demonstrated a strong positive correlation with change in GLS and GCS (p = 0.013, p = 0.126) while serum calcium showed a weak correlation with change in GLS and GCS following surgery. CONCLUSION: Myocardial strain imaging should be considered for all PHPT patients as early identification of subclinical ventricle dysfunction provides an opportunity for an early intervention and thereby preventing development of irreversible LV dysfunction.

Neonatal hypocalcaemic seizures unmasking asymptomatic maternal primary hyperparathyroidism.

Hypocalcaemia is a common cause of neonatal seizures. Here, we present a breastfed neonate with smooth perinatal transition and no family history of seizures presenting at 3 weeks with recurrent multifocal clonic seizures. On evaluation, the neonate was found to have low iCa and total calcium. 25-hydroxy vitamin D (25(OH)D) level was low and intact parathyroid hormone (iPTH) was inappropriately normal. The maternal evaluation revealed high calcium and low phosphate levels. iPTH was very high and 25(OH)D was very low in the mother. Sestamibi scan showed a left inferior parathyroid adenoma in the mother. Maternal primary hyperparathyroidism causing hypercalcaemia can suppress parathyroid activity in the fetus, resulting in inappropriate parathyroid response to hypocalcaemia after birth causing recurrent hypocalcaemic seizures. So neonatal hypocalcaemic seizures need careful evaluation of the neonate and the mother at times and can help both mother and neonate.

Improvement of mood and sleep quality in patients with primary hyperparathyroidism after parathyroidectomy: A prospective case-control study.

BACKGROUND: Primary hyperparathyroidism can impact patient quality of life with psychopathological symptoms like mood and sleep disturbances. In the latest recommendations published according to the primary hyperparathyroidism surgical consensus, these neuropsychological symptoms continue to be excluded. This study aims to assess the negative effects of mood and sleep on patients with primary hyperparathyroidism compared to healthy controls and analyze their improvement after surgery. METHODS: Prospective case-control study of patients with primary hyperparathyroidism. The Beck questionnaire and Pittsburgh Sleep Quality Index were used. The control group consisted of healthy people matched by age and sex. Preoperative results were compared with results at 3 and 12 months after surgery and compared with the control group. Statistical analysis consisted of the Kolmogorov-Smirnov test and Student's t test for correlations. RESULTS: Forty-nine patients who underwent parathyroidectomy were analyzed. In relation to depression, differences were observed between the results of the preoperative period and 3 months after surgery, with a significant decrease in depression score (16.80 ± 9.98 vs 13.08 ± 10.76; P = .001). This improvement was maintained after 1 year (P < .001). Regarding the quality of sleep, there were no differences 3 months after the intervention, but there were differences at 12 months (9.48 ± 4.76 vs 8.27 ± 4.38; P = .032). The dimensions of the Pittsburgh Sleep Quality Index were analyzed, observing significant differences only in daytime dysfunction after 3 months and 12 months after surgery (1.02 ± 0.99 vs 0.69 ± 0.82; P = .01 and 1.04 ± 0.98 vs 0.60 ± 0.76; P = .004). CONCLUSION: Mood changes and sleep quality improve after primary hyperparathyroidism surgery, although at different postoperative times, with this improvement being more pronounced in mood. This assessment should be taken into account in the preoperative consultation of patients with primary hyperparathyroidism.

Testing for Primary Hyperparathyroidism in 17,491 Patients With Hypercalcemia.

BACKGROUND: Primary hyperparathyroidism (PHPT) is underdiagnosed and associated with many adverse health effects. Historically, many hypercalcemic patients have not received parathyroid hormone (PTH) testing; however, underlying reasons are uncertain. Our goals are to determine the PTH testing rate among hypercalcemic individuals at a large academic health system and to assess for characteristics associated with testing versus not testing for PHPT to inform future strategies for closing testing gaps. METHODS: This retrospective study included adult patients with ≥1 elevated serum calcium result between 2018 and 2022. Based on the presence or absence of a serum PTH result, individuals were classified as "screened" versus "unscreened" for PHPT. Demographic and clinical characteristics of these groups were compared. RESULTS: The sample comprised 17,491 patients: 6567 male (37.5%), 10,924 female (62.5%), mean age 59 y. PTH testing was performed in 6096 (34.9%). Characteristics independently associated with the greatest odds of screening were 5+ elevated calcium results (odds ratio [OR] 5.02, P < 0.0001), chronic kidney disease (OR 3.63, P < 0.0001), maximum calcium >12.0 mg/dL (OR 2.48, P < 0.0001), and osteoporosis (OR 2.42, P < 0.0001). Characteristics associated with lowest odds of screening were age <35 y (OR 0.60, P < 0.0001), death during the study period (OR 0.68, P < 0.0001), age ≥85 y (OR 0.70, P = 0.0007), and depression (OR 0.84; P = 0.0081). CONCLUSIONS: Only 35% of hypercalcemic patients received PTH testing. Although the presence of PHPT-associated morbidity was generally associated with increased rates of screening, hypercalcemic patients with depression were 16% less likely to be tested.

Ultrasound-based quantitative tools in predicting renal involvement in asymptomatic primary hyperparathyroidism.

PURPOSE: Asymptomatic primary hyperparathyroidism (aPHPT) has been recognized as a condition that can lead to renal complications. Timely identification of prognostic indicators for renal impairment holds the potential to facilitate proactive monitoring and treatment strategies in these patients. This study aims to investigate the utility of acoustic radiation force impulse (ARFI) imaging and renal resistive index (RRI), in identifying renal parenchymal and vascular changes in patients with aPHPT. METHODS: Forty-two patients with aPHPT and 42 controls matched for age, sex, and body mass index were included in the study. The presence of renovascular changes was evaluated by RRI measurement with Doppler ultrasonography, and the presence of renal parenchymal involvement was evaluated by ARFI quantification, given as shear wave velocity (SWV). RESULTS: In aPHPT patients, both the mean RRI and mean SWV values exhibited substantial elevation compared to the control group (P < 0.001 for both). Significant associations were observed between SWV values and serum calcium, parathyroid hormone (PTH), and adenoma size within the patient group (P < 0.001, P < 0.001, P = 0.016, respectively). Similarly, the mean RRI demonstrated positive correlations with serum calcium and PTH levels in the patient group (P< 0.001, P = 0.011, respectively). Multivariate linear regression analysis underscored the connection between mean RRI and mean SWV values with serum calcium levels within the patient group. In addition, serum PTH levels affected mean SWV positively and significantly. CONCLUSION: The use of ARFI imaging and RRI measurements appears to hold potential in identifying renal involvement in patients with aPHPT.