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Context: A germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the GCM2 [(NM_ 004752.4) c.1181A> C; p.Tyr394Ser; rs142287570] variant was reported in PHPT Ashkenazi Jews (AJ)., Objective: To evaluate the presence of the GCM2 p.Tyr394Ser variant in Israeli patients addressed for genetic evaluation to characterize their phenotype and clinical management., Method: Patients with PHPT who underwent addressed for genetic screening for suspected familial hypocalciuric hypercalcemia (FHH), a family history of isolated hyperparathyroidism (FIHP), or failed parathyroidectomy with persistent PHPT were recruited. Those with normal initial selected gene sequencing or hyperparathyroid genetic panel completed the GCM2 p.Tyr394Ser variant sequencing. The prevalence of this variant was evaluated using our local genomic database., Results: A total of 42 single individuals from unrelated kindreds were evaluated. A disease-causing mutation was found in 11 (26.1%) patients: 10 were diagnosed with FHH (eight CASR and two AP2S1 mutations), and one patient had a CKN2B mutation. In 28 of the remaining patients, the GCM2 p.Tyr394Ser variant was positive in three (10.7%), and all were AJ. Within AJ (15/28, 53.5%), the rate of the p.Tyr394Ser variant was 3/15 (20%), and of those, two had a history of familial isolated hyperparathyroidism. Multi-glandular parathyroid adenoma/hyperplasia was also observed in two of these patients. No clinical or laboratory findings could discriminate patients with the GCM2 p.Tyr394Ser variant from those with FHH. Cinacalcet normalized the calcium levels in one patient. The prevalence of the GCM2 p.Tyr394Ser variant in 15,407 tests in our local genomic database was 0.98%., Conclusion: In contrast to previous observations, the GCM2 p.Tyr394Ser variant-associated phenotype may be mild in AJ with FIHP, sometimes mimicking FHH. Because surgery may be curative, surgeons should be aware of the possibility of multiple gland diseases in these patients. The clinical spectrum and clinical utility of screening for this variant warrant further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Szalat, Shpitzen, Pollack, Mazeh, Durst and Meiner.)

Background: Parathyroidectomy (PTX) is an effective treatment for primary hyperparathyroidism (PHPT) patients. Postoperative hypocalcemia is a common complication after PTX. This study aimed to analyze the factors influencing serum calcium levels and the incidence of hypocalcemia after parathyroidectomy in primary hyperparathyroidism patients., Methods: The retrospective study included 270 PHPT patients treated with PTX and collected their demographic and clinical information and their laboratory indices. Factors influencing serum calcium levels and hypocalcemia after PTX in PHPT patients were analyzed using univariate and multifactorial analyses., Results: First, in patients with normal preoperative serum calcium levels (2.20-2.74 mmol/L), the higher the preoperative alkaline phosphatase and serum phosphorus levels, the lower the postoperative serum calcium levels. Furthermore, the higher the preoperative serum calcium levels and the accompanying clinical symptoms, the higher the postoperative serum calcium levels. Low preoperative serum calcium levels were shown to be a risk factor for postoperative hypocalcemia (OR=0.022), and the optimal preoperative serum calcium threshold was 2.625 mmol/L (sensitivity and specificity were 0.587 and 0.712, respectively). Second, in the mild preoperative hypercalcemia group (2.75-3.00 mmol/L), the older the patient, the higher the preoperative and postoperative serum calcium levels, the higher the postoperative serum calcium; the lower the alkaline phosphatase and calcitonin levels, the higher the postoperative serum calcium levels. On the other hand, the younger the patient was, the more likely hypocalcemia blood was (OR=0.947), with an optimal age threshold of 47.5 years (sensitivity and specificity were 0.543 and 0.754, respectively). Third, in the preoperative moderate to severe hypercalcemia group (>3.0mmol/L), patients undergoing a combined contralateral thyroidectomy and a total thyroidectomy had low postoperative serum calcium levels., Conclusion: Patients with different preoperative serum calcium levels had various factors influencing their postoperative serum calcium levels and postoperative hypocalcemia, which facilitated the assessment of their prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mu, Zhao, Zhao, Zhao, Zhang, Li, Kou, Dionigi, Bian and Sun.)

Introduction: Near infrared autofluorescence (NIRAF) is a novel intraoperative technology that has shown promising results in the localisation of parathyroid glands (PGs) over the last decade. This study aimed to assess the potential utility of NIRAF in first time surgery for primary hyperparathyroidism (PHPT)., Methods: An observational study over a period of 3 years in patients who underwent surgery for PHPT was designed. Data on the use of NIRAF and fluorescent patterns in different organs (thyroid and parathyroid) and parathyroid pathology (single versus multi-gland disease) were explored. In addition, cure rates and operating times were compared between the NIRAF and no-NIRAF groups to determine the potential value of NIRAF in this cohort., Results: In 230 patients undergoing first time surgery for PHPT, NIRAF was used in 50 patients. Of these 50 patients, NIRAF was considered to aid parathyroid identification in 9 patients (18%). The overall cure rate at 6 months of follow-up was 96.5% (98% in NIRAF and 96.1% without NIRAF; p=1.0). The median (interquartile range) operating time was longer in the NIRAF arm at 102 minutes (74-120 minutes) compared to the no-NIRAF arm at 75 minutes (75-109 minutes); however, this difference was not statistically significant (p=0.542). Although the median parathyroid to thyroid (P/T) auto-fluorescence (AF) ratio was similar between single gland and multi gland disease (2.5 vs to 2.76; p=1.0), the P/T AF ratio correlated negatively with increasing gland weight (p=0.038)., Conclusion: The use of NIRAF resulted in some potential "surgeon-perceived" benefit but did not lead to improvements in cure rates. The negative correlation between fluorescent intensity and gland weight suggests loss of fluorescence with pathology, which needs further investigation. Further studies on larger cohorts of patients, in depth analysis of fluorescence patterns between normal, adenomatous, and hyperplastic glands and evaluation of user experience are needed. Primary hyperparathyroidism, hyperparathyroidism, autofluorescence, near-infrared fluorescence, parathyroid glands, endocrine, surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EleVision™ IR Platform was provided by Medtronic® to the endocrine surgery department at Sheffield Teaching Hospitals for this study. Medtronic® did not have any role in the design, conduct, analysis or write up of this study. EleVision™ IR Platform was provided free of charge for this study and no financial support was offered by the company to any research team member., (Copyright © 2023 Pannu, O’Connor-Manson, Wyld and Balasubramanian.)

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

Objective: We aimed to determine the incidence of major cardiovascular and cerebrovascular events in elderly patients with primary hyperparathyroidism (pHPT) and the impact of parathyroidectomy., Summary Background Data: pHPT is underdiagnosed and undertreated in the United States. It is associated with increased cardiovascular disease risk, but its association with cerebrovascular disease risk is not well-established. It is also unknown if parathyroidectomy reduces these risks., Methods: The incidence of major cerebrovascular and cardiovascular events in 108,869 patients with pHPT diagnosed in the Medicare database between 2008 and 2018 and a matched comparison group of 1,088,690 Medicare subjects was prospectively evaluated. We estimated hazard ratios (HR) for the association of pHPT and parathyroidectomy for the risk of these outcomes from Cox proportional hazards models. Survival curves were calculated to obtain 5-year disease-free survival estimates., Results: For patients with pHPT, five-year disease-free survival was lower, and HRs were higher than the comparison group for any outcome (75.9% vs. 78.4; HR 1.11, 95% confidence interval [CI] 1.09-1.13), major cerebrovascular events (84.5% vs. 86.3%; HR 1.14, 95% CI 1.12-1.17), and major cardiovascular events (87.7% vs. 88.8%; HR 1.06, 95% CI 1.03-1.08). However, in patients who had parathyroidectomy, the risks of major cerebrovascular and cardiovascular events did not differ from the comparison cohort. The lower risk in patients who had parathyroidectomy was maintained in subgroup analyses., Conclusions: Older patients with pHPT have an increased risk of major cerebrovascular and cardiovascular events compared with patients without the disease. Physicians treating older patients with primary hyperparathyroidism should consider parathyroidectomy.R.M.P. and N.N. contributed equally to the preparation of this manuscript., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Spontaneous or fine-needle aspiration (FNA)-induced remission of primary hyperparathyroidism (PHPT) is an extremely rare phenomenon with variable outcomes. We report a 75-year-old Male who initially presented with left ureteric calculi and was found to have PHPT. Imaging studies including ultrasound neck, parathyroid sestamibi scan and computed tomography of thorax, abdomen, and pelvis failed to identify the culprit lesion and exploratory parathyroidectomy was planned. Before surgery, he underwent FNA for cytology of a right cold thyroid nodule which was complicated with a large neck haematoma and dysphagia. The cytology of the aspirated fluid was consistent with a benign cyst. One month after the procedure, serum calcium and phosphate normalised along with resolution of haematoma. He remained in biochemical remission at 1-year follow-up with the latest ultrasound of neck showing resolution of a large colloid nodule that was previously seen occupying the right thyroid lobe., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Although parathyroid bone disease is rarely seen nowadays, skeletal manifestation can be the first sign of hyperparathyroidism (HPT) in some clinical practice. Nevertheless, the diagnosis of HPT is often overlooked. We describe three cases of multiple brown tumors (BT) in which bone pain and destruction were the first symptoms that masqueraded as a malignancy. However, according to the results of bone scan and targeted single-photon emission computed tomography/computed tomography (SPECT/CT), we considered BTs as the diagnosis in all of three cases. The final diagnoses were confirmed by laboratory tests and post-parathyroidectomy pathology. Parathyroid hormone (PTH) is significantly elevated in primary hyperparathyroidism (PHPT) as we know. However, such elevation is virtually never seen in malignancies. Diffuse or multiple foci of tracer uptakes in the bone scan were always seen in bone metastasis, multiple myeloma, and other bone neoplasm. When patients visited nuclear medicine for first consultation without biochemical results, radiological evidence from planar bone scan and targeted SPECT/CT can help in distinguishing the skeletal diseases. Lytic bone lesions with sclerosis, intra-focal or ectopic ossification and calcification, fluid-fluid level, and distribution of the lesions may be helpful in the differential diagnosis in these reported cases. In conclusion, when patients present with multiple foci of uptake on bone scan, targeted SPECT/CT is acquired for suspicious lesions, which can increase the diagnostic sensitivity and reduce unnecessary interventions and treatment. Moreover, BTs should be always kept in differential diagnosis of multiple lesions without a conclusive primary tumor., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes., Methods: A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020., Results: The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9)., Conclusions: Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

Objective: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45)., Design: Retrospective single-center cohort study., Patients and Measurements: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery., Results: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas., Conclusions: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient's normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.

Background: The extent of parathyroidectomy (PTX) recommendation in patients with lithium-associated hyperparathyroidism (LAH) remains controversial. The primary objectives of this study were to analyze extent of surgery, complications, and long-term outcomes., Methods: A population-based study, including all primary hyperparathyroidism (PHPT) patients who underwent PTX in Sweden between 2008 and 2017. Data on exhibited lithium prescriptions, morbidity, surgical approach, and outcomes were collected from relevant national registers and the Scandinavian Quality Register of Thyroid, Parathyroid, and Adrenal Surgery. Patients with lithium exposure before PTX were defined as having LAH. Descriptive summary statistics and regression models were used to evaluate differences in comorbidities, surgical approach, and outcomes between LAH and PHPT not exposed to lithium (non-LAH)., Results: Lithium exposure was significantly more common among PHPT (n = 202, 2.3%) than in controls (n = 416, 0.5%); OR 5.0 (95% CI 4.2-5.9). The risk of LAH correlated to the length of lithium exposure. In the LAH-group, the surgical procedures were more extensive and associated with a higher risk of postoperative bleeding, wound infections, persistent hypercalcemia, and hypocalcemia that remained after adjustment for the higher percentage of multiglandular disease. However, the cumulative risk of re-admission for PHPT was similar the first years after PTX and primarily elevated for patients with >5 years duration of lithium exposure prior to surgery., Conclusions: The findings support the perception of LAH as a complex entity. We recommend a functionally oriented approach, aimed to obtain and maintain normocalcemia for as long as possible, minimizing the risk of permanent hypoparathyroidism, and accepting some risk of recurrence., (© 2024 The Authors. World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Aim: Magnesium (Mg) homeostasis is closely related to calcium (Ca) metabolism. Hypercalcemia inhibits the reabsorption of Mg from the kidneys, leading to hypomagnesemia. Therefore, patients with primary hyperparathyroidism (PHPT) are predisposed to hypomagnesemia. However, there are few studies on the clinical significance of hypomagnesemia in PHPT. The aim of this study was to retrospectively evaluate the association of hypomagnesemia with the clinical outcomes of PHPT., Materials and Methods: A retrospective evaluation was made of the data of 538 consecutive patients (478 females, 60 males) diagnosed with PHPT in our center., Results: The mean age of the study population was 56.5 ± 11.66 years. The mean serum Mg level was 2 ± 0.26 mg/dl. Asymptomatic disease was present in 241 (44%) patients. Symptomatic patients with osteoporosis, Ca level ≥11.2 mg/dl, and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 had lower levels of Mg (p < 0.05). Hypomagnesemia was detected in 129 of 538 patients (23.9%). The patients with hypomagnesemia had a higher rate of symptomatic disease (80% vs. 48%, p < 0.0001). The serum parathormone (PTH) level was found to be higher in patients with hypomagnesemia and the lumbar and femur T-scores and serum vitamin D levels were lower (p < 0.05). Patients with hypomagnesemia had higher rates of kidney stones (34% vs. 21%, p = 0.003) and osteoporosis (74% vs. 32%, p < 0.001). Multivariate logistic regression analysis revealed that hypomagnesemia had a significant effect on the development of symptomatic disease (OR:6.88, CI 95%: 5.20-11.27, p < 0.001)., Conclusions: The current study results demonstrate that hypomagnesemia may be associated with a higher risk of osteoporosis and kidney stones in PHPT patients. Routine evaluation of serum Mg may predict the clinical outcomes of PHPT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Substantial disparities in the utilization of parathyroidectomy for primary hyperparathyroidism have been reported. This study aimed to analyse regional variations in parathyroidectomy incidence with respect to the patient's disease burden and socioeconomic status., Methods: A population-based case-control study included all patients with primary hyperparathyroidism who underwent parathyroidectomy in Sweden between 2008 and 2017 and 10 matched controls. Data on demographic and socioeconomic variables, co-morbidities and drug prescriptions were collected from relevant national registers. Conditional logistic regression was used to analyse predictors of parathyroidectomy., Results: A total of 8626 patients with primary hyperparathyroidism (77% women) underwent parathyroidectomy during the study interval. The annual incidence of parathyroidectomy was 9.0 per 100 000 persons. The annual age-adjusted regional incidences of parathyroidectomy varied between 3.3 and 16.9 operations per 100 000 inhabitants. Except for a small underrepresentation of patients with lower education, no effect of socioeconomic variables was observed. Compared with matched controls, the parathyroidectomy group had increased odds ratios of having developed classical symptoms of primary hyperparathyroidism and being prescribed medication against cardiovascular disorders and psychiatric illness at the time of parathyroidectomy. Increased risks of kidney stones and osteoporosis were observed 5 years before parathyroidectomy. Patients with primary hyperparathyroidism selected for parathyroidectomy from regions with a low incidence of operations had a higher prevalence of kidney stones, osteoporosis and hypertension, as well as larger adenomas and higher calcium levels at the time of parathyroidectomy compared with patients in high-incidence regions., Conclusion: The considerable variation in parathyroidectomy seems more likely associated with different clinical thresholds for detection of primary hyperparathyroidism and referral to surgery than socioeconomic disparities., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

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Objective: To investigate the utility of texture analysis in detecting osseous changes associated with hyperparathyroidism on neck CT examinations compared with control patients and to explore the best regions in the head and neck to evaluate changes in the trabecular architecture secondary to hyperparathyroidism., Methods: Patients with hyperparathyroidism who underwent a 4D CT of the neck with contrast were included in this study. Age-matched control patients with no history of hyperparathyroidism who underwent a contrast-enhanced neck CT were also included. Mandibular condyles, bilateral mandibular bodies, the body of the C4 vertebra, the manubrium of the sternum, and bilateral clavicular heads were selected for analysis, and oval-shaped regions of interest were manually placed. These segmented areas were imported into an in-house developed texture analysis program, and 41 texture analysis features were extracted. A mixed linear regression model was used to compare differences in the texture analysis features contoured at each of the osseous structures between patients with hyperparathyroidism and age-matched control patients., Results: A total of 30 patients with hyperparathyroidism and 30 age-matched control patients were included in this study. Statistically significant differences in texture features between patients with hyperparathyroidism and control patients in all 8 investigated osseous regions. The sternum showed the greatest number of texture features with statistically significant differences between these groups., Conclusions: Some CT texture features demonstrated statistically significant differences between patients with hyperparathyroidism and control patients. The results suggest that texture features may discriminate changes in the osseous architecture of the head and neck in patients with hyperparathyroidism., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Superscan on PET/CT has been reported in the literature and mainly involved metastatic diseases. We report an uncommon case of a metabolic superscan on 18 F-FDG PET/CT in a 56-year-old man with end-stage renal disease on hemodialysis who presented with secondary hyperparathyroidism. Parathyroid scintigraphy showed 2 lesions posteroinferior to both thyroid lobes, suggestive of parathyroid adenoma/hyperplasia. FDG PET/CT performed to assess for pulmonary nodules revealed diffuse FDG hypermetabolism involving the visualized skull, mandible, spine, sternum, ribs, and appendicular skeleton without corresponding CT lesion with no urinary radiotracer excretion, consistent with metabolic superscan secondary to renal osteodystrophy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy., Methods: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm 2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases., Results: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm 2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm 2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm 2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001)., Conclusion: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypercalcemia has been associated with hypergastrinemia in humans. Hypergastrinemia could be responsible for gastrointestinal (GI) signs in dogs with primary hyperparathyroidism (PHPT)., Hypothesis/objectives: (a) Determine whether hypergastrinemia occurs in dogs with PHPT, (b) assess for potential correlations among ionized calcium (iCa), parathyroid hormone (PTH), and serum gastrin concentrations, and (c) determine whether gastrin concentrations decrease after management of PHPT., Animals: Phase 1: 151 client-owned dogs at the time of PHPT diagnosis, Phase 2: 24 dogs that underwent treatment for PHPT., Methods: Dogs with azotemia, concurrent disease, or those receiving acid suppressants were excluded. Twenty-four treated dogs had baseline and repeat quantification of serum gastrin, PTH, and iCa concentrations 4 weeks after treatment. The effect of treatment on gastrin, iCa, and PTH concentrations was assessed using Wilcoxon signed rank sum tests. Fisher exact testing was used to compare the proportion of dogs with hypergastrinemia in dogs with and without GI signs., Results: Twenty-seven of 151 PHPT dogs (17.9%) had increased pre-treatment serum gastrin concentrations (median, 45.0 ng/L; interquartile range [IQR], 20.0 ng/L). Gastrin concentrations were not correlated with iCa (P = .92) or PTH (P = .60). Treatment of PHPT decreased PTH (P < .001) and iCa concentrations (P < .001), but not gastrin concentrations (P = .15). The proportion of dogs with hypergastrinemia with and without GI signs did not differ (P = 1.00)., Conclusions and Clinical Importance: Mild increases in serum gastrin concentrations may be seen in dogs with PHPT, but this finding is independent of the presence of GI signs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Differences in presenting symptoms of primary hyperparathyroidism and outcomes of parathyroidectomy between sexes have been described, but whether these can be assessed by perioperative use of a validated tool, such as the Pasieka Parathyroidectomy Assessment Score, is unknown., Method: All patients with primary hyperparathyroidism were asked to complete symptom assessment at the preoperative and postoperative visits. The assessment included a query for 13 Pasieka Parathyroidectomy Assessment Score parameters evaluated using a visual analog scale as described by Pasieka (summative score 0-1,300), and general quality of life and wellness. A review of a prospectively maintained database of primary hyperparathyroidism patients (January 2016-December 2019) was performed, and those who had a 6-month cure after initial parathyroidectomy were included., Results: The study cohort was mostly women (77%, 541/701). The median preoperative Pasieka Parathyroidectomy Assessment Score was higher in women (155, 0-1,190) than in men (80.5, 0-855, P < .001), although there were similar rates of asymptomatic primary hyperparathyroidism (Pasieka Parathyroidectomy Assessment Score = 0, 12.5% vs 7%, P = .042). After curative parathyroidectomy, women reported a substantial reduction in symptomatology, with Pasieka Parathyroidectomy Assessment Score declining by 35% at initial postoperative visit (median, 155 vs 100, P < .001), further decreasing to 48% by 6 months (155 vs 80, P < .001). The Pasieka Parathyroidectomy Assessment Score in men did change but to a much smaller degree at both the initial postoperative visit (80.5 vs 70; P = .036) and at 6 months (80.5 vs 57.5; P = .048)., Conclusion: When assessed with the Pasieka Parathyroidectomy Assessment Score, improvement in symptoms was clearly demonstrated for women after curative parathyroidectomy. Whether symptom improvement also occurs in men is less apparent but may be due to disparities in the development and validation of outcomes tools in general., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Measurement of bone mineral density (BMD) with quantitative CT (QCT) carries several advantages over other densitometric techniques, including superior assessment of the spine. As most QCT studies evaluated the lumbar spine, measurements of the thoracic spine are limited. We performed QCT analysis of the thoracic spine in a cohort of patients with primary hyperparathyroidism., Materials and Methods: This study was a retrospective QCT analysis of the thoracic spine on 18 F-fluorocholine PET/CT scans in patients with primary hyperparathyroidism patients between March 2018 and December 2022. Correlations between QCT-derived BMD or Hounsfield units (HU) and demographic data, laboratory parameters, results from histopathological examination after parathyroidectomy and results of DXA imaging were analyzed, when available., Results: In 189 patients, mean QCT-derived BMD at the thoracic spine was 85.6 mg/cm 3 . Results from recent DXA were available in 122 patients. Mean thoracic QCT-derived BMD and HU were significantly correlated with DXA-derived BMD in lumbar spine, total hip and femoral neck and with the lowest T-score at DXA imaging. Only weak correlations were found with BMI or 18 F-fluorocholine uptake, while no significant correlations were found with adenoma weight, PTH or calcium levels., Conclusion: Our study confirms correlation between QCT-derived BMD in the thoracic spine with age and DXA-derived BMD measurements within a population of patients with primary hyperparathyroidism. Establishment of reference BMD values for individual thoracic vertebrae, may allow direct osteoporosis classification on thoracic CT imaging., (Copyright © 2023 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Abstract: A 54-year-old woman diagnosed with multiple endocrine neoplasia syndrome type 1 and primary hyperparathyroidism underwent total parathyroidectomy with autotransplantation of parathyroid tissue fragments in the right forearm in 1999. Since several years later, follow-up laboratory examinations showed the relapse of hypercalcemia; the patient started cinacalcet therapy. To exclude the presence of hyperfunctioning parathyroid glands in ortotopic or ectopic sites, a PET/CT scan with 18F-fluorocholine was performed. The PET/CT scan excluded the presence of ortotopic and ectopic parathyroid glands but showed a hyperplastic parathyroid fragment in the right forearm, responsible for the patient's persistent hypercalcemia., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism., Research Design and Methods: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis., Results: The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes., Conclusions: Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies., (© 2023. The Author(s).)

Introduction: Patients with primary hyperparathyroidism (1HPT) undergoing reoperative or subtotal parathyroidectomy (PTX) may undergo autotransplantation (ATX) when the viability of remaining tissue is unknown. This study aims to identify whether intraoperative parathyroid hormone levels (IOPTH) can determine ATX candidacy., Methods: Patients with 1HPT who underwent PTX with ATX at our institution were identified. IOPTH and PTH values within 24 h, 2-4 weeks, and >1 month postoperative were analyzed. Patients were classified as either a candidate for ATX (low PTH after 2-4 weeks) or not a candidate based on postoperative PTH (normal PTH after 2-4 weeks). Associations of ATX candidate status with demographic and clinical attributes were studied., Results: 268 had a reoperative (49%) or subtotal PTX with ATX. 151 had data for PTH analysis, and 21 (14%) were identified as candidates for ATX. The mean % decline in IOPTH from baseline to 20 min post-excision was 51% in noncandidates vs 73% in candidates (P = .002). The mean change in IOPTH from baseline to final was 52% in noncandidates and 83% in candidates (P = .009). A decrease in IOPTH from baseline to 20 min post-excision of 23.4% or greater or a final PTH of 52 pg/mL or less would be an indication for ATX. Of the 21 who needed an ATX, it failed in 10., Conclusion: Parathyroid ATX is frequently unnecessary, and the viability is less than expected. While candidates for ATX have a greater IOPTH % decline at all points during surgery and a lower final IOPTH, the clinical practicality of using IOPTH to determine ATX candidacy is limited., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: to assess the hormonal and metabolic disorders in the Chernobyl nuclear power plant (ChNPP) accident survivors (AS), having got secondary normocalcemic non-renal hyperparathyroidism (HPT) in the late period upon exposure to ionizing radiation (IR)., Materials and Methods: The routine clinical, anthropometric, instrumental (thyroid and parathyroid diagnosticultrasound), laboratory (biochemical, hormonal), statistical methods were applied. In both prospective (n = 48, control group n = 19) and retrospective studies the data of 2,234 subjects including 1,372 irradiated adults (862 non-irradiated persons in the control group) were evaluated. Clinical consequences of exposure to IR on the endocrine system were evaluated in ChNPP AS., Results: High prevalence of vitamin D lack or deficiency was established retrospectively in 81.8 % of the ChNPP AS and in 89.5 % of the control group subjects. In general, there was neither effect of exposure to IR on the vitamin D status in study subjects, nor any difference between the study groups. According to diagnostic ultrasound patterns the parathyroid hyperplasia was diagnosed in 629 cases (28.2 %). Among the ChNPP AS it was found in 32.7 % of cases (n = 450) vs. 20.7 % (p > 0.005) in the control group (a 1.6-fold difference). HPT diagnosed as serum parathyroid hormone content > 65 ng/ml was diagnosed in 123 cases (21.1 %) i.e. in almost every fifth person. Increased serum level of parathyroid hormone was found in the 94 ChNPP AS and in 25 persons of the comparison group. In other words, the frequency of HPT was 23.7 % among the AS being significantly more than in the comparison group (13.2 %, p < 0.005). Frequency of normocalcemic non-renal HPT was slightly different by years of observation with a trend to the year-by-year increase., Conclusions: High prevalence of vitamin D lack or deficiency was established in the ChNPP AS, being however independent of exposure to IR. Frequency of parathyroid hyperplasia/adenoma was 1.6 times higher in the irradiated subjects than in persons of the control group. Annual increase in frequency of the non-renal normocalcemic HPT was also revealed reaching nowadays 23.7 % among the AS, which is significantly higher than in the comparison group., (O. V. Kaminskyi, O. V. Kopylova, D. E. Afanasyev, I. G. Chikalova, I. M. Muraviova, O. O. Dombrovska, O. P. Lischenko, L. O. Tsvet.)

The patient is a female in her 60s with a remote history of a near-total thyroidectomy in 1997 for multinodular goitre. At the initial operation, she sustained a left recurrent laryngeal nerve injury. A devascularised parathyroid gland was autotransplanted into the right sternocleidomastoid muscle. She had been off of thyroid hormone for long periods, and her most recent levothyroxine requirement had fallen to only 25 mcg daily. The patient presented more than 20 years after her thyroidectomy with hoarseness, fatigue and dyspnoea. Laboratory studies suggested primary hyperparathyroidism. Imaging demonstrated bilateral pulmonary emboli and bulky thyroid tissue extending into her mediastinum. She underwent a completion thyroidectomy with the removal of a parathyroid adenoma arising in the autotransplanted parathyroid. This case illustrates the possibility of regrowth of benign thyroid tissue after thyroidectomy. In addition, to our knowledge, this is the first case report of a parathyroid adenoma arising from autotransplantation of a normal parathyroid., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Parathyroid carcinoma (PC) affects 0.1-0.3% of the general population and represents the rarest malignant neoplasms among endocrinological diseases, comprising less than 1%. The best therapeutic treatment and management methods are still debated in the literature. The aim of this study is to evaluate the management and surgical treatment of parathyroid carcinoma after 6 years of enrolment with the Endocrine Surgery Unit of the University Hospital of Bari., Materials and Methods: A retrospective observational study was carried out using a prospectively maintained database of patients affected by primary hyperparathyroidism between January 2017 and September 2022. Consecutive patients over 18 years old with a final histopathological finding of PC were included in the study. Patients with secondary or tertiary hyperparathyroidism, parathyroid hyperplasia, and parathyroid adenoma were excluded. All patients underwent follow-up every 6 months for the first 2 years, and annually thereafter., Results: In this study, 9 out of 40 patients affected by hyperparathyroidism were included; 6 (66.6%) were female and 3 (33.3%) were male patients, with a median age of 59 years (IQR 46-62). None had a family history of PC. No mortality was recorded while the incidence of recurrence was 22.2%, with a disease-free survival of 8 and 10 months. Parathyroidectomy was performed in five patients, while four patients underwent parathyroidectomy with concurrent thyroidectomy for thyroid goitre. No intraoperative complications were recorded. Open parathyroidectomy was performed with a mini-cervicotomy in seven patients, while two patients underwent robotic surgery. All patients were discharged on the second postoperative day., Conclusion: PC represents a great challenge in terms of preoperative diagnosis, management and treatment. A surgical approach represents the first best option for PC in referral endocrine surgery units. The early identification of risky patients should be the dominant goal to plan an appropriate therapy and to perform adequate en bloc surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Laforgia, Tomasicchio, Cavalera, Sblendorio, Spadone, Anelli, Lobascio, Marzaioli, Panebianco and Pezzolla.)

Even though primary hyperparathyroidism (PHPT) is a common endocrine disorder, due to better and more regular screening, the usual presentation is only seen in less than 15% of cases of PHPT. The authors present the case of a young female patient with a previous medical history of depression and nephrolithiasis, with one year of bone pain, that had become progressively worse and disabling. In the initial work-up, several lytic bone lesions and moderate hypercalcemia were found, leading to admission of the patient in the Internal Medicine ward for investigation and treatment. The ensuing investigation revealed PHPT due to hyperfunctioning parathyroid adenoma. The patient underwent a parathyroidectomy and at the follow-up assessment two months after discharge, she reported no symptoms and a computer tomography scan showed regression of the lytic lesions. This case is a reminder that severe symptomatic PHPT, a rare form in developed countries nowadays, still exists, and even though it is a medical condition, collaboration with surgical specialties is necessary to ensure the best possible treatment and prognosis.

Background: Accurate preoperative localisation of parathyroid adenoma is imperative for the success of minimally invasive parathyroidectomy (MIP)., Objective: Our study aimed to evaluate the role of four-dimensional computer tomography (4D-CT) scan as an imaging modality in patients with failed and discordant localisation reported in the first-line imaging modalities (ultrasonography and 99m Tc-MIBI-SPECT/CT)., Methods: This is a prospective cohort study performed at a university teaching centre from March 2013 to July 2021. All patients with primary hyperparathyroidism who had failed localisation by ultrasonography and 99m Tc-MIBI-SPECT/CT (SpCT), or discordance between them, had 4D-CT performed in this study., Results: One hundred and two sporadic cases of pHPT with failed/discordant first-line imaging had 4D-CT imaging prior to parathyroidectomy. In 102 patients, 105 parathyroid adenomas were reported on histopathology. 4D-CT was able to localise 78% of them to the correct side and 64% to the correct quadrant in 102 patients, as compared with US (correct side 21%, correct quadrant 16%) and 99m Tc-MIBI-SPECT/CT (correct side 36%, correct quadrant 31%). 4D-CT had a sensitivity, precision, accuracy and F1 score for correct quadrant localisation as 79%, 81%, 66% and 80%; and for correct side localisation as 82%, 98%, 80% and 89%, respectively. 4D-CT was able to identify three ectopic adenomas (two in superior mediastinum and one in the oesophageal wall) which were not detected on US or SpCT., Conclusion: 4D-CT was found to be sensitive and accurate in preoperative localising of the diseased parathyroid glands after failed/discordant US and SpCT. This led to more patients being offered MIP as the primary surgery and improved operative outcomes.

Objective: Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)- related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT., Design, Patients and Measurements: This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021., Results: The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p < .001), had lower mean serum calcium (p = .01) and alkaline phosphatase (ALP; p = .03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p < .001) and femoral neck (p = .007). The prevalence of renal stones (p = .03) and their complications (p = .006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p < .001], ALP levels within reference range [OR 5.6, p = .02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p < .001]., Conclusions: Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT., (© 2023 John Wiley & Sons Ltd.)

Introduction: Parathyroidectomy is underperformed despite clear benefits in primary hyperparathyroidism (PHPT). We evaluated disparities in receipt of parathyroidectomy following PHPT diagnosis to explore barriers to care., Methods: Adults diagnosed with PHPT 2013-2018 at a health system were identified. Recommended indications for parathyroidectomy include age ≤50 y, calcium >11 mg/dL, or the presence of nephrolithiasis, hypercalciuria, nephrocalcinosis, decreased glomerular filtration rate, osteopenia, osteoporosis, or pathological fracture 1 y prior to diagnosis. Kaplan-Meier analysis assessed rates of parathyroidectomy within 12 mo following diagnosis as well as median time to parathyroidectomy, and multivariable Cox proportional hazards analyses assessed factors associated with undergoing parathyroidectomy., Results: Of 2409 patients, 75% were females, 12% aged ≤50 y, and 92% non-Hispanic White, while 52% had Medicaid/Medicare, 36% were commercial/self-pay or uninsured, and 12% unknown. Parathyroidectomy was performed within 1 y in 50% of patients. Within the 68% that met recommendations, parathyroidectomy was performed within 1 y in 54%; median time from diagnosis to surgery was shorter for males, patients aged ≤50 y, commercial/self-pay/no insurance patients (versus Medicaid/Medicare), and those with fewer comorbidities, P < 0.05. Multivariable analysis demonstrated non-Hispanic White patients and those with commercial/self-pay/uninsured were more likely to undergo parathyroidectomy after adjusting for comorbidity, age, and facility site. Among those strongly indicated, patients not on Medicare/Medicaid and aged ≤50 y were more likely to undergo parathyroidectomy after adjusting for race, comorbidity, and facility site., Conclusions: Disparities in parathyroidectomy for PHPT were observed. Insurance type was associated with undergoing parathyroidectomy; patients on governmental insurance were less likely to undergo surgery and waited longer for surgery despite strong indications. Barriers to referral and access to surgery should be investigated and addressed to optimize all patients' access to care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism in pregnancy is a rare disease that can have detrimental effects on both maternal and fetal/neonatal outcomes. The physiological changes that occur during pregnancy can complicate the diagnosis, imaging examinations, and treatment of this disorder. To enhance our understanding and management of primary hyperparathyroidism in pregnancy, experts from various fields, including endocrinology, obstetrics, surgery, ultrasonography, nuclear medicine, pediatrics, nephrology, and general practice in China, collaborated to develop a consensus addressing the critical aspects of the diagnosis and treatment of primary hyperparathyroidism in pregnancy with a multidisciplinary team approach. This consensus provides valuable guidance for healthcare professionals in managing this condition, ultimately improving outcomes for both mothers and their babies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: There is no specific recommendation for management in pregnant women: the aim of this review, based on a clinical case study, is to clarify its development, complications, risk factor and treatment., Methods: A review of the literature was performed by consulting the Pubmed, Cochrane Library, and Science Direct databases., Results: Primary hyperparathyroidism is defined as excessive production of parathyroid hormone resulting in hypercalcemia. The prevalence of primary hyperparathyroidism during pregnancy is not known. Indeed, the symptomatology, related to hypercalcemia, is not very specific and easily confused with the clinical manifestations of pregnancy. The physiological changes specific to the pregnant state frequently lead to a slight hypocalcemia which may complicate the diagnosis of primary hyperparathyroidism. Primary hyperparathyroidism results from a parathyroid adenoma in the majority of cases and is detected by ultrasound during pregnancy. Primary hyperparathyroidism in pregnancy causes significant risks to both mother and fetus. The maternal complication rate is 14-67%, however, the most serious complication is hypercalcemic crisis, which requires increased surveillance in the postpartum period. Obstetrical complications are also induced by primary hyperparathyroidism, such as acute polyhydramnios, or intrauterine growth retardation. The fetal complication rate can reach 45-80% of cases with neonatal hypocalcemia as the main complication. If medical treatment is based on hyperhydration, only surgical treatment is curative., Conclusion: Surgery should be proposed to symptomatic patients or those with high blood calcium levels, discussed in interdisciplinary committee and should be organized ideally in the second trimester to avoid maternal and fetal complications., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Radiofrequency ablation (RFA) has emerged as a minimally invasive approach to single parathyroid adenoma in primary hyperparathyroidism; however, there is limited evidence on its effectiveness., Objective: To evaluate the effectiveness and safety of RFA to treat hyper-functioning parathyroid lesions suggestive of adenomas., Material and Methods: A prospective study was conducted in consecutive patients with primary hyperparathyroidism treated with RFA for single parathyroid lesions in our reference center between November 2017 and June 2021. Pre-treatment (baseline) and follow-up analytical data were gathered on total protein-adjusted calcium, parathyroid hormone [PTH], phosphorus, and 24-h urine calcium. Effectiveness was defined as complete response (normal calcium and PTH), partial response (reduced but not normalized PTH with normal serum calcium), or disease persistence (elevated calcium and PTH). SPSS 15.0 was used for statistical analysis., Results: Four of thirty-three enrolled patients were lost to the follow-up. The final sample comprised 29 patients (22 females) with mean age of 60.93 ± 13.28 years followed up for a mean of 16.29 ± 7.23 months. Complete response was observed in 48.27%, partial response in 37.93%, and hyperparathyroidism persistence in 13.79%. Serum calcium and PTH levels were significantly lower at 1 and 2 years of post-treatment than at baseline. Adverse effects were mild, with two cases of dysphonia (self-limited in one patient) and no cases of hypocalcaemia or hypoparathyroidism., Conclusion: RFA may be a safe and effective technique to treat hyper-functioning parathyroid lesions in selected patients., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background: Primary hyperparathyroidism (PHPT) is an endocrine disorder with high serum calcium and parathyroid hormone (PTH) levels. Excessive secretion of PTH can cause bone loss and may have potential damage to implant fixation after total knee arthroplasty (TKA). However, there is currently no research or literature reporting prosthesis loosening after TKA associated with PHPT., Case Presentation: This case report describes a TKA failure of tibial prothesis loosening associated with PHPT. The patient faced aggravated pain and difficulty in walking 6 months after the primary TKA. Further examinations showed high serum calcium and PTH levels indicating the presence of PHPT. After the surgery of parathyroidectomy, the patient received revision TKA with 3D-printed metaphyseal cone. Knee symptoms and function were finally improved., Conclusion: PHPT is a risk factor for prosthesis loosening after TKA. Preoperative screening test of serum calcium and PTH levels is important to diagnose PHPT. For patients with PHPT undergoing TKA, preoperative endocrinotherapy and parathyroidectomy are recommended to improve the survival of prosthesis., (© 2023 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: There are few data on outcomes after reintervention for persistent or recurrent primary hyperparathyroidism (PHPT). The authors hypothesized that the variation in outcomes at the hospital level after reoperation would be significant. After accounting for this variability, some patient-level clinical criteria could be identified to help inform treatment decisions in this patient population. The aim of this study was to determine whether there is significant variation in outcomes after reoperation for PHPT between hospitals (hospital-level analysis) and identify clinical factors (patient-level analysis) that influence postoperative outcomes., Materials and Methods: This retrospective multicenter cohort study was performed using the Eurocrine registry. Data from 11 countries and 76 hospitals from January 2015 to October 2020 were extracted. A generalized linear mixed model was used to assess the variation in outcomes at the hospital level and to identify risk factors of postoperative outcomes at the patient level. The primary endpoint (textbook outcome) was achieved when all six of the following postoperative conditions were met: no hypocalcemia or persistent hypercalcemia, no laryngeal nerve injury, no negative exploration, no normal parathyroid gland only on histopathology, and no postoperative death., Results: Among 13 593 patients who underwent parathyroidectomy for PHPT, 617 (4.5%) underwent reoperative parathyroidectomy. At follow-up, 231 patients (37.4%) were hypocalcemic, 346 (56.1%) were normocalcemic without treatment, and 40 (6.5%) had persistent hypercalcemia. Textbook outcomes were achieved in 321 (52.0%) patients. The hospital-level variation in textbook outcome rates was significant ( P <0.001), and this variation could explain 29.1% of the observed outcomes. The criterion that remained significant after controlling for inter-hospital variation was 'a single lesion on sestamibi scan or positron emission tomography (PET) imaging' (odds ratio 2.08, 95% confidence interval 1.24-3.48; P =0.005)., Conclusion: Outcomes after reoperation are significantly associated with hospital-related factors. A 'single lesion observed on preoperative sestamibi scan or PET' appears relevant to select patients before reoperation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Primary hyperparathyroidism (PHPT) can be cured through surgery, but referral for treatment is often provider dependent. A conjoint analysis was performed to identify factors influencing referral for surgery., Methods: Online survey assessed endocrinologists and other physicians who reviewed 10 patient scenarios. They decided whether to refer for surgery or medical management based on clinical (age, comorbidities, etc) and biochemical factors (mild or classic disease)., Results: Classic PHPT, age below 50, absence of comorbidities, presence of osteoporosis, and seeing a surgical provider significantly increased the likelihood of surgery referral (p < 0.001). Physician characteristics such as gender, practice duration, and setting did not have a significant influence., Conclusion: Despite published benefits of surgery, non-surgical physicians were less likely to refer PHPT patients for surgical treatment if patients were older (age ≥ 50), had comorbid conditions, or had mild disease. More education and advocacy are needed for improved access to surgery., Competing Interests: Declaration of competing interest The authors affirm that there are no personal or professional conflicts of interest associated with this study. The research was conducted impartially, and there are no relationships, whether personal or professional, that could impact the results or interpretation of the presented findings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: For a comprehensive assessment of the effect of surgery in patients with primary hyperparathyroidism (PHPT) it sounds reasonable to evaluate quality of life (QoL) and symptoms in PHPT patients at long-term after parathyroidectomy (PTE). The purpose of this study was to study the quality of life of patients with PHPT before and at different times after PTE and to determine the factors associated with its improvement after surgery., Materials and Methods: During prospective observational study, patients filled out QoL questionnaires before, 3, 12, 24 months or more after surgery. Statistical analysis was performed using the Student's t-test, the Mann-Whitney U-test, χ2 criterion, the method of generalized estimating equations (GEE) and binary logistic regression. The differences were considered significant at the level of p&lt;0.05., Results: The study included 82 patients (mean age 53,7 years, 95% female) with symptomatic (73%) and asymptomatic (27%) PHPT. Median follow-up duration was 20 (3-31) months. At 3 months after PTE, there was a significant increase in QoL for all scales of the generic SF-36 questionnaire, except for the pain scale, compared with their preoperative values, followed by the preservation of positive changes at long term after surgery (GEE, p&lt;0.05). At the long term after surgery, scores for all SF-36 scales, except for role physical functioning (p=0.011), became similar with the ones in comparison group adjusted to patients by gender and age (n=60, 52.5±9.2 years, 95% were women). An independent predictor of significant improvement in QoL after PTE was the preoperative level of the mental component according to the PHPQoL questionnaire (p=0.001) - the lower its level, the greater the probability of significant improvement in QoL according to the total PHPQoL index after surgery (OR=0.924, p=0.004)., Conclusion: PTE is accompanied by significant improvement in QoL and regression of symptoms in patients with PHPT at long term follow-up after surgery. An independent predictor of significant QoL improvement after PTE is the preoperative level of the psychological component of QoL.

Context: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, yet long-term (5- and 10-year) recurrence rates after curative surgery have been unclear., Objective: To perform the first systematic review and meta-analysis investigating the long-term recurrence rates of sporadic PHPT after successful parathyroidectomy., Methods: A comprehensive search of multiple databases (including PubMed, EMBASE, Cochrane, EBSCO-CINHAL, EMBASE, Ovid, Scopus, and Google Scholar) was performed from each database's inception to January 18, 2023. Observational studies reporting at least 5 years of follow-up data after surgical resection were included. Two reviewers independently screened articles for relevance. Of 5769 articles initially identified, 242 were examined in full-text review and 34 were deemed eligible for inclusion. Two authors independently performed data extraction and study appraisal, using the National Institutes of Health study quality assessment tools., Results: Of 30 658 participants, 350 patients (1.1%) experienced recurrence after resection. A meta-analysis of proportions was performed to obtain the pooled recurrence rates. The pooled estimate for overall recurrence rate was 1.56% (95% CI 0.96-2.28%; I2 = 91%). The pooled estimates for 5- and 10-year recurrence rate after resection were 0.23% (0.04-0.53%, 19 studies; I2 = 66%) and 1.03% (0.45-1.80%, 14 studies; I2 = 89%), respectively. Sensitivity analyses did not find a statistically significant difference when adjusting for study size, diagnosis, or surgical approach., Conclusion: Approximately 1.56% of sporadic PHPT patients eventually develop recurrence following parathyroidectomy. The initial diagnosis and procedure type does not influence recurrence rates. Consistent long-term follow-up is warranted to help identify recurrent disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)