Patients with prediabetes improve insulin resistance after surgery for primary hyperparathyroidism.

BACKGROUND: The objective of this study was to evaluate the evolution of insulin resistance at 12 months after parathyroidectomy for primary hyperparathyroidism according to the preoperative severity of glucose metabolism abnormalities. METHODS: Observational study of patients who underwent parathyroidectomy between 2016 and 2021. Prediabetes and insulin resistance were defined as fasting glucose ≥1.00 g/L (American Diabetes Association) and homeostatic model assessment of insulin resistance >2.5, respectively. RESULTS: A total of 231 patients were included. Preoperatively, 75 patients (32%) had prediabetes, and 108 patients (47%) had insulin resistance. At 12 months postoperative, homeostatic model assessment of insulin resistance values significantly decreased in patients with prediabetes (-0.69; P = .04) and in patients with insulin resistance (-0.85; P < .001). In patients with prediabetes, 48/75 (64%) decreased their insulin resistance, including 15/48 (31%) with normalization of fasting glucose. In multivariate analysis, preoperative prediabetes (1.82, 1.03-3.21; P = .037) or preoperative homeostatic model assessment of insulin resistance >2.5 (3.90, 2.23-6.75; P < .001) remained independent predictors for insulin resistance reduction observed between preoperative and 12 months postoperative. CONCLUSION: Parathyroidectomy is more likely to reduce insulin resistance in patients with primary hyperparathyroidism and prediabetes or in patients with higher preoperative homeostatic model assessment of insulin resistance values. These data support the use of the preoperative prediabetes criterion in addition to the international workshop criteria for parathyroidectomy to better select patients for surgery.

Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism.

Objective: To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients. Methods: Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells. Results: No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes. Conclusion: These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.

Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma.

Primary hyperparathyroidism is a common endocrine disorder. Interestingly, the majority (75%) of parathyroid tumors are localized to the inferior parathyroid glands. To date, the reason for this natural bias has not been investigated. We assessed the global gene expression profile of superior and inferior glands obtained from forensic autopsies. The genes with significant differential expression between superior and inferior parathyroids were further assessed by RT-PCR in 19 pairs. As an iterative approach, additional genes with an established role in parathyroid disorders, i.e., CASR, MAFB, PAX9, TBCE, TBX1, VDR, MEN1, CCND1, and CDC73 were also evaluated by RT-PCR in all 19 pairs of superior and inferior parathyroid glands. Seven homeobox genes, namely HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, and one encoding for ALDH1A2 showed a lower expression in the inferior parathyroid glands than in the superior. Conversely, SLC6A1 showed a higher expression in the inferior glands. Of the nine genes with significant differential mRNA expression among superior and inferior glands HOXB9, HOXB4 and IRX1 could be detected by western blotting/mass spectrometry. The study is the first to show the differential expression of nine genes HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, ALDH1A2, and SLC6A1 in inferior versus the superior parathyroid glands. This could have potential implications for the preferential localization of parathyroid tumors to the inferior parathyroid glands as observed in patients with primary hyperparathyroidism.

Excessive proliferation and apoptosis of parathyroid cells contribute to primary hyperparathyroidism in rabbit model.

To explore the molecular pathogenesis of primary hyperparathyroidism (PHPT), we investigated the proliferation and apoptosis of parathyroid cells in a rabbit model of diet-induced PHPT. A total of 120 adult Chinese rabbits were randomly divided into normal diet (Ca:P, 1:0.7) group (control group) or a high-phosphate diet (Ca:P, 1:7) group (experimental group). The thyroid and parathyroid complexes were harvested for 1-month interval from month 1 to month 6. The expression of proliferation markers, including proliferating cell nuclear antigen (PCNA) and cyclin-D1, and B cell lymphoma-2 (Bcl-2), were evaluated by immunohistochemistry in thyroid and parathyroid tissues. Apoptosis was quantified by DNA-fragment terminal labeling. Our results demonstrated that parathyroid cells in the experimental group started proliferating from the end of the 2nd month, the expression of PCNA, Bcl-2, and cyclin-D1 were significantly higher in the PHPT group than those of the control group (p<0.05). Furthermore, the apoptosis index (AI) was positively correlated with the glandular cell count and expression of PCNA in the 6th month in the PHPT group. Overall, our results suggested that excessive proliferation and apoptosis of parathyroid cells may contribute to the pathogenesis of PHPT through PCNA-related, Bcl-2-related, and cyclin-D1-related pathways.

Total and free vitamin D metabolites in patients with primary hyperparathyroidism.

PURPOSE: To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio" in PHPT patients with low or insufficient vitamin D status. METHODS: Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. RESULTS: Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p < 0.001). The serum concentration of free 25(OH)D and total 1,25(OH)2D were similar between the two groups; but free 1,25(OH)2D levels were about 26% higher in the PHPT patients compared to controls (p < 0.001). PHPT patients had a significantly higher activation ratio (p < 0.01), although their total 25(OH)D were lower than controls. The free (but not total) 1,25(OH)2D level was inversely correlated with DBP (p < 0.01). Both free 1,25(OH)2D levels and activation ratio were positively correlated with iPTH and calcium levels (p < 0.01). The activation ratio was highly correlated with levels of total vitamin D stores and free vitamin D metabolites (p < 0.001). CONCLUSION: Patients with PHPT had significantly higher free 1,25(OH)2D levels and activation ratio compared to control subjects. We suggest that levels of free vitamin D metabolites and vitamin D activation ratio may provide additional values for the diagnosis and therapeutic choices in these patient populations with compromised vitamin D status.

CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study.

PURPOSE: Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. MATERIALS AND METHODS: We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. RESULTS: Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p < < 0.05). The mean histo-score of normal rims was intermediate between the two (p < < 0.05). Cytoplasmic expression was strong in all autopsy-derived tissues, weak/negative in hyperplasia (100%), moderate in 16% adenomas, and 43% carcinomas. CONCLUSIONS: Normal autopsy-derived parathyroid tissues showed strong but predominantly incomplete membranous expression. Surface CaSR expression decreased in PHPT and is probably an early event in parathyroid adenoma, seen even in normal rims. Whether there is a defect in CaSR trafficking from the cytoplasm to the cell surface in adenoma and carcinoma needs further evaluation.

Case Report: Severe Neonatal Course in Paternally Derived Familial Hypocalciuric Hypercalcemia.

Familial hypocalciuric hypercalcemia (FHH, [OMIM #145980]) is recognized as a benign endocrine condition affecting PTH and calcium levels due to heterozygous inactivating mutations in the calcium sensing receptor (CaSR). The condition is often un- or misdiagnosed but may have a prevalence as high as 74 in 100.000. Here, the neonatal courses of two brothers with paternally inherited FHH (CaSR c.554G>A; p.(Arg185Gln)) are described. The older brother was born preterm at 25 weeks gestation with hypercalcemia and hyperparathyroidism. The younger brother, born full-term, had severe hyperparathyroidism, muscular hypotonia, thrombocytopenia, failure to thrive and multiple metaphyseal fractures. Treatment with cinacalcet was initiated, which resulted in subsequent reduction of PTH levels and prompt clinical improvement. While it is known that homozygous mutations in CaSR may lead to life-threatening forms of neonatal severe hyperparathyroidism (NSHPT), few reports have described a severe clinical course in neonates with FHH due to heterozygous mutations. However, based on the pathophysiological framework, in de novo or paternally transmitted FHH the differing calcium needs of mother and fetus can be expected to induce fetal hyperparathyroidism and may result in severe perinatal complications as described in this report. In summary, FHH is a mostly benign condition, but transient neonatal hyperparathyroidism may occur in affected neonates if the mutation is paternally inherited. If severe, the condition can be treated successfully with cinacalcet. Patients with FHH should be informed about the risk of neonatal disease manifestation in order to monitor pregnancies and neonates.

Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy.

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.

Ex Vivo Intact Tissue Analysis Reveals Alternative Calcium-sensing Behaviors in Parathyroid Adenomas.

CONTEXT: The biochemical basis for clinical variability in primary hyperparathyroidism (PHPT) is poorly understood. OBJECTIVE: This study aimed to define parathyroid tumor biochemical properties associated with calcium-sensing failure in PHPT patients, and to relate differences in these profiles to variations in clinical presentation. METHODS: Preoperative clinical data from a sequential series of 39 patients undergoing surgery for PHPT at an endocrine surgery referral center in a large, public university hospital were evaluated for correlation to parathyroid tumor biochemical behavior. An intact tissue, ex vivo interrogative assay was employed to evaluate the calcium-sensing capacity of parathyroid adenomas relative to normal donor glands. Tumors were functionally classified based on calcium dose-response curve profiles, and clinical parameters were compared among the respective classes. Changes in the relative expression of 3 key components in the calcium/parathyroid hormone (PTH) signaling axis-CASR, RGS5, and RCAN1-were evaluated as potential mechanisms for calcium-sensing failure. RESULTS: Parathyroid adenomas grouped into 3 distinct functional classes. Tumors with diminished calcium sensitivity were the most common (18 of 39) and were strongly associated with reduced bone mineral density (P = 0.0009). Tumors with no calcium-sensing deficit (11 of 39) were associated with higher preoperative PTH (P = 0.036). A third group (6/39) displayed a nonsigmoid calcium/PTH response curve; 4 of these 6 tumors expressed elevated RCAN1. CONCLUSION: Calcium-sensing capacity varies among parathyroid tumors but downregulation of the calcium-sensing receptor (CASR) is not an obligate underlying mechanism. Differences in tumor calcium responsiveness may contribute to variations in PHPT clinical presentation.

Simplified intraoperative parathormone assay for primary hyperparathyroidism in a resource-limited setting.

Background: The optimum threshold of IOPTH decay remains a debate and numerous criteria have been described. In this study, we utilize a single-sample IOPTH taken 10 min post excision. Materials & methods: This 4-year query of a prospectively maintained database included primary hyperparathyroidism patients with pre-operative PTH done 1 week prior to surgery, and a 10-min post excision IOPTH value. Optimal cut-off for PTH and sensitivity/specificity were calculated. Results: A total of 93 patients had single-gland disease, of whom 79 (84.9%) were symptomatic. The 10-min post excision assay sensitivity in single-gland disease was 97.8% (50% fall), 95% (60% fall) and 83.9% (70% fall). Conclusion: A post excision single-shot IOPTH assay with a 50% fall offers a sensitivity of 97.8% in patients of primary hyperparathyroidism with single-gland benign disease.

Upfront F18-choline PET/CT versus Tc99m-sestaMIBI SPECT/CT guided surgery in primary hyperparathyroidism: the randomized phase III diagnostic trial APACH2.

BACKGROUND: The common endocrine disorder primary hyperparathyroidism (PHPT) can be cured by surgery. Preoperative localization of parathyroid adenoma (PTA) by imaging is a prerequisite for outpatient minimally invasive parathyroidectomy (MIP). Compared to inpatient bilateral cervical exploration (BCE) which is performed if imaging is inconclusive, MIP is superior in terms of cure and complication rates and less costly. The imaging procedure F18-choline (FCH) PET/CT outperforms Tc99m-sestaMIBI (MIBI) SPECT/CT for PTA localization, but it is much costlier. The aim of this study is to identify the most efficient first-line imaging modality for optimal patient care in PHPT without added cost to society. METHODS: We will conduct a multicenter open diagnostic intervention randomized phase III trial comparing two diagnostic strategies in patients with PHPT: upfront FCH PET/CT versus MIBI SPECT/CT. The primary endpoint is the proportion of patients in whom the first-line imaging method results in successful MIP and cure. Follow-up including biological tests will be performed 1 and 6 months after surgery. The main secondary endpoint is the social cost of both strategies. Other secondary endpoints are as follows: FCH PET/CT and MIBI SPECT/CT diagnostic performance, performance of surgical procedure and complication rate, FCH PET/CT inter- and intra-observer variability and optimization of FCH PET/CT procedure. Fifty-eight patients will be enrolled and randomized 1:1. DISCUSSION: FCH PET/CT is a highly efficient but expensive imaging test for preoperative PTA localization and costs three to four times more than MIBI SPECT/CT. Whether FCH PET/CT improves patient outcomes compared to the reference standard MIBI SPECT/CT is unknown. To justify its added cost, FCH PET/CT-guided parathyroid surgery should lead to improved patient management, resulting in higher cure rates and fewer BCEs and surgical complications. In the previous phase II APACH1 study, we showed that second-line FCH PET/CT led to a cure in 88% of patients with negative or inconclusive MIBI SPECT/CT. BCE could be avoided in 75% of patients and surgical complication rates were low. We therefore hypothesize that upfront FCH PET/CT would improve patient care in PHPT and that the reduction in clinical costs would offset the increase in imaging costs. TRIAL REGISTRATION: NCT04040946 , registered August 1, 2019.  Protocol version Version 2.1 dated from 2020/04/23.

Role of Bisphosphonates in The Prevention of Postoperative Hungry Bone Syndrome in Primary Hyperparathyroidism: A Meta-Analysis and Need for Randomized Controlled Trials.

Dear Editor,Hungry bone syndrome (HBS) is a clinico-biochemical entity characterized by the development of profound and prolonged hypocalcemia associated with hypophosphatemia, hypomagnesemia, and rising alkaline phosphatase which follows curative parathyroidectomy for severe primary and secondary hyperparathyroidism. The prevalence of HBS after parathyroidectomy in primary hyperparathyroidism (PHPT) is variable with several case series from Asia reporting remarkably higher prevalence rates of 24-87% 1.

Histologic hypercellularity in a biopsied normal parathyroid gland does not correlate with hyperfunction in primary hyperparathyroidism.

BACKGROUND: About 15% of patients with primary hyperparathyroidism have multiglandular disease, thus during resection of an apparent single adenoma, a visibly normal parathyroid may be identified and biopsied. Using long-term biochemical follow-up, we examined whether normal parathyroid hypercellularity correlates with multiglandular disease or primary hyperparathyroidism recurrence. METHODS: We reviewed all patients who from 2001 to 2015 had an initial operation for sporadic primary hyperparathyroidism with removal of 1 gland, routine normal parathyroid biopsy, intraoperative parathyroid hormone monitoring, and follow-up of ≥3 years. Recurrence was defined by hypercalcemia after documented cure at 6 months, and hypercellularity by standard histologic criteria. RESULTS: Of 134 patients with mean follow-up of 9.4 years (range, 3.1-15.9), 132 (98.5%) exhibited cure at 6 months. Two had initial failure, and 8 of 132 (6.1%) developed recurrent hyperparathyroidism (mean 5.8 y, range 4-10.6). The normal parathyroid was hypercellular in 14 of 132 (10.6%) of the cured patients, and this rate did not differ for those with long-term cure (12/124, 9.7%) versus recurrence (2/8, 25%, P = .2). The positive predictive value of normal parathyroid hypercellularity for recurrence was low (14.3%), and the negative predictive value of normal parathyroid normocellularity was high (94.9%). CONCLUSION: During the initial operation for primary hyperparathyroidism, 10% of normal parathyroids are hypercellular, but this does not signify missed multiglandular disease. In contrast, normal parathyroid normocellularity has high predictive value for durable cure (95%), slightly better than visual identification of a second normal parathyroid (94%).

[Analyses of risk factors for temporarily inhibited parathyroid hormone secretion of postoperative primary hyperparathyroidism].

Objective: To study relative risk factors for temporarily inhibited parathyroid hormone (PTH) secretion after surgery of primary hyperparathyroidism (PHPT). Methods: Seventy-two cases with PHPT from October 2017 to March 2019 in Beijing Chaoyang Hospital were analyzed retrospectively, including 22 males and 50 females aged from 13 to 83 years old. They were reviewed and divided into a complete inhibition group (24 cases, PTH=0 pg/ml), an incomplete inhibition group (23 cases, 0

Hereditary Parathyroid Disease: Sometimes Pathologists Do Not Know What They Are Missing.

Parathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases, these will be spot diagnoses of sporadic primary parathyroid adenomas or, perhaps, hyperplasias commonly in the setting of renal failure. However, a small but significant number of parathyroid gland excisions may be due to heritable disease. In most cases, hereditary disease is suspected by the referring clinicians. Nevertheless, a subset of these are undetected which is significant, particularly in the setting of the multiple endocrine neoplasia (MEN), and the hyperparathyroidism jaw tumour (HPT-JT) syndromes. There have been recent advances in recognition of the morphological and immunohistochemical characteristics of these tumours and hyperplasias. While hereditary kindreds are over-represented at specialist referral centres, with awareness of the characteristic clinical and morphological features, the general surgical pathologist is frequently able to suggest the possibility of hereditary parathyroid disease. We therefore provide a succinct guide for pathologists to increase the recognition of hereditary parathyroid disease.

Effects of PTH and PTH Hypersecretion on Bone: a Clinical Perspective.

PURPOSE OF REVIEW: Hyperparathyroidism may be due to an autonomous hypersecretion of parathyroid hormone (PTH) or occurs in response to a number of physiological stimuli. A number of recent findings have provided new insights into the importance of the calcium-parathyroid-vitamin D axis to bone in normal physiology and pathological conditions. RECENT FINDINGS: PTH is known to affect bone microarchitecture with different effects on cortical and trabecular bone compartments. In trabecular bone, PTH may exert anabolic effects, whereas PTH promotes bone resorption in cortical bone. Vertebral fractures are prevalent in primary hyperparathyroidism (PHPT), and patients seem to fracture at higher values of bone mineral density (BMD) than patients with osteoporosis. This may be explained by changes in bone microarchitecture, which cannot be detected by measuring BMD. Even in mild PHPT, bone seems to benefit from parathyroidectomy. In secondary hyperparathyroidism, bone seems much more susceptible to fracture with insufficient levels of vitamin D compared with a replete vitamin status. If elevated PTH levels cannot be explained by conditions known to cause secondary hyperparathyroidism, the condition is termed normocalcemic PHPT, which also has been associated with an increased risk of fractures. Hyperparathyroidism is harmful to bone, which is why it is of importance to normalize PTH levels either by parathyroidectomy in PHPT or by counteracting conditions known to increase PTH in secondary hyperparathyroidism.

Diferencias en el metabolismo mineral óseo hiperparatiroidismo primario normocalcémico respecto al hiperparatiroidismo primario clásico / Differences in bone mineral metabolism normocalcemicprimary hyperparathyroidism with respect to classicalprimary hyperparathyroidism

OBJETIVO: El hiperparatiroidismo primario normocalcémico es una variedad menos conocida del hiperparatiroidismo primario clásico. Presentamos en este estudio sus manifestaciones clínicas y los datos relacionados con el metabolismo mineral óseo, tanto desde el punto de vista analítico como densitométrico, comparando los mismos con un grupo de pacientes afectos de hiperparatiroidismo primario clásico, con hipercalcemia. MATERIAL Y MÉTODOS: Estudio de casos y controles donde consideramos caso a pacientes afectos de hiperparatiroidismo primario normocalcémico (n=25) y control (n=25) a pacientes con hiperpartiroidismo primario con hipercalcemia (hiperparatiroidismo primario clásico). Se les efectuó una evaluación clínica completa con recogida de datos clínicos y realizándose determinaciones analíticas en sangre y orina de 24h, así como la estimación de la densidad mineral ósea y el trabecular bone score por densitometría (absorciometría radiológica dual, DXA) y los parámetros ultrasonográficos en el calcáneo. RESULTADOS: En el estudio clínico, los pacientes afectos de hiperparatiroidismo primario clásico solo muestran una mayor prevalencia de urolitiasis (OR: 9,333; IC 95%: 1,50-82,7) en comparación con los pacientes que sufren un hiperparatiroidismo primario normocalcémico. En todos los demás parámetros clínicos, analíticos, densitométricos y ultrasonográficos, no se aprecian diferencias estadísticamente significativas entre ambos grupos. CONCLUSIONES: Con la excepción de los niveles séricos de calcio y la prevalencia de urolitiasis, el hiperparatiroidismo normocalcémico cursa de manera indistinguible del hiperparatiroidismo clásico

OBJECTIVE: Normocalcemic primary hyperparathyroidism is a less known variety of classical primary hyperparathyroidism. In this paper, we present its clinical expression and data related to bone mineral metabolism, both analytically and densitometrically, comparing them with a group of patients with classic primary hyperparathyroidism, with hypercalcemia. MATERIAL AND METHODS: Study of cases and controls where we consider case of patients with normocalcemic primary hyperparathyroidism (n=25) and control (n=25) of patients with primary hyperpartyroidism with hypercalcemia (classical primary hyperparathyroidism). A complete clinical assessment was carried out with clinical data collection and24h blood and urine analytical determinations were performed, as well as estimating bone mineral density and trabecular bone score by densitometry (dual x‐ray absorptiometry, DXA) and ultrasound parameters in the calcaneus. RESULTS: In this clinical study, patients with classic primary hyperparathyroidism only show a higher prevalence of urolithiasis (OR: 9.333; 95% CI: 1.50‐82.7) compared to patients suffering from a normocalcemic primary hyperparathy‐roidism. In all other clinical, analytical, densitometric and ultrasonographic parameters, there are no statistically significant differences between the two groups. CONCLUSIONS: Apart from serum calcium levels and the prevalence of urolithiasis, normocalcemic hyperparathyroidism is indistinguishable from classical hyperparathyroidism

Analysis of Bone Impairment by 3D DXA Hip Measures in Patients With Primary Hyperparathyroidism: A Pilot Study.

CONTEXT: Primary hyperparathyroidism (PHPT) has been related to bone loss. Dual-energy x-ray absorptiometry (DXA) cannot distinguish between trabecular and cortical bone compartments but the recently developed three-dimensional (3D)-DXA software might overcome this issue. OBJECTIVE: To examine the differences in DXA-derived areal bone mineral density (aBMD) and 3D-DXA parameters at the hip site between patients with PHPT and a healthy control group. DESIGN: Cross-sectional pilot study. SETTING: Hospital. PATIENTS: 80 adults (59.5 ± 9.1 yrs), 40 with PHPT and 40 age- and sex-matched healthy controls. MEASURES: aBMD (g/cm2) of the femoral neck, trochanter, shaft, and total hip was assessed using DXA. Cortical surface (sBMD, mg/cm2), cortical volumetric BMD (vBMD, mg/cm3), trabecular vBMD (mg/cm3), integral vBMD (mg/cm3) and cortical thickness (mm) was assessed using 3D-DXA software. RESULTS: Mean-adjusted values showed lower aBMD (7.5%-12.2%, effect size: 0.51-1.01) in the PHPT group compared with the control group (all P < 0.05). 3D-DXA revealed bone impairment (3.7%-8.5%, effect size: 0.47-0.65) in patients with PHPT, mainly in cortical parameters (all P < 0.05). However, differences in trabecular vBMD were not statistically significant (P = 0.055). The 3D mapping showed lower cortical sBMD, cortical vBMD, and cortical thickness at the trochanter and diaphysis in the PHPT group (P < 0.05) compared with the control group. In both groups, the presence of osteopenia or osteoporosis is related to lower cortical bone. CONCLUSIONS: aBMD and cortical 3D parameters are impaired in patients with PHPT versus healthy controls. The vBMD of the trabecular compartment seems to be affected, although to a lesser extent.

Vocal cord paralysis due to ectopic parathyroid adenoma and function recovery: a case report and review of the literature.

Ectopic parathyroid adenomas (PAs) can occur in numerous locations and are thought to be the cause of a significant portion of failed primary surgery for hyperparathyroidism. PA is a rare cause of hoarseness, which may be harbingers of a malignant process. Here, we describe an unusual case of an ectopic PA in the carotid sheath presenting as unilateral vocal cord paralysis (VCP). A 49-year-old lady presented with a 1-week history of hoarseness, irritating cough and shortness of breath. Fibreoptic laryngoscopy revealed left VCP. Ultrasound and computed tomography of the neck demonstrated a mass in the carotid sheath. Laboratory investigations revealed hypercalcemia (3.10 mmol/L), hypophosphatemia (0.81 mmol/L) and elevated intact parathyroid hormone (iPTH) level (381.6 pg/mL), despite of a negative 99mTc-sestamibi scan. After more rigorous tests, the ectopic tumor adjacent to the left vagus nerve was successfully resected, with subsequent histopathological confirmation of PA. The patient eventually got a normal iPTH level and serum calcium postoperatively, and regular voice function was also regained 4 months after surgery. This case emphasizes the importance of broad differential diagnosis and thorough workup. Although most patients with PA present with hypercalcemia, this disease entity also need to be considered in the differentials of neck masses and VCP.

Rising Glucagon-Like Peptide 1 Concentrations After Parathyroidectomy in Patients With Primary Hyperparathyroidism.

BACKGROUND: Although primary hyperparathyroidism has been associated with insulin resistance, potential optimal effects of parathyroidectomy (PTX) on glucose homeostasis remain controversial. Accordingly, the impact of PTX on glucose-stimulated incretin (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide) secretion has not been evaluated. The aim of this pilot study was to compare glucose-stimulated incretin secretion (GSIS) in patients with asymptomatic primary hyperparathyroidism with normal glucose homeostasis, before and after PTX. METHODS: Fourteen patients were included in the study. Fasting calcium, parathyroid hormone, glucose, insulin, GLP-1, and gastric inhibitory peptide were measured pre- and post-operatively. Homeostasis Model Assessment 2, QUICKI, and Matsuda indexes were used as markers of insulin sensitivity and resistance before and after PTX. Preoperatively, a 75 g oral glucose tolerance test (OGTT) was performed to evaluate the response of glucose, insulin, and GSIS. OGTT measurements were repeated 6 ± 2 wk post-PTX. RESULTS: Patients had a mean age of 52.93 ± 9.96 y, and female-to-male ratio was 12:2. Pre- and post-operatively, a positive correlation between parathyroid hormone and Homeostasis Model Assessment 2 for ß-cell function was evident (r = 0.74, P = 0.002 and r = 0.55, P = 0.04, respectively). After PTX, a significant increase in GSIS for GLP-1 during OGTT was observed (in 60 min: 63.06 ± 44.78 versus 102.64 ± 40.19 pg/mL, P = 0.02; and in 120 min: 71.20 ± 35.90 versus 102.49 ± 40.02 pg/mL, P = 0.03). CONCLUSIONS: The increase of GLP-1 response following oral glucose load after PTX may reflect an initial recovery phase of glucose homeostasis. Long-term studies are required to elucidate the physiological interplay between the normalization of calciotropic axis and the rising GLP-1 concentrations post-PTX.