The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells ex vivo for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive in vivo imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With in vivo confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive in vivo investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease.

BACKGROUND: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear.
OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients.
METHODS: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment.
METHODS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French Oncogenetic Network on Neuroendocrine Tumors network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants (ie, with genetically confirmed MEN4 diagnosis) in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database.
RESULTS: From 5600 MEN1-suspected patients analyzed, 4 with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, primary hyperparathyroidism (PHPT) and adrenal nodule, isolated PHPT, PHPT, and pancreatic neuroendocrine tumor. We listed 29 patients with CDKN1B class 4/5 variants from the literature. Compared with matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis.
CONCLUSIONS: The prevalence of MEN4 is low. PHPT and pituitary adenoma represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

UNASSIGNED: [18F]Fluorocholine positron emission tomography/computed tomography (PET/CT) is used frequently in addition to [99mTc]Tc-Sestamibi scintigraphy and ultrasonography for the location of hyperfunctioning parathyroid glands. The aim of this study is to evaluate the performance of quantitative criteria in [18F]fluorocholine PET/CT for localization of hyperfunctioning parathyroid glands. The secondary objective is to highlight a correlation between the detection rate of [18F]fluorocholine PET/CT and serum parathyroid hormone (PTH) level.
UNASSIGNED: In two academic centers, we retrospectively included patients with biological hyperparathyroidism (HPT) and who had [18F]fluorocholine PET/CT. After a visual analysis, to measure the overall performance of [18F]fluorocholine PET/CT, a blind reading was carried out with standardized measurements of maximum standardized uptake value (SUVmax), liver ratio, thyroid ratio, and size ratio. We analyzed the quantitative criteria of [18F]fluorocholine PET/CT compared to the histological results, in particular to identify differences between adenomas and hyperplasias. We compared the performance of each quantitative criterion to the overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F]fluorocholine PET/CT. The detection rate of hyperfunctioning parathyroid glands was calculated in subgroups of serum PTH level.
UNASSIGNED: The quantitative criteria in [18F]fluorocholine PET/CT were measured for 120 patients (135 lesions). The areas under the receiver operating characteristic (ROC) curve representing SUVmax and liver ratio were significantly increased. The optimal cut-off values represented by the maximum Youden index was >4.12 for SUVmax and >27.4 for liver ratio. Beyond certain threshold values of SUVmax (>4.12) or liver ratio (>38.1), all the lesions were histologically proven adenomas. SUVmax and liver ratio were significantly higher for adenomas than for hyperplasias and differential diagnosis (p = 0.0085 and p = 0.0002). The positivity of [18F]fluorocholine PET/CT was correlated with PTH level. Detection rates were 55.56, 75.56, and 87.5%, respectively, for serum PTH < 70, 70 to 120, and >120 ng/ml.
UNASSIGNED: Semi-quantitative measurements (SUVmax and liver ratio) should be considered as additional tools in interpretation of [18F]fluorocholine PET/CT. These quantitative parameters have lower overall performance but higher specificity than overall visual analysis in identifying an adenoma. Above certain threshold values, all lesions are adenomas. [18F]fluorocholine PET/CT confirms excellent performance for the detection of hyperfunctional parathyroids. For serum PTH levels < 70 ng/ml, the detection rate of [18F]fluorocholine PET/CT is strongly decreased.

OBJECTIVE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated.
METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test.
RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients.
CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

Intraoperative identification of parathyroid glands is a tough task for surgeons performing thyroid or parathyroid surgery, because the small size, color and shape of these glands hinder their discrimination from other cervical tissues. In 2011, Paras described the autofluorescence of parathyroid glands, a property that could facilitate their intraoperative identification. Parathyroid glands submitted to a 785 nm laser beam emit fluorescence in the near infrared range, with a peak at 822 nm. As the intrinsic properties of secretory tissues may be affected by the exposure to the near infrared light, a situation that could preclude their intraoperative utilization, the authors compared the structural and ultra-structural patterns of rat\'s thyroid and parathyroid glands submitted to irradiation replicating the conditions that allow their intraoperative identification, with those of non irradiated animals. Twenty-four Wistar rats were divided into six groups: animals of Groups 1, 3 and 5 were submitted under general anesthesia to direct irradiation of the cervical area with a 780 nm LED light for 3 minutes through a cervical incision, and animals of Groups 2, 4 and 6 were submitted to cervical dissection without irradiation. Animals of were euthanized immediately (Groups 1 and 2), at Day 30 (Groups 3 and 4) at and at Day 60 (Groups 5 and 6) and thyroid and parathyroid glands were removed: one lobe was prepared for conventional pathological examination and the other lobe for electron microscopy observed by three experienced pathological experts. Twenty-four samples were prepared for conventional histology and there were no alterations reported in any group. Due to technical problems, only 21 samples were observed by electron microscopy and there were no differences in the ultrastructure of parathyroid and thyroid glands, namely the nuclear pattern, mitochondria, endoplasmic reticulum or secretory granules, in any of the groups. These results confirm the innocuity of near infrared irradiation\', allowing its intraoperative utilization.

OBJECTIVE: 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.
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.

OBJECTIVE: To identify and understand parathyroid lesions of patients with primary hyperparathyroidism (PHPT) more accurately under ultrasound.
METHODS: This retrospective study involved 423 adult patients with PHPT with a single parathyroid nodule and positive parathyroid ultrasonography between 2018 and 2019. The clinical characteristics of the study patients and histopathologic sections were reviewed.
RESULTS: According to the main grayscale echogenicity features of parathyroid nodules, 423 cases were divided into groups: iso-hyperechogenicity solid (61/423), hypoechogenicity solid (304/423), and mixed-echogenicity cyst-solid (58/423) groups. Comparison among the 3 groups showed that the iso-hyperechogenicity group included more asymptomatic patients with PHPT and fewer patients with severe symptoms like bone fractures (P < .05). The mixed-echogenicity group showed higher median serum parathyroid hormone (PTH) and serum calcium levels and larger lesion sizes (P < .05), and the iso-hyperechogenicity group showed the lowest median serum PTH level. No difference in lesion size was noted between the 2 solid groups, but the median serum PTH level in the hypoechogenicity group was higher than that in the iso-hyperechogenicity group (P < .05). According to histopathology, the hypoechogenic area of the samples may contain more functional components (chief cells), whereas the iso-hyperechogenic area has more nonfunctional components (eg, lipocytes and connective tissues).
CONCLUSIONS: The PHPT nodules distinguished by ultrasound echogenicity features showed different histopathologic components, reflected by different clinical characteristics of the patients with PHPT.

The aim of this study was to develop a low-cost prototype near-infrared fluorescence device that enables contrast-free, real time, high-resolution intraoperative visualization of normal and pathological parathyroid glands (PGs) by imaging their autofluorescence (AF).
A novel near-infrared parathyroid AF (NIR-PAF) imaging device with visible laser PG targeting was developed. The device was evaluated during parathyroid and thyroid operations in a pilot clinical study.
Overall, of the 6 parathyroidectomies carried out in the study population a parathyroid adenoma was found to exhibit AF ex vivo in 6/6 (100%) of cases, and in vivo in 3/3 (100%) of these cases. Two of 4 thyroidectomies were evaluated in vivo and all PGs (6 PGs total) were identified by the NIR-PAF device. The NIRPAF device cost less than $1200 Canadian to build.
The inexpensive NIR-PAF device that we developed can successfully intraoperatively identify both normal and pathological PGs.

To evaluate the use of preoperative vitamin D levels and postoperative vitamin D supplementation among endocrinologists for the prevention of post-thyroidectomy hypocalcaemia.
Endocrinologist members of the American Thyroid Association (ATA) were contacted via email to complete a 21-question survey, which included both questions about demographic information, and preventing and managing postoperative hypocalcaemia after thyroidectomy. Univariate and multivariate analysis was performed to determine the respondents\' use of preoperative vitamin D levels, dose and duration of preoperative vitamin D repletion, decision to delay surgery for low vitamin D levels in the case of a benign or malignant disease, and routine prescription of postoperative calcium or vitamin D supplementation.
225 endocrinologists who were ATA members responded to the questionnaire. When compared to endocrinologists practicing in other countries, those that practice in the United States were 2.5 times more likely to check preoperative vitamin D levels (95% CI[1.404, 4.535], P = .002), significantly more likely to replete vitamin D deficient patients with high-dose vitamin D (ie ≥50K IU/week), 4.458 times more likely to prescribe prophylactic supplemental calcium (95% CI[2.446, 8.126]; P < .0001) and 3.48 more likely to prescribe supplemental vitamin D (95% CI [1.906, 6.355]; P < .0001). Endocrinologists who have been in practice for >10 years were also 1.915 times more likely to prescribe supplemental vitamin D (95% CI (1.080, 3.395); P = .0263). Physicians that treat >50 thyroidectomy cases/year were 2.083 more likely to recommend a vitamin D repletion duration of >1 month than those that treat ≤50 cases/year ([1.036, 4.190], P = .0395). Lastly, if the patient has low preoperative vitamin D levels, 47.05% of respondents chose to delay surgery in a benign disease, while only 11.61% of respondents would do so in a case of malignant disease.
Approximately one-half of surveyed endocrinologists reported using preoperative vitamin D levels to assess a patient\'s risk for post-thyroidectomy hypocalcaemia. Endocrinologists practicing in the United States, compared to those practicing in other countries, were more likely to both test for preoperative vitamin D levels and to recommend prophylactic post-thyroidectomy calcium and vitamin D supplementation.

Background Studies have linked vitamin D deficiency with the risk of type 2 diabetes mellitus (T2DM) and to the development of chronic complication of diabetes. Vitamin D receptors (VDR) have been found in many tissues in the body including the pancreas, a finding that indicates its role in insulin secretion. In addition, many studies have demonstrated the role of vitamin D and its receptor in insulin sensitivity and signal transduction. Vitamin D deficiency is common throughout the world, but not all vitamin D deficiencies are accompanied by a rise in parathyroid hormone (PTH). The present study was conducted to assess vitamin D deficiency in type 2 diabetic patients in comparison to healthy control and to determine parathyroid gland response to vitamin D deficiency in both groups. Methods This observational study was performed during a period from January to October 2018. The study included 151 type 2 diabetic patients selected from three diabetes clinics and 43 age and sex-matched healthy subjects. Informed consent and clinical information were obtained from all participants before the study. Results of the laboratory analysis for serum 25-hydroxyvitamin D (25-OHD), PTH, calcium, and phosphorous were recorded. The data was analyzed using the statistical package for the social sciences (SPSS) Statistics 17. Results The results showed low vitamin D concentration in both groups; however, there was no significant difference in vitamin D concentration between diabetic patients and the control patients. A high percentage of PTH level was found in severe vitamin D deficient diabetic patients and healthy controls. The higher percentage of diabetic and normal subjects with mild vitamin D deficiency had a normal PTH level. All healthy subjects with vitamin D insufficiency showed normal PTH concentration. About 10% of diabetic patients with severe vitamin D deficiency had a low PTH level. Conclusion The population in our study was generally deficient in 25-OHD irrespective of diabetes mellitus, indicating a greater need for vitamin D supplementation. Not all vitamin D deficient patients have high PTH levels, a finding that supports the emergence of new criteria for vitamin D deficiency, diagnosis and treatment, and highlights the importance of testing PTH in this regard.