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A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) in pregnant women is a rare condition, often remaining undiagnosed due to non-specific clinical symptoms. However, it can lead to life-threatening complications for both the mother and fetus. In vitro fertilization (IVF) is also associated with an increased probability of adverse outcomes compared to the general population. Timely diagnostics and personalized treatment, taking into account the extremely high risk of complications if PHPT and pregnancy result from IVF, require attention of healthcare professionals and formation of a multidisciplinary team.

Background- Primary Hyperparathyroidism (PHPT) has been associated with increased cardiovascular morbidity and early death. Data on the extent and clinical significance of cardiovascular abnormalities in primary hyperparathyroidism (PHPT) are conflicting. The main objective of this study was to evaluate the cardiac function in patients with PHPT without other known risk factors and to analyze the effect of parathyroidectomy. Methodology- In a Prospective Observational Cohort design, sixteen patients with Primary Hyperparathyroidism underwent Two-dimensional echocardiography, Electrocardiography, serum N-terminal pro-brain natriuretic peptide (NT-proBNP, a myocardial damage marker), before and 3 months after successful parathyroidectomy. Result- We observed significant improvement in Left ventricular ejection fraction (p = 0.010) in patients undergoing parathyroid surgery after 3 months postoperatively. There is significant reduction in LVMI (p=0.044) & posterior wall thickness (p=0.007), which are indicators of left ventricular hypertrophy after 3 months of surgery. Conclusion- Patients with PHPT who are symptomatic exhibit significant cardiovascular dysfunction, which improves three months following successful parathyroidectomy. As a part of screening, we should consider routine cardiovascular evaluation in all symptomatic patients of PHPT. Symptomatic PHPT patients should undergo early curative surgery for the reversal of the cardiovascular dysfunction and in asymptomatic PHPT patients also early surgery is recommended for the prevention of end organ damage. [ABSTRACT FROM AUTHOR]

Wongel Tena Shale,1 Tolasa Dibisa Jirata,2 Mekbeb Chere Enawgaw,1,3 Ararso Gonfa Metekia,2 Yosef Lemma Kelecha1 1Jimma University College of Public Health and Medical Sciences, Department of Surgery, Jimma University, Jimma, Oromia, Ethiopia; 2Jimma University College of Public Health and Medical Sciences, Department of Orthopedic Surgery, Jimma University, Jimma, Oromia, Ethiopia; 3Jimma University College of Public Health and Medical Sciences, Department of Surgery, Urology Unit, Jimma University, Jimma, Oromia, EthiopiaCorrespondence: Wongel Tena Shale, Jimma, Oromia, Ethiopia, Tel +251911636127 ; +251913862475, Email tenawongel@gmail.comBackground: The endocrine disorder known as hyperparathyroidism (HPT) is characterized by excessive parathyroid hormone (PTH) secretion, and when it is accompanied with hypercalcemia it is called primary HPT (PHPT). PHPT is characterized by the hyper-functioning of one or more parathyroids. The most common form of PHPT is sporadic parathyroid adenoma.Case Presentation: A 33-year-old male presented to our emergency room with the classic presentation of PHPT affecting the skeletal, gastrointestinal, genitourinary, and neurologic systems including, multiple long bone fractures and bilateral nephrolithiasis with preserved renal function. Diagnosis was made by elevated serum PTH and calcium levels, as well as, bone imaging. Neck ultrasound and fine needle aspiration cytology (FNAC) of the neck mass were done to localize the lesion. After pre-operative optimization, bilateral neck exploration and en-bloc resection of the left inferior parathyroid with the left lobe of the thyroid was done. In the post-operative period, he developed persistent hypotension and severe hypocalcemia.Conclusion: Although it is uncommon in the industrialized countries, the traditional PHPT presentation with “Bones, Stones, abdominal groans, and psychic moans” is nevertheless common in impoverished nations like Ethiopia. Surgery is the mainstay of treatment but complications such as hungry bone syndrome can increase the post-operative morbidity following parathyroidectomy.Keywords: primary hyperparathyroidism, PHPT, bones, stones, abdominal groans, psychic overtones, brown tumor, hungry bone syndrome, case report

Context The glial cells missing 2 (GCM2) gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of GCM2 , p.Y394S, has been reported in patients with familial primary hyperparathyroidism. Objective To determine whether the GCM2 p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model. Methods CRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous Gcm2 variant p.Y392S that corresponds to the human GCM2 p.Y394S variant. Wild-type (Gcm2 +/+) and germline heterozygous (Gcm2 +/Y392S) mice were evaluated for serum biochemistry and parathyroid gland morphology. Results Gcm2 +/Y392S mice did not show any change compared to Gcm2 +/+ mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size. Conclusion The mouse model of the p.Y392S variant of Gcm2 shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of Gcm2 +/Y392S mice to study the effect of this variant of Gcm2 on early events in parathyroid gland development will be of interest. [ABSTRACT FROM AUTHOR]

Abstract Background As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion’s location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. Case presentation We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient’s symptoms disappeared and serum levels of PTH and calcium normalized. Conclusions SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

Background: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion's location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. Case presentation: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient's symptoms disappeared and serum levels of PTH and calcium normalized. Conclusions: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT. [ABSTRACT FROM AUTHOR]

The continuous cell line of epithelial human parathyroid cells has been proven difficult. Previously, PTH-C1 cell line was only established rat parathyroid tissue cell line known to express the parathyroid hormone-related peptide (Pthrp) gene. The paucity of continuous cell line of human parathyroid cells secreting parathyroid hormone (PTH) has imposed hurdle in in vitro assessment of the mechanisms involved in the control of parathyroid cell function and proliferation. The primary cell cultures of human parathyroid cells were derived from parathyroid adenoma tissue biopsy (n = 5). The cells were subsequently subcultured to maintained primary subclones. Karyotyping analysis was performed to analyze the genotypic identity of derived subclones. The expression of calcium-sensing receptor (CaSR) and intact parathyroid hormone (iPTH) were analyzed using immunocytochemistry and immunofluorescence. In the present study, we have used a defined condition medium to generate the continuous culture of human parathyroid cells derived from patients with parathyroid adenoma due to primary hyperparathyroidism. The subcultured primary subclones were maintained epithelial and polygonal morphology, doubling time of approximately 25 h, displaying a diploid chromosome number, and secretion of PTH. This cell line produces PTH and expresses the calcium-sensing receptor (CaSR) known to be involved in parathyroid function. Altogether these findings indicate the uniqueness of the human parathyroid cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology. [ABSTRACT FROM AUTHOR]

Abstract Background The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium.

Background: The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation: Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion: Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium. [ABSTRACT FROM AUTHOR]

Background: Cinacalcet is a calcimimetic drug that has increasingly been used as a bridging therapy for primary hyperparathyroidism (pHPT), especially during the COVID-19 pandemic. The aim of our study was to investigate if preoperative cinacalcet therapy affects intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy, which is an important indicator for the success of surgery. Methods: In this single-center retrospective analysis, we studied the outcomes of 72 patients who underwent surgery for pHPT. We evaluated two groups: those with cinacalcet therapy before operation—the cinacalcet group (CG)—and those without medical therapy preoperatively (non-CG). In order to perform a between-group comparison of time trends, we fit a linear mixed-effects model with PTH as the response variable and predictors PTH levels preoperatively, group (cinacalcet yes/no), time, the group-by-time interaction, and a random intercept (per subject). Results: Our cohort included 51 (71%) women and 21 (29%) men, who were operated upon for pHPT in the period from January 2018 until August 2021. All patients were diagnosed with pHPT and 54% of the cohort were symptomatic for hypercalcemia. Moreover, 30% of the patients were treated with cinacalcet as a bridging therapy preoperatively, and this increased during the COVID-19 pandemic, as 64% of this group were treated in the last two years. Calcium values were significantly different before (p < 0.001) and after (p = 0.0089) surgery, but calcium level change did not differ significantly between the CG and non-CG. Parathyroid hormone (PTH) levels dropped significantly in both groups during 10 min IOPTH monitoring (p < 0.001), but there was no significant difference between the two groups (p = 0.212). Conclusions: In the examined patient cohort, the use of cinacalcet did not affect the value of IOPTH monitoring during surgery for pHPT. [ABSTRACT FROM AUTHOR]

Background: Spontaneous or fine-needle aspiration biopsy (FNAB)-induced remission of primary hyperparathyroidism (PHPT) is an extremely rare and generally transient phenomenon. Methods: A 40-year-old woman with a history of recurrent kidney stones was diagnosed with PHPT (serum calcium, 14.2 mg/dL; parathyroid hormone [PTH], 380 pg/mL). Ultrasonography and scintigraphy findings were consistent with a left enlarged parathyroid. Ultrasound-guided-FNAB cytology of the lesion did not confirm a parathyroid nature. However, levels of PTH within the needle-washing fluid were elevated. Results: After few days, there was evidence of biochemical remission of the hypercalcemia (calcium, 8.1 mg/dL), and at subsequent follow-up visits, the enlarged parathyroid showed progressive shrinkage with eucalcemia and normalized PTH levels throughout 12 months of follow-up. Conclusions: Rarely, remission of PHPT may occur after ultrasound-guided-FNAB performed on a hyperfunctioning parathyroid lesion.

Hyperparathyroidism-Jaw Tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the most deleterious SNPs mutations on CDC73 gene and to predict their influence on the functional and structural levels using different bioinformatics tools. Method: Computational analysis using twelve different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, P-Mut, I-Mutant ,Project Hope, Chimera, COSMIC and dbSNP Short Genetic Variations were used to identify the impact of mutations in CDC73 gene that might be causing jaw tumor. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven SNPs (G49C, L63P, L64P, D90H, R222G, W231R, P360S, R441C, R441H, R504S and R504H) has deleterious effect on the function and structure of protein and expected to cause the syndrome. Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene identified that could serve as diagnostic markers for hyperparathyroidism-jaw tumor (HPT-JT).

A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Misgar et al.)

In this article, we discuss difficulties in parathyroid localization modalities in diagnosis of primary hyperparathyroidism. Most often, superior parathyroid glands are located on the posteromedial surface of the right and left lobes of the thyroid gland, however, they also could be found at the carotid bifurcation, behind pharynx and esophagus, as well as inside thyroid gland. Location of the inferior parathyroid glands is more variable: on the side or back surface, or below the lower pole of the thyroid gland, as well as in thymus, posterior or anterior mediastinum, or inside thyroid. Localization modalities of primary hyperparathyroidism are based on neck ultrasonography, scintigraphy with sestamibi, computed tomography of neck and mediastinum. In cases with combination of multinodal goitre and an intrathyroid location of the parathyroid gland, there might be additional difficulties in verification of various patterns (thyroid nodules or parathyroid glands). In this article, we present two clinical cases of intrathyroid location of parathyroid glands. The algorithm of parathyroid adenoma localization is shown. Determination of PTH level in washing liquid after fine-needle aspiration biopsy from necessary punctures of the nodule formations, which can be either intrathyroid parathyroid glands or thyroid nodules, can also help to avoid diagnostic mistakes.

• Ectopic parathyroid adenomas located deeper in the mediastinum remain a surgical challenge. • Their incidence reaches up to 20% of the general population and they tend to constitute a severe cause of failed primary surgery for PHPT. • Such aberrations seem to be more common than described in the literature and there are possible anatomic aberrations that have not been described yet. • Preoperative detection of the mediastinal parathyroid adenoma and detailed exposure of the operative field are essential for a safe mid-sternal thoracotomy. Ectopic parathyroid glands occur in 6–16% of cases of PHPT and they constitute a potential cause of failed primary surgical therapy. In particular, aberrant adenomas located deeper in the mediastinum, as in the presented case, remain a severe challenge for the surgeons. A 54-year-old Caucasian female proceeded to our institution with signs and symptoms of PHPT. Imaging studies performed identified a large mass localized in the lower anterior mediastinum, on the left of the median line. A mid-sternal thoracotomy was performed and the aberrant adenoma was finally detected anterior to the pericardium and the left pericardiophrenic vessels and the left phrenic nerve. The operation was uneventful. A meticulous review of the literature was conducted as well. Single parathyroid adenomas are the key culprits of PHPT. Anatomic aberrations of the location of the parathyroid glands and their adenomas are more common than described in the literature and there are possible anatomic aberrations that have not been described yet. All these anatomic variations constitute major risk-factors of thoracic bleeding and of nerve injury. Detailed preoperative detection in addition to meticulous exposure of the operative field are fundamental in order to perform a safe adenoma excision without harmful impacts to the patient. [ABSTRACT FROM AUTHOR]

The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of 'stones, bones, and groans' to becoming increasingly asymptomatic as a result of more frequent serum calcium screening. However, many developing countries are still reporting predominantly symptomatic PHPT with the classic complications of skeletal disease and nephrolithiasis still being quite common. Furthermore, the exact prevalence of PHPT in children is not known but it is thought to be uncommon and the clinical presentation and outcomes in this subgroup of patients are not well described in the literature. Two cases of PHPT occurring in adolescent boys are reported. Both cases initially presented with chronic bone pain involving the lower limbs and had a long delay before the diagnosis of PHPT was confirmed. They developed progressive deformities of the lower limbs, which resembled rickets clinically. Radiological features were also suggestive of rickets. However, biochemistry confirmed parathyroid hormone mediated hypercalcaemia in both cases and after parathyroid surgery a parathyroid adenoma was confirmed histologically as the aetiology of hypercalcaemia. Therefore, PHPT occurring in adolescence may have a clinical presentation almost identical to that of rickets. All patients presenting with skeletal deformities including a rickets phenotype must have serum calcium and phosphate levels measured as part of the diagnostic workup. [ABSTRACT FROM AUTHOR]

The Publisher regrets that this article is an accidental duplication of an article that has already been published in “International Journal of Surgery Case Reports, 57C (2019) 106–109”, https://doi.org/10.1016/j.ijscr.2019.03.014. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal, (Copyright © 2019 LABORATORY OF ANATOMY, FACULTY OF NURSING, UNIVERISTY OF ATHENS. Published by Elsevier Ltd.. All rights reserved.)