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Hypercalcemia can result from either hyperparathyroidism or non-parathyroid conditions. When hypercalcemia is accompanied by undetectable parathyroid hormone (PTH) levels, hyperparathyroidism is rarely considered the diagnosis. Herein, we report the case of a 65-year-old Caucasian woman referred to our hospital for further evaluation of hypercalcemia. Her symptoms included fatigue and brain fog, with undetectable PTH levels. A comprehensive workup, including a series of laboratory and imaging tests, excluded common non-parathyroid causes such as malignancy and familial hypocalciuric hypercalcemia. Ultrasound identified a likely enlarged parathyroid gland, which was further confirmed by a sestamibi scan. After 2 weeks of cinacalcet treatment, the patient's calcium levels decreased, indicating the parathyroid gland as the likely source of hypercalcemia. Parathyroidectomy was subsequently performed, revealing a 1927 mg adenoma. Postoperatively, the patient's calcium levels normalized, PTH levels became detectable within the normal range, and her symptoms resolved, with a marked improvement in energy. This case demonstrates that primary hyperparathyroidism can present with hypercalcemia and undetectable PTH. A genetic mutation in the PTH gene within the adenoma may explain the undetectable PTH levels preoperatively. Plain Language Summary: This case report discusses a 65-year-old woman who was found to have high calcium levels in her blood, a condition known as hypercalcemia. Typically, hypercalcemia can result from either a condition where the parathyroid glands produce too much parathyroid hormone (PTH) or from other non-parathyroid-related issues like cancer. However, when hypercalcemia occurs with undetectable levels of PTH, it is unusual for hyperparathyroidism to be the cause. In this patient's case, she experienced symptoms like fatigue and brain fog, but her initial tests showed undetectable PTH levels. Further tests ruled out other common causes of high calcium, such as cancer or a genetic condition called familial hypocalciuric hypercalcemia. An ultrasound and a special scan called a sestamibi scan revealed an enlarged parathyroid gland, suggesting the presence of a parathyroid adenoma, a non-cancerous tumor. To confirm this, the doctors gave the patient a medication called cinacalcet, which is known to lower calcium levels if the parathyroid glands are involved. After two weeks of treatment, her calcium levels dropped, indicating that the parathyroid gland was indeed the source of the problem. The patient underwent surgery to remove the adenoma, which weighed nearly two grams. Following the surgery, her calcium levels returned to normal, and her PTH levels became detectable again within the normal range. Her symptoms, including fatigue, improved significantly, and she reported feeling more energetic. This case is unusual because it demonstrates that primary hyperparathyroidism can still be the cause of hypercalcemia even when PTH levels are initially undetectable. The doctors suspect that a genetic mutation in the adenoma might explain why PTH levels were undetectable before surgery. This case emphasizes the importance of thorough clinical evaluation, even when initial test results are not typical. [ABSTRACT FROM AUTHOR]

Metastatic calcifications are a rare but potentially fatal complication of primary hyperparathyroidism (PHPT). In this case, a 76-year-old man with a previously asymptomatic PHPT developed a hypercalcemic crisis with severe pancreatitis following elective urologic surgery. Despite initial treatment focused on pancreatitis and subsequent organ failure, hypercalcemia persisted, leading to rapid progressive metastatic calcifications in multiple organs. Parathyroidectomy during ongoing pancreatitis successfully reduced calcium levels but not the calcifications. After 4 months of complications and persistent pain, the patient declined further treatment and ultimately succumbed to the disease. The current literature primarily reports single-organ metastatic calcifications due to PHPT. This case represents the only lethal case of systemic metastatic calcifications in the current century. Physicians should be aware of the potential deterioration of hypercalcemia following elective surgery, particularly in the context of renal impairment. Rapid correction of calcium levels may prevent severe complications such as fatal metastatic calcifications. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with Primary hyperparathyroidism (PHPT) and identify miRNA biomarkers of bone homeostasis. Background: PHPT is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. Methods: We performed a prospective case-control study of postmenopausal females with PHPT and control subjects matched for race, age, and bone mineral density (BMD). We collected clinical and biochemical data, assessed BMD by dual-energy x-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers, and BMD. Results: A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, 9 (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a- 3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a, and miR- 19b-3p) were differentially expressed in PHPT compared with matched control subjects. All 9 differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and 8 of the 9 correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these 9 miRNAs on principle component analysis. Conclusions: These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by hypercalcemia due to inappropriately high parathyroid hormone secretion. While in the typical, symptomatic form of the disease diagnosis is set easily and standard management is surgical removal of the hyperfunctioning parathyroid (HP), this may not be the case in more subtle forms of PHPT, such as the asymptomatic and the normocalcemic PHPT. Localization of the HP could also be challenging, especially in small-sized adenomas, ectopic lesions or multiglandular disease. An experienced surgical team is essential to achieve curative parathyroidectomy. In this article, we used illustrative clinical vignettes to dissect the approach to the patient with PHPT, from the diagnosis establishment to the suggested investigation to identify classical and non-classical PHPT features and the methodology to locate the abnormal tissue. Accordingly, we elaborated on appropriate management, both surgical and conservative. [ABSTRACT FROM AUTHOR]

Purpose: The management of primary hyperparathyroidism (PHPT) during pregnancy may be surgical or conservative. This study compared adverse outcomes between surgical and non-surgical treatments. Additionally, the study investigated the correlation between serum calcium values and complication rates. Methods: A systematic review of retrospective studies, case series, and case reports. Biochemical parameters, interventions, and outcomes of each pregnancy were recorded. The study population comprised two groups: the non-surgical and surgical groups. Adverse outcomes were categorized as maternal, obstetric, or neonatal. Results: The surgical and non-surgical groups consisted of 163 and 185 patients, respectively. A positive correlation was observed between the mean maternal gestational calcium value and both maternal and obstetric complication. Neonatal complications were more prevalent in patients treated conservatively across all maternal calcium values (p < 0.001). No significant differences were observed in maternal outcomes and overall obstetric outcomes between the study groups, albeit a higher mean serum calcium value in the surgical group (12.3 mg/dL) compared with the non-surgical group (11.1 mg/dL). Conclusions: Given the significantly lower neonatal adverse outcomes in the surgical group compared to the non-surgical group, along with non-inferior maternal and obstetric outcomes in the surgical group, the overall data of this study suggest that parathyroidectomy is favorable to non-surgical management even in cases of mild hypercalcemia. [ABSTRACT FROM AUTHOR]

Context Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Objective Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. Methods We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet Results Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P =.01) likely explained by a lesser PTH decrease (P =.02). However, a strong negative association (P <.0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. Conclusion Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones. [ABSTRACT FROM AUTHOR]

Background: Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. Case presentation: We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. Conclusions: Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we analyse the possibility to omit pre-incision PTH measurement since we routinely measure it at the time of pre-surgery ambulatory admission. Methods: A total of 435 patients were enrolled. All patients with pHPT included underwent pre-surgical PTH level assessment as part of the pre-admission preparation to surgery. Intraoperative PTH was routinely assessed after induction of the anaesthesia (pre-incision PTH) and 15 min after resection of the enlarged gland(s) (post-excision PTH). Moreover, calcium and PTH levels were routinely assessed on the first postoperative day. Cure was defined as an intraoperative drop of > 50% or into normal range on first post-operative day. Results: The median value of the preoperative and pre-incision PTH were both 127 pg/ml (p = ns). Thirty-two patients (7.3%) exhibited a not appropriate drop of post-excision PTH level. Nevertheless, nineteen of them (59.3%) showed a satisfying PTH drop on 1st POD. Ten patients (2.3%) experienced a persistent disease with six achieving cure through reoperation. Additionally, three patients (0.6%) showed normalization of calcium and PTH values during the follow-up. Three patients, apparently deemed cured after an adequate PTH-drop on the day of surgery, showed persistence. Cure rate at primary surgery was 98.4%. Accuracy of our simplified protocol is 99.3%. Conclusion: Pre-incision PTH is not superior to preoperative PTH blood test and can be omitted without compromising the sensitivity of cure prediction. One blood sample 15 min after resection, along with the postoperative PTH value on the day after surgery, is sufficient to predict the surgical outcome bearing the cost of a very low reoperation rate. [ABSTRACT FROM AUTHOR]

Background: Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease "osteitis fibrosa cystica" is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. Case presentation: A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. Conclusion: In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition. [ABSTRACT FROM AUTHOR]

Primary Hyperparathyroidism (PHPT) is characterized by excessive parathormone (PTH) secretion and disrupted calcium homeostasis. Untargeted metabolomics offers a valuable approach to understanding the complex metabolic alterations associated with different diseases, including PHPT. Plasma untargeted metabolomics was applied to investigate the metabolic profiles of PHPT patients compared to a control group. Two complementary liquid-phase separation techniques were employed to comprehensively explore the metabolic landscape in this retrospective, single-center study. The study comprised 28 female patients diagnosed following the current guidelines of PHPT diagnosis and a group of 30 healthy females as a control group. To evaluate their association with PHPT, we identified changes in plasma metabolic profiles in patients with PHPT compared to the control group. The primary outcome measure included detecting plasma metabolites and discriminating PHPT patients from controls. The study unveiled specific metabolic imbalances that may link l-amino acids with peptic ulcer disease, gamma-glutamyls with oxidative stress, and asymmetric dimethylarginine (ADMA) with cardiovascular complications. Several metabolites, such as gamma-glutamyls, caffeine, sex hormones, carnitine, sphingosine-1-phosphate (S-1-P), and steroids, were connected with reduced bone mineral density (BMD). Metabolic profiling identified distinct metabolic patterns between patients with PHPT and healthy controls. These findings provided valuable insights into the pathophysiology of PHPT. [ABSTRACT FROM AUTHOR]

Objective Renal function and the skeleton are classic target organs in primary hyperparathyroidism (PHPT), affected by the chronic course of the disease. Most patients diagnosed today exhibit mild PHPT, characterized by slight hypercalcemia and no or unspecific symptoms. Concerns have been raised that PHPT could promote deteriorating kidney function and increase cardiovascular risk directly. To examine the effect of parathyroidectomy (PTX) on mild PHPT on renal function and markers for bone turnover, cardiovascular disease (CVD), and vascular inflammation. Design Prospective randomized controlled trial. ClinicalTrials.gov : NCT00522028. Setting Eight Scandinavian referral centers. Participants From 1998 to 2005, 191 patients with mild PHPT were included in Sweden, Norway, and Denmark. Of these 150 were included in the present analyses. Intervention Seventy patients were randomized to PTX and 80 to observation without intervention (OBS). Measures e-GFR was calculated based on creatinine and cystatin C. Markers of CVD and systemic inflammation: osteoprotegerin, vascular cell adhesion molecule 1, soluble CD40 ligand, interleukin-1 receptor antagonist, von Willebrand factor. Bone turnover markers: C-terminal telopeptide of type 1 collagen (CTX-1) and serum Procollagen type 1 N-terminal propeptide. Results No differences in the development of renal function or vascular and systemic inflammation were detected. CTX-1 was lower in PTX after 10 years. Limitations Secondary analyses of a randomized controlled trial. Conclusion PTX does not appear to affect renal function or markers of CVD and vascular inflammation in mild PHPT in a ten-year perspective. [ABSTRACT FROM AUTHOR]

Diagnosing primary hyperparathyroidism in pregnancy is difficult due to pregnancy-related changes in parathyroid hormone (PTH); calcium; 1,25 vitamin D; and renal calcium excretion. Parathyroid hormone–related peptide (PTHrP) produced by the placenta adds additional complexity. Our case is the first to demonstrate an increased rate of PTH degradation within a pregnant individual who returned unexpectedly low PTH levels. We describe a 27-year-old female patient who presented at 25 weeks gestation with pancreatitis and hypercalcemia. Primary hyperparathyroidism was suspected but variable PTH results led to uncertainty and an assay error was considered. PTH samples were collected in both serum-separating tubes (SST) and EDTA tubes and compared to controls (5 nonpregnant and 5 pregnant individuals). Samples were retested every 2 hours for a period of 10 hours. A rapid decline in the measured PTH was noted in the index case, an observation which differed from controls. We postulated that internal and/or external factors influenced the PTH measurement obtained from our patient. From our observations, rapid PTH degradation in pregnancy, and individual variation in PTH stability and laboratory processes, can influence PTH results and impact on interpreting hypercalcemia in pregnancy. [ABSTRACT FROM AUTHOR]

Calcium metabolism dysregulation in the setting of primary hyperparathyroidism (PHPT) mediated chondrocalcinosis is implicated in joint pain, a key element in the decision regarding arthroplasty for osteoarthritis. The relationship between hypercalcemia and joint pain, before and after arthroplasty, is unknown. This study investigates the association between preoperative hypercalcemia and postoperative outcomes following total knee (TKA) and total hip arthroplasty (THA). A retrospective chart review was conducted on patients who underwent initial elective THA or TKA. Patients with a preoperative serum calcium >10.2 mg/dL were matched (1:2-1:4) with nearest neighbor to patients with normal serum calcium. THA and TKA functional outcomes were measured at baseline and 1-y postoperatively using patient-reported Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores surveys. Postoperative complications, readmissions, length of stay, and functional outcome scores were compared. Four hundred ninety-five patients (106 hypercalcemic cases, 389 matched controls) were included. Of these, 223 patients underwent THA (46 cases; 177 controls) and 272 patients underwent TKA (61 cases; 211 controls). There were no differences in Hip Disability and Osteoarthritis Outcome Scores and Knee Injury and Osteoarthritis Outcome Scores scores, postoperative complications, readmissions, or length of stay between cases and controls. Only 19/106 (18%) hypercalcemic patients had a parathyroid hormone (PTH); of these, 9 (47%) had possible PHPT (PTH > 40). Patients with hypercalcemia undergoing arthroplasty have similar functional and postoperative outcomes as normocalcemic patients. As PTH was obtained in <20% of hypercalcemic cases and 50% had possible PHPT, we recommend that hypercalcemic patients undergo PHPT workup. Additional investigation is needed to determine the effect of PHPT on arthroplasty outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Primary hyperparathyroidism (PHP) is the third most common endocrine disorder, with surgery being the only curative treatment. The outcomes depend on the pre-surgical evaluation and the surgical technique employed. Objective: A description of the outcomes from historical cohorts of bilateral cervical exploration (BCE) and focused exploration (FE) is provided. Materials and Methods: BCE and FE, both utilizing intraoperative PTH (ioPTH), performed by a head and neck surgeon at two university clinical centers, were compared. Results: The study included 138 patients treated for PHP, 94 with BCE and 44 with FE. A decline according to the Miami and Rome criteria was achieved in most patients. Upon follow-up, both groups showed normalization of calcium and PTH levels, with no significant difference (p > 0.05). Multiglandular disease was diagnosed in 3 out of 11 cases without a preoperative suspicion based on imaging in the BCE group and none in the FE group. Discussion: The outcomes of BCE and FE with ioPTH measurement are similar in terms of results, with differences in the diagnosis of multiglandular disease. Conclusion: BCE (expert group) can be considered a first-line alternative. [ABSTRACT FROM AUTHOR]

Summary: In this large population-based matched cohort study, patients with primary aldosteronism were at increased risk of hip fracture, particularly subgroups traditionally considered at higher risk of osteoporosis such as women, patients older than 56 years at diagnosis, patients with established cardiovascular disease at diagnosis, and patients treated with MRA. Purpose: Previous studies suggest that primary aldosteronism (PA) is associated with dysregulated bone homeostasis. The aim of this study was to evaluate the incidence of hip fractures in patients with PA. Methods: We studied a nationwide cohort of 2419 patients with PA (1997–2019) and 24 187 age and sex matched controls from the general population. Hip fractures were identified by ICD codes in the Swedish National Patient Register. We estimated hazard ratios (HRs) for incident hip fractures, adjusted for prior fractures, socioeconomic factors, diabetes, osteoporosis, hyperparathyroidism, and cardiovascular disease (CVD). Pairwise subgroup comparisons were performed by age (18–56 and > 56 years), sex, CVD at baseline, and treatment for PA. Results: During a mean follow up of 8 ± 5 years, 64 (2.6%) patients had a hip fracture after being diagnosed with PA, compared to 401 (1.7%) controls. After adjustments, PA was associated with a 55% increased risk of hip fracture compared to controls (HR 1.55 [1.18–2.03]). HRs were increased in women (HR 1.76 [95% CI 1.24–2.52]), patients aged > 56 years (HR 1.62 [95% CI 1.21–2.17]), and patients with CVD at diagnosis (HR 2.15 [95% CI 1.37–3.37]). PA patients treated with adrenalectomy did not have higher risk than controls (HR 0.84 [95% CI 0.35–2.0]), while patients treated with mineralocorticoid receptor antagonists (MRA) retained a greater risk (HR 1.84 [95% CI 1.20–2.83]). Conclusion: PA is associated with increased hip fracture risk, especially in women, patients diagnosed after the age of 56 years and patients with established CVD at diagnosis. Also, patients treated with MRA seem to have an increased risk of hip fractures, while adrenalectomy may be protective. [ABSTRACT FROM AUTHOR]

Introduction: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. With parathyroidectomy, a cure rate of over 95% at initial surgery is reported. Localization of the abnormal parathyroid gland is critical for the operation to be successful. The aim of this study is to analyze data of patients with single gland disease (SGD) and positive concordant localization imaging undergoing minimally invasive parathyroidectomy (MIP) and intraoperative parathyroid hormone monitoring (IOPTH) to evaluate if IOPTH is still justified in patients with localized SGD. Methods: A retrospective database analysis of all minimally invasive operations with IOPTH for PHPT and positive concordant localization in ultrasound (US) and 99mTc-sestamibi scintigraphy (MIBI) between 2016-2021. When both US and MIBI were negative, patients underwent either choline or methionine PET-CT. The patients were also analyzed a second time without applying IOPTH. Results: In total, 198 patients were included in the study. The sensitivity of US, MIBI and PET-CT was 96%, 94% and 100%, respectively. Positive predictive value was 88%, 89% and 94% with US, MIBI and PET-CT, respectively. IOPTH was true positive in 185 (93.4%) patients. In 13 (6.6%) patients, no adequate IOPTH decline was observed after localizing and extirpating the assumed enlarged parathyroid gland. Without IOPTH, the cure rate decreased from 195 (98.5%) to 182 (92%) patients and the rate of persisting disease increased from 2 (1.0%) to 15 (7.5%) patients. Conclusion: Discontinuing IOPTH significantly increases the persistence rate by a factor of 7.5 in patients with concordantly localized adenoma. Therefore, IOPTH appears to remain necessary even for this group of patients. [ABSTRACT FROM AUTHOR]

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]

The mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear. A retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov–Smirnov, Kruskal–Wallis tests. All 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success. Parathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success. • There are minimal intraoperative adjuncts to guide resection of parathyroid cancer. • >50% intraoperative parathyroid hormone decrease into normal reference predicts complete surgical excision. • Intraoperative parathyroid hormone monitoring with complete en bloc excision should be completed. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report describes a 52‐year‐old patient presenting with recurrent episodes of pancreatitis and renal stones. Further investigation revealed hypocalcemia and elevated parathyroid hormone (PTH) levels, leading to diagnosis of a parathyroid adenoma. This case highlights the importance of considering primary hyperparathyroidism in patients with recurrent pancreatitis and renal stones, as early diagnosis and surgical intervention can prevent recurrence and reduce morbidity. Primary Hyperparathyroidism secondary to Parathyroid adenoma, rarely presents as acute pancreatitis. A 38‐year‐young male with a history of recurrent renal stones referred from a local center, presented to the emergency services, with a diagnosis of acute pancreatitis and bilateral renal stones. Laboratory evaluation showed an elevated calcium level, elevated PTH levels, low vitamin D, and low phosphorus levels. CT scan done outside was suggestive of acute pancreatitis along with bilateral renal calculi. USG neck and MIBI scan done as a part of hypercalcemia evaluation showed presence of a right parathyroid adenoma. Parathyroid adenoma was later removed, and calcium and parathyroid levels were normal on subsequent follow ups. [ABSTRACT FROM AUTHOR]

Purpose: Multiple groups have created clinical practice guidelines (CPGs) for the management of primary hyperparathyroidism (PHPT). This report provides a rigorous quality assessment using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) to identify high-performing guidelines and areas for improvement. Methods: A systematic review was conducted to isolate CPGs addressing the management of PHPT. Guideline data was extracted and quality ratings were assigned by four independent reviewers. Intraclass correlation coefficients (ICC) were calculated to ensure interrater reliability. Results: Twelve guidelines were assessed. The American Association of Endocrine Surgeons (AAES) guideline had the highest mean scaled score across all domains (73.6 ± 31.4%). No other published guideline achieved a "high" quality designation. The highest scoring domain was "clarity of presentation" (mean 60.5 ± 26.5%). The lowest scoring domain was "applicability" (mean 19.8 ± 18.2%). Scoring reliability was excellent, with ICC ≥ 0.89 for all AGREE II 6 domains. Conclusion: Although several working groups have developed guidelines to address PHPT management, only those published by the AAES meet all methodologic quality criteria necessary to ensure incorporation of recommendations into clinical practice. Future guidelines would benefit from the development of tools, resources, monitoring criteria that enhance applicability. [ABSTRACT FROM AUTHOR]

Context Primary hyperparathyroidism (PHPT) increases the risk of bone loss, debilitating fractures, kidney stones, impaired renal function, and neurocognitive symptoms. Studies describing the natural history of PHPT have been limited to small samples, single institutions, or specific populations. Objective We assessed the natural history of PHPT through a large, diverse national cohort from an electronic health record dataset representing more than 100 million patients. Methods The TriNetX database was queried for adult patients with PHPT. We extracted demographics, comorbidities, and longitudinal biochemistries. Primary outcomes included major osteoporotic fracture (MOF) and chronic kidney disease (CKD). Outcomes were stratified by treatment strategy (surgical parathyroidectomy [PTX] vs nonsurgical) and age. Results Among 50 958 patients with PHPT, 26.5% were treated surgically at a median of 0.3 years postdiagnosis. At diagnosis, median age was 65 years, 74.0% were female, and median calcium level was 10.9 mg/dL. Black and older patients underwent PTX less frequently than White and younger patients. MOF 10-year incidence was 5.20% (PTX) and 7.91% (nonsurgical), with median 1.7-year delay with PTX compared to nonsurgical. PTX-associated MOF absolute risk reduction was 0.83% (age < 65 years) and 3.33% (age ≥ 65 years). CKD 10-year incidence was 21.2% (PTX) and 33.6% (nonsurgical), with median 1.9-year delay with PTX. PTX-associated CKD absolute risk reduction was 12.2% (age < 65 years) and 9.5% (age ≥ 65 years). Conclusion We report 1 of the largest, representative, population-based natural histories of PHPT with different management strategies. A minority of patients underwent PTX, especially in older age. Patients managed surgically had lower incidence of fracture and CKD, and older patients experienced differential benefit. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age–sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of S ubdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism has emerged as a prevalent endocrine disorder in clinical settings, necessitating in most cases, surgical intervention for the removal of the diseased gland. This condition is characterised by overactivity of the parathyroid glands, resulting in excessive parathyroid hormone production and subsequent disturbances in calcium homeostasis. The primary mode of management is surgical treatment, relying on the accurate localisation of the pathological parathyroid gland. Precise identification is paramount to ensuring that the surgical intervention effectively targets and removes the diseased gland, alleviating the hyperfunctioning state. However, localising the gland becomes challenging, as discrepancies between the clinical manifestation of active parathyroid and radiological identification are common. Based on our current knowledge, to date, no comprehensive review has been conducted that considers all factors collectively. This comprehensive review delves into the factors contributing to false-negative 99mTc-Sestamibi scans. Our research involved an exhaustive search in the PubMed database for hyperparathyroidism, with the identified literature meticulously filtered and reviewed by the authors. The results highlighted various factors, including multiple parathyroid diseases, nodular goitre, mild disease, or the presence of an ectopic gland that causes discordance. Hence, a thorough consideration of these factors is crucial during the diagnostic workup of hyperparathyroidism. Employing intraoperative PTH assays can significantly contribute to a successful cure of the disease, thereby providing a more comprehensive approach to managing this prevalent endocrine disorder.

Brown tumors, resulting from elevated osteoclast activity, are uncommon skeletal symptoms of hyperparathyroidism. Because of their similar characteristics, it is challenging to differentiate these tumors from multiple myeloma or osteolytic metastases. A 24-year-old female with a painful lump in her left thigh and arm in the past 10 months. The patient reported a history of left femoral bone fracture over a year ago due to low-impact trauma. Plain radiograph images and chest MSCT showed osteolytic lesions at the skull, ribs, and extremities, followed by increased Tc99 bone scan image uptake. Thyroid ultrasound and cervical MSCT showed parathyroid mass. Biochemical and pathologic examination supported the diagnosis of brown tumor. A multidisciplinary approach, including clinical evaluation, biochemical assessment, pathological examination, and advanced imaging modalities such as CT scan, MRI, and bone scintigraphy, is necessary for the differential diagnosis of brown tumors from bone metastasis. Medical history, PTH, calcium levels in the blood, and additional systemic symptoms can all be used to help distinguish between the 2 disorders. The clinical presentation and imaging findings of brown tumors may mimic bone metastasis, necessitating comprehensive evaluation. Multidisciplinary collaboration plays a vital role in reaching an accurate diagnosis. Increased awareness of brown tumors as a potential mimic of bone metastasis may help prevent misdiagnosis and ensure optimal care for patients presenting with osteolytic bone lesions associated with hyperparathyroidism.

Abstract Background Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease “osteitis fibrosa cystica” is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. Case presentation A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. Conclusion In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition.

Abstract Background Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. Case presentation We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. Conclusions Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

Abstract Primary Hyperparathyroidism (PHPT) is characterized by excessive parathormone (PTH) secretion and disrupted calcium homeostasis. Untargeted metabolomics offers a valuable approach to understanding the complex metabolic alterations associated with different diseases, including PHPT. Plasma untargeted metabolomics was applied to investigate the metabolic profiles of PHPT patients compared to a control group. Two complementary liquid-phase separation techniques were employed to comprehensively explore the metabolic landscape in this retrospective, single-center study. The study comprised 28 female patients diagnosed following the current guidelines of PHPT diagnosis and a group of 30 healthy females as a control group. To evaluate their association with PHPT, we identified changes in plasma metabolic profiles in patients with PHPT compared to the control group. The primary outcome measure included detecting plasma metabolites and discriminating PHPT patients from controls. The study unveiled specific metabolic imbalances that may link l-amino acids with peptic ulcer disease, gamma-glutamyls with oxidative stress, and asymmetric dimethylarginine (ADMA) with cardiovascular complications. Several metabolites, such as gamma-glutamyls, caffeine, sex hormones, carnitine, sphingosine-1-phosphate (S-1-P), and steroids, were connected with reduced bone mineral density (BMD). Metabolic profiling identified distinct metabolic patterns between patients with PHPT and healthy controls. These findings provided valuable insights into the pathophysiology of PHPT.

Brown tumors are rare skeletal manifestations of hyperparathyroidism. It is a form of osteitis fibrosa cystica caused by hyperparathyroidism due to excessive secretion of parathyroid hormone. Then, hypercalcemia results in excessive osteoclastic activity in the bones. Brown tumors are considered a rare complication of hyperparathyroidism, as their reported existence is only about 1.5-4.5%. Herein, we report a rare case of brown tumor arising from the left maxilla due to primary hyperparathyroidism, its challenge in diagnosis with giant cell tumor, and its literature review.

Objective: Near‐infrared autofluorescence (NIRAF) characteristics of parathyroid glands in primary hyperparathyroidism (pHPT) vary, with unclarity regarding the underlying mechanism. Similarly, 99mTc‐sestamibi uptake in diseased parathyroid glands is variable. There is a suggestion that oxyphilic cell content may influence both imaging modalities. This study aims to analyze the relationship between NIRAF imaging characteristics, 99mTc‐sestamibi uptake, and cellular composition in pHPT. Study Design: Retrospective analysis of an Institutional Review Board‐monitored prospective database. Setting: Single tertiary referral center. Methods: NIRAF characteristics of parathyroid glands of patients with pHPT between 2019 and 2024 were compared with 99mTc‐sestamibi scan findings from a prospective database. Using third‐party software, brightness intensity and heterogeneity index (HI) of the glands were calculated. A subgroup of parathyroid glands obtained from consecutive patients with pHPT in 2020 to 2021 underwent histological analysis. Results: A total of 428 patients with 638 diseased parathyroid glands were analyzed. Forty‐seven percent of the glands showed an uptake on 99mTc‐sestamibi scans. The brightness intensity of the NIRAF signals from parathyroid glands that were seen versus not seen on sestamibi was 2.1 versus 2.3 (P =.002) and HI 0.18 versus 0.17 (P =.35), respectively. On multivariate analysis, low autofluorescence intensity, high gland volume, and single adenoma were associated with detectability on 99mTc‐sestamibi scan (P <.0001). Intraglandular adipose tissue content was lower in diseased glands that were detected on 99mTc‐sestamibi scans (0% vs 5%, P <.0001). Conclusion: Our findings indicate an inverse relationship between autofluorescence intensity and detectability on 99mTc‐sestamibi scans and a lack of correlation between different cell types and autofluorescence properties. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism is a common endocrine disorder. It is characterised by elevated parathyroid hormone (PTH) level causing hypercalcemia. 90-95% of cases have a spontaneous cause, with the remaining 5-10% having a genetic basis. On routine examination, a 47-year-old patient was found to have hypercalcemia, vitamin D deficiency, normal PTH levels and no hypercalciuria. Despite vitamin supplementation, calcemia remained unchanged. Single photon emission computed tomography (SPECT) examination detected possible adenomas in the lower parathyroids regions, and ultrasound revealed an adenoma of the lower left parathyroid gland and hypertrophy of the lower right parathyroid gland. The atypical clinical presentation - young age, inadequate normal PTH levels and the location of the lesions within the two parathyroid glands suggested genetic testing, which confirmed the presence of a genetic mutation - the GCM2 variant. Treatment included exploration of the parathyroid area using fluorescence. Both lower parathyroid glands were dissected. PTH monitoring showed a decrease in baseline levels of more than 50% after surgery. One month after surgery, PTH and calcium levels remained normal. Primary hyperparathyroidism is usually asymptomatic, detected when laboratory tests are performed for another cause. Symptoms include nephrolithiasis, bone and joint pain, osteoporosis, arrhythmias and fatigue. The typical patient has high PTH levels and hypercalcemia, but not every case will be schematic. High serum calcium levels do not always result in increased PTH levels and an in-depth diagnosis is required. The GCM2 mutation, detected in the patient presented here, may occur in familial isolated hyperparathyroidism. Correct diagnosis and treatment is crucial not only for the patient, as it significantly improves their quality of life, but also for their family members, who may also have a genetic mutation and be unaware of the disorder developing in their body. [ABSTRACT FROM AUTHOR]

This paper reviews epidemiological data on primary hyperparathyroidism (PHPT). PHPT is an endocrine disease caused by a tumor or hyperplastic changes in the parathyroid glands (PTG); it leads to disturbances in calcium-phosphorus homeostasis and can cause organ dysfunction. The results of epidemiological studies in various countries indicate an "epidemic" of PHPT at the end of the 20th century. Currently, PHPT ranks as the third endocrine problem in the world. Its prevalence is about 0.86-1% in people under 50 and 2% in people over 50. It was found that PHPT occurs more often in people aged 40-60 years, with an increase in the frequency of its detection after 25 years of age, especially in women after menopause. The review emphasizes the importance of PHPT, which represents a severe medical and social problem. Regular screening and the introduction of modern diagnostic methods play a vital role in the timely detection and management of PHPT, which is of great importance for improving patients' quality of life and preventing severe complications. When compiling the literature review, we used the following databases: PubMed, Embase, Medline, ScienceDirect, Cochrane Library, eLibrary, and CyberLeninka. The literature search was carried out using the following keywords: "epidemiology of primary hyperparathyroidism", "prevalence", "incidence", "normocalcemic hyperparathyroidism", "parathyroid gland", and "parathyroid hormone". The search identified more than 1070 scientific papers, from which 48 studies were selected. These studies cover the epidemiological aspects (incidence and prevalence) of PHPT conducted in various countries. The selection was done without considering each study's specific period and volume of observations. The selection process focused on studies using automated blood calcium analyzers to evaluate the impact of regular screening on the effectiveness of detecting PHPT. Works presenting both global and regional data were also included in the analysis. Studies that did not meet the established selection criteria were excluded.

Abstract Background Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. Methods A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. Results Statistically significant (P

Acute pancreatitis as an initial manifestation of primary hyperparathyroidism (PHPT) has been rarely reported. We report a case of acute pancreatitis from a hyperfunctioning parathyroid tumor in an 87-year-old woman with drowsy state. Laboratory tests showed high lipase, calcium, and intact parathyroid hormone level, and abdominal computed tomography scan revealed acute pancreatitis. Neck ultrasound and scintigraphy gave rise to the diagnosis of primary hyperparathyroidism due to a left parathyroid tumor. The patient underwent radiofrequency ablation of the parathyroid tumor. After the procedure, symptoms subsided and patient was discharged from the hospital 2 weeks later. Six months of treatment, the PTH and calcium serum significantly reduced, her clinical presentation was stable, and there were no signs or symptoms of recurrence pancreatitis.

Focused parathyroidectomy is the preferred surgical method for treating primary hyperparathyroidism (pHPT) sustained by the pre-operatively well-localized parathyroid adenoma. We aimed to compare the effectiveness, safety, and short-term clinical outcome of minimally invasive video-assisted parathyroidectomy (MIVAP) in locoregional anaesthesia (LA) vs. general anaesthesia (GA) by means of propensity score matching (PSM) analysis. Retrospective research of patients who underwent MIVAP between January 2014 and December 2022 was carried out. Patients were divided into two groups based on the anaesthesiologic procedure (LA vs. GA). Overall, 553 patients underwent MIVAP. After PSM, 115 patients in the LA group and 230 patients in the GA group were included. MIVAP under LA was associated with shorter median operative time (16 vs. 35 min, p < 0.001), shorter median operative room occupation time (44 vs. 73 min, p < 0.001), and lesser median post-operative visual analogue scale pain, with comparable post-operative hospital stay and complication rate. MIVAP under LA is a safe and feasible procedure with significant advantages over GA in terms of post-operative pain and operative room occupation time. This last step can finally result in more efficient utilisation of the operative room and the health care system’s resources.

Background/Objective: Although common in adults, primary hyperparathyroidism (PHPT) is a rare condition in children with the most common etiology being solitary parathyroid adenoma (PTA). The typical presentation is symptomatic hypercalcemia. Management of PHTP secondary to PTA requires excision of the adenoma. Case Report: A 13-year-old adolescent boy presented because of orbital cellulitis and was noted to have hypercalcemia. Despite this, the patient was curiously asymptomatic. Further investigations yielded an elevated parathyroid hormone (PTH) level and a normal urine calcium-to-creatinine ratio making the most likely cause of hypercalcemia PHTP secondary to PTA. Imaging demonstrated PTA. The patient underwent parathyroidectomy with the pathology demonstrating PTA. Postoperatively, the PTH levels were undetectable; hence, the patient was treated with calcitriol and calcium supplementation for 1 month and 4 months, respectively. Genetic work-up for multiple endocrine neoplasia 1 and rearranged during transfection mutations was negative. Discussion: Solitary PTA is the most common cause of PHPT. Adenomas are mostly sporadic or may be a manifestation of an inheritable syndrome, such as multiple endocrine neoplasia. Although symptomatic disease is more common in children, our patient denied any hypercalcemia symptoms. The distinguishing biochemical feature of PHPT because of PTA is high or inappropriately normal PTH level in the context of high-normal or elevated serum calcium levels. Urinary calcium excretion is usually normal or high. PTAs are localized by ultrasound and Tc-99m-Sestamibi scintigraphy. Management includes parathyroidectomy and monitoring for postoperative hypocalcemia. Conclusion: In a child or adolescent presenting with hypercalcemia and elevated PTH levels, it is important to consider PHPT secondary to PTA, because an early diagnosis will aid in preventing complications from hypercalcemia.

Simple Summary: Parathyroid glands are four in number and usually located adjacent to the thyroid gland, however, variations in location and number can exist. Parathyroid glands produce and release parathyroid hormone (PTH) important for maintaining blood calcium levels. In primary hyperparathyroidism (PHPT), there is increased secretion of PTH with resultant elevated blood calcium levels due to causes within the parathyroid gland, such as a single or multiple tumours which could be benign or malignant. The role of imaging is to locate abnormal parathyroid gland including its presence in unusual location if any, localise tumour within the parathyroid gland and plan surgical approach. Additional role of imaging in a suspected case of parathyroid malignancy is to look for any distant spread. There is emerging evidence to suggest that incidental detection of enlarged parathyroid glands on routine CT by the radiologist, can lead to early diagnosis of PHPT before obvious symptoms and signs develop. In this article, we have described the various imaging modalites available for evaluation of various types of parathyroid tumours, along with their imaging appearances and advantages and disadvantages. In addition, we have prepared a flowchart for guiding management decisions for parathyroid tumours. Parathyroid pathologies are suspected based on the biochemical alterations and clinical manifestations, and the predominant roles of imaging in primary hyperparathyroidism are localisation of tumour within parathyroid glands, surgical planning, and to look for any ectopic parathyroid tissue in the setting of recurrent disease. This article provides a comprehensive review of embryology and anatomical variations of parathyroid glands and their clinical relevance, surgical anatomy of parathyroid glands, differentiation between multiglandular parathyroid disease, solitary adenoma, atypical parathyroid tumour, and parathyroid carcinoma. The roles, advantages and limitations of ultrasound, four-dimensional computed tomography (4DCT), radiolabelled technetium-99 (99mTc) sestamibi or dual tracer 99mTc pertechnetate and 99mTc-sestamibi with or without single photon emission computed tomography (SPECT) or SPECT/CT, dynamic enhanced magnetic resonance imaging (4DMRI), and fluoro-choline positron emission tomography (18F-FCH PET) or [11C] Methionine (11C -MET) PET in the management of parathyroid lesions have been extensively discussed in this article. The role of fluorodeoxyglucose PET (FDG-PET) has also been elucidated in this article. Management guidelines for parathyroid carcinoma proposed by the American Society of Clinical Oncology (ASCO) have also been described. An algorithm for management of parathyroid lesions has been provided at the end to serve as a quick reference guide for radiologists, clinicians and surgeons. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is a rare endocrine malignancy and an uncommon cause of primary hyperparathyroidism. Metastatic disease confers a guarded prognosis with limited systemic treatment options available. We describe a case of a 64-year-old woman with primary hyperparathyroidism secondary to PC. Despite initial surgical resection, the patient relapsed within 6 months with widespread cerebral and skeletal metastatic disease. She developed worsening parathyroid hormone-mediated hypercalcemia that was refractory to escalating doses of cinacalcet and antiresorptive therapy. Molecular genomics identified high tumor mutation burden within the malignant tissue and singleagent nivolumab immunotherapy was administered. After one dose, there was resolution of her refractory hypercalcemia and primary hyperparathyroidism. The patient has tolerated ongoing treatment with 3 weekly cycles of nivolumab. She remains in biochemical remission as of June 2024, which is now 12 months after commencement of nivolumab. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism in pregnancy is uncommon. Consequently, there are no randomized controlled studies that address treatment of primary hyperparathyroidism in pregnancy, and the efficacy and safety of medical management with cinacalcet in this setting is unknown. We report a case of a 28-year-old woman with primary hyperparathyroidism and hypercalcemia that worsened during her third trimester of pregnancy. Cinacalcet led to achievement of normocalcemia, allowing the delay of parathyroidectomy until after delivery of the baby. We also review the published literature on cinacalcet use in the management of primary hyperparathyroidism during pregnancy. Cinacalcet is typically reserved for pregnant patients with severe and symptomatic hypercalcemia, primarily serving as a last resort to delay parathyroidectomy until either the second trimester or the postpartum period. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for "Primary hyperparathyroidism" and "Malignant neoplasm". Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13–0.25; I2 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06–0.08; I2 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03–0.07; I2 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23–1.33; I2 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy. [ABSTRACT FROM AUTHOR]

The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30 causative rearranged during transfection (RET) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous RET germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891). There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5-50 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward. [ABSTRACT FROM AUTHOR]

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]

A 54-year-old woman was admitted to the hospital with a left neck mass. Enhanced CT and ultrasound examinations revealed a lesion in the left sternocleidomastoid muscle. The patient undergone right thyroid lobe resection 8 years ago. Interestingly, the lesion on the sternocleidomastoid muscle, along with the left lobe of the patient's thyroid, visually appears to form a displaced and complete thyroid in the early Tc-99m-MIBI parathyroid scintigraphy. Combined with Tc-99m-MIBI scintigraphy and abnormal PTH and blood calcium levels, the consideration was given to the lesion in the sternocleidomastoid muscle as an ectopic parathyroid adenoma. Subsequent surgical pathology confirmed this suspicion. [ABSTRACT FROM AUTHOR]

Background: Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). Materials and methods: The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level – with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12–2.62 mmol/l), without other causes for secondary hyperparathyroidism. Results: The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. Conclusion: The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures. [ABSTRACT FROM AUTHOR]

Objective: Currently, the relationship between parathyroidectomy and objective neuropsychiatric outcomes are not clearly defined. The purpose of this study is to perform the first ever Meta‐analysis of preoperative and postoperative PHQ‐9 and GAD‐7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy with the goal of identifying a specific psychometric score that could be used as an indication for surgical intervention. Data Sources: A comprehensive search of the literature was performed using PubMed, Embase, PsycINFO, Web of Science, and Ovid All EBM Reviews. Review Methods: Studies met inclusion criteria if they evaluated preoperative and postoperative PHQ‐9 and/or GAD‐7 scores in patients with primary hyperparathyroidism undergoing parathyroidectomy. Random effects Meta‐analyses were used to analyze the compiled data. Results: The literature search returned 1433 articles for initial review of which 6 (1105 participants) met criteria for inclusion and Meta‐analysis. Meta‐analysis revealed that primary hyperparathyroidism patients had significantly higher presurgical PHQ‐9 scores when compared to control groups. Additionally, patients experienced a statistically significant and sustained decrease in PHQ‐9 scores following parathyroidectomy. Notably, there was a dramatic decrease in the percentage of patients with PHQ‐9 scores ≥10 (considered clinically significant for depression) following parathyroidectomy. Conclusion: Patients with primary hyperparathyroidism experience a statistically significant and sustained improvement in PHQ‐9 scores following parathyroidectomy. Additionally, symptoms of anxiety and suicidal ideation appear to decrease after parathyroidectomy. We propose that a PHQ‐9 score ≥10 could potentially be used as an indication for parathyroidectomy in patients with asymptomatic primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

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

An 83‐year‐old woman presented with an acute course of dropped head syndrome (DHS) with muscle weakness localized to the neck. Serum calcium and intact parathyroid hormone (iPTH) levels were elevated to 12.2 mg/dL and 173 pg/mL, respectively, and 99mTc‐MIBI scintigraphy showed a hyperfunctioning parathyroid gland. Electromyography revealed myopathic features in the posterior neck extensor muscles. Primary hyperparathyroidism (PHPT)‐associated myopathy was diagnosed as the cause of the DHS. Oral administration of evocalcet ameliorated DHS and normalized the elevated serum calcium levels, whereas iPTH levels remained elevated. Subsequently, parathyroidectomy reduced the iPTH level to normal, and DHS did not flare‐up. Cases of PHPT with DHS as the initial symptom are extremely rare, and to our knowledge, this is the first report of remission of DHS with evocalcet. Therefore, serum iPTH levels may not necessarily correlate with muscle weakness. [ABSTRACT FROM AUTHOR]

A 32-year-old man with sickle cell disease (SCD) was admitted to the hospital for sickle cell crisis, during which laboratory workup revealed primary hyperparathyroidism. His treatment regimen included hydration, calcitonin, and calcimimetics. A parathyroid nuclear scan revealed anomalous parathyroid tissue. The precise relationship between primary hyperparathyroidism (PHPT) and SCD remains incompletely understood but may involve factors such as vitamin D deficiency, elevated erythropoietin levels, and the influence of growth factors on the development of parathyroid adenomas. Furthermore, the concurrent occurrence of both PHPT and SCD at an earlier age may potentiate adverse long-term outcomes. Effective management of PHPT in SCD entails addressing hypercalcemia and treating the underlying cause of hyperparathyroidism. While a potential association between PHPT and SCD exists, further research is essential to better elucidate their interaction, prevalence, clinical presentations, and outcomes. [ABSTRACT FROM AUTHOR]

Focused parathyroidectomy is the preferred surgical method for treating primary hyperparathyroidism (pHPT) sustained by the pre-operatively well-localized parathyroid adenoma. We aimed to compare the effectiveness, safety, and short-term clinical outcome of minimally invasive video-assisted parathyroidectomy (MIVAP) in locoregional anaesthesia (LA) vs. general anaesthesia (GA) by means of propensity score matching (PSM) analysis. Retrospective research of patients who underwent MIVAP between January 2014 and December 2022 was carried out. Patients were divided into two groups based on the anaesthesiologic procedure (LA vs. GA). Overall, 553 patients underwent MIVAP. After PSM, 115 patients in the LA group and 230 patients in the GA group were included. MIVAP under LA was associated with shorter median operative time (16 vs. 35 min, p < 0.001), shorter median operative room occupation time (44 vs. 73 min, p < 0.001), and lesser median post-operative visual analogue scale pain, with comparable post-operative hospital stay and complication rate. MIVAP under LA is a safe and feasible procedure with significant advantages over GA in terms of post-operative pain and operative room occupation time. This last step can finally result in more efficient utilisation of the operative room and the health care system's resources. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess vitamin D status and its impact on the initial characteristics of primary hyperparathyroidism (PHPT). Methods: This study included consecutive participants diagnosed with PHPT aged 18 years and/or older at a tertiary center between November 2017 and December 2023. A total of 195 subjects not taking vitamin D replacement were reviewed retrospectively. The study population was categorized into three groups according to their vitamin D levels at the time of admission: Group 1: vitamin D ≤19 ng/mL, Group 2: vitamin D 20-29 ng/mL, and Group 3: vitamin D ≥30 ng/mL. Demographic, clinical, biochemical, radiological findings, and postoperative complications were compared between the three groups. Results: Among 195 patients, 157 (80.5%) were women, and 38 (19.5%) were men. The mean age was 56.4±14.5 years. Sixty-five patients (33.3%) had vitamin D deficiency (VDD), and 48 patients (24.7%) had vitamin D insufficiency. Of the 195 patients, 74 (37.9%) had kidney stones, and 90 (46.2%) had osteoporosis. Fracture frequency was 9.7% (n=19). VDD was associated with higher parathyroid hormone (PTH) levels (p=0.000) and better estimated glomerular filtration rate (p=0.021). When all groups were compared, there were no differences in terms of nephrolithiasis, osteoporosis, and fractures. Conclusion: The present study revealed that VDD was associated with higher PTH levels and better renal function. However, vitamin D status was not associated with classical target organ involvement in PHPT. [ABSTRACT FROM AUTHOR]

Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT. Using the input from radiologists, endocrinologists, and surgeons, we apply patient criteria such as large body habitus, concomitant multiglandular disease, multinodular thyroid disease, confusing previous imaging, and unsuccessful previous surgery to create an imaging paradigm that uses 4D SPECT/CT yet is cost-effective, accurate, and limits extraneous radiation exposure. 4D SPECT/CT capitalizes on the strengths of SPECT and 4D CT and addresses limitations that exist when these modalities are used in isolation. In select patients with complicated clinical parameters, preoperative imaging with 4D SPECT/CT can improve accuracy yet remain cost-effective. [ABSTRACT FROM AUTHOR]