Resection of a massive substernal parathyroid adenoma below the aortic arch via a cervical approach: A case report

ABSTRACTA parathyroid adenoma is defined as a benign tumor in the parathyroid glands. A type of parathyroid adenoma is giant parathyroid adenoma that weighs > 3.5 g and has a size of more than 2 cm. A 37‐year‐old woman presented with coughs and dyspnea without fever, hemoptysis, and weight loss. Examination of the patient revealed a diffusely enlarged thyroid gland and a positive Pemberton's sign. On the CT scan, the hypodense mass in the superior mediastinum was noted with tracheal compression. The resected mass weighed 15 g, and histopathology indicated a giant parathyroid adenoma (GPA). Giant parathyroid adenoma, as a rare cause of hyperparathyroidism, is diagnosed by imaging and laboratory methods. This case showed that the differential diagnosis of GPA is necessary and should be considered. In addition, the main method of treatment for this disease is surgery and removal of the parathyroid adenoma.

Rationale:Primary hyperparathyroidism is an endocrine disease primarily caused by a single benign parathyroid adenoma. It is characterized by symptoms such as hypercalcemia, hypophosphatemia, kidney stones, and bone destruction. Parathyroid adenomas are generally located on the posterior aspect of the thyroid gland, while giant parathyroid adenomas in the anterior superior mediastinum are relatively rare. Typically, benign anterior superior mediastinal tumors are managed through sternotomy or thoracoscopic surgery, which can be associated with significant trauma or complications.Patient concerns:We present a case of a patient with hypercalcemia and hyperparathyroidism. Biochemical analysis showed that the serum calcium level was 2.72 mmol/L and the parathyroid hormone level was 1050 pg/mL. Physical examination, ultrasound, and CT scans revealed a lesion in the right anterior superior mediastinum, suggesting it originated from the right inferior parathyroid gland.Diagnoses:Based on the physical examination, biochemical, and imaging findings, the patient was preliminarily diagnosed with a parathyroid tumor in the right anterior superior mediastinum.Interventions:The patient underwent successful resection of a giant anterior superior mediastinal parathyroid adenoma via a neck incision.Outcomes:At the 1-year follow-up, the patient was alive and had normal voice function. There was no abnormal increase in serum calcium or parathyroid hormone levels.Lessons:For certain benign anterior superior mediastinal tumors, a neck incision is recommended to minimize surgical trauma and promote faster postoperative recovery.

Objective: Four-dimensional computed tomography (4DCT) demonstrates superior diagnostic capability in localizing parathyroid adenomas that are non-detectable by conventional ultrasonography (USG) or scintigraphy. 4D-CT demonstrates particular utility in spatial differentiation, allowing precise localization of adenomas while distinguishing them from adjacent thyroid tissue and lymphatic structures. This study evaluated the accuracy of 4D-CT for localizing parathyroid adenomas in primary hyperparathyroidism patients with non-diagnostic or conflicting ultrasound and sestamibi scan results. Materials and Methods: This prospective study enrolled 25 patients with primary hyperparathyroidism whose parathyroid adenomas either could not be localized by either ultrasonography or scintigraphy or showed discordant imaging results between the two modalities. A 4DCT scan was performed for each of the 25 study participants diagnosed with primary hyperparathyroidism. The diagnostic findings of USG, scintigraphy, and 4DCT were correlated with histopathological results. Results: 4DCT demonstrated 100% detection sensitivity, markedly superior to ultrasonography's 68% and scintigraphy's mere 12%. For lateralization, 4DCT achieved 92% sensitivity versus ultrasonography's 88% and scintigraphy's notably poorer 33%. In precise localization, four-dimensional computed tomography's 80% accuracy exceeded ultrasonography's 64%, while scintigraphy demonstrated a complete inability to localize lesions. Conclusion: In our study, 4DCT was found to be the most sensitive method for detection, lateralization, and localization of parathyroid adenomas compared to USG and scintigraphy. In cases with primary hyperparathyroidism, 4DCT is able to accurately detect and localize these lesions hence providing a chance for cure by surgical resection.

A 70-year-old man with primary hyperparathyroidism underwent 18F-choline PET/CT to localize a parathyroid adenoma before surgery. 18F-choline PET/CT confirmed the right superior parathyroid adenoma but also revealed skin uptake corresponding to an inflammatory epidermoid cyst of the left neck. Two months later, the patient underwent successful minimally invasive parathyroidectomy. The epidermoid cyst was also excised. Inflammatory epidermoid cysts can be a cause of false-positive 18F-choline skin uptake.

Ectopic parathyroid adenoma: successful localization with 18F-fluorocholine PET/CT and parathyroid venous sampling in two cases.

The authors present surgical treatment of a patient with follicular thyroid tumor and parathyroid gland adenoma. Subsequent analysis recognized oncocytic thyroid gland adenoma manifested by clinical and laboratory picture of primary hyperparathyroidism. Multinodular goiter imitating parathyroid gland adenoma when one of the nodes is located behind thyroid lobe and intrathyroid location of parathyroid gland adenoma are factors complicating differential diagnosis. Therefore, this case of thyroid gland adenoma imitating functionally active parathyroid gland adenoma illustrates the need for alertness with respect to combination and mutual imitation of tumors of thyroid and parathyroid glands requiring surgical intervention. In addition, such cases require differential diagnosis between thyroid and parathyroid neoplasms based on all available laboratory and topical methods.

Ectopic parathyroid adenomas (EPAs) pose significant challenges in the diagnosis and management of primary hyperparathyroidism (PHPT) due to their atypical locations. This study aims to categorize EPAs based on their anatomical locations, describe the associated diagnostic strategies, and present case studies to illustrate clinical management. EPAs were retrospectively reviewed based on cases from published literature and our institutional experience. Relevant studies were identified through a systematic search of PubMed and Embase. A comprehensive anatomical classification system was developed, categorizing EPAs into pharyngocranial, cervical, and mediastinal regions. From a total of 1278 screened publications, 137 studies encompassing 875 EPAs were identified and included. Combined with 13 original cases from our institute, these cases were comprehensively analyzed to develop an anatomically based classification system. EPAs were categorized into four types based on anatomical location: Type I (pharyngocranial), Type II (cervical, adjacent to the thyroid), Type III (cervical, distant from the thyroid), and Type IV (mediastinal). A combination of imaging modalities, including ultrasonography, CT, MRI, sestamibi scintigraphy, and SPECT, proved effective for preoperative localization. Case studies highlight clinical outcomes and challenges associated with each type. A comprehensive anatomical classification system for EPAs, integrated with advanced imaging modalities and correlated with biochemical profiles, improves preoperative identification and guides targeted treatment strategies.

CHEK2 is a moderate-penetrance tumor suppressor gene primarily linked to hereditary breast cancer, yet growing evidence implicates it in a wider tumor spectrum. Data from underrepresented populations, such as Türkiye, remains limited. We retrospectively analyzed 895 individuals referred for hereditary cancer evaluation between 2019 and 2025 who underwent multigene panel testing. Germline CHEK2 variants were identified using the Hereditary Cancer Solution Kit (Sophia Genetics) and classified per ACMG guidelines. Clinical, tumor, and histopathological data were reviewed. Twenty-four carriers (83.3% female) were detected: 45.8% harbored pathogenic, 41.6% likely pathogenic, and 12.5% variant of uncertain significance. Breast cancer was the most frequent (66.6%), followed by bladder cancer (8.3%), with isolated cases of ovarian, cervical, lung, papillary thyroid cancers, parathyroid adenoma, and thymoma. Missense variants predominated (75%), clustering in the FHA (66.6%) and kinase (33.4%) domains. Recurrent c.470T > C and c.1427C > T variants comprised 41.6% of all cases. Our findings highlight variant- and sex-specific patterns and underscore the relevance of population-based data in refining cancer risk assessment and management of CHEK2 carriers.

A 46-year-old woman with hypercalcemic primary hyperparathyroidism underwent a Tc-99m SestaMIBI scintigraphy and SPECT-CT, which identified 3 distinct radiotracer-avid intrathyroidal nodules. Following a right hemithyroidectomy and subsequent histopathologic evaluation, it turned out that she had 3 pathologically distinct nodules, that is, intrathyroidal parathyroid adenoma, invasive encapsulated follicular variant of papillary thyroid carcinoma, and tall-cell variant of papillary thyroid microcarcinoma. Our case serves as an important reminder that at times even distinct pathologies can present with identical anatomic features and radiotracer uptake patterns.

Primary hyperparathyroidism (PHPT) is a systemic endocrine disorder characterized by elevated parathyroid hormone (PTH) levels and hypercalcemia. Gene-specific epigenetic modifications like histone methylation play a pivotal role in PHPT by altering expression of parathyroid-specific genes. However, global histone modifications in parathyroid tumors and their implications for tumor behavior remain underexplored. We performed comparative histone modification profiling in blood and tissue samples from sporadic parathyroid adenomas (PA; n=30), atypical parathyroid tumors (APT; n=05), and parathyroid carcinomas (PC; n=05) along with controls using histone H3 multiplex immunoassay. Significantly dysregulated modifications were validated by western blotting (WB) and expression data was correlated with clinicopathological features. We performed pathway enrichment analysis to elucidate molecular pathways potentially linked to histone H3 modifications in parathyroid tumorigenesis. We observed dynamic alterations in histone H3 modifications of lysine (K) residues across parathyroid tumor phenotypes in blood and tissue samples. A reduction in H3K4, H3K36 trimethylation (<60%) and increase in H3K27 trimethylation and H3K9 monomethylation (>130%) than controls was observed. WB confirmed lower H3K4me3 (0.5±0.4 vs 4.4±0.7, p=0.02; 0.4±0.2 vs 4.4±0.7, p=0.004) and H3K36me3 (0.4±0.2 vs 1.0±0.3, p=0.03; 0.2±0.1 vs 1.0±0.3, p=0.02) in APT and PC than controls, and higher H3K27me3 expression in PA (2.9±1.2 vs 1.1±0.21, p=0.04), APT (4.2±2.9 vs 1.1±0.21, p=0.007), and PC (6.9±3.1 vs 1.1±0.21, p=0.0002) relative to controls. Pathway enrichment analysis identified molecular pathways, including calcium signaling, Wnt, and Hippo signaling, associated with histone H3 modifications. Increased expression of repressive H3K27me3 in blood and tissue samples, while decreased H3K4me3 and H3K36me3, suggest a shift towards transcriptional repression. Identifying their functional mechanisms may facilitate discovery of novel insights for therapeutic targeting in parathyroid tumors.

Introduction: Parathyromatosis is an extremely rare cause of recurrent or persistent primary hyperparathyroidism (PHPT), usually resulting from intraoperative seeding of parathyroid tissue following capsular rupture drecurruring surgery. Its diagnosis is difficult and may mimic parathyroid carcinoma. Case Report: We report the case of a 50-year-old woman with recurrent PHPT after three parathyroid surgeries. The first operation in 2012 for a right inferior parathyroid adenoma achieved temporary remission. Two further recurrences occurred in 2017 and 2022, each treated surgically, but postoperative hypercalcemia and elevated parathyroid hormone (PTH) persisted. Cervical ultrasound and 18F-fluorocholine PET/CT revealed multiple small hypermetabolic nodules scattered in the right neck region, consistent with secondary parathyromatosis. Given the patient’s refusal of further surgery, medical treatment with the calcimimetic cinacalcet was initiated, allowing long-term biochemical control at a dose of 120 mg/day. Conclusion: Parathyromatosis should be considered in any patient with multiple recurrences of PHPT after parathyroidectomy. High-performance imaging, especially 18F-fluorocholine PET/CT, is essential for localization. Careful handling of parathyroid glands during surgery is crucial to prevent this rare but challenging complication. While surgery remains the treatment of choice, cinacalcet can represent an effective alternative for non-surgical candidates.

Background/aimRadiofrequency ablation of solitary parathyroid adenoma has been used to treat primary hyperparathyroidism (pHPT) in high-risk patients for parathyroidectomy. This study aimed to evaluate the clinical efficacy of radiofrequency ablation for treating pHPT in patients with parathyroid adenomas.Materials and methodsThe sample for this retrospective study comprised all consecutive patients with solitary parathyroid adenoma treated with radiofrequency ablation between 2013 and 2021. Patients’ baseline serum calcium and parathyroid hormone (PTH) values were obtained. The patients were followed up with serial biochemical measurements after the intervention, then at the first-week, first-month, third-month, sixth-month, and twelfth-month follow-ups. The study’s primary outcome was a biochemical cure, defined as the reestablishment of normal serum calcium and PTH levels, persisting for at least 6 months after the ablation.ResultsThe changes in the serum calcium and PTH levels were significant (p < 0.05). The biochemical cure rate was 30.2% at 1 year. At the end of 1 year, the rate of patients with normal serum calcium levels was 86.6%, whereas the rate of patients with normal serum calcium and higher PTH levels was 55.8%.ConclusionRadiofrequency ablation of a solitary parathyroid adenoma may be considered an alternative treatment for pHPT, given that more than half of the cases investigated in this study had normocalcemic hyperparathyroidism at 1 year.

In primary hyperparathyroidism, preoperative localisation of a parathyroid adenoma enables focussed excision rather than full neck exploration, with reduced complication rates, recovery time and cost. In this study, we sought to improve parathyroid adenoma localisation on 99m Tc-sestamibi so more patients can benefit from focussed excision. We performed a baseline audit of our 99m Tc-sestamibi service, followed by three sequential changes: cycle 1: acquisition of new single-photon emission computed tomography/computed tomography (SPECT/CT) scanners, cycle 2: optimisation of image acquisition and reconstruction, cycle 3: addition of arterial phase iodinated contrast to SPECT/CT. We classified reporter confidence using a 5-point Likert scale. We correlated adenoma location on imaging with 'gold standard' location based on surgical and pathology results. We calculated the sensitivity, specificity, and receiver operator characteristics following each change cycle. Results comparing each cycle to the baseline audit: Baseline: 44% confidently located, 31% failed to identify an adenoma. Sensitivity: 69.8%, specificity: 95.7%, area under the curve (AUC): 0.92. Cycle 1: 54% confidently located, 24% failed to identify an adenoma. Sensitivity: 77.6%, specificity: 93.3%, AUC: 0.95. Cycle 2: 48% confidently located, 18% failed to identify an adenoma. Sensitivity: 84.3%, specificity: 95.9%, AUC: 0.98. Cycle 3: 67% confidently located, 6% failed to identify an adenoma. Sensitivity: 94.7%, specificity: 90%, AUC: 0.99 ( P < 0.001). Our study demonstrated that sequential improvements in 99m Tc-sestamibi SPECT/CT significantly improved test performance by reducing the number of localisation failures, increasing test sensitivity, and reducing the number of false negatives. As a result, more patients can benefit from focussed excision parathyroidectomy.

Surgical outcome of primary hyperparathyroidism and factors correlated with preoperative serum iPTH concentration.

Primary hyperparathyroidism is one of the most common endocrine disorders and it is only curable by surgery. This study aimed to accurately localize parathyroid adenomas (PTAs) in patients with negative results from conventional diagnostics, consisting of MIBI SPECT/CT and ultrasound, by utilizing F-18-ethylcholine-PET/ultrasound real-time fusion imaging. Fusion ultrasound is a well-established diagnostic tool that enables precise identification and localization of target structures by superimposing MRI, CT, or PET/CT with real-time B-mode ultrasound. The goal was to detect occult PTAs and enable curative targeted parathyroidectomy. A total of 49 patients with primary hyperparathyroidism were consecutively recruited from routine clinical workflows. Given negative standard diagnostics, patients were referred for FEC-PET/CT followed by FEC-PET/ultrasound. PTAs were categorized as positive, ambiguous, or negative based on FEC-PET/ultrasound findings. A retrospective data analysis was performed, examining PTA volume (ml) based on ultrasound results, SUVmax of PTAs and locoregional lymph nodes, as well as parathyroid hormone, calcium, and phosphate levels. Maximal, minimal, median, mean values, and SDs were reported. Forty-nine PTAs were identified, of which 45 were solitary, whereas 2 patients had double adenomas each. The study showed relatively high rates of ectopic PTAs (28%). No significant differences were observed in FUS-based detection rates between ectopic and orthotopic lesions. PTAs, exhibited significantly higher (P<0.05) tracer uptake [SUVmax 4.5±2.7 (4, 1.4-11.9)] compared with lymph nodes [SUVmax 2.7±1.7 (2.5, 1.2-11.8)]. SUVmax was significantly higher in positive lesions compared with ambiguous cases (P<0.05). No significant SUVmax difference was found for lymph nodes in ambiguous cases. FUS-based PTA volume ranged from 0.2 to 2.6ml (mean 0.5±0.5ml). Twenty-seven patients underwent surgery, and the diagnosis was confirmed in 90% of cases. This study shows that FEC-PET/ultrasound offers valuable support for preoperative localization and thus can be considered as an effective and precise method for detecting parathyroid adenomas in primary hyperparathyroidism. Because of its high time and technical demands, it is reserved for challenging cases unresolved by standard diagnostics. Future technical advances may increase its accessibility.

Maternal hypercalcemia is a rare but potentially serious cause of late-onset neonatal hypocalcemia. Data on the clinical characteristics and outcomes of mother-baby couplets with maternal hypercalcemia and subsequent neonatal hypocalcemia remains scarce. This retrospective study reviewed medical records of neonates with late-onset hypocalcemia (≥3 days after birth) caused by maternal hypercalcemia at a tertiary medical center in Taiwan from 2014 to 2021. A stepwise diagnostic approach was applied to exclude other secondary causes. The etiologies of maternal hypercalcemia were assessed. Clinical outcomes and treatment responses of the mother-infant dyads were extracted from follow-up records documented during routine clinical care. A total of seven neonates (6 males, 1 female) were documented. All affected neonates presented with seizure between 5 and 12 days of age. Laboratory findings revealed hypocalcemia (median: 5.3 mg/dL), hyperphosphatemia (median: 10.2 mg/dL), inappropriately intact parathyroid hormone (median: 18.4 pg/mL), and low 25-hydroxyvitamin D3 levels. Neonates born to mothers with severe hypercalcemia (≥11 mg/dL) had lower serum calcium and higher phosphorus levels compared to those with maternal calcium <11 mg/dL. For all neonates, hypocalcemia and hyperphosphatemia normalized within one month with calcium and 1,25 (OH)2 Vit. D3 supplement. During a median 2-year follow-up period, there were no recurrent hypocalcemia cases. One child had delayed speech. Maternal evaluation revealed functional parathyroid adenomas in six of seven (86%) mothers; four underwent parathyroidectomy; two received conservative treatment. One mother with a CASR mutation achieved normocalcemia with calcimimetics. All mothers recovered without serious sequelae. Late-onset neonatal hypocalcemia should prompt maternal calcium evaluation even in asymptomatic mothers. Maternal total serum calcium levels ≥11 mg/dL may require more intensive neonatal monitoring and prolonged treatment. Genetic testing should be considered in mother with negative result of parathyroid scan. This study provides the first comprehensive analysis of maternal hypercalcemia-induced neonatal hypocalcemia, identifying functional parathyroid adenomas as the predominant cause (86%). Maternal calcium levels ≥11 mg/dL correlate with more severe neonatal hypocalcemia, establishing evidence-based risk stratification for clinical management. Emphasizes routine maternal calcium screening in late-onset neonatal hypocalcemia and genetic testing when parathyroid imaging is negative. Demonstrates excellent prognosis with complete biochemical normalization in all neonates within three months and minimal long-term neurodevelopmental sequelae.

A 44-year-old male presented with a 19-year history of urinary calculi and a 1-year history of polydipsia and weight loss. Laboratory tests revealed hyperparathyroidism and evidence of glucagonoma-associated diabetes. Imaging studies identified masses in the pancreatic head and body/tail, suggestive of glucagonoma and a parathyroid adenoma. Furthermore, the patient exhibited hypercalcitoninemia and elevated cortisol and adrenocorticotropic hormone levels. Genetic testing revealed a heterozygous MEN1 mutation [c.65T>G (p.Leu22Arg)], confirming the diagnosis of multiple endocrine neoplasia type 1 (MEN-1). The patient subsequently underwent near-total parathyroidectomy and total pancreatectomy. Postoperative immunohistochemical staining of the pancreatic tail tumor was positive for glucagon and calcitonin. The patient's postoperative hormone levels (calcitonin, glucagon, adrenocorticotropic hormone, cortisol) normalized, suggesting a rare pancreatic neuroendocrine tumor (pNET) that was co-secreting multiple hormones. Postoperative management included pancreatic enzyme supplementation, calcium supplementation, vitamin D supplementation, and insulin for glycemic control. Follow-up evaluations at 10 months demonstrated a stable clinical condition, well-controlled blood glucose and biochemical parameters, and an acceptable quality of life. This case study highlights that the presence of pNETs should be considered in patients with MEN-1 and multiple abnormal hormone levels. Timely surgical management of the involved glands and postoperative complications can effectively improve prognosis.

This study aimed to evaluate the diagnostic performance of biochemical markers in normocalcemic primary hyperparathyroidism (nPHPT), analyse their temporal variations, and assess their correlation with adenoma localisation and size. In this multicenter retrospective study-the largest patient cohort reported in the literature to date (n = 474) we comprehensively profiled normocalcemic patients diagnosed with primary hyperparathyroidism nPHPT was diagnosed based on persistently elevated PTH levels with normal serum calcium after excluding secondary causes such as vitamin D deficiency, renal impairment, and other conditions. This retrospective multicenter study included a large cohort of patients whose biochemical markers-including serum calcium, phosphorus, magnesium, vitamin D, parathyroid hormone (PTH), and glomerular filtration rate (GFR)-were measured at three time points, using standardised laboratory protocols. Although in routine clinical practice these measurements are typically performed at regular intervals of 3-6 months, resulting in approximately three assessments during an 18-month follow-up period. Urinary calcium and creatinine levels were also determined, and imaging modalities (ultrasonography, sestamibi scintigraphy, and computed tomography) were employed for adenoma detection. Statistical analyses comprised repeated measures ANOVA, logistic regression, correlation analysis, and ROC analysis, performed using Jamovi software. Serial evaluations revealed significant temporal changes in key biochemical parameters, including a significant decline in serum calcium and PTH levels alongside a significant increase in urinary calcium excretion. Logistic regression analysis identified higher PTH levels, higher corrected calcium, and larger adenoma size as independent predictors of adenoma localisation, while ROC analysis confirmed that PTH exhibited the highest diagnostic accuracy (AUC = 0.91, 95% CI: 0.84-0.95, p < 0.001). The large scale of our patient cohort reinforces the robustness of our statistical analyses and provides comprehensive insight into the dynamic nature of nPHPT. Our findings demonstrate that, even in normocalcemic patients, higher PTH levels and relatively higher calcium levels within the normal range are important indicators of parathyroid adenoma. Integrating serial biochemical measurements with targeted imaging can facilitate earlier diagnosis, potentially preventing future complications and informing more tailored management strategies.

Tacrolimus-associated parathyroid adenoma with hyperparathyroidism following liver transplantation: A case report and clinical insight