Case 328: Brown Tumor in Hyperparathyroidism Due to Parathyroid Adenoma.

HISTORY: A 45-year-old female patient with diffuse osteoarticular pain, particularly low back pain, was referred by a rheumatologist for an updated radiologic evaluation. The patient had experienced these symptoms for many years and was diagnosed with human leukocyte antigen B27-negative spondyloarthritis approximately 11 years prior, based on findings of bilateral erosive sacroiliitis at pelvic radiography and bone scintigraphy with technetium 99m (99mTc) methylene diphosphonate. After 3 years of treatment with a tumor necrosis factor-α inhibitor (adalimumab), which was effective for pain, the patient was lost to follow-up. At the current presentation, approximately 8 years after being lost to follow-up, the patient presented with worsening low back pain. The presence of nonobstructing kidney stones on US images confounded the underlying cause of worsening pain. The patient also experienced fatigue and depressed mood. Routine blood tests revealed a normal blood cell count, creatinine level of 0.64 mg/dL (56.58 µmol/L) (normal range, 0.30-1.1 mg/dL [26.52-97.24 µmol/L]), C-reactive protein level of 1.1 mg/dL (normal, <1 mg/dL), and vitamin D level of 21 ng/mL (52.42 nmol/L) (normal range, 30-100 ng/mL [74.88-249.60 nmol/L]). Noncontrast MRI of the thoracic and lumbar spine, MRI of the sacroiliac joints, and CT of the abdomen and pelvis were performed.

Detection of Muscular Metastasis in a Case of Parathyroid Carcinoma Using 18 F-FAPI-04 PET/CT.

ABSTRACT: A 46-year-old woman underwent surgery for parathyroid carcinoma 2 years ago. During follow-up, the patient presented with elevated parathyroid hormone (127.50 pg/mL; normal, 15-65). No abnormal uptake of 18 F-FDG or 11 C-choline was observed on 18 F-FDG and 11 C-choline PET/CT imaging. The patient was enrolled in a clinical trial for 18 F-FAPI PET/CT imaging, revealing a lesion with intense focal uptake within the left sternocleidomastoid muscle. The patient underwent surgery. Postoperative pathology and immunohistochemical analysis confirmed parathyroid carcinoma metastasis.

Ectopic parathyroid adenoma proved by diagnostic CT.

Primary hyperparathyroidism (PHPT) is the most prevalent cause of hypercalcaemia, affecting 0.3% of the population. The only curative procedure is parathyroidectomy. Ectopic adenomas are challenging to localize and frequently result in persistent PHPT. This is a case report of a 29-year-old male patient who was diagnosed with PHPT prior to neck surgery and reoperated with bilateral neck exploration. However, the PHPT was not cured, until diagnostic CT with contrast had helped localizing a 1 cm ectopic parathyroid adenoma in the right horn of the thymus gland. The adenoma was then removed successfully.

Incidental synchronous intrathyroidal parathyroid carcinomas and papillary thyroid microcarcinoma with compressive neck mass and primary hyperparathyroidism: case report and literature review.

BACKGROUND: Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience. CASE PRESENTATION: We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter. CONCLUSION: Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma.

Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography.

Importance: Accurate preoperative localization is critical to success in targeted parathyroidectomy for primary hyperparathyroidism. Objective: To determine if the association between the long axis of a parathyroid adenoma (PTA) candidate and strap musculature on sagittal ultrasonography (US) can be used to predict the embryologic origin of the gland. Design, Setting, and Participants: This diagnostic study was performed using the Stanford Research Repository. Patients 18 years or older with primary hyperparathyroidism who underwent parathyroidectomy between January 2009 and October 2021 were considered. Additional inclusion criteria were having clear sagittal view of the adenoma candidate on US, confirmation of the gland of origin intraoperatively, and confirmation of hypercellular parathyroid on final pathology. Data were analyzed from October 2021 to June 2022. Exposures: B-mode US and surgical parathyroidectomy. Main Outcomes and Measures: The index test was using US to measure the angle between the long axis of an adenoma candidate and the strap musculature in the sagittal plane. This angle was used to test whether inferior and superior PTAs could be accurately assigned. The hypothesis was formulated prior to data collection. Results: A total of 426 patients (mean [range] age, 61.1 [20-96] years; 316 [74.2%] female) with 442 adenomas met inclusion criteria. Of the 442 adenomas, 314 (71.0%) had measurable angles, of which 204 (46.2%) were assigned a superior origin, 238 (53.8%) were assigned an inferior origin, and 128 (29%) were indeterminate. Of the surgically identified superior PTAs, 144 (70.6%) had a definable angle, and of the surgically identified inferior PTAs, 170 (71.4%) had a definable angle. The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. This supported using 90° as a break point for US review. True positives were considered superior adenomas with an angle greater than 90°; true negatives were inferior adenomas with an angle less than 90°. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively. A subgroup analysis of 426 adenomas using the posterior carotid artery border on transverse US as a surrogate for predicting gland origin showed the following for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 49.5% (95% CI, 42.6%-56.4%), 82.3% (95% CI, 77.3%-87.3%), 71.4% (95% CI, 63.9%-78.9%), 64.6% (95% CI, 59.1%-70.1%), and 66.9%, respectively. Conclusions and Relevance: This diagnostic study showed that PTA angulation on sagittal plane US can be used to predict gland of origin and guide surgery. The relationship between adenoma and posterior carotid artery border on transverse US can also be used to predict gland origin. These easy-to-apply US-based tests can be used in conjunction with other imaging modalities to guide targeted parathyroidectomy.

Primary hyperparathyroidism caused by a tiny mediastinal parathyroid adenoma with non-localising imaging studies.

Variations in parathyroid gland positions often cause failure in initial parathyroid adenoma surgery, especially when imaging fails to localise the adenoma. This report describes a female patient with primary hyperparathyroidism for which preoperative localisation studies did not determine the position of the hyperfunctioning gland. The initial approach with bilateral cervical exploration and intraoperative parathyroid hormone monitoring was performed unsuccessfully. A mediastinal adenoma was suspected due to meticulous negative neck exploration and repeated negative images for a neck adenoma. Subsequently, a second approach involving mediastinal exploration was performed. After the removal of remnant thymic tissue in the mediastinal space, a significant drop in intraoperative parathyroid hormone levels was achieved. The pathological result confirmed the presence of a tiny pathological parathyroid adenoma within the thymus. At 6 months follow-up, postoperative biochemical assessment was consistent with normal calcium and parathyroid hormone levels.

Cost-effectiveness of one-stop-shop [18F]Fluorocholine PET/CT to localise parathyroid adenomas in patients suffering from primary hyperparathyroidism.

PURPOSE: We conducted a cost-effectiveness analysis in which we compared a preoperative [18F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [18F]Fluorocholine PET/CT is only recommended after negative or inconclusive [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. METHODS: We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients' hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [18F]Fluorocholine PET/CT and the sensitivity of [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. RESULTS: The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [18F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. CONCLUSION: Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.

F18-Choline PET/CT or MIBI SPECT/CT in the Surgical Management of Primary Hyperparathyroidism: A Diagnostic Randomized Clinical Trial.

Importance: Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear. Objective: To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery. Design, Setting, and Participants: A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible. Interventions: Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery. Main Outcomes and Measures: The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality. Results: Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported. Conclusions: This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT04040946.

Update in imaging tests used for the localization of parathyroid pathology.

Preoperative localization of parathyroid pathology, generally a parathyroid adenoma, can be difficult in some cases due to the anatomical variants that these glands present. The objective of this review is to analyse the different imaging techniques used for preoperative localization of parathyroid pathology (scintigraphy, ultrasound, CT, MRI and PET). There is great variability between the different tests for the preoperative localization of parathyroid pathology. The importance of knowing the different diagnostic options lies in the need to choose the most suitable test at each moment and for each patient for an adequate management of primary hyperparathyroidism (PHP) with surgical criteria.

Esophageal schwannoma mimicking non-functional parathyroid adenoma on 99mTc-sestamibi imaging: a case report.

Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (99mTc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was 99mTc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal 99mTc-sestamibi uptake in the neck region.

Papillary Thyroid Cancer, Small Cell Lung Cancer, and Parathyroid Adenoma Synchronously Visualized on 99m Tc-MIBI SPECT/CT in a Patient With Hyperparathyroidism : Comparison With 18 F-FDG PET/CT.

ABSTRACT: 99m Tc-MIBI scintigraphy is a nuclear medicine imaging modality commonly used for the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. In addition, 99m Tc-MIBI can also be used for imaging various tumors due to its unique mechanism of intracellular accumulation. Here, we introduced a case of a single 99m Tc-MIBI SPECT/CT simultaneously visualized two different malignant tumors, such as papillary thyroid cancer and small cell lung cancer, along with a parathyroid adenoma in a patient with hyperparathyroidism. The clinical usefulness of 99m Tc-MIBI SPECT/CT was also explored by comparing it with 18 F-FDG PET/CT among the three tumors.

Ultrasonographic Detective Flow Imaging for Evaluating Parathyroid Adenoma in Patients with Primary Hyperparathyroidism.

BACKGROUND: Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow, which is difficult to visualize on conventional color Doppler ultrasonography (CDU). In this study, we compared the usefulness of DFI with that of CDU and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for detecting parathyroid adenoma (PA) in patients with primary hyperparathyroidism (PHPT). METHODS: From March 2021 to March 2023, 87 PHPT patients underwent surgery, and 66 had a single PA. We performed preoperative conventional ultrasonography with CDU, MIBI scintigraphy, and DFI for 42 patients (5 males and 37 females; mean age: 61.6 ± 15.4 years). RESULTS: MIBI scintigraphy detected PA in 85.7% (36/42) patients, and both CDU and DFI detected PA in all patients. The rates of vascularity in PA detected by CDU and DFI were 71.4% (30/42) and 85.7% (36/42), respectively. Vascularity was detected by DFI in 6 patients who were negative for vascularity on MIBI scintigraphy. Furthermore, DFI detected blood supply in 6 of the 12 patients with undetectable blood supply on CDU. Fisher's exact test revealed that high or low blood flow, as determined by DFI, was significantly associated with detection of feeding vessels in PA by CDU (P < 0.001). CONCLUSIONS: DFI was useful for preoperative detection of PA blood flow.

Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report.

RATIONALE: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial. PATIENT CONCERNS: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan. DIAGNOSES: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake. INTERVENTIONS: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy. OUTCOMES: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months. LESSONS: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.