Hyperfunctioning Parathyroid Research Articles

Hyperfunctioning Intrathyroidal Parathyroid: a Misleading Preoperative Diagnosis.

Hyperfunctioning parathyroid glands may be rarely located in the thyroidal parenchyma and not identified by imaging or during surgical procedures. We present three patients with primary hyperparathyroidism related to hyperfunctioning intrathyroidal parathyroid retrospectively selected among 732 cases from own Institutional parathyroid PET/CT registry from 2018 to 2022. Intrathyroidal parathyroids showed intense 18F-fluorocholine uptake but a variable echographic pattern, inconstant 99mTc-MIBI uptake, and atypic iodine-contrast enhancement. Although rare, the possibility of an intrathyroidal parathyroid should be considered when no hyperfunctioning gland is found on preoperative imaging and thorough bilateral neck exploration.

Engineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications

BackgroundRecent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research. MethodsUsing our recently developed fine needle aspiration–based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed. ResultsWe have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties. ConclusionOur novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.

ODP111 PERSISTENT TERTIARY HYPERPARATHYROIDISM AFTER TOTAL PARATHYROIDECTOMY AND KIDNEY TRANSPLANTATION: THE CASE OF THE SUPERNUMERARY GLANDS

Abstract Secondary hyperparathyroidism in patients with kidney failure and hemodialysis usually resolves after total parathyroidectomy or kidney transplantation. Case report We report a case of a 53 year-old women polycystic kidney disease diagnosed at the age of 32, with end-stage renal disease and hemodialysis between 45-51 yrs. At the age of 50 she developed hypercalcemia (10.4-10.8 mg/dl) with very high PTH levels of 1100 pg/ml, and was referred forparathyroidectomy. Intraoperatively the four parathyroid glands were identified in canonical sites and a total parathyroidectomy was performed; postoperative total serum Calcium 8.9-9.6 mg/dl, PTH 510-680 pg/ml, suggesting the presence of a functional remnant parathyroid tissue. One year later she underwent kidney transplantation, immediate preoperative serum Calcium 10.4 mg/dl. 2 yrs later, she was referred to our clinic for hypercalcemia (11.8-12.5 mg/dl; increasing 5 mo post-transplant), high serum PTH 229-316 pg/ml) and low bone mass (lumbar spine T-score = -4.4 DS, femoral neck T-score = - 2.6 DS). She was asymptomatic and the biochemistries were: total serum calcium 12.8 mg/dl (11.8 mg/dl after hydration), serum PTH 228 pg/ml, hypophosphatemia 1.9 mg/dl, Alkaline Phosphatase 102 U/l, creatinine 1.13 mg/dl (0.85 mg/dl after hydration). 99m Tc-sestamibi SPECT-CT imaging revealed an ectopic hyperfunctional parathyroid gland above pulmonary artery bifurcation. Waiting for surgical decision, the patient was treated with denosumab 60 mg, lowering serum Calcium at 11 mg/dl at 1 mo, 11.5 mg/dl at 3 mo, PTH 511 pg/ml. Conclusion This case illustrates the needfor more accurate preoperative localization of abnormal parathyroid glands in patients with tertiary hyperparathyroidism besides the standard 4-gland exploration. Presentation: No date and time listed

PSAT212 Hyperparathyroidism Secondary to Ectopic Parathyroid Adenoma

Abstract Background In the majority of cases, primary hyperparathyroidism is caused by a parathyroid adenoma, most commonly located within the parathyroid glands. However, in some cases, the parathyroid adenoma can be located aberrantly. Clinical case A 78 year old female was referred due to hypercalcemia (ionized calcium 1.63mmol/L). Patient has been known to have elevated calcium (both total and ionized) levels for 3 years and osteoporosis. Initial work up on presentation had been unremarkable hence no further investigation was done and treatment was given. Prior to consult, patient had symptoms of bone pains, particularly in her lower extremities. Kidney function was normal. Patient had never had kidney stones but x-ray demonstrated compression fracture of L2 vertebrae. Work up for hypercalcemia was done, revealing the following results: PTH 196.60 pg/mL, TSH 1.810 mIU/mL, FT4 16.46 pmol/L, FT3 3.55 pmol/L, 24 hour urine calcium 88.40 mg/24 hours, and 25 (OH) D 18.32 ng/dL. Neck ultrasound showed findings of normal-sized thyroid gland with mild parenchymal change, benign cystic nodules and no definite evidence of parathyroid nodule. Parathyroid subtraction imaging was done and demonstrated no scintigraphic evidence of parathyroid adenoma or hyperplasia. Patient was prescribed with calcimimetics (Cinacalcet). However, the patient experienced nausea and body pains and opted to discontinue the medication. Further investigation was performed. Radionucleotide parathyroid imaging using Technitium-99m sestamibi was done which revealed slightly increased tracer activity in the lower midline neck on SPECT imaging, an atypical scintigraphic finding of an aberrantly located parathyroid adenoma possibly in the tracheoesophageal or retroesophageal region. There was no definite scintigtaphic evidence of parathyroid adenoma or hyperplasia in the thyroidal beds or ectopic parathyroid in the mediastinum. A second parathyroid scan with SPECT-CT was performed in another institution and showed a 1.2×1.0 cm, sestamibi avid nodule inseparable from the esophagus and left posterior aspect, anterior to the T2 vertebra, consistent with a thoracic retro-esophageal hyperfunctioning parathyroid adenoma. Patient refused surgery at this point and was given medical management with hydration, Vitamin D correction and antiresorptive agent. Conclusion Multiple imaging may be needed to reach an accurate diagnosis for persistent hypercalcemia and elevated parathyroid hormone levels with an absence of lesions in the neck. If the criteria for surgery are met, as with parathyroid adenomas within the parathyroid gland, surgical resection is also the gold standard of therapy for ectopic parathyroid adenomas. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Application value of contrast-enhanced ultrasound in preoperative localization of microwave ablation for primary hyperparathyroidism.

Ultrasonography (US) and 99m Technetium-sestamibi scintigraphy (99m Tc-MIBI) are currently first-line imaging modalities to localize parathyroid adenomas with sensitivities of 80% and 84%, respectively. Therefore, finding other modalities to further improve the diagnostic accuracy for preoperative localization is critically needed. To evaluate the application value of contrast-enhanced ultrasound (CEUS) in the preoperative localization of microwave ablation (MWA) for primary hyperparathyroidism (PHPT). Between December 2012 and May 2021, 100 PHPT patients (34 males and 66 females; mean age, 56.31±13.43 years; age range, 25-85 years) with 130 suspected parathyroid nodules were enrolled. US, CEUS, and 99m Tc-MIBI were performed for the localization of pathological parathyroid glands. All patients were performed MWA under ultrasound guidance. All the suspected parathyroid nodules underwent core needle biopsy under ultrasound guidance during MWA to confirm the pathology. The diagnostic performance of all the imaging tests was analyzed in comparison with the pathological results. A total of 130 nodules suspected to be of parathyroid origin from preoperative localization images were confirmed by pathological results, of which 116 were of parathyroid origin, and 14 were not of parathyroid origin. The sensitivity, specificity, accuracy, and the area under receiver operating characteristic curve of CEUS in the localization of pathological parathyroid glands were 100%, 92.86%, 99.23%, and 0.964, which were significantly higher than those of US (93.10%, 42.86%, 87.69%, and 0.680) and 99m Tc-MIBI (81.90%, 42.86%, 77.69%, and 0.624) (p<0.05). The sensitivity and accuracy of CEUS were 100% and 97.22%, which were higher than those of 99m Tc-MIBI (65.62% and 63.89%) or US (75.00% and 72.22%) in patients with multiple parathyroid glands (p<0.05). For smaller parathyroid adenomas (≤2cm in diameter), the sensitivities of CEUS in locating hyperfunctioning parathyroid glands were 100%, which was significantly higher than that of 99m Tc-MIBI (73.68% and 84.31%, p<0.05). CEUS is a valuable preoperative localization method for PHPT patients performed MWA, especially for the patients with smaller pathological parathyroid gland and multiple glandular lesions.

Positive predictive values of ultrasound-guided fine-needle aspiration with parathyroid hormone assay and Tc-99m sestamibi scintigraphy in sporadic primary hyperparathyroidism

ObjectivesUltrasonography (US) and Tc-99m sestamibi scintigraphy (SS) are usually performed as preoperative imaging modalities for patients with sporadic primary hyperparathyroidism (SPHP). Fine-needle aspiration (FNA) under US guidance for parathyroid hormone (PH) assay can enhance the diagnostic accuracy of US. The main aim of the present study was to compare positive predictive values between US-FNA and SS. The secondary aim was to draw up a decision-tree for FNA and SS. MethodsThe single-center retrospective study included patients with previously non-operated SPHP. They underwent US-guided FNA, PET-CT SS, and 18 F-choline scintigraphy if the first two methods were inconclusive. PH washout level was considered pathological when greater than the serum PH level. Postoperative histology data were correlated to imaging data. ResultsIn total, 117 patients were included, with a mean age of 64 years (range, 26–89 years). A single adenoma was identified on pathology in 101 patients (89%). FNA findings were pathologic for 64 patients (55%), with a mean PH level of 2,604ng/L [range, 585–9,074ng/L], higher than the serum level of 179ng/L [range, 60–1,000ng/L]. US-guided FNA showed sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of respectively 72%, 92%, 99% and 28%, compared to 89%, 42%, 93% and 32% for SS. The rate of error in locating the parathyroid gland was 8% for US-guided FNA versus 12% for SS. Comparison of the two methods showed better sensitivity for SS (P=0.0052) and better specificity for FNA (P=0.0143), with no significant difference in PPV or NPV. 18 F-choline scintigraphy detected the hyperfunctioning parathyroid in 11 out of the 15 patients. ConclusionPPV did not significantly differ between FNA and SS. US-guided FNA performed by an experienced operator could be a simple first-line method for more than 50% of patients with non-operated SPHP, with 99% PPV. In case of negative or doubtful FNA findings, SS can be performed in second line.

Case report: coexistence of primary hyperparathyroidism with giant toxic nodular goiter

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

Performance of quantitative measurements in [18F]fluorocholine positron emission tomography/computed tomography for parathyroid imaging (P2TH study).

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

Preoperative Imaging with [18F]-Fluorocholine PET/CT in Primary Hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received 18F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes 18F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of 18F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of 18F-FCH PET/CT for successful surgical guidance.

Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

ObjectivePreoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual‐isotope subtraction scintigraphy with 99mTc‐MIBI/123Iodide using SPECT/CT and planar pinhole imaging (Di‐SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11C‐Choline PET/CT (faster with a lower radiation dose) is non‐inferior to Di‐SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies.DesignThis is a prospective, GCP‐controlled cohort study.Patients and MeasurementsOne hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard.ResultsAmong the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%–88%) and 87% (95% CI: 79%–92%) for Choline PET and Di‐SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases.ConclusionCholine PET and Di‐SPECT performed equally well and are both appropriate as first‐line imaging modalities for preoperative imaging of PHPT. When the first‐line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

The utility of 18F-fluorocholine PET/CT in the imaging of parathyroid adenomas.

The aim of the study was to estimate the sensitivity of ¹⁸F-FCH PET/CT in preoperative localisation of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism (PHPT). Sixty-five consecutive patients with PHPT, who underwent neck ultrasound (US) and 99mTc/99mTc-MIBI dual-phase parathyroid scintigraphy, were prospectively enrolled. Twenty-two patients had unsuccessful parathyroid surgery prior to the study. PET/CT scans were performed 65.0 ± 13.3 min after injection of 218.5 ± 31.9 MBq of 18F-fluorocholine (FCH). Three experienced nuclear medicine physicians assessed the detection rate of hyperfunctioning parathyroid tissue. Response to parathyroidectomy and clinical follow-up served as a reference test. Per-patient sensitivity and positive predictive value (PPV) were calculated for patients who underwent surgery. ¹⁸F-FCH PET/CT was positive in 61 patients, and negative in 4. US and parathyroid scintigraphy showed positive and negative results in 20, 45 and 17, 48, respectively. US showed nodular goitre in 31 patients and chronic thyroiditis in 9 patients. Parathyroid surgery was performed in 43 (66%) patients. ¹⁸F-FCH PET/CT yielded a sensitivity of 100% (95% CI: 87.99-100) and PPV of 85.7% (95% CI: 70.77-94.06). Similar values were observed in patients with chronic thyroiditis, nodular goitre, and patients after an unsuccessful parathyroid surgery. PET/CT identified hyperparathyroidism complications (kidney stones, osteoporotic bone fractures, and brown tumours) in 11 patients. ¹⁸F-FCH PET/CT effectively detected hyperfunctioning parathyroid tissue and its complications. The method showed excellent sensitivity and positive predictive value, including patients with nodular goitre, chronic thyroiditis, and prior unsuccessful parathyroidectomy. PET/CT performance was superior to neck ultrasound and parathyroid scintigraphy.

Multiple endocrine neoplasia type 1 or 4: detection of hyperfunctioning parathyroid glands with 18F-fluorocholine PET/CT. Illustrative cases and pitfalls.

18F-fluorocholine (FCH) PET/CT is now well established to detect the hyperfunctioning parathyroid glands (HFPTG) in a case of sporadic primary hyperparathyroidism (pHPT), but only limited evidence is available about the utility of FCH PET/CT to detect the HFPTG in patients with multiple endocrine neoplasia (MEN) type 1 or 4. The pHPT in this context frequently consists in a multiglandular disease with small hyperplastic glands rather than adenomas, which is challenging for imaging modalities. The data of patients with MEN1 or MEN4 after parathyroidectomy referred to FCH PET/CT for presurgical localization of HFPTG were retrospectively reviewed, including follow-up after parathyroidectomy, in search for diagnostic performance and for potential pitfalls. In the present cohort, 16 patients referred to FCH PET/CT as part of their initial pHPT work-up were subsequently operated, 44 abnormal parathyroid glands (PT) were resected, of which 32 (73%) had been detected on FCH PET/CT and 2 considered as equivocal foci. Nine patients referred to FCH PET/CT for recurrent pHPT who were subsequently operated, 14 abnormal PT were resected, all had been detected on FCH PET/CT. FCH PET/CT permitted a unilateral approach for PTx in 4 of them. In one patient with MEN4 and pHPT, the HFPTG could not be visualized on FCH PET/CT but was localized by ultrasonography. Several causes of false positive or false negative results, incidental finding and pitfalls are listed and discussed. FCH PET/CT has a positive benefit/risk ratio in the detection of HFPTG in case of MEN1 (the data in MEN4 being currently very limited) with the most effective detection rate of current imaging modalities for HFPTG, few pitfalls, and an adequate impact on patient management compared to sesta MIBI SPECT and ultrasonography.

DIAGNOSTIC PERFORMANCES OF 18F-FLUOROCHOLINE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY AND REPEATED ULTRASONOGRAPHY IN DETECTING UNDEFINED LESIONS IN PATIENTS WITH AN INDICATION FOR PRIMARY HYPERPARATHYROIDISM SURGERY.

18F-fluorocholine (FCH) has been used as a positron emission tomography (PET) tracer in the localization of hyper-functioning parathyroid glands (HPGs). We performed this methodological study to evaluate the diagnostic performance of 18F-FCH PET/computerized tomography (CT) and repeated ultrasonography (USG) in detecting unidentified lesions in patients with primary hyperparathyroidism (PHPT). In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and a repeated USG in detecting unidentified parathyroid lesions. Twenty-eight patients who were diagnosed with PHPT, had an indication for surgery following the current guidelines and had no identified lesion on 99mTc-MIBI SPECT/CT, USG, or other imaging methods than 18F-FCH PET/CT, included in the study. While lesions were detected in 26 patients via 18F-FCH PET/CT among 28 patients [92.9% (95% CI: 76.6%-99.1%)], the lesion detection rate was 95.7% (95% CI: 78.1%-99.9%) in 23 patients who underwent a repeated USG. The sensitivity and the accuracy of both 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. This study supports that the combination of 18F-FCH PET/CT and repeated USG has promising potential for being an imaging technique for early detection and localization of HPGs.

Diagnostic Performance of Cervical Ultrasound, 99mTc-Sestamibi Scintigraphy, and Contrast-Enhanced 18F-Fluorocholine PET in Primary Hyperparathyroidism.

Preoperative localization of pathologic parathyroids is crucial for minimally invasive treatment of primary hyperparathyroidism (PHPT). This study compared contrast-enhanced 18F-fluorocholine PET/CT, cervical ultrasonography (CU), and conventional scintigraphic imaging modalities (MIBI scintigraphy, consisting of 99mTc-sestamibi/123I-sodium iodide SPECT/CT, 99mTc-sestamibi/123I-sodium iodide planar subtraction imaging, and 99mTc-sestamibi planar dual-phase imaging), combined and individually, for preoperative localization of hyperfunctional parathyroids in PHPT. The gold standard was histologic examination. Methods: Data from consecutive patients with clinically suspected PHPT were retrospectively collected. All 3 imaging modalities were systematically performed. The ability of 18F-fluorocholine PET/CT, CU, and MIBI scintigraphy to identify a hyperfunctional parathyroid and specify the side or identify an ectopic location was noted. Patients underwent surgical exploration if at least 1 examination was positive. The findings of CU + MIBI scintigraphy combined were considered positive if CU and MIBI scintigraphy separately showed a hyperfunctional parathyroid gland on the same side or in the same ectopic location; any findings other than these were considered negative. The composite judgment criterion for pathologic parathyroid was a combination of histologic analysis and normalization of parathyroid hormone and calcium levels. Results: In total, 149 pathologic parathyroids were found in 143 of the 144 included patients. 18F-fluorocholine PET/CT diagnosed 148 of 149 pathologic parathyroids. Only 4 false-positives and 1 false-negative were found. The 18F-fluorocholine PET/CT sensitivity of 99.3% was superior to that of CU, at 75.2% (P < 0.0001); MIBI scintigraphy, at 65.1% (P < 0.0001); and CU + MIBI scintigraphy, at 89.9%, (P = 0.0009). Five of the 5 ectopic locations were diagnosed by 18F-fluorocholine PET/CT, 2 of the 5 by MIBI scintigraphy, and none by CU. Accuracy was better for 18F-fluorocholine PET/CT, at 98%, than for CU, at 84% (P < 0.0001); MIBI scintigraphy, at 81% (P < 0.0001); or CU + MIBI scintigraphy, at 91% (P < 0.0001). Among the 72 (50%) patients who had a negative CU + MIBI scintigraphy result, 18F-fluorocholine PET/CT correctly identified hyperfunctional thyroids in 70 (97.2%). Average uptake in the 18F-fluorocholine PET/CT hyperfunctional parathyroid was higher than that in the adjacent thyroid (SUVmax adjusted for lean body mass, 6.45 vs. 2.15) (P < 0.0001). Conclusion: The accuracy of 18F-fluorocholine PET/CT is higher than that of CU and MIBI scintigraphy for localization of hyperfunctional parathyroids, justifying the systematic use of 18F-fluorocholine PET/CT as the first-line method for PHPT diagnosis.

Methods of medical visualization and thermal ablation as a new approach to treatment of hyperparathyroidism

The pathologies of parathyroid glands are widespread among endocrine system diseases, excluding diabetes and thyroid pathology. There are only two methods that are used to treat hyperparathyroidisms, such as surgery and conservative therapy. However, transracial thermal destruction methods (ablation) have recently appeared in clinical practice. The methods have good precision and connect with physical phenomena, such as interaction laser, radiofrequency, microwave, and HIFU irradiation with bio substance. The review is dedicated to critically analyze the modern methods for local thermal destruction of the hyper-functioning parathyroid glands. The review includes data from randomized clinical trials from 2012 to 2021. The studies were from Google Scholar and Pubmed with a total number of 1,938 patients (laser ablation ― 216 patients, radiofrequency ablation ― 225, microwave ablation ― 1467, high-density ultrasound ablation ― 30 patients). Recommendations methods of thermal destruction application were obtained during the review. Furthermore, we have designed some algorithms for hyperparathyroidism treatment. Moreover, thermal destruction methods were observed. There are four modern methods of thermal destruction which have been analyzed like alternatives to surgery. Each of them has advantages and disadvantages, its profile of safety and effectiveness. After processing information from a proven database, the most popular among specialists is methods of microwave ablation. However, laser ablation is more effective than other ways.

ONCOCYTIC INTRATHYROID PARATHYROID ADENOMA MASQUERADING AS HURTHLE CELL NEOPLASM: FINE NEEDLE ASPIRATION CYTOLOGY OF TWO CASES

Ectopic parathyroid adenomas in thyroid tissue are uncommon (0.7 - 6%), and their oncocytic variants are exceedingly rare. We report two cases of intrathyroid parathyroid adenoma which were diagnosed as Hurthle cell adenoma on cytology. Case 1 is a 49-year-old female with a 2.4 cm hypoechoic nodule in the left lateral neck. Electrochemiluminescent immunoassay of the aspirate revealed PTH level of 422 pg/ml, conrming the presence of hyperfunctional parathyroid tissue. Subsequent resection of the left thyroid lobe revealed an enlarged intrathyroidal parathyroid. Case 2 is a 58-year-old female with a 2.1 cm hypoechoic nodule in the posterior-mid left thyroid lobe. Strong overexpression of parathyroid hormone and Chromogranin A genes and low expression of thyrocyte-related genes suggested parathyroid origin of the cells sampled. MEN1 mutation and multiple copy number alterations indicated the neoplastic nature of the nodule. Parathyroid oxyphil cells and oncocytic thyrocytes share cytomorphological ndings and distinguishing them by cytology alone is challenging, especially when the targeted lesion is intrathyroidal. Distinguishing intrathyroid oncocytic parathyroid adenoma from oncocytic thyroid follicular lesions has signicant clinical implications as Bethesda-IV category lesions have 20%–30% risk of malignancy. While stippled chromatin or intracytoplasmic fat vacuoles may be suggestive of parathyroid origin, these are not specic. Classifying the origin of a nodule as parathyroid vs thyroid rests upon the detection of PTH in aspirate material by ECL, immunocytochemistry or next-generation sequencing. In parathyroid aspirates, PTH level 100 pg/mL is suggestive of the presence of PTH-secre ≥ ting tissue at the site biopsied or along the needle track.

18F-Fluorocholine-PET combined with contrast-enhanced CT for localizing hyperfunctioning parathyroid glands and optimizing surgical treatment in patients with hyperparathyroidism

Hyperparathyroidism (HPT) is a common disorder. A cure can only be achieved by removing all diseased glands. It is critical to localize the hyperfunctioning glands exactly to prevent extensive surgical exploration. The number of false negative/inconclusive results in standard imaging techniques is high. We aimed to evaluate the diagnostic accuracy of 18F-Fluorocholine-PET in combination with contrast-enhanced CT (FCH-PET/CT) and its sensitivity in patients with primary, secondary/tertiary, and familial HPT with negative and/or discordant findings in ultrasound and/or 99mTc-sestamibi scintigraphy/SPECT/CT. A total of 96 patients with HPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. In this retrospective, single institution study, 69 patients, who have undergone surgery and histopathologic workup, were analyzed. Of the 69 patients included, 60 patients suffered from primary HPT, four from secondary or tertiary HPT, and five from familial HPT. Sensitivities, positive predictive values, and accuracies were calculated. Sensitivity/positive predictive value (PPV) per lesion was 87.5/98.3% for primary HPT, 75/100% for secondary/tertiary HPT and 25/66.7% for familial HPT. Sensitivity/PPV per patient was 91.5/98.2% for primary HPT, 100/100% for secondary/tertiary HPT and 50/100% for familial HPT. All patients showed normalized serum calcium levels in the postoperative period. The follow-up rate was 97%. Of the patients included in the study, 58 of 60 patients with primary HPT, and four of four patients with secondary/tertiary HPT showed normal calcium and parathyroid hormone (PTH) levels after six months and were cured. Of the patients with familial HPT, four of five patients were cured. Diagnostic accuracy of 18F-Fluorocholine-PET/CT for patients with pHPT is excellent. 18F-Fluorocholine-PET/CT is a valuable tool for endocrine surgeons to optimize the surgical treatment of patients with hyperparathyroidism.

Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study

BackgroundUse of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases.PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss’ kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard.ResultsIntra-observer agreement was ‘good’ to ‘near perfect’ for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were ‘high’ in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts.Conclusion11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline.The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

Head-to-head comparison among 18F-choline PET/CT, 4D contrast-enhanced CT, and 18F-choline PET/4D contrast-enhanced CT in the detection of hyperfunctioning parathyroid glands: a systematic review and meta-analysis.

In primary hyperparathyroidism (PHPT), the localization of hyperfunctioning parathyroid gland (HPTG) allows tailored surgery. Although Four-Dimensional Contrast-enhanced Computed Tomography (4DCeCT) and 18F-choline Positron Emission Tomography/Computed Tomography (PET/CT) are reported to be promising second-line imaging procedures, no meta-analysis of their comparison exists. we conducted a systematic review and meta-analysis to find original papers reporting the head-to-head comparison of 4DCeCT, 18F-choline PET/CT and integrated 18F-choline-PET/4DCeCT. this systematic review was conducted according to PRISMA. PubMed, CENTRAL, Scopus, and Web of Science were searched until January 2021. Studies comparing the ability of 4DCeCT, 18F-choline PET/CT and 18F-choline PET/4DCeCT to identify HPTG in patients with PHPT were selected. A per patient-based analysis of the three procedures was conducted in all patients (detection rate, DR) and in those with histologically confirmed HPTG (sensitivity). Of the 78 records identified, five articles (153 PHPT patients) published between January the 1st, 2018 and January the 31st, 2021 were included. The pooled DR of 18F-choline PET/CT, 4DCeCT and 18F-choline PET/4DCeCT was 0.86, 0.69, and 0.86, respectively, while their pooled sensitivity was 0.89, 0.77 and 0.93, respectively. The analysis of pooled discrepancy showed that the sensitivity of 18F-choline PET/CT and 18F-choline PET/4DCeCT was higher than that of 4DCeCT by 0.11 and 0.13, respectively, the sensitivity of 18F-choline PET/4DCeCT being 0.06 higher than that of 18F-Choline PET/CT. This meta-analysis suggests that the sensitivity of 18F-choline PET/CT and 18F-choline PET/4DCeCT is higher than that of 4DCeCT, while only a slight difference was observed between 18F-choline PET/CT and 18F-choline PET/4DCeCT.