False-negative 99mTc-sestamibi scans: factors and outcomes in primary hyperparathyroidism.

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.

The Parathyroid Gland: An Overall Review of the Hidden Organ for Radiologists.

Parathyroid glands are small endocrine glands that regulate calcium metabolism by producing parathyroid hormone (PTH). These are located at the back of the thyroid gland. Typically, four glands comprise the parathyroid glands, although their numbers may vary among individuals. Parathyroid diseases are related to parathyroid gland dysfunction and can be caused by problems with the parathyroid gland itself or abnormal serum calcium levels arising from renal disease. In recent years, as comprehensive health checkups have become more common, abnormal serum calcium levels are often found incidentally in blood tests, after which several additional tests, including a PTH test, ultrasonography (US), technetium-99m sestamibi parathyroid scan, single-photon-emission CT (SPECT)/CT, four-dimensional CT (4D-CT), and PET/CT, are performed for further evaluation. However, the parathyroid gland remains an organ less familiar to radiologists. Therefore, the normal anatomy, pathophysiology, imaging, and clinical findings of the parathyroid gland and its associated diseases are discussed here.

The Right Hand Must Know What the Left Hand is Doing: A False-Positive Hotspot on the Sestamibi Scan.

Objective: Imaging studies in the setting of primary hyperparathyroidism are performed to rule out an ectopic parathyroid adenoma. Although rare, false-positive scans can cause confusion and possibly more extensive procedures. Method: A 68-year-old woman with parathyroid hormone-dependent hypercalcemia was found to have uptake in the left midclavicular area on the parathyroid scan with sestamibi. Retention of the isotope was considered a possibility, and the sestamibi scan was repeated after injecting the isotope in the right hand and this did not show uptake in the left midclavicular area. Results: Sestamibi is taken up by the mitochondrial-rich adenoma cells and can help identify an ectopic location of the adenoma. Sestamibi scans are commonly performed before neck exploration to rule out an ectopic adenoma and to localize the parathyroid adenoma. Thyroid adenoma and thyroid cancer can also cause retention of isotopes. Retention of the isotope in the vein can also give an illusion of an ectopic parathyroid adenoma. Injecting the isotope in the contralateral hand can overcome this retention issue. Conclusion: Uptake on parathyroid scan outside of normal embryologic decent of the parathyroid gland should raise the possibility of a false-positive uptake.

INTERRELATION BETWEEN PREOPERATIVE TESTS, INTRAOPERATIVE FINDINGS AND OUTCOMES OF 99M-TECHNETIUM-SESTAMIBI SCAN IN PRIMARY HYPERPARATHYROIDISM.

Context: Primary hyperparathyroidism is one of the most common endocrinological disorder and surgery of parathyroid glands is the main therapy of this disease. Minimally invasive surgery is getting more prominent in these days and its success in parathyroid surgery mostly depends on accuracy of the localization studies. Objective: The aim of this study is to understand the relationship between preoperative biochemical tests, intraoperative findings and Technetium-99m-methoxyisobutylisonitrile (MIBI) scan results. Design: Retrospective clinical study. Subjects and Methods: A total of 185 patients, who have been diagnosed with primary hyperparathyroidism (PHPT) and operated between January, 2010 and October, 2018, were included to the study. Patients with less than 6 months of follow up are excluded from the study. Results: Patients were divided into two groups according to their scintigraphy results; with positive scintigraphy findings as group 1 (n:135) and negative scintigraphy findings as group 2 (n:50). Mean preoperative serum parathyroid hormone (PTH) values were significantly different between the two groups (p<0.02). Mean preoperative serum calcium, creatinine, magnesium, phosphorus, alkaline phosphatase, 25-OH Vitamin D3 levels of both groups were analyzed and there were no statistical differences between the two groups considering these parameters. Also, mean diameter and mean volume of parathyroid adenomas were significantly higher in group 1 (2.1±1.0 cm vs. 1.55±0.72 cm, respectively, p<0.0001; 2.66±5.35 cm3 vs. 1±1.9 cm3, respectively, p<0.0001). Optimal cut-off values of parathyroid adenoma diameter for MIBI scan positivity were 1.55 cm, parathyroid volume for MIBI scan positivity were 0.48 cm3, preoperative serum PTH for MIBI scan positivity were 124.5 ng/L. Conclusions: Preoperative serum PTH levels, diameter and volume of adenomas might be helpful for the prediction of MIBI scan accuracy and possible need of another localization studies.

Predicting coexisting thyroid cancer with primary hyperparathyroidism in an endemic region of multinodular goiter: evaluating the effectiveness of preoperative inflammatory markers.

Purpose: The aim is to examine the efficacy of inflammatory indicators to predict thyroid cancer in patients with primary hyperparathyroidism (PHPT) in an endemic region of nodular goiter. Methods: The prospective database was reviewed to identify patients operated on with the diagnosis of PHPT and thyroid disease between April 2015 and June 2021. Permanent pathologic reports were used as the gold standard for diagnosis. Detailed imaging data with peripheral blood inflammation indices were analyzed to assess their predictive values for concomitant PHPT with thyroid cancer. Postoperative complications and the duration of hospitalization were also reviewed. Results: Thyroid malignancy accompanying PHPT was found in 13 patients (26.0%) out of 50 who had concurrent surgery. The analysis regarding inflammatory indexes revealed nothing significant between thyroid cancer and preoperative blood biochemistry (P > 0.05). In the concurrent surgery group, recurrent laryngeal nerve injury was observed in 1 patient (2.0%) and the mean hospital stay was longer. Conclusion: In endemic regions of nodular thyroid disease, thyroid cancer might accompany PHPT. The value of inflammatory indexes to predict thyroid malignancy in PHPT is controversial and should not be employed in the surgical decision-making process.

Primary Hyperparathyroidism: Outcomes of Repeated Imaging After Initial Negative Radiological Localization.

BACKGROUND: Radiological localization imaging aids in the identification of abnormal parathyroid glands resulting in primary hyperparathyroidism (PHPT), thereby facilitating minimally invasive parathyroid surgery. Sometimes initial imaging may fail to identify the abnormal gland and imaging may therefore be repeated. This study explored patient outcomes of repeated parathyroid localization imaging, after initial negative gland localization, at a United Kingdom institution. METHODOLOGY: Data was retrospectively collected and analyzed for patients with PHPT undergoing repeated imaging during a five-year period (2015-2020). The total number of episodes of scanning, types of scans performed, the time interval between scans and the imaging success of gland localization were recorded. We explored the reasons for repeated imaging and attempted to identify any factors that might predict subsequent positive radiological localization. RESULTS: A total of 45 patients were identified who underwent repeated localizing imaging after first localizing imaging was negative. Of these, 39 did not undergo surgery despite repeat imaging being undertaken; 11 out of these 39 patients (28%) had subsequent positive localization scans. Again, a large proportion of patients were managed conservatively, despite the repeated sets of imaging being done. Patients undergoing three or four sets of repetitive imaging did not have imaging or surgical success. CONCLUSION: A streamlined parathyroid pathway should be followed whereby patients should be triaged for suitability for surgery prior to repeated imaging. A second set of scans should be offered when patients are unsuitable for conservative management and are willing and fit to undergo surgery. There is no merit to repeating imaging more than twice.

A Case of Delayed Diagnosis of Idiopathic Infantile Hypercalcemia Due to CYP24A1 Mutation: A 10-Year Journey.

The parathyroid gland is responsible for the synthesis and secretion of parathyroid hormone, which is synthesized and released at an inverse relationship to the level of ionized calcium in the blood. Primary hyperparathyroidism affects women more than men. There are various causes for hyperparathyroidism-induced hypercalcemia and the most common cause is parathyroid adenoma. A less common cause of vitamin D-mediated parathyroid hormone-independent hypercalcemia is the loss of function mutation of the CYP24A1 gene. The CYP24A1 gene encodes the vitamin D 24-hydroxylase enzyme, responsible for hydroxylating the active form of vitamin D into an inactive form, and mutations in the CY24A1 gene can lead to elevated active vitamin D metabolite levels. It can result in hypercalcemia and hypercalciuria-related complications. We present a case of a 72-year-old male patient referred to the endocrine clinic, who had repeated treatments for hypercalcemia and recurrent renal calculi. He underwent ultrasound, computerized tomography, and sestamibi scans, all reported as normal. Following this, the patient underwent a positron emission tomography (PET) scan, which was also normal. He then finally underwent genetic testing and tested positive for the CYP24A1 gene. He was started on fluconazole 50mg once a day and cinacalcet 30mg twice with normalization of calcium level. Three of his family members also tested positive for the condition.

Parathyroid Cystic Adenoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To review diagnostic imaging modalities for parathyroid cystic adenomas (PCA). Since PCAs are a rare (0.5%-1%) subclass of parathyroid adenomas, and due to their cystic component, imaging modalities known to be efficient for diagnosing solid adenomas might fail in localizing them. METHODS: We conducted a systematic review using the PubMed and Cochrane databases for English articles on PCAs published between 1995 and 2020. A meta-analysis of the retrieved data was performed. RESULTS: Overall, 39 studies, reporting on a total of 160 patients, were included in the analysis. Two thirds (68%) of the patients were female, with a mean age of 53.9 years. A single cystic adenoma was detected in 98.1% of cases. The mean blood calcium corrected for albumin level was 12.6 ± 2.7 mg/dL, and the mean parathyroid hormone level was 565.5 ± 523.8 pg/mL. The mean PCA sizes as measured by ultrasound (US), computed tomography (CT), and ex vivo measurement were 4.8 ± 3.6, 5.2 ± 3.2, and 3.5 cm, respectively. The median weight was 8.1 g. PCA was detected in 86% of US examinations; 100% of US-guided fine needle aspiration, 4-dimensional computed tomography (4D-CT), or magnetic resonance imaging examinations; and 61% of 99m-technetium sestamibi scan with single-photon emission computed tomography ((99m)Tc-SPECT). (99m)Tc-SPECT showed a significantly lower diagnostic rate than US (odds ratio, 3.589), US-guided fine needle aspiration, CT combined with 4D-CT, and the combination of US, CT, 4D-CT, and magnetic resonance imaging (P < .001). CONCLUSION: Although US and 4D-CT showed a significantly high rate in diagnosing PCA, (99m)Tc-SPECT showed a lower PCA diagnostic rate. These findings suggest that larger cystic lesions suspected as PCAs should be further evaluated using 4D-CT rather than (99m)Tc-SPECT.

Accuracy of Four-Dimensional Computed Tomography and Different Imaging Modalities in Primary Hyperparathyroidism.

Background This study aimed to compare the accuracy of different imaging modalities in the preoperative localization of parathyroid pathology in primary hyperparathyroidism. Methodology This prospective study enrolled 70 patients who were biochemically diagnosed with primary hyperparathyroidism between 2021 and 2022 at our center. Patients underwent scanning using three imaging modalities, namely, Tc99m sestamibi scan (sestamibi), parathyroid ultrasonography, and four-dimensional computed tomography (4DCT). A descriptive analysis was performed to determine and compare the respective localizing sensitivities. Results The most common site of parathyroid adenoma (PA) was the left inferior parathyroid gland, seen in 28 (40%) patients. Three patients had false-positive imaging studies with no parathyroid pathology identified surgically or on histological examination. The median levels of parathyroid hormone decreased significantly (p < 0.001) after the surgery, with a median of 24.3 (1.90-121). Furthermore, 4DCT accomplished a sensitivity of 97.14% for diagnosing the side and 94.03% for overall localization of PA. This sensitivity was superior to the sensitivity of ultrasonography and sestamibi scan to detect the side and quadrant of the adenoma. 4DCT was significantly higher in sensitivity when compared to the combination of ultrasound and sestamibi (p < 0.001). Conclusions 4DCT yielded the highest sensitivity in localizing parathyroid pathology from the imaging modalities studied with the lowest false-negative rate. Using ultrasound with 4DCT could be the most cost-effective combination for detecting primary hyperparathyroidism.

Questionable value of [99mTc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound.

PURPOSE: A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [99mTc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. METHODS: A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. RESULTS: From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13-93) years and 71% were female. Neck ultrasound was carried out in 91.7% and localized a PA in 76.6%. In 23.4% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [99mTc]-sestamibi correctly identified PA in only 25.4% of patients. In contrast, in the same cohort, the use of [11C]-methionine or [11C]-choline PET resulted in the correct identification of PA in 79.4% of patients (OR 13.23; 95% CI 5.24-33.56). CONCLUSION: [11C]-Methionine or [11C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.