Oxyphil Cell Content Research Articles

THU396 Digital Spatial Profiling Of Human Parathyroid Tumors Reveals Distinct Cellular And Molecular Alterations Linked To Vitamin D Deficiency

Abstract Disclosure: C. Tu: None. W. Chang: None. J.A. Sosa: Advisory Board Member; Self; Novo Nordisk, AstraZeneca, Eli Lilly & Company. Grant Recipient; Self; Exelixis, Inc., Eli Lilly & Company. J. Koh: None. Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population, but the pathophysiological basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from 9 vitamin D-deficient or 34 vitamin D-replete PHPT patients with 12 eucalcemic cadaveric donor parathyroid glands as normal tissue controls. Parathyroid oxyphil cell content is markedly higher in tumors from vitamin D-deficient PHPT patients (Def-Ts) relative to tumors from vitamin D-replete PHPT patients (Rep-Ts) (47.8% vs 17.8%, respectively; p <0.0001) and normal donor parathyroid glands (7.7%). Def-Ts display increased expression of genes encoding electron transport chain (corr. coefficient=0.546), proteasomal catabolism (corr. coefficient=0.587), and oxidative phosphorylation (corr. coefficient=0.982) pathway components. In contrast, Rep-Ts are characterized by upregulation of the ras (corr. coefficient=0.632) and myc (corr. coefficient=0.811) signaling pathways, suggestive of an oncogene-driven etiology. Parathyroid oxyphil cells are comparable to chief cells at the transcriptional level, and vitamin D-status is reflected in the transcriptional profiles of both cell types in a similar manner. Among PHPT patients who did not present as vitamin D deficient, three distinct tumor transcriptional profile clusters showed a dose-dependent relationship to pre-operative 25OHD levels (p <0.0001 by ANOVA). Relative to normal tissue, the abundance of calcium sensing receptor (CaSR) protein is reduced in Def-Ts (mean protein count 253.6 vs 492.3, respectively; p=0.039 for difference), while the type B γ-aminobutyric acid receptor 1 (GABAB1R) is increased (mean protein count 114.5 vs 64.65, respectively; p=0.0099 for difference). These expression changes resulted in a vitamin D dose-dependent reduction in the ratio of CaSR to GABAB1R receptors in Def-T tumor cells (r2 = 0.218, p<0.0001), favoring the formation of calcium sensing-attenuated CaSR:GABAB1R heteromers. The abundance of the amyloid precursor protein (APP) peptide derivative Aβ1-42, a putative GABAB1R ligand, is preferentially increased in Def-Ts compared to normal tissue (mean protein count 5797 vs 4500, respectively; p=0.0318). Collectively, these findings suggest a novel mechanism where chronic vitamin D deficiency can contribute to tonic PTH hypersecretion in PHPT patients by increasing GABAB1R-mediated antagonism of CaSR activity in parathyroid adenomas. Presentation: Thursday, June 15, 2023

Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.

Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1-3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.

Clinicopathological variables that correlate with sestamibi positivity in uniglandular parathyroid disease: a retrospective analysis of 378 parathyroid adenomas.

Technetium-99m sestamibi parathyroid scintigraphy (MIBI scan) has been used to localize abnormal glands in patients with primary hyperparathyroidism to guide parathyroidectomy. This series aimed to identify the biochemical and histopathological correlates of MIBI scan findings in patients with parathyroid adenoma. A total of 378 patients with histologically and biochemically proven parathyroid adenoma were included. The results of MIBI scan, histopathological (gland volume and weight, oxyphil cell ratio), biochemical (blood and 24h urine calcium, creatinine, glomerular filtration rate, parathormone, alkaline phosphate, and vitamin D3) variables were recorded. A positive uptake on the MIBI scan referred to a localized adenoma. Among histological variables, a cutoff of 30% was applied to define parathyroid adenomas with low (≤ 30%) and high (> 30%) oxyphil cell content. Statistical analyses were performed to assess the relationship among variables. MIBI scan localized the adenoma in 306 patients. Parathyroid gland volume and weight, and oxyphil ratio were significantly higher in the MIBI scan-positive group. Among the biochemical variables, only PTH was found to be significantly increased in the MIBI scan-positive group. Binary logistic regression models identified statistically significant cutoffs for the gland volume (1700mm3), gland weight (1.3g) and PTH levels (170pg/mL) that can be used to predict the MIBI scan positivity. In addition to PTH levels, this series underscored the impact of cellular composition along with the parathyroid gland volume and weight, both of which correlate with sestamibi positivity in patients with benign uniglandular parathyroid disease.

Relationship between parathyroid gland scintigraphy and its histopathology, oxyphil cell content and volume: a retrospective study.

Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between 99mTc MIBI accumulation and oxyphil cell content or parathyroid gland volume. The aim of our work was to assess the relationship between the pathological structure of parathyroids, their volume, oxyphil cell content and parathyroid 99mTc-MIBI retention. A total of 62 hyperfunctioning parathyroid glands in 46 patients were retrospectively analyzed. Preoperative 99mTc-MIBI scintigraphy was performed according to the double-phase and subtraction protocol. After surgery all glands were evaluated histologically, oxyphil cell content was assessed and volume of each excised gland was calculated. Scintigraphy was positive in 41 of 62 parathyroid glands (66%). The median volume of positive glands was larger than that of negative glands (1.33 ml vs 0.7 ml, p = 0.015). Of the parathyroid lesions, there were 14 (22.6%) cases of nodular hyperplasia, 23 (37.1%) cases of diffuse hyperplasia, and 25 (40.3%) cases of adenomas. A high (≥ 25%) oxyphil cell content was found in 16 glands (25.8%) and a low ( < 25%) oxyphil cell content in 46 (74.2%) glands. Histopathology of parathyroid glands was related to the scintigraphy result (p = 0.002), but not to the 99mTc-MIBI uptake pattern (p = 0.868). The overall result of scintigraphy was not related to the oxyphil cell content (p = 0.797). 99mTc-MIBI uptake pattern wasn't related to the oxyphil cell content (p = 0.833). In general, parathyroid lesions with low oxyphil cell content were larger than parathyroid glands with high oxyphil cell content (1.33 ml vs 0.5 ml, respectively; p = 0.01). The median volume of parathyroids containing a high number of oxyphil cells and having a prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.62 ml vs 0.3 ml, respectively; p = 0.008). The median volume of parathyroids with low oxyphil cells content and showing prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.95 ml vs 1.07 ml, respectively; p = 0.014). Our findings suggest that a positive scintigraphy result depends on parathyroid histopathology and gland volume and does not depend on the presence of oxyphil cells. Prolonged 99mTc-retention is not related to the parathyroid gland histopathology and the presence of oxyphil cells but to the gland volume.

Are oxyphil cells responsible for the ineffectiveness of cinacalcet hydrochloride in haemodialysis patients?

Parathyroid glands consist primarily of chief cells. In some cases, the proportion of parathyroid oxyphil cells increases in patients with chronic kidney disease. We describe a case of secondary hyperparathyroidism (SHPT) in a patient treated with haemodialysis who initially received large doses of vitamin D and calcium (Ca) supplements, as well as high doses of cinacalcet hydrochloride (C-HCl), but without any effect on parathyroid hormone levels. Following a successful parathyroidectomy, histopathological examination revealed that two of the parathyroid glands consisted of 40% of oxyphil cells. Oxyphil cells have significantly more Ca-sensing receptors (CaSRs) than chief cells, suggesting that CaSRs are involved in the transdifferentiation of chief cells to oxyphil cells. C-HCl treatment leads to a significant increase in parathyroid oxyphil cell content. This case suggests that C-HCl may induce specific phenotypic alterations in hyperplastic parathyroid glands in patients with severe SHPT.

Association of Histological Findings with Tc-99m Sestamibi Parathyroid Imaging in Hyperfunctional Parathyroid Gland

Background: Hyperthyroidism is a relatively common disorder that results from increased production of parathormone. Tc-99m sestamibi (MIBI) scanning is used for localization of abnormal parathyroid gland, with high reported sensitivities. However, there exists a group of patients in whom MIBI scan is either equivocal or negative. Objectives: The aim of this study was to see association of the histological features of pathologic parathyroid gland with MIBI scan in hyperfunctional parathyroid gland. Methodology: This retrospective study was conducted with primary hyperthyroidism who underwent MIBI scan. The data were collected from the record from January 2012 to December 2014 for a period of two years. All patients underwent parathyroid surgery followed by histopathological examination. According to oxyphil cell distribution patients are divided in three groups. Group I comprised of &gt;25.0% oxyphil cell; group II included the 25 to 75% oxyphil cell and group III included &gt;75% of oxyphil cell. Result: A total 56 patients with hypercalcaemia and high serum parathyroid hormone (PTH) level were studied. Mean age was 41.3(±19.8) years with a range of 21 to 63 years. MIBI scan was true positive in 34(60.7%) cases and false negative in 22(39.3%) cases. In group I MIBI scan was true positive in 4(36.3%) cases and false negative in 7(63.7%) cases. In group II MIBI scan showed positive in 17(62.9%) cases and negative in 10(37.1%) cases. In group III out of 18 patients 13(72.2%) showed MIBI scan positive whereas, 5(27.8%) showed negative scan. The sensitivity was 36.3% in group I whereas, 62.9% and 72.2% in group II and group III respectively. Conclusion: Based on these findings, it could be say that Tc–99m setamibi uptake correlate with parathyroid oxyphil cell content, and false negative scan can occur with parathyroid glands containing predominantly clear cell.Journal of National Institute of Neurosciences Bangladesh, 2016;2(1):14-18

Paricalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell content in patients with chronic kidney disease

The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.

Distribution and regulation of the 25-hydroxyvitamin D3 1α-hydroxylase in human parathyroid glands

Parathyroid glands express the 25-hydroxyvitamin D3 1α-hydroxylase (1αOHase). 1,25-dihydroxyvitamin D3 (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1αOHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1αOHase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. Recent findings indicate that oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1αOHase in human parathyroid cultures. Additionally, we found that the 1αOHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D3 in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid cells. Therefore, local production of 1αOHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.

Correlation of subtraction parathyroid scintigraphy with weight, pathohistologic finding and oxyphil cell content of parathyroid glands in parathyroid hyperplasia

Parathyroid hyperplasia (PHP) is defined as an absolute increase in the mass of parenchymal cells of the parathyroid gland. PHP is classified as primary, secondary and tertiary. The enlargement of parathyroid glands (PG) is usually asymmetric, resulting in a "dominant" gland. In order to confirm the diagnosis, at least two glands should be examined histologically. Subtotal parathyroidectomy, i.e. removal of the three PG and leaving a small remnant of the forth, is the treatment of choice. High percent of PHP recurrence imposes the need for preoperative high sensitivity localizing procedures. Parathyroid scintigraphy localizes about 60% of hyperplastic glands. The aim of this study was to correlate findings of subtraction parathyroid scintigraphy (SPS) with weight, pathohistologic finding and oxyphil cell (OC) content of PG in patients with primary, secondary and tertiary parathyroid hyperplasia. Twenty-seven patients with primary/secondary PHP underwent SPS before surgery. Scintigraphic results were graded from 1-5, in relation to the degree of uptake. SPS graded 3, 4 and 5 were considered positive. The number and weight of operated PG were evaluated macroscopically. Pathohistologic and cellular types were defined on standard stained hematoxylin-eosin slides. OC content was defined as a percent of OC and graded from 1 to 3: grade 1 < 10%, grade 2 > or = 10% and grade 3 > or = 20% of OC. SPS localized dominant gland in all patients with sensitivity 100%, and 51 from 73 hyperplastic PG, with sensitivity per gland of 70%. PG weighed 0.1 g to 6.7 g (median 1 g). A significant positive correlation (p < 0.0001) was found between the SPS results and PG weight. A significant positive correlation was found between PG weight and OC content (p = 0.0002). An insignificant correlation was found between SPS and OC content. Thirty-eight PG had < 10% of OC, 32 PG had > or = 10% and 3 PG had > or = 20% of OC. Four patients had diffuse PHP and 23 patients nodular PHP. There was no statistically significant difference in SPS results compared to hyperplasia type, and between OC content and hyperplasia type. A significant positive correlation (p = 0.05) was found between PG weight and hyperplasia type. A high positive correlation was found between SPS results and PG weight, PG weight and OC content and PG weight and hyperplasia type. Between SPS results and OC content, and between SPS results and hyperplasia type, an insignificant correlation was found. Our results showed that SPS is a reliable and very sensitive diagnostic tool in detecting abnormal PG in parathyroid hyperplasia, reaching 100% sensitivity in detecting a "dominant gland" and sensitivity per localized gland of 70%. Causes that affect increased uptake of liposolubile Tc99m radiopharmaceuticals (RF) in the hyperfunctional PG tissue and conditions which prevent RF admission into the PG cells still remain to be accurately and precisely determined.

The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism

Background Although the sensitivity of sestamibi scanning (MIBI) is high in patients with solitary parathyroid adenomas, negative sestamibi scan results are inevitable. The exact mechanism of visualization of abnormal and hyperfunctioning parathyroid tissue is not yet clear. The aims of this clinical study were (1) to evaluate positive and negative sestamibi scan results with regard to adenoma weight and oxyphil cell content and (2) to compare the effects of adenoma weight and oxyphil cell content on the results of sestamibi scanning. Patients The patients were divided in 2 groups according to their sestamibi scan results. Group 1 consisted of 27 patients with positive sestamibi scan results, and group 2 consisted of 20 patients with negative sestamibi scan results. Parathyroid adenoma weight and oxyphil cell content were determined in all patients. Results The weight and oxyphil cell content of the parathyroid adenomas in the patients of group 1 were significantly higher than those in the patients of group 2 ( P = .001). An adenoma weight >600 mg and an oxyphil cell content >20% increased the rate of obtaining a positive sestamibi scan result 10- and 4-fold, respectively. Conclusions Both adenoma weight and oxyphil cell content were found to significantly correlate with positive sestamibi scan results. In patients with high-weight adenomas, adenoma weight was the most significant factor in obtaining positive MIBI scan results, whereas in patients with low adenoma weights, high oxyphil cell content was the most significant factor in obtaining positive MIBI scan results.

Relation between Tc-99m sestamibi uptake and biological factors in hyperparathyroidism

The aim of this study was to evaluate the relation between uptake ratios of Tc-99m sestamibi (MIBI) and tumor volume, serum biochemical values (i-PTH, Ca, P) and oxyphil cell content. The study population consisted of 19 patients (2 M, 17 F; mean +/- SD: 47 +/- 12 y). Anterior planar images of the neck and chest were acquired early (15 min) and triple late phase (1, 2 and 3-4 h) after intravenous injections of 740 MBq MIBI. Each of the surgical materials was reviewed retrospectively. The percentage of cell type (chief, oxyphil and clear cells) in the tumors was calculated by light microscopy. The uptake ratio obtained from L1 (1 hour) phase was found to be higher than the uptake ratio obtained from early phase, and the difference was statistically significant (1.57 +/- 0.34 and 1.43 +/- 0.29, p = 0.004, respectively). There was no significant correlation between uptake ratios that were obtained from 4 different imaging phases and lesion volumes, i-PTH levels and calcium levels (p > 0.05). However, there was a significant adverse correlation between L2 and L3 uptake ratios and serum phosphorus values (r = -0.44, p = 0.04 and r = -0.46, p = 0.04, respectively). Additionally, no significant correlation between MIBI uptake ratios of each imaging phase and the laboratory data, volume of lesion or oxyphil percentage volume was found after the multiple regression analysis (E: p = 0.46, r = 0.49; L1: p = 0.24, r = 0.58; L2: p = 0.27, r = 0.57; L3: p = 0.32, r = 0.55, respectively. There was no correlation between gland oxyphil percentage volume and MIBI uptake ratios (p > 0.05). The results of our study show that the optimal imaging times after intravenous injection of MIBI are 15 minutes and 1 hour because of the shorter examination time without loss of diagnostic ability. In the present study, there was no significant correlation between MIBI uptake ratios and increased gland volume, or serum Ca and i-PTH levels. Besides, we think that oxyphil cell content may not have a main effect on MIBI uptake and retention. The fact of an adverse relation between phosphorus and MIBI retention in our study suggests that phosphorus level should be considered prior to MIBI imaging.

Relationship of Technetium Tc 99m Sestamibi Scans to Histopathological Features of Hyperfunctioning Parathyroid Tissue

To investigate the histopathological features of pathologic parathyroid specimens associated with negative preoperative technetium Tc 99m sestamibi scans. Retrospective study. Tertiary care center. One hundred fourteen patients who underwent sestamibi scans before surgical exploration for primary hyperparathyroidism between 1996 and 2001. Surgical exploration and removal of parathyroid adenomas. Histopathological characteristics associated with true-positive and false-negative sestamibi scans, including parathyroid specimen weight, size, relative oxyphil and chief cell content, parathyroid hormone staining patterns, cellular architecture, and various immunohistochemical staining patterns. Twenty-three (24%) of 98 patients with parathyroid adenomas had negative sestamibi scan results. Among 20 age- and sex-matched patients with false-negative results vs 20 patients with true-positive results, tumor size (P = .04) and oxyphil cell content (P = .03) were found to be significantly different. Parathyroid gland size and oxyphil content are descriptive and predict differences between sestamibi properties of parathyroid adenomas but have no current therapeutic implications for parathyroid surgery.

Clinicopathologic and Radiopharmacokinetic Factors Affecting Gamma Probe–Guided Parathyroidectomy

The kinetics of technetium Tc 99m sestamibi (MIBI) in primary hyperparathyroidism are variable and affected by the cellular size of the abnormal glands, the parathyroid hormone levels, and the functional expression of P-glycoprotein (Pgp). The success of gamma probe-guided parathyroidectomy is closely related to the parathyroid-to-thyroid activity ratio at the time of surgery. Preoperative determination of maximum uptake ratio may improve the surgical outcome. Thirty-one patients with primary hyperparathyroidism attributed to a solitary parathyroid adenoma (27 patients) or multiglandular hyperplasia (4 patients) underwent dynamic MIBI imaging preoperatively. Maximum MIBI activity and activity elimination half-life in the abnormal parathyroid glands and thyroid glands were measured, and the maximum uptake ratio was calculated. After a second MIBI injection on the day of surgery, all patients underwent gamma probe-guided parathyroidectomy and cervical exploration. Timing of surgery after MIBI injection was individualized according to the optimal time to surgery (time to maximum uptake ratio), which was determined by preoperative scintigraphy. During surgery, the gamma probe was used to measure ex vivo counts of excised lesions and adjacent postexcision normal tissue (background). Image characteristics, MIBI kinetics, and gamma probe findings were correlated with gland volume, oxyphil cell content, Pgp expression, and serum parathyroid hormone levels. Probe localization of abnormal glands at maximum uptake ratio was successful in all patients. The volume of the parathyroid lesion ranged from 0.03 to 9.8 mL (median, 0.7 mL). Parathyroid maximum MIBI activity correlated with the volume of the gland (r = 0.54, P = .002) and serum parathyroid hormone level (r = 0.58, P = .001). No correlation between maximum MIBI activity and oxyphil cell content or Pgp expression could be demonstrated. Elimination half-life of MIBI from parathyroid inversely correlated with Pgp (r = -0.36, P = .05). The ex vivo lesion-background count ratio positively correlated with volume of the gland (r = 0.66, P = .001) and parathyroid hormone level (r = 0.48, P = .006). Ex vivo lesion counts and Pgp expression were negatively correlated (r = -0.37, P = .04). A strong relationship between volume of the parathyroid gland, serum parathyroid hormone levels, and MIBI uptake exists in primary hyperparathyroidism. Gamma probe-guided localization of abnormal gland(s) can be more successful if surgery is undertaken at maximum uptake ratio. High Pgp expression increases MIBI parathyroid clearance rate, decreases gamma probe counts, and may significantly alter the optimal time to surgery.

Preoperative parathyroid localization: correlating false-negative technetium 99m sestamibi scans with parathyroid disease.

The recent trend toward minimally invasive directed parathyroid surgery has increased the surgeon's reliance on preoperative parathyroid localization. Technetium Tc 99m sestamibi scanning is generally viewed as the gold standard for preoperative localization, with reported sensitivities of 75% to 100% and specificities of 75% to 90%. However, in each reported series there exists a group of patients in whom preoperative localization is either equivocal or negative. We focused on a subset of patients from our parathyroid database with false-negative sestamibi (MIBI) scans, in an attempt to elucidate features that could affect these studies. We identified 20 patients with negative preoperative scans and confirmed parathyroid disease. We compared them with 22 consecutive patients with positive scans, correlating the following variables: patient age, gender, concomitant thyroid disease (Hashimoto's thyroiditis, papillary thyroid carcinoma, thyroid adenoma), preoperative parathyroid hormone values, location and number of enlarged parathyroid glands, parathyroid weight, and the relative proportion of chief cells, clear cells, oxyphil cells, and adipose tissue. Retrospective chart review of clinicopathological and radiological findings. We found that patients with false-negative scans were more likely to have an enlarged parathyroid containing a high proportion of clear cells (P =.01). A trend was seen (P =.1) correlating increased parathyroid fat content and false-negative scans. Conversely, positive preoperative scans were more likely to be associated with a higher percentage of oxyphil cells (P =.02). Univariate analysis for other variables, as well as logistic regression analysis, did not achieve statistical significance. To date, the present study is the largest clinicopathological review of patients with false-negative sestamibi scans. Technetium Tc 99m uptake correlates with parathyroid oxyphil cell content, and false-negative scans can occur with parathyroid glands containing predominantly clear cells.