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Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings.

The major factor to influence localization of parathyroid adenomas is tumor size. P-glycoprotein (P-gp) expression in parathyroid adenomas has been considered to be an another possible factor to influence localization of parathyroid adenomas because false-negative studies have been reported with large tumors and true-positives reported with very small tumors in previous studies. The aim of this study was to characterize Tc-99m MIBI uptake and retention by parathyroid adenomas and to correlate this with cell surface expression of P-gp. Sixteen patients with parathyroid adenoma (larger than 1.5 gm) underwent dual-phase (10min and 2hr) Tc-99m MIBI parathyroid image immediately before parathyroid exploration. Tissues were obtained from normal and abnormal parathyroid glands and from the thyroid gland. Immunohistochemistry (IHC) was obtained with monoclonal antibodies to identify P-gp expression in all tissues. All of the 16 parathyroid adenomas and 32 normal control specimens (16 normal parathyroid and 16 normal thyroid specimens) were submitted for P-gp detection by IHC. The dual-phase Tc-99m MIBI parathyroid image accurately localized 14 parathyroid adenomas, but not the remaining 2 adenomas. The 14 parathyroid adenomas with significant Tc-99m MIBI uptake in delayed 2hr images revealed negative P-gp expression, but the 2 adenomas without significant Tc-99m MIBI uptake, as well as normal parathyroid and normal thyroid specimens, revealed positive P-gp expression when evaluated by IHC. Not only the size of parathyroid adenomas, but also significant P-gp expression limited the sensitivity of dual-phase Tc-99m MIBI parathyroid image to localize parathyroid adenomas before operation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Diagnosis of dysfunctions of replanted parathyroid gland tissue by bilateral analysis of intact parathyroid hormones in cubital vein blood. A prospective study].

AIM: In a prospective long-term follow-up study after operative therapy of hyperparathyroidism the value of bilateral determination of parathyroid hormone levels in cubital venous blood after total parathyroidectomy/autologous parathyroid gland reimplantation (musculus brachioradialis) for diagnosis of dysfunctioning grafted tissue is evaluated. PATIENTS AND MATERIAL: From August, 1, 1987 to March, 31, 1994 68 of 243 patients operated on for hyperparathyroidism underwent total parathyroidectomy. Autologous reimplantation of parathyroid gland was carried out simultaneously in 64 patients. Twice delayed reimplantation of cryopreserved tissue was carried out, and there was no reimplantation in two patients up to this day. Three patients were operated on for hyperfunctioning parathyroid autograft after former total parathyroidectomy/reimplantation. RESULTS: During follow-up 5 patients developed dysfunction of (reimplanted) parathyroid gland. Because of low or unprovable levels of intact parathormone the gradients of intact parathyroid hormone between grafted and nongrafted forearm were about 1:1 in postoperative hypoparathyroidism as well as in hypofunction of parathyroid gland. After successful replantation of cryopreserved parathyroid tissue gradients of intact parathyroid hormone increased (> 1:10). In hyperfunction of grafted parathyroid tissue hormone gradients were high (> 1:20 to 1:45,3) because of excessive high levels of intact parathormone in the cubital vein of the graft bearing arm. Successful reduction of parathyroid graft was followed by decrease of parathyroid hormone gradients. CONCLUSION: Regular follow-up of intact parathormone gradients together with intact parathyroid hormone levels and serumcalcium analysis allow the determination of parathyroid graft function. Also differentiation between graft dependent hyperparathyroidism and hyperfunctioning parathyroid tissue in the neck or mediastinum seems to be possible by bilateral determination of intact parathormone. Normal values or a normal range for intact parathyroid hormone gradients can not yet be defined.

Adult↗

Decrease in serum immunoreactive parathyroid hormone in rats and in parathyroid hormone secretion in vitro by 1,25-dihydroxycholecalciferol.

The present study determined the effects of 1,25-dihydroxycholecalciferol on serum immunoactive parathyroid hormone and on parathyroid hormone secretion in vitro. Rats injected i.p. with 1,25-dihydroxycholecalciferol, 130 pmol (2 U)/140 g body wt, which is probably a physiologic dose, had a significant 43% decrease in serum immunoreactive parathyroid hormone at 4 h. In addition, this dose of 1,25-dihydroxycholecalciferol inhibited the serum immunoreactive parathyroid hormone response to hypocalcemia induced by phosphate injection. Because the increment in serum immunoreactive parathyroid hormone was less but the decrement in serum calcium more in phosphate plus 1,25-dihydroxycholecalciferol-treated than in phosphate plus vehicle-treated rats, the impaired serum immunoreactive parathyroid hormone response to 1,25-dihydroxycholecalciferol could not be attributed to the change in serum calcium. In studies of parathyroid hormone secretion from bovine parathyroid tissue in vitro, the concentration of 1,25-dihydroxycholecalciferol used for most experiments was 1nM, which is in the range found in rat serum. 1,25-Dihydroxycholecalciferol at 1 or 100 nM significantly inhibited parathyroid hormone secretion when medium calcium concentration was normal (1.5 mM), high (3.0 mM), and low (1.0 mM). Maximum inhibition ranged from 19 to 74%; inhibition was generally seen after 2 h of incubation; and inhibition was sustained or progressive thereafter. Vitamin A, 0.1 muM, caused a marked stimulation of parathyroid hormone secretion. 1,25-Dihydroxycholecalciferol at 1 nM markedly reduced (44%) the effect of vitamin A to stimulate parathyroid hormone secretion. This effect of 1,25-dihydroxycholecalciferol was maximal at 1 h and persisted thereafter. Another steroid, hydrocortisone, 10 muM, did not inhibit parathyroid hormone secretion, suggesting that the 1,25-dihydroxycholecalciferol effect was not a nonspecific inhibitory effect on parathyroid cells. Because other workers have shown that parathyroid hormone directly stimulates 1,25-dihydroxycholecalciferol secretion, our results are consistent with the concept that there is a feedback loop where parathyroid hormone directly stimulates secretion of 1,25-dihydroxycholecalciferol, which in turn directly inhibits secretion of parathyroid hormone.

Animals↗

Using technetium 99m tetrofosmin parathyroid imaging to detect parathyroid adenoma and its relation to P-glycoprotein expression.

BACKGROUND: The purpose of this study was to retrospectively evaluate technetium 99m tetrofosmin (Tc-TF) uptake in parathyroid adenomas and compare the results with their expression of multidrug resistance-mediated 170-kDa P-glycoprotein (Pgp). METHODS: Twenty patients with larger parathyroid adenomas (> 1.5 g) and the other 40 patients with smaller parathyroid adenomas (0.5-1.5 g) underwent early and delayed (10-minute and 2-hour) Tc-TF parathyroid imaging before operation. In this retrospective study, immunohistochemical analyses were performed on multiple nonconsecutive sections of the 40 parathyroid adenomas and 40 normal control specimens (20 normal parathyroid glands and 20 normal thyroid specimens) to detect Pgp expression. RESULTS: The Tc-TF parathyroid image accurately localized 17 larger and 16 smaller parathyroid adenomas, but not the remaining 3 larger and 4 smaller adenomas. The 17 larger and 16 smaller parathyroid adenomas with significant Tc-TF uptake on the delayed 2-hour parathyroid images revealed negative Pgp expression, but the 3 larger and 4 smaller adenomas without significant Tc-TF uptake, as well as 20 normal parathyroid glands and 20 normal thyroid specimens, revealed positive Pgp expression. CONCLUSIONS: Not only the size of parathyroid adenomas, but Pgp expression also limited the sensitivity of Tc-TF parathyroid image to localize parathyroid adenomas before the operation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Immunoperoxidase staining in the differential diagnosis of parathyroid from thyroid origin in fine needle aspirates of suspected parathyroid lesions.

OBJECTIVE: To determine whether immunoperoxidase staining could be used for differential diagnosis of parathyroid from thyroid origin in fine needle aspirates of suspected parathyroid lesions. STUDY DESIGN: Immunoperoxidase staining of parathyroid hormone and thyroglobulin was performed on aspirated smears from 10 patients with parathyroid lesions (6 of 10 patients also associated with thyroid lesions) and 10 patients with thyroid lesions. All of them had surgical tissue proof of the diagnosis. RESULTS: Aspirated smears of six patients with parathyroid lesions had strong to moderate staining for parathyroid hormone and negative staining for thyroglobulin. Another four patients with parathyroid lesions had equivocal staining for parathyroid hormone and negative staining for thyroglobulin. All aspirated smears from the 16 thyroid lesions had negative staining for parathyroid hormone and positive staining for thyroglobulin. CONCLUSION: Immunoperoxidase staining of parathyroid hormone and thyroglobulin, done for each suspected parathyroid lesion, was helpful in the differential diagnosis of parathyroid vs. thyroid origin.

Adenoma↗

Parathyroid biopsy to facilitate the preservation of functional parathyroid tissue during thyroidectomy.

BACKGROUND: The preservation of viable parathyroid tissue, either by preserving parathyroid glands in situ with an intact blood supply or by autotransplantation, is an integral element of thyroid surgery. There is a general impression that nonviable parathyroid glands can be recognized on the basis of black or purple-black discoloration of the gland. We came to believe that this is not a reliable way to assess the viability of parathyroid glands because we observed that when we excised parathyroid glands (with the intention of reimplanting them) in situations where it was not feasible to preserve their blood supply, they did not become discolored. METHODS: To assess the status of the parathyroid blood supply, we performed incisional biopsies of suspected parathyroid glands during 14 consecutive thyroid operations (9 hemithyroidectomies, 1 completion thyroidectomy, 4 total thyroidectomies), and observed the biopsy site for evidence of active bleeding. RESULTS: Thirty-four of 36 possible parathyroid glands were histologically confirmed. Seventeen bled actively from the biopsy site and were preserved in situ. The other 17 were felt to be nonviable: 5 were severely discolored (black) and either no bleeding or minor venous oozing was seen when they were biopsied; 12 with normal coloration (3 were harvested prior to biopsy), did not bleed actively following an incisional biopsy. Parathyroid glands that were judged to be devascularized were autotransplanted into the sternocleidomastoid muscle. CONCLUSIONS: The absence of discoloration is not a reliable way to determine whether the parathyroid blood supply is intact. Biopsy of the parathyroid glands during thyroid surgery facilitates the identification of devascularized parathyroid glands that can be salvaged with autotransplantation.

Adult↗

Intraoperative parathyroid aspiration and parathyroid hormone assay as an alternative to frozen section for tissue identification.

Most people would agree that successful parathyroidectomy depends on two important variables: the surgeon's recognition and excision of the abnormal parathyroid gland(s) and the pathologist's confirmation that the removed tissue is parathyroid tissue. Frozen section is usually employed to confirm the identity of parathyroid tissue, but occasionally confirmation cannot be made without a permanent section, as with intrathyroidal glands. This study proposes a new method of expeditious and easy confirmation of parathyroid tissue utilizing the immunoassay for quick measurement of intraoperative parathyroid hormone (IOPTH). By directly aspirating the suspected adenoma, the assay becomes a rapid diagnostic tool that can be used as an alternative to frozen section. In cases where the surgeon is already planning to employ the assay, the elimination of frozen section is cost-effective. Intraoperative aspiration of histologically confirmed parathyroid adenomas was performed on 12 consecutive patients undergoing parathyroid surgery. Parathyroid glands were aspirated with a 22-gauge syringe after gland excision. Aspirates were placed in 1 to 3 ml of buffered saline. A similar process was performed on 12 thyroid controls. Specimens were centrifuged, aliquotted, and stored at -70 degrees C. The parathyroid hormone value was analyzed electively by rapid assay and the values recorded. For all parathyroid aspirates, the rapid assay value was > 1500 pg/ml, exceeding the uppermost limit of the diagnostic chart. Values for thyroid aspirates ranged from 58 to 85 pg/ml (mean 75.7 pg/ml). In all cases tissue confirmation was achieved with permanent section. Values were 100% sensitive and specific. Measurement of PTH from intraoperative aspiration of suspected parathyroid adenomas is clinically useful in patients for whom frozen section would routinely be employed. Values > 1500 pg/ml secure the tissue diagnosis. There is no additional cost in cases where IOPTH monitoring is already being utilized to confirm cure. The elimination of frozen section could be cost-effective and, for some institutions, actually decrease the operating time as the IOPTH assay takes only 15 minutes. PTH assay is an accurate diagnostic technique and to date is 100% sensitive and specific for differentiating between parathyroid tumors and thyroid nodules.

Biopsy, Needle↗

Parathyroid histology and cytology with monoclonal antibodies recognizing a calcium sensor of parathyroid cells.

Two monoclonal antibodies reacting with surface structures on exclusively parathyroid cells and proximal kidney tubule cells were evaluated in the microscopic diagnosis of parathyroid disease. Immunostained cryosections of adenomatous and hyperplastic parathyroid glands from 30 hypercalcemic patients with primary or uremic hyperparathroidism (HPT) showed a reduced and heterogeneous staining with the antibodies. This contrasted with the intense and even staining of normal and suppressed human parathyroid glands, as well as lymph node metastases of parathyroid carcinoma. Fine-needle aspiration biopsies and imprints of the parathyroid glands showed a conspicuous antibody staining that enabled the identification of parathyroid cells. The antibodies seem to provide new means for histologic and cytologic identification of normal and pathologic parathyroid tissue, in conjunction with their highly restricted tissue reactivity. Because one of the antibodies interacts with a surface receptor mechanism of the parathyroid cells that is involved in the sensing and gating of calcium and, thereby, also with the regulation of parathyroid hormone release, the unequivocal demonstration of reduced staining of the adenomatous and hyperplastic parathyroid tissue suggests that HPT is associated with reduced expression of the calcium sensoring mechanism of the pathologic parathyroid tissue.

Adenoma↗

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease.

OBJECTIVE: To evaluate the utility of a rapid intraoperative parathyroid hormone (PTH) immunoradiometric assay in the surgical management of parathyroid disease, particularly with reference to limiting extent of cervical exploration. DESIGN: Nonrandomized prospective study. SETTING: Academic tertiary care center. PATIENTS: Forty-three consecutive patients undergoing parathyroid exploration for adenoma or hyperplasia had rapid PTH assays performed from blood drawn at induction and 7 minutes after resection of all hyperfunctioning parathyroid tissue. OUTCOME MEASURES: Excision of all hyperfunctioning parathyroid tissue as assessed by bilateral neck exploration, postoperative normalization of serum calcium and PTH levels, and resolution of clinical symptoms. RESULTS: The intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning parathyroid tissue was excised in every patient. In 41 patients, all hyperfunctioning parathyroid tissue was resected at the time of surgery and confirmed by a corresponding decrease in the intraoperative postexcision rapid PTH determination as well as by subsequent normalization of postoperative serum calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the postexcision rapid PTH assay determination was not consistent with removal of all hyperfunctioning parathyroid disease and both patients demonstrated persistent hyperparathyroidism postoperatively. CONCLUSIONS: The intraoperative rapid PTH assay may be of significant benefit in permitting directed unilateral parathyroid explorations for adenoma when combined with preoperative localization with a technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be of benefit in confirming excision of all hyperfunctioning parathyroid tissue in patients with multiple gland hyperplasia, particularly those who may harbor ectopic parathyroid tissue.

Adenoma↗

Primary hyperparathyroidism: four- to eight-year postoperative follow-up demonstrating persistent functional insignificance of microscopic parathyroid hyperplasia and decreased autonomy of parathyroid hormone release.

Thirty-nine patients with primary hyperparathyroidism were studied four to eight years after their initial operation. In six patients, both the pathologist and surgeon agreed on the diagnosis of solitary adenoma; in 16 patients, the surgeon diagnosed solitary adenoma and the pathologist parathyroid hyperplasia (microscopic hyperplasia). In 16 patients, primary chief cell hyperplasia was agreed upon by the pathologist and surgeon. In the 16 patients with microscopic hyperplasia, there have been no long-term recurrences of hypercalcemia, but, in two patients, plasma parathyroid hormone levels are high. Parathyroid hormone--total calcium regression curves demonstrate significant preoperative correlation in solitary adenoma, p less than 0.01, and primary chief cell hyperplasia, p less than 0.05. After operation, significant correlations were not found between parathyroid hormone and total calcium. T-testing slope differences of pre- and postoperative parathyroid hormone--total calcium regression curves demonstrates a significant (p less than 0.01) shift to the right of the microscopic hyperplasia patients after operation, moving them to a broader range of total calcium per picogram parathyroid hormone. We conclude that 1) in primary hyperparathyroidism, positive regulation of total calcium by autonomously released parathyroid hormone exists in patients with solitary adenoma and chief cell hyperplasia; 2) autonomously functioning parathyroid tissue has been removed by operation for solitary adenoma with coexistent microscopic parathyroid hyperplasia. In this four- to eight-year follow-up period, it is clear that microscopic parathyroid hyperplasia is not associated with recurrent hypercalcemia. Two functionally distinct forms of parathyroid suppression are suggested; positively regulated microscopic hyperplasia and negatively regulated pathologically suppressed glands.

Adenoma↗

Experimental parathyroid transplantation: human parathyroid grafts survived and functioned in mice treated with anti-CD4 monoclonal antibody.

Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. To examine the possibility that xenotransplantation can be used to treat hypoparathyroidism, human parathyroid tissues were transplanted into mice. Human parathyroid tissue was taken from specimens excised from patients with hyperparathyroidism. Fresh human parathyroid tissue was implanted under kidney capsule of CBA (H2k) mice. Some mice were treated intraperitoneally with depleting anti-CD4 monoclonal antibody (mAb, YTA 3.1, 100 microg/dose, days -1. 0. 1, 2, 3, and 5). Mice were killed 30 days after transplantation. Survival of parathyroid grafts was examined microscopically and human parathyroid hormone in serum was measured by ELISA. All parathyroid grafts survived under kidney capsule and human parathyroid hormone was strongly detected in serum (621 +/- 576 pg/mL) when recipients were treated with short-course treatment of anti-CD4 mAb. Conversely, no parathyroid tissue was seen microscopically in any recipient mice without anti-CD4 mAb treatment. Human parathyroid hormone was undetectable by ELISA in naive mice and mice transplanted with human parathyroid tissue without short-course treatment of anti-CD4 mAb. Xenogeneic human parathyroid tissue survived and functioned in mice treated with short-course treatment of anti-CD4 mAb.

Animals↗

The presence of immunoreactive parathyroid hormone-related protein in parathyroid adenoma cells.

Parathyroid hormone-related protein (PTHrP) was first identified in human malignant tumors associated with humoral hypercalcemia of malignancy. We immunohistochemically examined the distribution of PTHrP both in 7 normal parathyroid glands and in a 20 parathyroid adenomas. Sixty-five percent of parathyroid adenomas (13 cases) were positive for PTHrP, whereas only one normal parathyroid gland was positive for PTHrP in the area of transitional oxyphil cells. Many parathyroid adenomas (12 cases) were composed of both PTHrP-positive cells and--negative cells, and these two different type of cells showed a tendency to form nodules respectively in parathyroid adenoma. Although both chief cells and oxyphil or transitional oxyphil cells were positive for PTHrP in parathyroid adenoma, oxyphil or transitional oxyphil cells were more responsible for PTHrP production than chief cells. Chief cells are thought to produce parathyroid hormone mainly in parathyroid adenoma. On the other hand, little is known concerning the function and role of oxyphil or transitional oxyphil cells. Our results suggest that oxyphil or transitional oxyphil cells in parathyroid adenoma may have some functional roles different from those of chief cells through the production of PTHrP.

Adenoma↗

Ontogeny of parathyroid hormone-related protein in the ovine parathyroid gland.

PTH-related protein (PTHrP) has been implicated in calcium regulation during fetal life. In this study the ontogeny of PTHrP was examined in ovine parathyroid glands. Immunohistochemical techniques, Western blot analysis, and a RIA with antisera raised against synthetic fragments of human (h) PTHrP (i.e. 1-34, 1-40, 50-69, and 107-141) were used to detect the presence of immunoreactive PTHrP in parathyroid glands from fetal and neonatal lambs and maternal ewes. Positive immunostaining for PTHrP was observed in fetal (from 116 days of gestation) and lamb (up to 180 days post birth) but not maternal parathyroid glands with the PTHrP(50-69) antiserum. Fetal and lamb parathyroid glands consisted entirely of one cell type in which PTHrP immunoreactivity to PTHrP(50-69) antiserum was found. In contrast, immunoreactivity to PTHrP could not be detected in sections of fetal, lamb, or maternal parathyroid glands with antisera raised against PTHrP(1-34) or PTHrP(107-141). However, PTHrP immunoreactivity in urea/acid extracts of newborn lamb parathyroid glands could be detected by Western blot analysis and RIA with antisera raised against the N-terminal portion of PTHrP. Western blot analysis with the PTHrP(1-34) antisera revealed that urea/acid extracts of newborn lamb parathyroid glands contained a substance with a mol wt of 14.4K, which corresponded in size to that of hPTHrP(1-84). Newborn lamb parathyroid glands contained 0.35 ng PTHrP/micrograms extract, whereas maternal parathyroid glands contained only 0.035 ng PTHrP/micrograms extract when tested in a RIA employing recombinant hPTHrP(1-84) as standard and an antibody raised against hPTHrP(1-40). The detection of immunoreactive PTHrP in the developing ovine parathyroid gland provides further evidence to support the suggestion that PTHrP produced in the parathyroid gland is involved in the normal hormonal regulation of calcium metabolism in the mammalian fetus and neonate.

Animals↗

Nuclear area measurements of parathyroid adenoma, parathyroid hyperplasia and thyroid follicular adenoma. A comparison.

OBJECTIVE: To determine whether nuclear area (NA) measurement could help to differentiate parathyroid adenoma, parathyroid hyperplasia and thyroid follicular adenoma in aspirated smears. STUDY DESIGN: Aspirated smears of 15 patients with parathyroid adenoma, 11 patients with parathyroid hyperplasia and 11 patients with thyroid follicular adenoma were included. NA of 100 cells in each case were measured by image analysis; then the mean and coefficient of variation were calculated. RESULTS: There was no statistically significant difference in the mean of NA between parathyroid adenoma and parathyroid hyperplasia, but the former displayed greater NA variation. Thyroid follicular adenoma revealed a significant elevation in the mean of NA when compared with parathyroid lesions and also shared the feature of greater NA variation when compared with parathyroid hyperplasia, as noted in parathyroid adenoma. CONCLUSION: Quantitative assessments on NA and calculation of their coefficient of variation are helpful in differentiating between parathyroid adenoma, parathyroid hyperplasia and thyroid follicular adenoma.

Adenoma↗

Inhibition of parathyroid hormone-related protein release by extracellular calcium in dispersed cells from human parathyroid hyperplasia secondary to chronic renal failure and adenoma.

The relationship between parathyroid hormone-related protein (PTHrP) release from parathyroid cells and extracellular calcium ion concentration was investigated in three cases of parathyroid hyperplasia secondary to chronic renal failure and in four cases of parathyroid adenoma. Amounts of PTHrP released from individual parathyroid cells dispersed from surgical specimens were estimated by cell immunoblot assay. Parathyroid cells from both hyperplasias and adenomas showed significant suppression in the release of PTHrP with increase in extracellular calcium ions, but the amounts of PTHrP released from adenoma cells were significantly larger than from hyperplasia cells. The maximal value for PTHrP released within 120 minutes from adenoma cells was 2.91 +/- 2.11 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 1.32 +/- 0.35 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). On the other hand, the maximal value for PTHrP released from hyperplasia cells was 1.79 +/- 1.56 x 10(-2) fmol/cell ([Ca2+], 0.4 mmol/L), and the minimal value was 0.32 +/- 0.19 x 10(-2) fmol/cell ([Ca2+], 2.0 mmol/L). These results demonstrate actual release of PTHrP from abnormal parathyroid tissues into the extracellular space with the response to extracellular calcium ions depending on the cell status. Given the lack of definite histological criteria to differentiate between hyperplasias and adenomas in the parathyroid gland, the presently demonstrated significant difference in the ability to release PTHrP is important in pointing to parathyroid hyperplasia secondary to chronic renal failure as a distinct pathological entity separate from parathyroid adenoma.

Adenoma↗

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

OBJECTIVE/HYPOTHESIS: 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. STUDY DESIGN: 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. METHODS: Retrospective chart review of clinicopathological and radiological findings. RESULTS: 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. CONCLUSIONS: 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.

False Negative Reactions↗