Shiro Noguchi

Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism–jaw tumour syndrome

Backgroundu2002 A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism–jaw tumour syndrome (HPT‐JT).

Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism

BACKGROUNDnMost commercial intact parathyroid hormone (intact PTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH). Using a whole-molecule PTH (whole PTH) assay that specifically measured only 1-84 PTH, we compared the kinetics of whole PTH and intact PTH after parathyroidectomy in patients with primary hyperparathyroidism (HPT) and secondary HPT.nnnMETHODSnThis study comprised 74 patients with primary HPT caused by a single adenoma and 18 patients with secondary HPT who underwent parathyroidectomy. Blood samples were drawn after anesthesia, just before excision of a single adenoma in primary HPT, and just before excision of the last parathyroid gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the whole PTH value from the intact PTH value.nnnRESULTSnThere was a difference between the percentage of 7-84 PTH/intact PTH in plasma samples from patients with primary HPT and secondary HPT (28%+/-12% vs 35%+/-9%; P<.05). Plasma whole PTH decreased more rapidly than intact PTH after parathyroidectomy in patients in both the primary HPT (P<.0001) and secondary HPT groups (P<.0001). Decline of intact PTH was slower in patients with secondary HPT than in patients with primary HPT; however, there was no significant difference in the decline of whole PTH between the 2 groups.nnnCONCLUSIONSnThe quick intact PTH assay is not used frequently during surgery in patients with secondary HPT; however, our results suggest that a quick whole PTH assay may be a more useful adjunct to parathyroidectomy in both secondary HPT and primary HPT.

Role of Cyclase Activating Parathyroid Hormone (1-84 PTH) Measurements During Parathyroid Surgery: Potential Improvement of Intraoperative PTH Assay

Summary Background DataQuick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay. MethodsThis study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value. ResultsThe percentage of 7-84 PTH in iPTH in plasma samples was 27.5 ± 14.4% in pHPT and 39.6 ± 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 ± 10.8 and 32.0 ± 11.3% of the preexcision level at 5 minutes, 10.6 ± 7.7 and 21.1 ± 8.8% at 10 minutes, and 8.5 ± 4.9 and 16.1 ± 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 ± 20.2 and 66.1 ± 19.7% at 5 minutes, 28.6 ± 16.6 and 53.6 ± 18.1% at 10 minutes, and 14.2 ± 9.0 and 41.0 ± 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 ± 85.9 and 62.1 ± 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands. ConclusionsThe percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.

Intraoperative parathyroid hormone assay in patients with Graves' disease for prediction of postoperative tetany

We measured intraoperative parathyroid hormone (IOPTH) levels before and after thyroidectomy in a large group of patients to test whether changes in IOPTH can predict postoperative tetany. Subjects were 111 consecutive patients (94 females and 17 males) with Graves’ disease undergoing subtotal thyroidectomy. Blood samples for IOPTH assay were obtained after anesthesia (basal) and following skin closure (postoperative). Data were compared between patients who developed tetany (n = 9) and those who did not (n = 102). There was no significant difference in sex, age, period of antithyroid drug administration, or the weight of the thyroid between the two groups. The preoperative serum calcium level was significantly lower (p < 0.05) and the basal IOPTH significantly higher (p < 0.05) in the tetany group than in the non-tetany group. The IOPTH level was significantly lower (p < 0.005) and the average percent decrease in IOPTH levels was higher (p < 0.001) in the tetany group than in the non-tetany group. A decrease in IOPTH of more than 70% was shown to be 78% sensitive, 94% specific, and 93% accurate, and it has 78% positive predictive value and 94% negative predictive value for the development of tetany. Our study shows that a postoperative decrease of IOPTH level is the most predictive of postoperative tetany of the clinical risk factors investigated. We recommend IOPTH measurement as an adjunct to postoperative management of patients with Graves’ disease to assist in preventing hypocalcemia and determining the earliest time for safe discharge.

Sequential Changes in Plasma Intact and Whole Parathyroid Hormone Levels during Parathyroidectomy for Secondary Hyperparathyroidism

Most commercial assays for intact parathyroid hormone (iPTH) cross-react with non-PTH1-84 fragments (likely to be PTH7-84). We aimed to evaluate a whole PTH assay that measured only PTH1-84 by comparing it with an assay measuring iPTH levels during parathyroidectomy in secondary hyperparathyroidism (HPT). Twenty-eight patients with secondary HPT who underwent total parathyroidectomy with autotransplantation served as subjects. Blood samples for postoperative assay were drawn after anesthesia; immediately prior to excision of the last parathyroid gland; and at 5, 10, and 15 minutes after excision. The PTH7-84 level was calculated by subtracting the whole PTH value from the iPTH value. Plasma whole PTH decreased more rapidly than iPTH after parathyroidectomy (p < 0.0001). PTH levels that decreased by 50% or more from levels prior to excision to 10 minutes after excision were used to predict successful parathyroidectomy; decreases in whole PTH substantiated curative surgery for all patients without introducing false-positive and false-negative results. iPTH levels decreased by at least 50% in only 16 patients at 10 minutes after excision without false-positive results. Out of 11 cases in which iPTH decreased less than 50%, two were true-negatives and nine were false-negatives. Decreases in whole PTH levels more accurately reflect surgical outcome than do decreases in iPTH levels during parathyroidectomy in secondary HPT patients. Even though the quick iPTH assay is used infrequently during surgery for secondary HPT, our results suggest that a quick whole PTH assay may be more useful than the iPTH assay currently used in parathyroidectomy procedures for secondary HPT.

Biallelic inactivation by somatic mutations of the MEN1 gene in sporadic parathyroid tumors

We report three sporadic parathyroid tumors with biallelic inactivation of the multiple endocrine neoplasia type 1 (MEN1) gene. Three parathyroid tumors had two somatic mutations (K119del and 864del8, 363insT and 1767delT, and 508del33 and W341X, respectively). The mutations in both alleles detected by long-range polymerase chain reaction and subcloning in three tumors would likely result in a nonfunctional menin protein in parathyroid glands. These results show that the MEN1 gene is inactivated not only by a combination of somatic mutations and loss of heterozygosity, but also by somatic double mutations located on different alleles. The results directly confirmed the participation of MEN1 in the tumorigenesis of sporadic parathyroid tumors.

Usefulness of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer

Pre-operative evaluation of esophageal infiltration is sometimes difficult in patients with advanced thyroid cancer even with recent imaging modalities. We evaluated the accuracy of endoscopic ultrasonography (EUS) in diagnosing esophageal infiltration of thyroid cancer. Twenty-nine patients with advanced thyroid cancer underwent EUS and other imaging examinations before surgery. The diagnostic accuracy of EUS was compared with that of magnetic resonance imaging (MRI) and esophagography based on pathologic findings in 27 of the 29 cases. EUS clearly demonstrated the 5-layer structure of the esophageal wall. EUS detected cancer invasion into the muscularis propria of the esophagus correctly in 8 of 10 patients diagnosed pathologically with muscular infiltration. EUS was significantly more accurate than MRI and esophagography (88.9% vs 63.0% and 66.7%, respectively). The specificity of EUS was also significantly better than the specificities of MRI or esophagography (94.1% vs 58.8% and 64.7%, respectively). The sensitivity, positive predictive value and negative predictive value of EUS tended to be better than those of MRI and esophagography. EUS is useful in evaluating the esophageal infiltration of thyroid cancer. This method has the further advantage of detecting the exact depth of cancer invasion into the esophageal wall.

Intraoperative Parathyroid Hormone Levels Measured by Intact and Whole Parathyroid Hormone Assays in Patients with Graves' Disease

PurposeTo find out if the whole parathyroid hormone (wPTH) assay has practical advantages over the intact (iPTH) assay in patients with Graves’ disease.MethodsWe measured iPTH and wPTH levels before and after subtotal thyroidectomy in 111 consecutive patients (94 women and 17 men) with Graves’ disease. Blood samples for assays were obtained after the induction of anesthesia (basal) and following skin closure (postoperative).ResultsThere was a significant correlation between wPTH and iPTH in both the basal and postoperative levels. Logistic regression analyses examining the relationship between the reduction in parathyroid hormone (PTH) levels and the incidence of tetany revealed that both the wPTH and iPTH assays were significantly equally predictive of postoperative tetany.ConclusionWe found that both the wPTH and iPTH assays were useful for predicting postoperative tetany in patients with Graves’ disease, yielding similar results.