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PubMed1996

Molecular genetics of primary and secondary hyperparathyroidism.

Hyperparathyroidism (HPT) can be caused by solitary parathyroid adenomas and carcinomas, and primary and secondary multiglandular parathyroid disease. Primary HPT is also a feature of several hereditary diseases e.g. multiple endocrine neoplasia type 1 and type 2A (MEN1 and 2A), familial hypocalciuric hyperparathyroidism (FHH), the HPT-jaw tumor syndrome (HPT-JT), and familial isolated HPT. Summarizing data from the literature and our own observations, various genetic abnormalities are observed in the pathogenesis of HPT. These include chromosomal deletions of the MEN1 locus on 11q in sporadic and MEN1 associated primary HPT, of RB1 on 13q in carcinomas, and of the FHH gene located on 3q in sporadic primary and secondary HPT. Genetic material is also lost from chromosomes 1p, 6q, 15q and X suggesting loss of yet unidentified tumor suppressor genes in these regions. In addition the HRPT2 gene on 1q, as well as the proto-oncogenes RET on 10q and PRAD1 on 11q are associated with a subset of parathyroid tumors.

Gene Deletion↗
PubMed2002

[Intraoperative monitoring of intact parathyroid hormone during surgery for primary hyperparathyroidism].

The aim of the present study was to evaluate a new immunometric assay for intraoperative parathyroid hormone monitoring. The test was applied in 70 patients who underwent surgery for primary hyperthyroidism (pHPT) between 6/1999 and 6/2001. Among these patients, 61 showed a solitary adenoma, eight a hyperplasia and one a double adenoma. Intraoperative iPTH samples were taken at the beginning of the operation and 5, 10 and 15 min after removal of the parathyroid gland. Criterion for a successful operation were a decrease of iPTH levels of more than 50 % within 5 min and of more than 60 % within 15 min after parathyroidectomy. Following the removal of a solitary adenoma, iPTH levels decreased by 63 % (+/- 13 %) after 5 min and by 76 % (+/- 10 %) after 15 min respectively. In case of hyperplasia, a significant decrease of iPTH levels was not observed until a subtotal parathyroidectomy had been carried out. In the present study there were 2 false negative and one false positive results corresponding with a sensitivity of 97 % and a specificity of 89 % for prediction of a solitary adenoma. In our opinion, intraoperative iPTH monitoring using this new assay allows the safe distinction between adenoma and multiglandular disease. It represents a valuable adjunct to surgical skill as it permits minimally invasive operations for solitary adenomas, and in case of recurrent surgery helps to detect the region of interest by selective venous sampling for parathyroid hormone.

Adenoma↗
PubMed2001

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience.

BACKGROUND: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas. METHODS: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease. RESULTS: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%. CONCLUSIONS: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Adenoma↗
PubMed2001

Indications and results of video-assisted parathyroidectomy by a lateral approach in patients with primary hyperparathyroidism.

BACKGROUND: Different minimally invasive techniques of parathyroidectomy have been described. We performed a retrospective study to evaluate the indications and results of video-assisted parathyroidectomy by lateral approach (VAPLA) in the management of our patients with primary hyperparathyroidism (PHPT). METHODS: From December 1997 to December 2000, we operated on 293 patients with PHPT. VAPLA was proposed for patients with sporadic PHPT in whom a single adenoma was localized by means of sonography or sestamibi scanning, or both. VAPLA was performed on the anterior border of the sternocleidomastoid muscle. A quick parathormone (PTH) assay was used during the surgical procedures. RESULTS: Of the 293 patients, 127 (43.3%) were not eligible for VAPLA: ipsilateral previous neck surgery (28 cases), associated nodular goiter (59 cases), suspicion of multiglandular disease (15 cases), no preoperative localization (17 cases), and miscellaneous causes (8 cases). VAPLA was performed in 166 patients (56.7%). Conversion to conventional parathyroidectomy was required in 26 patients (15.6%). Morbidity included 2 local hematomas, 1 definitive recurrent nerve palsy, and 4 capsular fractures. All of the 166 patients were normocalcemic, with follow-up ranging from 3 to 33 months. CONCLUSIONS: VAPLA is safe and effective. It should be reserved for patients with sporadic PHPT, with a small single adenoma clearly localized preoperatively.

Adult↗
PubMed2002

Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism.

BACKGROUND: Delayed technetium-99m sestamibi single photon emission computed tomography (SPECT) scans were prospectively analyzed in a large series of patients with primary hyperparathyroidism. METHODS: Three hundred thirty-eight patients underwent sestamibi-SPECT and were explored. Prospective data included preoperative demographics, clinical, sestamibi, and operative findings, laboratory values, and pathologic and follow-up laboratory results from all patients. RESULTS: Between 1994 and 2000, 287 unexplored patients (85%) and 51 re-explored patients (15%) participated. The abnormal parathyroid glands excised from 336 of 338 patients included 299 single adenomas (88%) and 23 double adenomas (7%), and 14 patients had multigland hyperplasia (4%). Sestamibi SPECT correctly lateralized 349 of 400 abnormal parathyroid glands, with an overall sensitivity of 87%, an accuracy of 94%, and a positive predictive value of 86%. Precise localization occurred in 82% of the abnormal parathyroid glands. Sestamibi sensitivity was similar in unexplored (87%) and reoperative (92%) cases; two hundred eighty-six of 299 (96%) solitary adenomas, 38 of 46 (83%) double adenomas, but only 25 of 55 (45%) hyperplastic glands were identified. The mean weight of the true-positive glands (1252 +/- 1980 mg) was greater than that of the false-negative glands (297 +/- 286 mg) (P <.005). Three patients had persistent primary hyperparathyroidism, in spite of the excision of sestamibi-identified lesions in 2 cases. Follow-up indicated curative resection in 99% of the unexplored cases and 94% of the remedial cases. CONCLUSIONS: Sestamibi SPECT is highly accurate for the localization of parathyroid adenomas in unexplored and re-explored cases, where it is often the only imaging required. Its sensitivity is limited in multiglandular disease.

Adenoma↗
PubMed2002

Elevated serum parathormone level after "concise parathyroidectomy" for primary sporadic hyperparathyroidism.

BACKGROUND: Cure after parathyroid exploration is traditionally assessed by serum calcium concentration 6 months postoperatively. Postoperative normocalcemic elevation of serum parathormone (PTH) level has been described but is of unclear significance. METHODS: In a 6-year prospective study of outcomes in 380 patients undergoing initial parathyroidectomy for primary sporadic hyperparathyroidism, we measured intact serum PTH and calcium levels at more than 5 months. Those with normocalcemic high PTH levels were begun on oral calcium + vitamin supplements and monitored. RESULTS: At more than 5 months postoperatively, normocalcemic elevation in serum PTH level occurred in 28% of patients, was more common after resection of double adenomas (P =.01), and predated the onset of recurrent hypercalcemia in 3 of 3 patients with unrecognized multiglandular disease. Although delayed treatment with calcium and vitamin supplements produced no clear benefit, patients who took such supplements from the date of surgery were much less likely to have an elevated serum PTH level more than 5 months later (P =.0005). CONCLUSIONS: After successful parathyroid surgery, compensatory normocalcemic elevation in serum PTH level is frequent and may arise from dietary deficiency. Monitored supplemental intake of calcium and vitamin D appears to prevent or to normalize the condition in most patients. Patients with normocalcemic elevation in serum PTH level should receive evaluation for dietary deficiencies as well as follow-up for possible residual disease.

Adenoma↗
PubMed2002

Utility of rapid intraoperative parathyroid hormone assay to predict severe postoperative hypocalcemia after reoperation for hyperparathyroidism.

BACKGROUND: Patients undergoing reoperative parathyroidectomy may develop severe transient or permanent hypoparathyroidism. This study's purpose was to determine the utility of intraoperative parathyroid hormone (IO-PTH) values in predicting the development of severe hypocalcemia for patients undergoing reoperation for primary hyperparathyroidism. METHODS: Between March 1999 and October 2001, 68 patients with persistent or recurrent hyperparathyroidism underwent reoperation using IO-PTH measurements. The maximum percent decrease and lowest actual PTH value obtained at surgery were compared to determine any correlation with the development of postoperative hypocalcemia requiring supplementation. RESULTS: Of 68 patients, 25 required calcium and calcitriol postoperatively and 43 did not. There was a significant difference between the 2 groups with respect to lowest IO-PTH value (18.4 +/- 2.6 vs 28.0 +/- 3.9 pg/mL; P =.02), percent decrease in IO-PTH (89% +/- 1% vs 80% +/- 3%; P =.03), and lowest postoperative ionized calcium (1.06 +/- 0.01 vs 1.19 +/- 0.01 mmol/L; P <.001). A percent decrease in IO-PTH of 84% or greater was found to be predictive of patients experiencing hypocalcemia requiring supplementation with a positive predictive value of 46% and a negative predictive value of 82%. CONCLUSIONS: Although a maximum percent decrease in IO-PTH of 84% or greater was associated with an increased incidence of postoperative hypocalcemia requiring supplementation in the 68-patient cohort, on further analysis the association was significant only for patients with multiglandular disease and not those with single adenomas. This value may be useful for identifying patients who will need closer postoperative monitoring or prophylactic supplementation.

Adult↗
PubMed2002

Limited versus radical parathyroidectomy in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated primary hyperparathyroidism (FIHPT) is characterized by earlier onset, higher incidence of multiglandular disease, and higher recurrence rate when compared with sporadic primary hyperparathyroidism. Excision of 3.5 or 4 glands with autotransplantation has been recommended; however, these approaches lead to permanent hypoparathyroidism in 13% to 41% of patients. It is reported that many patients with FIHPT return to normocalcemia after single-gland excision. The use of preoperative localization and intraoperative parathyroid hormone assay permits limited resection of only hypersecreting glands. We report the outcome of this operative approach. METHODS: Fifteen consecutive patients with FIHPT underwent limited parathyroidectomy with resection guided by intact parathyroid hormone secretion in 2 university centers. Patients were followed up postoperatively for serum calcium and intact parathyroid hormone levels. RESULTS: With an operative success of 93%, 14 patients had only single-gland excision and 80% had unilateral neck exploration. All initial patients had their hypercalcemia corrected. In 4 reoperations, permanent hypoparathyroidism occurred in 2 patients. One recurrence was observed in 40 (8-122) months of follow-up. CONCLUSION: Limited parathyroidectomy allows successful single-gland excision in many patients with FIHPT, thus decreasing the risk of hypoparathyroidism. In these patients, a low incidence of hypoparathyroidism may be preferable to the possibility of late recurrence.

Adolescent↗
PubMed1999

Correlation of parathyroid scanning and anatomy in 261 unselected patients with sporadic primary hyperparathyroidism.

BACKGROUND: Despite abundant literature on parathyroid scanning with technetium 99m-labeled cationic complexes, comprehensive clinical reports that unequivocally correlate scanning findings with the anatomy of parathyroid glands in extensive and homogeneous cohorts of patients are lacking. METHODS: We analyzed the records of patients with sporadic primary hyperparathyroidism who had had a preoperative scan with either 99mTc-labeled sestamibi or 99mTc-labeled tetrofosmin at our institution and who were cured after a bilateral surgical neck exploration procedure. RESULTS: In 261 patients, 710 normal and 347 abnormal glands (1494 +/- 2626 mg), including 15 glands within the mediastinum, were identified. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of scanning were 82%, 98%, 91%, 94%, and 94%, respectively, in 197 patients with uniglandular disease and 53%, 98%, 98%, 60%, and 72%, respectively, in 64 patients with multiglandular disease. False-positive uptakes were encountered in 17 patients (7%), 3 false-positive uptakes being within the mediastinum. If the unilateral approach had been followed, guidance with preoperative scanning would have significantly increased the number of effective unilateral neck exploration procedures (164 patients (63%) vs 78 patients (30%); P < .001). One abnormal gland would also have been neglected in 28 patients (11%). CONCLUSIONS: Preoperative scanning would limit neck exploration procedures in two thirds of patients with sporadic primary hyperparathyroidism but may also increase the risk of failure in the most challenging cases.

Adult↗
PubMed1999

The validity of quick intraoperative parathyroid hormone assay: an evaluation in seventy-two patients based on gross morphologic criteria.

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism has conventionally required identification of all parathyroid glands with excision of grossly abnormal glands. Using this approach, cure rates exceed 95%. Directed cervical exploration has been advocated using quick intraoperative parathyroid hormone (QPTH) assay with preoperative localization. Adoption of this approach requires validation of the accuracy of QPTH assay. METHODS: Patients with primary hyperparathyroidism undergoing bilateral neck exploration during a 31-month period were reviewed. Uniglandular (UGD) or multiglandular (MGD) disease was determined by gross morphologic criteria. QPTH assays were performed before skin incision and at 5, 10, and 20 minutes after excision of each abnormal gland. A 10-minute QPTH decrease of 50% from baseline levels indicated curative excision. These data were not used to guide extent of exploration or tissue resection. RESULTS: Of 72 patients, 55 (76%) had UGD and 17 (24%) had MGD. QPTH assay accurately predicted the disease state in 89%. Four (7%) UGD patients did not have an appropriate QPTH decline at 10 minutes. Four (24%) MGD patients had an inappropriate QPTH decline at 10 minutes. CONCLUSIONS: Using QPTH guided exploration, 6% (4 of 72) of patients would undergo unnecessary extended exploration and 6% (4 of 72) (95% CI, 1% to 13%) may require reoperation for unidentified MGD. These results validate the accuracy of QPTH assay.

Calcium↗
PubMed2003

New components of the honey bee (Apis mellifera L.) queen retinue pheromone.

The honey bee queen produces pheromones that function in both releaser and primer roles such as attracting a retinue of workers around her, attracting drones on mating flights, preventing workers from reproducing at the individual (worker egg-laying) and colony (swarming) level, and regulating several other aspects of colony functioning. The queen mandibular pheromone (QMP), consisting of five synergistic components, is the only pheromone chemically identified in the honey bee (Apis mellifera L.) queen, but this pheromone does not fully duplicate the pheromonal activity of a full queen extract. To identify the remaining unknown compounds for retinue attraction, honey bee colonies were selectively bred to have low response to synthetic QMP and high response to a queen extract in a laboratory retinue bioassay. Workers from these colonies were then used in the bioassay to guide the isolation and identification of the remaining active components. Four new compounds were identified from several glandular sources that account for the majority of the difference in retinue attraction between synthetic QMP and queen extract: methyl (Z)-octadec-9-enoate (methyl oleate), (E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-en-1-ol (coniferyl alcohol), hexadecan-1-ol, and (Z9,Z12,Z15)-octadeca-9,12,15-trienoic acid (linolenic acid). These compounds were inactive alone or in combination, and they only elicited attraction in the presence of QMP. There was still unidentified activity remaining in the queen extract. The queen therefore produces a synergistic, multiglandular pheromone blend of at least nine compounds for retinue attraction, the most complex pheromone blend known for inducing a single behavior in any organism.

Animals↗
PubMed2002

99mTc-MIBI radio-guided minimally invasive parathyroidectomy: experience with patients with normal thyroids and nodular goiters.

The surgical approach to primary hyperparathyroidism (HPT) is changing. In patients with a high probability to be affected by a solitary parathyroid adenoma (PA), a unilateral neck exploration (UNE) or a minimally invasive radio-guided surgery (MIRS) using the intraoperative gamma probe (IGP) technique have recently been proposed. We investigated the role of IGP in a group of 84 patients with primary HPT who were homogeneously evaluated before surgery by a single-day imaging protocol including 99mTcO4/MIBI subtraction scan and neck ultrasound (US) and then operated on by the same surgical team. Quick parathyroid hormone (QPTH) was intraoperatively measured in all cases to confirm successful parathyroidectomy. In 70 patients with scan/US evidence of a single enlarged parathyroid gland (EPG) and with a normal thyroid gland, MIRS was planned. In the other 14 patients, the IGP technique was utilized during a standard bilateral neck exploration (BNE) because of the presence of concomitant nodular goiter (11 cases) or multiglandular disease (MGD) (3 cases). The IGP technique consisted of the following: (1) in the operating room, a low 99mTc-MIBI dose (37 MBq) was injected intravenously during anesthesia induction; (2) subsequently, the patient's neck was scanned with the probe by the surgeon to localize the cutaneous projection of the EPG; (3) in patients who underwent MIRS, the EPG was detected intraoperatively with the probe and removed through a small, 2 to 2.5 cm skin incision; (4) radioactivity was measured on the EPG both in vivo and ex vivo, the thyroid, the background and the parathyroid bed after EPG removal. In patients with concomitant nodular goiter, the radioactivity was also measured on the thyroid nodules. Surgical and pathologic findings were consistent with a single PA in 78 patients, parathyroid carcinoma in 2, and MGD in 4. MIRS was successfully performed in 67 of the 70 patients (97.7%) in whom this approach was planned. It must be pointed out that the IGP technique was particularly useful in detecting the PAs located in ectopic site (5 in the upper mediastinum, 2 at the carotid bifurcation) and deep in the neck (6 in the paratracheal/paraesophageal space). Moreover, MIRS was also successfully performed in the seven patients who had undergone previous parathyroid or thyroid surgery. In the other 3 of 70 patients (4.3%), a conversion to BNE was required because a parathyroid carcinoma (2 cases) and a MGD (1 case) were diagnosed during surgical intervention. It is worth noting that in this latter patient affected by MGD, in contrast with the other patients from our series, QPTH remained elevated after the removal of the preoperatively visualized EPG suggesting the persistence of occult hyperfunctioning parathyroid tissue, and another contralateral EPG was found at BNE. Regarding the group of patients in whom a BNE was planned, the IGP helped the surgeon to localize a supernumerary EPG ectopic in the thymus in a patient with MGD, and to localize a PA ectopic to the right carotid bifurcation in a patient with nodular goiter. However, it has to be pointed out that it was difficult for the surgeon to differentiate intraoperatively with the probe the radioactivity of the EPG from that of thyroid nodule(s) in the other 10 patients with HPT with a concomitant nodular goiter, particularly in 6 patients in whom 99mTc-MIBI uptake was higher in thyroid nodule(s) than in EPG. On the basis of these data we can conclude that: (1) in patients with primary HPT with a high scan/US probability to be affected by a single PA and with a normal thyroid gland, IGP appears to be an useful technique with the aim of performing MIRS; (2) a 99mTc-MIBI dose as low as 37 MBq appears to be adequate to successfully perform MIRS; (3) the measurement of QPTH is strongly recommended in patients with HPT selected for MIRS to confirm complete removal of hyperfunctioning parathyroid tissue; (4) MIRS can be useful also in patients with HPT who previously received parathyroid/thyroid surgery with the aim of limiting surgical trauma at reoperation and minimizing the related risk of complications; (5) with the exception of PA located in ectopic sites, IGP does not seem to be a recommendable technique in patients with HPT concomitant nodular goiter.

Adenoma↗
PubMed2003

Distinct localization of MUC5B glycoforms in the human salivary glands.

Salivary mucins, encoded by the MUC5B gene, make up a heterogeneous family of molecules, which are secreted by several glands, including the submandibular, sublingual, and palatine glands. Previous studies have shown that heterogeneity in the salivary mucin population is related to its multiglandular origin. In the present study we address the question to what extent the mucin (MUC5B) population from a single human salivary gland is made up of different glycoforms. Using monoclonal antibodies to defined protein and sulfated carbohydrate epitopes specific to MUC5B, we conduct an immunohistochemical study of different salivary gland types, including submandibular, sublingual, and labial glands. In all tissues studied we found a mosaic expression pattern of sulfo-Lewis a antigen, recognized by mAb F2, which in salivary glands is exclusively present on MUC5B. On the other hand, mucous acini were uniformly labeled by mAb EU-MUC5Bb, evoked against a peptide-stretch of the tandem repeat region of MUC5B. Double staining with both antibodies confirmed the presence of MUC5B-positive/sulfo-Lewis a-positive cells, as well as MUC5B-positive/sulfo-Lewis a-negative cells within one glandular unit. These results indicate that one and the same salivary gland synthesizes different MUC5B glycoforms.

Antibodies, Monoclonal↗
PubMed2000

Direct, minimally invasive adenomectomy for primary hyperparathyroidism: An alternative to conventional neck exploration?

OBJECTIVE: To evaluate the feasibility and efficacy of a direct, minimally invasive adenomectomy (MIA) as an alternative to conventional neck exploration (CNE) in patients with primary hyperparathyroidism. SUMMARY BACKGROUND DATA: Because primary hyperparathyroidism is caused by a solitary adenoma in 85% to 90% of patients, a direct adenomectomy through a mini-incision would theoretically suffice whenever an adenoma is correctly localized on preoperative imaging. If effective, a less invasive method could spare the patient an unnecessary bilateral neck exploration, thus saving time and rendering future surgical procedures in the neck less problematic. METHODS: Between October 1994 and October 1998, 110 consecutive patients with biochemically proven primary hyperparathyroidism who were to undergo surgery were enrolled in this study. Ultrasound and spiral CT were routinely performed as standard preoperative imaging modalities in the first series of 65 patients. In the second series of 45 patients, ultrasound was performed as the sole initial modality; it was supplemented by CT only in case of inconclusive test results. If test results were unequivocal (one adenoma), the patient was offered MIA. CNE was performed if the results were equivocal or if multiglandular disease was suspected. RESULTS: Overall, 84 patients were selected for MIA and 26 for CNE. In the first series, 2 MIA procedures (2/51) were converted to CNE because of negative perioperative findings. All 65 procedures resulted in normocalcemia. In the second series, all but five (4/33 MIAs, 1/12 CNEs) resulted in normocalcemia. A reexploration (CNE) was performed in three patients, resulting in normocalcemia after resection of a second or third adenoma. Two patients are still awaiting reexploration. In both series together, 78 of the 110 patients were successfully treated with MIA and spared CNE. CONCLUSION: MIA is a safe and effective alternative to CNE that may replace CNE in approximately two thirds of all patients.

Adenoma↗
PubMed2004

Progress in the operative management of sporadic primary hyperparathyroidism over 34 years.

BACKGROUND: Progress in the diagnosis, localization of abnormal parathyroids, and intraoperative management of primary hyperparathyroidism has been observed over the past 34 years. The goal of this study is to report the outcome of patients undergoing 2 different operative approaches in a single institution, showing the evolution of surgical management of sporadic primary hyperparathyroidism (SPHPT). METHODS: Parathyroidectomy was performed in 890 (827 initial, 63 reoperative) patients with SPHPT using 2 different approaches: traditional bilateral neck exploration (BNE, n = 396) or limited parathyroidectomy guided by parathormone dynamics (LPX, n = 494). Seven hundred eighteen patients (335 BNE, 383 LPX) followed > or = 6 months or identified as operative failures were studied. Operative failure is defined as hypercalcemia and high intact (1-84) parathyroid hormone molecule (iPTH) within 6 months after operation. Successful parathyroidectomy is normocalcemia for 6 months; hypercalcemia and elevated iPTH after this time is recurrent hyperparathyroidism. RESULTS: There were 20 (6%) of 335 operative failures in the BNE group and 11 (3%) of 383 failures in the LPX group (P = 0.04). The incidence of multiglandular disease (MGD) determined by gland size (10%) versus hormone hypersecretion (3%) was statistically different (P < 0.001). Since most of the recurrences occurred later than 30 months, the incidence of recurrent hyperparathyroidism in patients followed for longer than 2.5 years was 4% (11/287) in the BNE group (average, 11.5 years) and 3% (5/183) in the LPX group (average, 4.2 years). CONCLUSION: LPX, with its reported advantages of minimal dissection, shorter operative time, and use in ambulatory settings, compares favorably with the traditional BNE. Parathyroidectomy guided by parathormone dynamics has an improved success rate and should be considered as a standard operative approach in SPHPT.

Calcium↗
PubMedDate not supplied

Levels of trimethoprim and sulphamethoxazole in human seminal plasma.

An oral dose of the combination trimethophim/sulphamethoxazole (160 and 800 mg, respectively) gave concentrations of trimethoprim in seminal plasma that were equal to or higher than that in blood plasma 2--4 hours after intake. Trimethoprim was excreted by both the prostate and seminal vesicles. With a trimethoprim resistant strain it was possible to demonstrate in three patients with subclinical prostatitis that the concentrations of sulphamethoxazole two hours after the oral intake were 20, 26, and 74 microgram/ml in the blood plasma, respectively. This study was carried out on patients who had been on treatment for 2--5 days prior to investigation. In view of published reports on the pH of the fluids from the human prostate and seminal vesicles, respectively, and the importance of the hydrogen ion concentrations for the excretion of lipid soluble substances into the prostatic fluid it was unexpected to find similar concentrations of trimethoprim in both the "prostatic" and "vesicular" fluids. Preliminary studies on the pH of these fluids indicated, however, that they were in the same order of magnitude, i.e. 7.5 to 8.0. The multiglandular origin of the human seminal plasma must be considered in all studied concerning the excretion of drugs into the semen. Many problems related to the excretion of drugs, e.g. organ specificity, kinetics, and influence on organ and spermatozoal functions remain to be investigated.

Administration, Oral↗
PubMed2005

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing.

INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.

Australia↗
PubMed1977

Diagnosis of hyperparathyroidism.

States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years.

Bone Diseases↗