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PubMed2005

Are frozen sections useful and cost-effective in the era of intraoperative qPTH assays?

BACKGROUND: Since intraoperative quick parathormone (IOqPTH) assays are available, the role of frozen sections (FS) during parathyroid exploration has become questionable. This study compares the results of FS and IOqPTH in primary hyperparathyroidism (pHPT). METHODS: FS and IOqPTH assays were performed in 102 patients who underwent bilateral neck explorations or targeted parathyroidectomy for pHPT. The operation was considered complete when both an IOqPTH drop >50% and a FS diagnosis of parathyroid adenoma were obtained. RESULTS: Cure was achieved in all patients. Potential pitfalls for successful operation were encountered in 14 patients with multiglandular diseases and in 4 patients who had nonparathyroid tissue removed. FS correctly predicted the definitive histologic diagnosis with an accuracy of 81%. FS failures potentially misguided the operative therapy in 19% (14 insufficient explorations and 5 unnecessarily prolonged explorations), while IOqPTH identified all potential pitfalls and correctly guided the operative strategy, suggesting further exploration, in 100% of cases (P < .0001). After bilateral neck exploration, FS and IOqPTH correctly guided operative strategy in 86% and 100% of cases, respectively (P < .05), but both techniques were never indispensable, because potential pitfalls were already evident by macroscopic intraoperative appearance. The turnaround time and costs for IOqPTH were lower (P < .001). CONCLUSIONS: The role of FS should be reconsidered, since it can misguide the operative strategy. IOqPTH is indispensable for a focused approach and, although unnecessary in bilateral neck exploration, is more useful and cost-effective than FS.

Adult↗
PubMed2002

Independent genetic events associated with the development of multiple parathyroid tumors in patients with primary hyperparathyroidism.

Multiple parathyroid tumors, as opposed to hyperplasia, have been reported in a subset of patients with sporadic primary hyperparathyroidism (PHPT). It is not clear whether these multiple tumors are representative of a neoplastic process or whether they merely represent hyperplasia that has affected the parathyroid glands differentially and resulted in asynchronous growth. The molecular genetic techniques of comparative genomic hybridization (CGH), loss of heterozygosity (LOH), and MEN1 mutation analysis were performed on a series of five patients with multiglandular PHPT, each of which had two parathyroid tumors removed. Analysis of these multiple parathyroid tumors from patients with PHPT revealed that independent genetic events were associated with the development of a subset of these tumors. The DNA sequence copy number changes, identified by CGH analyses, either involved different chromosomal regions in the paired glands of a patient (two patients), or those regions implicated in one gland were not changed in a second gland from the same patient (two patients). Each of the three patients exhibiting LOH demonstrated different changes between the paired glands. Where LOH was detected in one gland from a patient, the other gland from the same patient either exhibited no allelic loss or the loss detected was in another region. Each of the three tumors exhibiting LOH at 11q13 was found to contain a somatic MEN1 mutation in the remaining allele, however these mutations were not present in the germline or in the paired gland from the same patient. Although it is possible that a separate series of genetic changes has arisen randomly in two separate glands within the same individual, it seems more likely that the development of these multiple tumors has arisen because of the involvement of other unknown factors. These factors may be genetic [such as the involvement of one or more germline mutations in an unknown low-penetrance gene(s), germline mosaicism or alterations in calcium-sensing receptor gene(s)], epigenetic, physiological, or environmental.

Cell Transformation, Neoplastic↗
PubMed1996

Evaluation of single isotope technetium 99M-sestamibi in localization efficiency for hyperparathyroidism.

BACKGROUND: Regardless of surgical effectiveness, ongoing activity in parathyroid localization in hyperparathyroidism (HPT) is an established enterprise. Sestamibi (MIBI), the most recent new modality, is being assessed in this regard. METHODS: Twenty mCI of 99 TC Sestamibi was administered intravenously in patients with prospective HPT. Images were assessed by pinhole and full-field gamma camera at 20 minutes and 2 hours. Dual-phase one isotope only was utilized. Patients were then studied for pathology and MIBI correlation. RESULTS: Sixty-three cases underwent MIBI scanning, 50, or 79%, of which were due to a single adenoma. Sensitivity showed in 41 of 50 adenomas and was 82% correct. Quadrant localization was 97%. Eleven patients showed hyperplasia with MIBI sensitivity of 82% on a case basis but only 31% for multiglandular disease. Overall MIBI sensitivity is 80%. One false-positive and one true-negative case were observed. All patients achieved eucalcemia. No operative morbidity of significance occurred. CONCLUSION: Scanning with 99M Sestamibi dual-phase technique is the preferred mode of parathyroid localization in current practice. It is of assistance in primary HPT, essential in recurrent HPT, and of use in ectopic gland detection. It can support surgical intervention in the marginal HPT patient. Scanning still requires bilateral exploration for complete assessment.

Adenoma↗
PubMed1996

Preoperative parathyroid localization with sestamibi.

PURPOSE: Results of noninvasive preoperative parathyroid localization with technetium99m-labeled sestamibi are reported in a series of 51 patients. PATIENTS AND METHODS: Forty-four patients had hyperparathyroidism surgically treated for the first time and seven patients underwent reexploration for recurrent or persistent hyperparathyroidism. Preoperative scintigraphy with sestamibi was performed in all patients before surgical exploration. Results of the radionuclide studies were compared with surgical and pathologic findings. RESULTS: Twenty-six patients had solitary adenomas. All 26 were localized preoperatively by the scans. Among 18 patients with multiglandular pathology, 69 pathological glands were found at surgery. Thirty-six of these glands, in 15 patients, were localized by the scans. Among the 7 patients evaluated after failed exploration or recurrent hyperparathyroidism, 7 pathologic glands were found, of which 6 were correctly localized by the scan. Ectopic lesions in 2 patients were correctly localized by the scan. CONCLUSIONS: The authors conclude that sestamibi parathyroid localization is an effective method for preoperative parathyroid localization, with accuracy exceeding that of other noninvasive studies.

Adenoma↗
PubMed1997

Effectiveness and safety of 100 consecutive parathyroidectomies.

BACKGROUND AND METHODS: In order to evaluate the indications for operation for patients with primary hyperparathyroidism, prospective information was gathered on 100 consecutively operated patients from 1991 to 1996. A standard evaluation for outcomes and patient satisfaction was instituted. Patients consisted of 73 women and 27 men. Major symptoms existed in 48 patients, and 52 patients were referred to as "asymptomatic" because they fit the National Institutes of Health Consensus Development Conference Statement with abnormal laboratory values. The pathology was 94 single adenomas, 4 double adenomas, and 2 cases of hyperplastic multiglandular disease. RESULTS: All 100 patients had abnormal parathyroids removed, resulting in normocalcemia in 97. Three patients had persistent hypercalcemia until a second operation removed additional abnormal parathyroids, resulting in normocalcemia. No operative complications or mortality occurred. Overnight stay occurred in 88 patients. During long-term follow-up of patients, only 2 developed recurrent hyperparathyroidism. When asked whether the operation improved their health, 94% of patients with major symptoms and 72% of asymptomatic patients responded affirmatively. CONCLUSION: Parathyroidectomy is an efficient and safe operation with excellent normalization of serum calcium and a high rate of patient satisfaction.

Adolescent↗
PubMed1998

Pediatric thyroid nodules: management in the era of fine needle aspiration.

BACKGROUND/PURPOSE: Thyroid nodules are rare in children. The need to uncover malignancy is the most challenging dilemma in management. The aim of this report was to determine whether management of pediatric thyroid nodules has changed in the era of fine-needle aspiration (FNA) cytology. METHODS: Twenty-four children with thyroid nodules comprised the study group. Demographic characteristics, clinical manifestations, imaging results, FNA cytology results, surgical therapy, complications, and pathological reports were reviewed retrospectively. FNA cytology results were categorized as either benign, malignant, suspicious, or insufficient. RESULTS: Girls outnumbered boys (five to one) with a mean age of 14.9 years. Nineteen nodules were benign and five malignant. Malignancy was characterized by localized tenderness, multiglandular appearance, and fixation to adjacent tissues. Ultrasound scans and nuclear scans gave no clue toward management because cystic, hot, and warm nodules figured among malignant cases. FNA in 18 children achieved 80% accuracy, 60% sensitivity, 90% specificity, 75% positive, and 81% negative predictive value. Physical examination findings, persistence of the nodule, and progressive growth decided for surgery in most children. CONCLUSIONS: FNA is a safe adjunctive test that plays a minor role in the decision to withhold surgery. Its greatest strength is to resolve, in case of suspicious or malignant cytology, that a more radical procedure will be needed. Clinical judgement as determined by serial physical findings continues to be the most important factor in the management of thyroid nodules in children.

Adenocarcinoma, Follicular↗
PubMed2003

Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1.

BACKGROUND: Hyperparathyroidism in patients with multiple endocrine neoplasia type 1 (MEN1) is characterized by multiglandular disease and a propensity for recurrence after parathyroidectomy (PTx). This study analyzes outcomes of a cohort of MEN1 patients undergoing initial PTx at one institution. METHODS: Between April 1960 and September 2002, 92 patients with MEN1 underwent initial PTx. Outcomes were analyzed based on extent of parathyroid resection. RESULTS: Fourteen percent had 2.5 or fewer glands resected, 69% had subtotal PTx, and 17% had total PTx (88% with immediate autotransplantation). The initial surgical cure rate was 98%. Excluding 6 patients lost to follow-up, 33% have developed recurrent hyperparathyroidism (in 46% after < or =2.5 PTx, in 33% after subtotal, and in 23% after total PTx). Median recurrence-free survival was not statistically significantly different between subtotal versus total PTx, but it was longer for subtotal and total PTx compared with lesser resection (16.5 vs 7.0 years, respectively, P=.03). The incidence of severe hypoparathyroidism was 46% after total versus 26% after subtotal PTx. CONCLUSIONS: Subtotal and total PTx result in durable control of MEN1-associated hyperparathyroidism and have longer recurrence-free intervals compared with lesser resection. The high incidence of severe hypoparathyroidism after total PTx suggests that subtotal PTx is the initial operation of choice in this setting.

Adolescent↗
PubMed1995

Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary.

BACKGROUND: An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Adolescent↗
PubMed1996

Intraoperative parathyroid hormone monitoring as an adjunct to parathyroidectomy.

BACKGROUND: Parathyroidectomy has a success rate of greater than 95% in the hands of experienced surgeons. To maintain this result in a more cost-effective way, intraoperative monitoring of intact parathyroid hormone (iPTH) has been used to decrease operative times. This technique signals when all hyperfunctioning tissue has been excised or when further dissection is necessary. METHODS: Eighty-nine consecutive patients with hyperparathyroidism had plasma samples measured for iPTH levels during parathyroidectomy. Nine patients had previous neck explorations. Perioperative iPTH measurements using immunochemiluminescent assays with a turnaround time of 10 minutes were done after excision of each suspected abnormal parathyroid gland. RESULTS: All patients except one returned to and maintained normal calcium levels during the follow-up period of 8 months (range, 1 to 25 months). Prediction of postoperative calcium levels by means of quick immunochemiluminescent assay has a sensitivity of 97%, specificity of 100%, and an overall accuracy of 97%. Specific influence on surgical judgment was noted in four patients with multiglandular disease, in seven with difficult localization problems, and in one patient in whom the hyperfunctioning parathyroid tissue was not recognized. Monitoring the plasma iPTH levels during parathyroidectomy directly aided the surgeon's operative approach in these 12 patients. CONCLUSIONS: Intraoperative iPTH assay is useful with predictive accuracy of 97%. It influenced or changed the operative approach in 13% of patients.

Calcium↗
PubMed1987

Natural history of treated primary hyperparathyroidism.

A follow-up study of patients operated on for primary hyperparathyroidism revealed that recurrent hypercalcemia is uncommon in patients with solitary adenoma, but common in patients with multiglandular disease. The result of parathyroidectomy on the different symptoms of primary hyperparathyroidism is good. On the other hand, even after successful surgery, patients with primary hyperparathyroidism have poorer health than controls, and they also have a higher mortality rate. Most of the deaths in the primary hyperparathyroidism group are caused by cardiovascular disease. The effect of the preoperative serum calcium level on the later state of health is evident.

Adult↗
PubMed2000

Usefulness of quick intraoperative measurements of intact parathyroid hormone in the surgical management of hyperparathyroidism.

We investigated the use of quick measurement of intraoperative intact parathyroid hormone (I-PTH) to predict the outcome of parathyroidectomy. We examined intraoperative monitoring of I-PTH in 34 consecutive primary hyperparathyroidism (pHPT) patients operated on between April and December 1999. The average patient age was 56 +/- 13 years, and all but one were women. Four had a history of thyroidectomy. Blood samples were drawn before excision of enlarged parathyroid gland(s) and at 2, 5, 10, and 15 minutes afterward. Plasma I-PTH was measured by a two-site immunochemiluminometric assay. Twenty-three patients were shown to have single gland disease, and ten had multiglandular disease. All patients, except one, underwent successful parathyroidectomies. The plasma I-PTH value 15 minutes after removal of enlarged gland(s) had dropped to 26 +/- 10% of pre-excision I-PTH value. In one patient with a previous history of thyroidectomy for thyroid papillary cancer, no gland enlargement was found in the area where the lesion had been suggested by both ultrasonography and 99mTc sestamibi scanning. In this case, intraoperative measurements of I-PTH in the bilateral internal jugular veins identified an ectopic parathyroid tumor, which was successfully removed. We conclude that quick measurement of intraoperative I-PTH is a valuable tool for decision-making, especially for reoperative parathyroid surgery, for patients with previous history of thyroidectomy, and for patients in whom unilateral neck exploration or a single-gland approach is scheduled based upon preoperative localization.

Female↗
PubMed2002

Intraoperative quick parathyroid hormone assay in the surgical management of hyperparathyroidism.

Intraoperative quick parathyroid hormone (QPTH) assay is claimed to prevent failure during parathyroidectomy for hyperparathyroidism. The causes of operative failure have included multiglandular disease, ectopic parathyroid glands, supernumerary parathyroid glands, errors in frozen section evaluations, and missed diagnosis. A QPTH assay has been recognized as a useful method of determining whether hyperfunctioning tissues have been completely excised. However, an intraoperative QPTH assay may fail to detect the presence of double parathyroid adenomas. Use of this assay in conjunction with preoperative and intraoperative localization studies has led to the advocacy of more directed cervical procedures, such as limited, video-assisted, and endoscopic parathyroidectomy.

Biological Assay↗
PubMed2002

Video-assisted parathyroidectomy.

A parathyroid tumor is not larger than other tumors, so minimally invasive surgery has long been a major focus of parathyroid surgeons. Improving endoscopic instruments has facilitated the recent changes in approaches to parathyroid surgery. Endoscopic parathyroidectomy is developed in a totally closed space with CO2 gas insufflation. This method has a risk of complications, such as extensive emphysema or hypercarbia. Minimally invasive video-assisted parathyroidectomy (MIVAP) has greater safety, low cost, easy procedure and flexibility in changing the working space including conversion to open method when compared with endoscopic parathyroidectomy. MIVAP can be performed with only a 1-1.5-cm small incision on the neck. MIVAP is indicated in the patient with parathyroid adenoma or renal hyperplasia that is defined preoperatively using ultrasonography and 99mTc-methoxyisobutylisonitrile (MIBI) scan. Furthermore, the radio-guided technique using nuclear navigation after preoperative administered MIBI is being developed. This method is so useful during MIVAP that we combined MIVAP and radio-guided surgery to develop minimally invasive radio-guided and video-assisted parathyroidectomy (MIRVAP). After injection of 600 MBq of MIBI, intraoperative nuclear mapping was performed using a hand-held gamma probe. Then we expected to find swollen parathyroid tumor at surgery when radioactivity at a level relatively higher than background was found. Following this mapping result, MIVAP was started and succeeded. The radio-guided technique is also indicated for open parathyroidectomy (radio-guided open parathyroidectomy, RGOP) in multiglandular disease (MGD) when it was not possible to identify those lesions completely, for instance in asymmetric hyperplasia, such as multiple endocrine neoplasia (MEN) 1. In conclusion, MIVAP is beneficial for minimal invasiveness and cosmesis. Furthermore, radio-guided parathyroidectomy (MIRVAP and RGOP) is more useful and feasible. Improvement of endoscopic instruments and modification of the dose of MIBI administered might facilitate treating more cases by MIRVAP instead of RGOP.

Animals↗
PubMed1998

Measurement of parathyroid hormone in patients with primary hyperparathyroidism undergoing first and reoperative surgery.

BACKGROUND: The distinction between solitary parathyroid adenoma and hyperplasia can sometimes be difficult during surgery for primary hyperparathyroidism (pHPT), especially in patients who have undergone previous thyroid or parathyroid surgery. The use of intraoperative parathyroid hormone (PTH) monitoring as a possible diagnostic tool was therefore investigated. METHODS: Intraoperative levels of PTH were measured in 119 patients during 121 operations (including 14 reoperations) for pHPT. The mean(s.d.) preoperative serum calcium level was 2.79(0.21) mmol/l. Blood samples were drawn before, and at 5 and 15 min after, excision of the first enlarged parathyroid gland. PTH was analysed electively in 61 patients and on-line by a modified assay for intact PTH in 48 patients. Both procedures were used in ten patients. RESULTS: The mean(s.d.) decline in PTH concentration in 101 patients with primary exploration due to solitary adenoma was 63(17) per cent after 5 min (n=84) and 83(10) per cent after 15 min. The patients with primary exploration because of multiglandular disease (n=6) were correctly predicted not to have parathyroid adenoma. CONCLUSION: Measurement of PTH levels during surgery for pHPT is a highly sensitive method for differentiating between single and multiple gland disease. The on-line monitoring of PTH is clinically useful in patients who have undergone previous neck surgery. Its role in pHPT surgery at primary exploration should be evaluated in prospective trials.

Adenoma↗
PubMed1998

Radionuclide scanning in parathyroid diseases.

BACKGROUND: New radionuclide agents and scanning procedures have markedly improved preoperative parathyroid gland localization. The aim of this review was to evaluate the results of parathyroid scanning and to clarify its current place in the clinical management of parathyroid diseases. METHODS: The literature describing the different radioisotopes and available scanning techniques was analysed and their clinical outcome in various parathyroid diseases was evaluated. RESULTS: Using 99mTc-radiolabelled sestamibi or other 9mTc-labelled cationic complexes, parathyroid scintigraphy detects 87 per cent of solitary adenomas (n=894), 55 per cent of abnormal glands in patients with multiglandular disease (n=303) and 75 per cent of persistent or recurrent lesions in patients with previous neck surgery (n=240). If necessary, three-dimensional imaging techniques can clarify the spatial localization of an ectopic uptake focus. The positive predictive value of the available scanning procedures is over 95 per cent, but false-positive uptake may be encountered. CONCLUSION: Radionuclide parathyroid gland scanning with 99mTc-labelled cationic complexes is the initial non-invasive method of choice for preoperative parathyroid gland localization in patients at special risk and/or with previous neck exploration. While scanning has also been proposed to facilitate parathyroidectomy, there is no objective evidence to support its routine use before a first-time surgical procedure.

False Positive Reactions↗
PubMed1998

Clinical profile of primary hyperparathyroidism in adolescents and young adults.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed condition among adolescents and young adults. We review the clinical characteristics of these patients based on our institutional experience. SUBJECTS: Patients aged 12-28 years treated for PHPT at our institution from 1990 to 1996 were evaluated by a review of medical records and current follow-up data. This consisted of 22 patients (8M:14F), constituting approximately 3% of all patients operated for PHPT during this period. MEASUREMENTS: Serum and urinary calcium concentrations, renal function, and serum intact parathyroid hormone (IPTH) levels were measured in all patients. After biochemical confirmation of diagnosis, the patients completed a questionnaire to evaluate the presence of symptoms and/or conditions associated with PHPT. All the patients underwent parathyroidectomy and their tumour characteristics were evaluated. Surgical outcome was determined by measurements of serum calcium and IPTH levels postoperatively and during long-term follow-up. RESULTS: A third of the patients were diagnosed by routine serum chemistry whereas two-thirds presented with symptoms or conditions associated with hypercalcaemia. Non-specific complaints such as fatigue or exhaustion, and weakness or lethargy constitute the most common findings on questionnaire review. A family history of PHPT was present in only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to 4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young adults (aged 19-28 years) revealed no differences in the clinical, pathological or laboratory profiles, except for a male predominance in adolescent patients. Fifteen patients had resection of one or more adenomas while 7 underwent subtotal parathyroidectomy. Six patients (27%) were reoperated cases, all received primary treatment elsewhere. All patients with benign PHPT were cured surgically, with a median follow-up of 47 months (range 3-77 months). One reoperated patient developed permanent hypocalcaemia. One patient with carcinoma underwent several operations for recurrence; he is now eucalcaemic despite persistent disease at 80 months from diagnosis. CONCLUSIONS: We found a high incidence of multiglandular disease and relatively non-specific symptomatology in our adolescent and young adult patients with primary hyperparathyroidism. In view of the heterogeneous clinical expression noted in young patients, one should consider primary hyperparathyroidism in the differential diagnosis of unexplained non-specific complaints, and perform serum calcium estimations more readily in these subjects. Our experience suggests that primary hyperparathyroidism can be a serious disease with significant morbidity if left untreated, whereas parathyroidectomy provides successful results.

Adolescent↗
PubMed2003

Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant disorder characterized by uniglandular or multiglandular parathyroid tumours that occur in the absence of other endocrine tumours. The disorder may represent either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an allelic variant of MEN1, or a distinct entity involving another locus. We have explored these possibilities in seven families in whom primary hyperparathyroidism occurred as the sole endocrinopathy. METHODS: Seven FIHP families were ascertained and venous blood samples obtained from 35 members (17 affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean (+/- SD) follow-up period in the 17 affected members was 15.06 (+/- 8.83) years. RESULTS: Four heterozygous germline mutations of the MEN1 gene were identified. These consisted of two 4-bp intragenic deletions that would result in prematurely truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. Furthermore, analysis of parathyroid tumour DNA from one individual revealed a loss of the wild-type allele and retention of the mutant allele, consistent with Knudson's 'two-hit' model of hereditary cancer and a tumour suppressor role for MEN1 in FIHP. CONCLUSIONS: Our results provide further support for FIHP being a distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to date indicate that FIHP is associated with a higher frequency of missense MEN1 mutations.

Adenoma↗
PubMed2000

Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism.

UNLABELLED: Calcimimetic NPS R-568 prevents parathyroid hyperplasia in rats with severe secondary hyperparathyroidism. BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in chronic renal insufficiency (CRI) is characterized by multiglandular hyperplasia. METHODS: In this study, we investigated the effects of the calcimimetic NPS R-568 on the parathyroid gland in rats with CRI induced by ligation of the renal arteries and severe secondary HPT induced by dietary phosphorus loading. Six days after surgery, high-phosphorus diet feeding was started, and NPS R-568 was administered to the rats for 56 days either by daily gavage (30 or 100 micromol/kg) or by continuous subcutaneous infusion (20 micromol/kg. day). RESULTS: After 54 days, serum PTH levels in vehicle-treated CRI rats were 1019 vs. 104 pg/mL in sham-operated controls. Infusion of NPS R-568 maintained serum PTH at levels comparable with those of sham-operated controls, whereas daily gavage also prevented much of the increase in CRI controls and decreased PTH levels intermittently in a dose-dependent fashion. Parathyroid gland enlargement was caused predominantly by hyperplasia. Total cell number per kg body wt was 3.5-fold higher in vehicle-treated CRI rats than in sham-operated controls. Both infusion and high-dose gavage of NPS R-568 completely prevented the increase in parathyroid cell number. CONCLUSION: These results demonstrate that the calcimimetic compound NPS R-568 can prevent both the increase in serum PTH levels and parathyroid hyperplasia in rats with CRI and severe secondary HPT. Moreover, these changes occurred despite decreases in serum 1, 25(OH)2D3 and increases in serum phosphate, suggesting a dominant role for the calcium receptor in regulating parathyroid cell proliferation.

Aniline Compounds↗