Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene.

BACKGROUND: Familial isolated primary hyperparathyroidism (FIHP) is an autosomal dominant disorder that can represent an early stage of either the multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) syndromes; alternatively, the condition can be caused by an allelic variant of MEN1 or HRPT2 (hyperparathyroidism 2 gene), or caused by a distinct entity involving another locus. We have explored these possibilities in a patient with primary hyperparathyroidism, whose mother had a history of renal calculi and primary hyperparathyroidism. INVESTIGATIONS: Serum biochemistry and radiological investigations for primary hyperparathyroidism, MEN1 and HPT-JT, and genetic testing for MEN1 and HRPT2 mutations were undertaken. DIAGNOSIS: FIHP with primary hyperparathyroidism as the sole endocrinopathy due to a previously unreported heterozygous missense germline MEN1 mutation, Tyr351Asn. In addition, another unreported heterozygous missense germline MEN1 mutation, Trp220Leu, was identified in an unrelated male patient with FIHP, whose mother and sister also had primary hyperparathyroidism. DNA from a parathyroid tumor from the sister revealed a loss of heterozygosity in which the mutant allele was retained. This is consistent with Knudson's 'two-hit' model of hereditary cancer and a tumor suppressor role for MEN1 in FIHP. MANAGEMENT: The patient underwent parathyroidectomy and has remained normocalcemic over a follow-up period of 6 years. The other four patients have remained normocalcemic for a follow-up period of 4-15 years following parathyroidectomy. None has developed abnormalities of the MEN1 syndrome, providing further support that FIHP is a distinct genetic variant of the MEN1 syndrome.

Clinical outcomes and fiscal consequences of bilateral neck exploration for primary idiopathic hyperparathyroidism without preoperative radionuclide imaging or minimally invasive techniques.

BACKGROUND: Radionuclide imaging-directed, minimally invasive parathyroid operation is promoted in the surgical literature and public domain as the fastest, most successful, and cheapest means of treating primary idiopathic hyperparathyroidism. The validity of these claims is unproven. This study reviews the treatment outcome results of a large series of patients treated with standard parathyroid operation without preoperative localization studies. Cost comparisons are made between this series and previous reports of selected patients in whom preoperative radionuclide imaging preceded minimally invasive parathyroid operation. METHODS: Diagnosis, treatment, and outcome data for 688 consecutive patients undergoing first neck exploration for primary idiopathic hyperparathyroidism were prospectively collected. All patients in our series underwent standard bilateral neck exploration without preoperative localization studies. Intraoperative methylene blue was used to aid identification of all parathyroid glands. Surgical findings, pathological diagnosis, operative time, length-of-stay, and treatment success data were collected. Cost data were calculated for our series using the identical calculations used in previous reports. Our outcome and calculated cost data were compared with previous reports by centers advocating scan-directed, minimally invasive parathyroid operation. RESULTS: Of 2,752 predicted total glands, 2,520 (91.6%) were identified using standard neck exploration without radionuclide localization studies. Single adenoma, with at least 1 normal gland, was found in 542 patients (78.8%), with 8 in a fifth gland. Multiple-gland hyperplasia was identified in 98 patients (14.2%) and of these 22 (3.2%) were double adenomas. Ten patients had parathyroid carcinoma (1.5%), and all received definitive surgical treatment during the primary operation. Cure rates were assessed by measurement of normal serum calcium and parathyroid hormone levels at 3 and 12 months after operation, and were 97.7% in our series. Mean operating time for the entire series was 65 minutes, decreased to 35 minutes in patients with single adenomas, and mean recovery room time was 30 minutes. Mean total costs for patients undergoing standard exploration for single adenoma was US dollars 1,107, and increased to US dollars 1,243 when patients with multigland disease, hyperplasia, or malignancy were included. CONCLUSIONS: Our series demonstrates operative times and treatment outcomes with costs that are approximately one-third less than those for scan-directed, minimally invasive operation for primary idiopathic hyperparathyroidism. Thus, claims that scan-directed parathyroid operation is the cheapest, fastest, and most successful means of treatment are not supported by these data.

Utilization of fine-needle aspiration in patients undergoing thyroidectomy at two academic centers across the Atlantic.

Although fine-needle aspiration (FNA) has been accepted as a first-line test in patients with thyroid masses, the utilization of FNA varies even among experienced surgeons. To determine its utility we compared FNA results, pathology, and clinical results in patients who underwent thyroidectomy in two major endocrine centers on both sides of the Atlantic: one in the United States (US) and another in the United Kingdom (UK). Between January 1997 and March 1998 a total of 84 patients underwent thyroid surgery at the UK center, and 143 underwent thyroidectomy at the US center. The most common indication for thyroidectomy at the UK center was compressive goiter (CG), whereas follicular neoplasm (FN) was the most common indication at the US center. Bilateral thyroid resections, frozen section utilization, and thyroid cancer surgery were more common at the US center. Thyroidectomy for symptomatic multinodular goiter and Graves' disease was more prevalent at the UK center. Thyroid gland weights were also significantly greater in the UK, indicating a higher incidence of endemic goiter. FNA was more commonly employed in the US center (84% vs. 52%; p < 0.001). Despite the differing utilization of FNA at these major endocrine centers, only one thyroid cancer at each institution was not detected preoperatively (both patients had a benign FNA result). Therefore there were no clinically significant thyroid cancers found in patients who did not undergo preoperative FNA. In conclusion, FNA appears to be differentially utilized depending on the incidence of endemic goiter, Graves' disease, and thyroid cancer. In this series no clinically significant thyroid cancers were found in patients who did not undergo preoperative FNA. Therefore in the hands of experienced thyroid surgeons, FNA can be utilized selectively based on the clinical presentation.