BACKGROUND AND OBJECTIVE: Surgical neck exploration of the 4 parathyroid glands is quite an aggresive procedure for most patients with primary hyperparathyroidism (PHPT) due to a parathyroid adenoma. Intraoperatory measurement of parathyroid hormone (PTH) seems to be a useful tool for the management of these cases, allowing the use of minimally invasive surgical techniques with a lower morbility. Our aims was to assess the usefulness of PTH intraoperatory measurement for the surgical mananagement of PHPT.PATIENTS AND METHOD: We studied 27 consecutive patients, diagnosed with PHPT secondary to parathyroid adenoma. Localization studies included neck ultrasonography and Tc-MIBI scintigraphy. PTH at the stage of anesthesia induction as well as 5 and 10 minutes after the removal of the adenoma was determined. A PTH decrement greater than 50% at 10 minutes was considered as curative. PTH was measured by an immunoluminometric method (Advantage, Nichols).RESULTS: In all cases, calcium levels were normal 24 hours after the operation, and therefore all them were considered as cured. PTH levels decreased more than 50% in all patients. In one case, PTH levels remained high after the exeresis of a preoperatorely localized lesion. The pathlogic study confirmed that it was a normal parathyroid gland. We then continued the surgical exploration which eventually allowed us to find a contralateral adenoma. A further PTH measurement showed an over 50% decrease. Therefore, PTH was predictive of surgical succes in all 28 measurements.CONCLUSIONS: Intraopertory determination of PTH is useful for the surgical management of PHPT and it could allow the use of minimally invasive surgical techniques.

Background. Only 9 families with familial medullary thyroid carcinoma due to V804M mutation have been reported until now. We describe a large kindred with not only heterozygous but also homozygous members with the V804M mutation. This is, to our knowledge, the first report of a homozygous RET mutation. Methods. Fifty-three members from 4 successive generations of a family with a high level of consanguinity underwent genetic analysis. The pentagastrin provocative test and biochemical screening to rule out either hyperparathyroidism or pheochromocytoma were performed only on gene carriers of the mutation. Results. Twenty-six gene carriers for V804M mutation were identified (4 homozygous and 22 heterozygous). Three of 4 homozygous patients underwent total thyroidectomy. In 1 patient neither medullary thyroid carcinoma nor C-cell hyperplasia was detected, and in another patient only 3 small foci of C-cell hyperplasia were found on the histologic examination. The pentagastrin stimulation test result was within the normal range in all the heterozygous gene carriers and, consequently, thyroidectomy was not indicated. The screening for both hyperparathyroidism and pheochromocytoma was negative in all patients. Conclusions. In the family reported, the V804M mutation in heterozygous patients seems not to be enough to express the full disease. This finding strongly supports the concept of the indolent behavior of V804M RET proto-oncogene mutation. In addition, our results suggest that when counseling for preventive total thyroidectomy, the specific mutation of RET proto-oncogene and also the natural history of the disease within a particular family should be considered. (Surgery 2002;131:509-14.)

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

BACKGROUND:To study distinctive clinical features of pheochromocytoma in the setting of multiple endocrine neoplasia type 2A (MEN 2A) in comparison with sporadic pheochromocytoma.PATIENTS AND METHOD:All patients diagnosed of sporadic pheochromocytoma (n = 29) and in the setting of MEN 2A (n = 16) between 1976 and 1998 in a tertiary hospital were included in the study. The following variables were compared: age at diagnosis, symptoms, presence and characteristics of hypertension, size of the tumor, localization and malignancy. The accuracy of diagnostic tests was also evaluated.RESULTS:The pheochromocytoma associated to MEN 2A had a higher prevalence in our study (35.5%) and the diagnosis was performed earlier than for sporadic pheochromocytoma (29.1 [7.8] vs. 47,5 [10. 9] years; p < 0.001). Other distinctive features in comparison with sporadic pheochromocytoma were: bilaterality (81.25 vs. 3.44%; p < 0. 001), absence of symptoms (44 vs 11%; p < 0.05) and paroxysmal hypertension. Concerning the diagnostic tests, it must be noted the low sensitivity (60%) of vanillylmandelic acid in MEN 2A.CONCLUSIONS:The pheochromocytoma in the setting of MEN 2A is diagnosed at younger age and frequently asymptomatic and bilateral. In view of the high prevalence of MEN 2A in our country, a genetic analysis should be performed in all patients with pheochromocytoma, especially when it is bilateral.

BACKGROUND:There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the type of recurrence (local recurrence or distant metastases).PATIENTS AND METHODS:Thirty-four patients with recurrent DTC recruited in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and 131INa ablation of postsurgical thyroid remnants. The follow-up included Tg measurement and WBS performed in hypothyroid state.RESULTS:Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%. In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By contrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative.CONCLUSIONS:The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.

BACKGROUND: TO study distinctive clinical features of pheochromocytoma in the setting of multiple endocrine neoplasia type 2A (MEN 2A) in comparison with sporadic pheochromocytoma.PATIENTS AND METHOD: All patients diagnosed of sporadic pheochromocytoma (n = 29) and in the setting of MEN 2A (n = 16) between 1976 and 1998 in a tertiary hospital were included in the study. The following variables were compared: age at diagnosis, symptoms, presence and characteristics of hypertension, size of the tumor, localization and malignancy. The accuracy of diagnostic tests was also evaluated.RESULTS: The pheochromocytoma associated to MEN 2A had a higher prevalence in our study (35.5%) and the diagnosis was performed earlier than for sporadic pheochromocytoma (29.1 [7.8] vs. 47,5 [10.9] years; p < 0.001), Other distinctive features in comparison with sporadic pheochromocytoma were: bilaterality (81.25 vs. 3.44%; p < 0.001), absence of symptoms (44 vs 11%; p < 0.05) and paroxysmal hypertension. Concerning the diagnostic tests, it must be noted the low sensitivity (60%) of vanillylmandelic acid in MEN 2A.CONCLUSIONS: The pheochromocytoma in the setting of MEN 2A is diagnosed at younger age and frequently asymptomatic and bilateral. In view of the high prevalence of MEN 2A in our country, a genetic analysis should be performed in all patients with pheochromocytoma, especially when it is bilateral.

BACKGROUND: There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the thype of recurrence (local recurrence or distant metastases).PATIENTS AND METHODS: Thirty-four patients with recurrent DTC recluted in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and (INa)-I-131 ablation of postsurgical thyroid remmants, The follow-up included Tg measurement and WBS performed in hypothyroid state.RESULTS: Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%, In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By constrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative.CONCLUSIONS: The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.

This work attempts to determine if there are differences in protein metabolism in post-surgical patients who receive parenteral nutrition with amino acids plus glucose (G+AA) or conventional gluco-salinal solution (GS). Eighteen patients submitted to gastrointestinal surgery were randomized and double-blindly administered either G+AA (1 g AA/kg x d and 28 kJ/kg x d), or GS (28 kJ/kg x d). Protein metabolism was determined 12 h after surgery (day 0) and after 5 days of nutritional support. On day 0, protein breakdown was similarly elevated, with respect to reference values, in both groups (GS: 4.62 +/- 0.25; G+AA: 5.25 +/- 0.50 g prot/kg x d) as a result of surgical stress. These values increased significantly at day 5 (P < 0.03) with the administration of GS to 6.93 +/- 1.00 g prot/kg x d, while they decreased (P < 0.002, 3.30 +/- 0.42 g prot/kg x d) with G+AA. Protein synthesis was increased (5.69 +/- 0.86 g prot/kg x d) with GS (P < 0.02), and was decreased (2.79 +/- 0.44 g prot/kg x d) with G+AA (P < 0.0002). Both synthesis and breakdown were inside normal reference values after 5 days for group G+AA. In both groups, nitrogen balance did not change significantly at day 5 compared to day 0. G+AA is effective in curbing the hypermetabolism produced by postoperative stress, achieving normal protein metabolism in 5 days, while GS increases the protein breakdown and synthesis. Nitrogen balance does not detect these modifications of the protein metabolism. Undernutrition on prognosis is not yet fully recognized.

The effect of the lipidic composition of the diet on the proteic synthesis of the male Sprague-Dawley rats fed parenterally for four days has been studied. All animals received identical nitrogen and caloric intake, but the ratio of medium to long-chain triglycerides (MCT/LCT) varied: group 1, control (0/100); group 2 (30/70); group 3 (50/50) and group 4 (70/30). Hepatic and jejunal protein synthesis were determined with L-(1-14C)-leucine. In groups 1, 3 and 4 muscle protein synthesis was measured with L-(3,4-3H)-phenylalanine. In liver, there were no significant differences in the fractional synthesis rate among the groups. In jejunum, the control group showed a higher fractional synthesis rate with statistically significant differences among the groups. In muscle, group 3 presented the highest fractional synthesis rate with statistically significant differences (p less than 0.05).