Leptin and perioperative neuroendocrine stress response with two different anaesthetic techniques.

BACKGROUND: Stress response to surgery is modulated by several factors, including magnitude of the injury, pain, type of procedure and choice of anaesthesia. Our purpose was to compare intra- and post-operative hormonal changes during total intravenous anaesthesia (TIVA) using propofol and remifentanil vs. sevoflurane anaesthesia in a low stress level surgical model (laparoscopy). METHODS: We randomly allocated 18 patients undergoing laparoscopic surgery for benign ovarian cysts in two groups to receive either TIVA (group A=9) or sevoflurane anaesthesia (group B=9). Perioperative plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), cortisol and leptin were measured. Blood samples were collected pre-operatively (time 0), 30 min after the beginning of surgery (time 1), after extubation (time 2), and 2 h (time 3) and 4 h after surgery (time 4). RESULTS: The comparative analysis between the groups shows significantly higher values of NE (P<0.001 at time 1 and P<0.01 at time 3), E (P<0.001 at times 1 and 2; P<0.01 at time 3 and P<0.05 at time 4), ACTH (P<0.001 at times 1 and 2; P<0.05 at time 3) and cortisol (P<0.001 at times 1 and 2; P<0.01 at time 3; P<0.05 at time 4) in group B. The serum values of leptin were not significantly different between the two groups. CONCLUSION: The choice of anaesthesia does not seem to affect the leptin serum levels but influences the release of stress response markers: ACTH, cortisol, NE and E.

Clinical significance of focal and diffuse thyroid diseases identified by (18)F-fluorodeoxyglucose positron emission tomography.

(18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET) thyroid incidentalomas are defined abnormal FDG uptake in the thyroid gland found at PET scan performed as part of a staging protocol and follow-up of patients with various kinds of malignancies. In the present study we report two cases of FDG PET thyroid incidentalomas, and review the literature with regard to the meaning of this new category of thyroid "disease". Since the advent of whole body FDG PET scan, a relatively high incidence of cases of thyroid FDG uptake has been reported as an incidental finding as in one of our patient. Focal uptake was found to be more likely associated to a malignant lesion, while a diffuse thyroid uptake to a benign thyroid disease. However, differential diagnosis is difficult, and reported data in literature are somewhat discordant. A focal thyroid uptake of FDG incidentally discovered at PET scan cannot be invariably considered a malignant thyroid nodule, however a prompt and complete work-up including laboratory examinations, ultrasonography and fine needle aspiration cytology, should be obtained to exclude a thyroid carcinoma. On the other hand, patients with a PET finding of diffuse FDG uptake can be considered at low risk of malignancy, being more likely associated to chronic thyroiditis or diffuse thyroid autonomy.

Thyroid cancer in suppressed contralateral lobe of patients with hot thyroid nodule.

We studied 60 patients with thyrotoxicosis due to single toxic nodule. At surgery in 3 patients (5%) a papillary carcinoma has been detected in the contralateral suppressed lobe. Thyroid function tests and thyroid scan confirmed thyrotoxicosis. Thyroid stimulating hormone (TSH) was undetectable in all patients. It is common opinion that differentiated thyroid tumour growth is TSH dependent. On the basis of our study two hypotheses are possible: (1) the development of thyroid carcinoma precedes the adenoma and suppressed TSH levels inhibit tumour growth; (2) suppressed TSH levels do not protect patients from the occurrence of cancer. In the evaluation of hot thyroid nodule we suggest careful ultrasonographic control in order to look for nodules outside the adenoma. A complete surgical examination of the whole thyroid gland is required and intraoperative biopsies are advocated in abnormal areas.

Vitamin B12 and folic acid plasma levels after ileocecal and ileal neobladder reconstruction.

OBJECTIVES: To compare the plasma levels of vitamin B12 and folic acid following resection of ileocecal or ileal segments used for orthotopic bladder substitution. METHODS: Hemoglobin, hematocrit, and plasma levels of vitamin B12 and folic acid were measured in 34 patients with ileocecourethrostomy (ICUS) and in 16 patients with ileal reservoir (IR), with a mean follow-up of 59.8 +/- 41.9 months. The results were compared with regard to both the type of operation and the length of time since surgery. RESULTS: The level of folic acid was normal in all patients. The mean level of vitamin B12 in the ICUS group was 413.67 +/- 160.45 ng/mL compared to 257.63 +/- 121.36 for the IR group. This difference was statistically significant. In the IR group, 18.75% of the patients had a level of vitamin B12 below normal. CONCLUSIONS: There is a tendency for vitamin B12 levels to fall in patients in whom the ileum is used. Resection of the ileocecal segment including the junction does not alter the level of vitamin B12.

AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma.

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.

Hyperfiltration in patients with type I diabetes mellitus: a prevalence study.

AIM: An increase in glomerular filtration rate (GFR) and renal plasma flow (EFPR) may be considered as prognostic factors for the progression of diabetic nephropathy; however the real predicting value of hyperfiltration in the development of incipient and overt nephropathy is as yet unknown. We have examined the prevalence of hyperfiltration in a population of normotensive adult IDDM patients and the possible effect of long-term metabolic control on glomerular hemodynamics. MATERIALS AND METHODS: We measured GFR and ERPF values in 177 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 30 healthy subjects by single bolus intravenous injection of 1 miroCu/kg [51Cr]-EDTA and 0.2 microCu/kg [125I]-Hippuran intravenously. We have correlated the GFR values with parameters of metabolic control over the last 3 years and with age, sex, and duration of diabetes. RESULTS: Patients with a GFR greater than the 95 degrees percentile value of controls (135 ml/min/1,73 m2) were defined as hyperfiltering. They represented the 55.9% (99/177) of our population. We found a strong correlation between GFR and ERPF (p <0.001), and between GFR and average HbA1c levels (p = 0.016) in multiple regression analysis, with age, sex, ERPF, and average HbA1c levels entered as variables (r2 = 0.45). There appeared to be no correlation with the duration of the disease. CONCLUSIONS: Long-term hyperglycemia provides a significant contribution in GFR and a poor metabolic control is predictive of overt nephropathy. In this study hyperfiltration does not appear to be the major factor of diabetic nephropathy. A follow-up of these patients is necessary to clarify the role of hyperfiltration in the development of overt nephropathy in diabetes.

Clinical and laboratory follow-up in differentiated thyroid carcinoma.

Thyroid carcinoma is the most frequent endocrine malignant neoplasm even if a rare occurrence (0.5%-1.0%) of all human malignant tumors. Primary differentiated (papillary and follicular) forms represent over 90% of the total. Since recurrence of thyroid carcinoma can occur even after several years, patients must undergo a life-long follow-up. Thyroglobulin, being organ-specific, plays a major role as tumor marker and it is used essentially in the monitoring and follow-up of patients with differentiated thyroid carcinoma, both during L-thyroxine suppressive therapy and when it is discontinued or after recombinant TSH administration. The presence of antithyroglobulin antibodies masks the real value of thyroglobulin and therefore, at the same time, antithyroglobulin antibodies should always be determined.

Thyrotoxicosis: clinical and laboratory assessment.

Thyroid hormones are triiodothyronine (T3) and thyroxine (T4). The hypophysial thyrotropic hormone, thyroid stimulating hormone (TSH) is their physiologic regulator. Thyrotoxicosis is characterized by clinical symptoms caused by high thyroid hormone concentrations. The commonest forms are: 1) toxic diffuse goiter (Basedow-Flajani-Graves disease), 2) toxic multinodular goiter, 3) toxic adenoma. Other less frequent forms are the iodide-induced, that during Hashimoto thyroiditis, that from inappropriate TSH secretion. The diagnosis is predominantly clinical and confirmed by hormone level determination associated in some cases to functional and morphofunctional tests (TRH test, scintigraphy, thyroid I uptake) and antithyroid antibody assay.

The possible use of radioiodinated metaiodobenzylguanidine (MIBG) in medullary thyroid carcinoma.

The value of radioiodinated metaiodobenzylguanidine (MIBG) in imaging thyroid medullary carcinoma (MTC) was investigated (18 studies) in 12 patients with proven MTC. Calcitonin (CT), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were also determined. The patients were divided into two groups. Group I comprised 7 patients who had relapsed; two of them were also studied before total thyroidectomy. In the 2 cases studied before total thyroidectomy 123/131I-MIBG imaged the primary tumor (partially) and the residual tumor involved lobe. The residual/recurrent tumor present in 4 and some of the remote metastases in 3 out of 5 were detected. Group II includes 5 patients studied postoperatively with no evidence of disease. A residual tumor in one of the 2 patients without evidence of disease on the basis of conventional diagnostic modalities but with elevated tumor markers was visualized; the outcome was correctly negative in 3. One patient underwent treatment with 131I-MIBG. A total dose of 27.1 GBq (733 mCi) was given. Relief of pain and partial regression of the lesions was achieved.

A slightly suppressive dose of L-thyroxine does not affect bone turnover and bone mineral density in pre- and postmenopausal women with nontoxic goitre.

There are controversial reports on the potential role of L-thyroxine administration as a risk factor for osteoporosis. We studied bone mass and metabolism in a homogeneous series of 50 Caucasian women, 25 premenopausal and 25 postmenopausal, having nontoxic goitre treated with slightly suppressive L-thyroxine doses (50-200 micrograms/day) with subnormal serum TSH and normal thyroid hormone levels. These patients were matched with 50 controls for age, sex, body mass index, menopausal and thyroid disease. Patients and controls were also investigated for minor determinants of bone loss, such as hereditary and life-style factors. Patients and controls filled in a questionnaire and underwent physical examination, routine laboratory tests and calciotropic and thyroid hormone assay. Bone mineral turnover was evaluated by determining serum osteocalcin, alkaline phosphatase, tartrate-resistant acid phosphatase, calcium, phosphate, urine hydroxyproline/creatinine and calcium/ creatinine ratio. Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, trochanter and Ward's triangle. No difference in bone mineral density or biochemical markers was found between patients and controls; bone density and turnover were significantly affected by menopausal status. No relationship between bone density or turnover values and L-thyroxine administration was found. A significant positive correlation was found between osteocalcin and the hydroxyproline/creatinine ratio in premenopausal and postmenopausal patients, but not in controls. Our study suggests that slightly suppressive L-thyroxine administration in nontoxic goitre can activate bone turnover but constitutes neither an actual risk factor for bone loss nor, consequently, for osteoporotic fractures.

Evaluation of plasma iodothyronines in various stages of pregnancy.

Evaluation of thyroid status during the whole normal pregnancy was carried out by measuring serum total thyroxine (TT4), total 3,5,3' triiodothyronine (TT3), T3 resin uptake (T3(U)), 3,3',5' triiodothyronine (rT3), free thyroxine index (FTI), free thyroxine (FT4) and thyrotrophin (TSH) in 70 serum samples from 42 pregnant women being in a variable period from the 6th to the 40th week of pregnancy and in 14 serum samples from 14 non pregnant healthy women. The serum samples were divided in 7 groups, according to the gestational age of the subjects. Every group was formed by 10 samples collected within the same five weeks period. The levels of TT4, TT3, T3 (U) and rT3 were found significantly elevated during pregnancy, above the levels of the control group (p less than 0.01); the increase is very early. FTI remained in the range of normal non pregnant subjects without any significant change in all groups studied. FT4 concentration showed a progressive downward trend with gestational age. This fall became significant in the second group (11th to 15th weeks), when compared to the levels of non pregnant women (p less than 0.01) TSH mean values remained in the normal range within the three trimesters, though they showed some fluctuations.

Solitary liver metastasis from Hürthle cell thyroid cancer: a case report and review of the literature.

Metastasis to the liver from thyroid cancer is a rare event with a reported frequency of 0.5%. Metastatic liver involvement from differentiated thyroid cancer (DTC) is nearly always multiple or diffuse and usually found along with other distant metastases (lung, bone and brain). The authors describe a patient with a solitary liver metastasis from Hürthle cell thyroid cancer, which appeared during long-term follow-up. The lesion was diagnosed by progressive increase of thyroglobulin in the serum and imaged with I-131 whole body scan, ultrasonography, magnetic resonance imaging (MRI) and F-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scan. For patients with a Tg level above some arbitrary limit, the administration of a large dose (3.7-5.5 GBq; 100-150 mCi) of I-131, in order to obtain a highly sensitive Tx whole body scan (WBS), remains the best diagnostic strategy. However, on very rare occasions, physiological enteric radioactivity can hide possible abdominal lesions and further indepth studies, such as FDG-PET scans, are sometimes necessary.

[Naloxone doesn't determine the response of growth hormone to clonidine in obese patients]. / La naloxone ne détermine pas de réponse de l'hormone de croissance à la clonidine chez les obèses.

The effect of naloxone (opioid receptor blocker) on the impairment of growth hormone (GH) release after clonidine (alfa 2-adrenergic agonist) was investigated in 10 volunteer obese subjects. The patients (4 males and 6 females, 16-22 year old) with fat excess (15 +/- 2 kg) estimated by bioelectrical impedance analysis (BIA) were studied repeatedly. The patients, were perfused by a slow saline infusion. 30 min later they received a bolus dose of clonidine (150 micrograms p.o.), followed 30 min later by a bolus dose of naloxone (10 mg i.v.) or a corresponding volume of isotonic sodium cloride (I.S.) for control. No significant changes occurred in blood GH concentration after clonidine administration and naloxone did not induce GH response at clonidine. These results suggest that in obese subjects the impairment of GH release after clonidine is not mediated via receptors sensitivity to naloxone.

[Endogenous opiate modulators of insulin secretion in the obese]. / Les opioïdes endogènes modulateurs de la sécrétion d'insuline chez les obèses.

The effects of endogenous opiates on insulin response to oral glucose load were studied in obese subjects and in lean healthy volunteers. None of these having a family diabetes. After 3 days on an 1,800 cal./m2, 40% carbohydrate diet all subjects underwent two standard 75 g oral glucose tolerance tests (OGTT), one of which was accompanied by an i. v. administration of 10 mg of, an antagonist of opiates, the naloxone. In one group of obese impaired oral glucose tolerance test occurred. All obese, but not the lean healthy volunteers, showed: 1) increased basal plasma insulin levels, 2) higher insulin response to OGTT, 3) a decrease in insulin response to OGTT after naloxone administration, with significant differences at 60 min (p less than 0.01) and 90 min (p less than 0.025). In none of the subjects significant differences were observed in blood glucose levels after OGTT plus naloxone administration. These data suggest that increased endogenous opiates may affect insulin response to glucose in obese with impaired or normal oral glucose tolerance test. At present there seems to be no satisfactory explanation for unchanged blood glucose levels during OGTT with and without naloxone despite a decrease in insulin secretion in the obese patients.

Evaluation of stress-related hormones after surgery by laparoscopy or laparotomy.

STUDY OBJECTIVE: To evaluate the stress hormone response after pelvic surgery performed by laparoscopy versus laparotomy. DESIGN: Prospective study. SETTING: A tertiary care university hospital. PATIENTS: Ten women were scheduled to undergo laparoscopic surgery and 10 laparotomy for either tubal disease or endometriosis. INTERVENTIONS: Surgical procedures were performed by laparoscopy or laparotomy for stage III-IV endometriosis, pelvic adhesions, or distal tubal occlusion. The following hormones were measured before the induction of anesthesia in the ward, 60 minutes after the beginning of surgery, at the end of surgery after extubation, and 2 hours and 6 hours after the end of the operation: norepinephrine (NE), epinephrine (E), dopamine (D), adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), and GH. MEASUREMENTS AND MAIN RESULTS: The mean duration of surgery was not significantly different between the two groups. Surgery-related adrenergic activation (E, NE, D) appears more pronounced in the laparotomy group (p<0.005) during surgery and in the postoperative period. More elevated values for laparotomy were observed also for the other stress hormones (ACTH, cortisol, PRL, GH), even though statistical significance was not always reached. CONCLUSIONS: Compared with laparotomy, activation of stress-related factors during laparoscopy seems to be less intense and of shorter duration.

Comparison between TRH-stimulated TSH and basal TSH measurement by a commercial immunoradiometric assay in the management of thyroid disease.

In order to assess the current diagnostic role of the TRH test following the introduction of more sensitive "second generation" TSH assays, we studied a series of 259 outpatients, 237 women and 22 men, mean age 44.7 years (range 12-82), 91 of whom (35%) with untreated simple goiter, 133 (51%) with simple nodular goiter on steady state I-thyroxine treatment, 18 (7%) with overt or subclinical hyperthyroidism and 17 (7%) with overt or subclinical hypothyroidism, compared to a control group of 26 euthyroid healthy subjects. Serum TSH was measured by a commercial immunoradiometric assay (clinical sensitivity 0.1 microU/ml). TSH response to TRH was evaluated 30 minutes after giving 200 micrograms TRH i.v. bolus, the results being analyzed both as absolute increase (delta-TSH=stimulated TSH minus basal TSH) and as relative increase (R-TSH stimulated TSH/basal TSH). Using cut-off values of 0.3-3.2 microU/ml, basal TSH measurement was able to detect hypothyroidism (specificity = 100%) and to exclude hyperthyroidism (sensivity = 96.9%), but failed to accurately prove hyperthyroidism (specificity = 93.4%) and, above all, to exclude hypothyroidism (sensitivity = 35.3%) in our ambulatory patients. The delta-TSH values showed a basal TSH dependent linear increase (r = + 0.87, p < 0.001) both including only patients (n = 139) with basal TSH level in the euthyroidism range and including all patients (n = 223) having TSH responsive to TRH. All the patients with detectable basal TSH level displayed detectable TSH response to TRH, as did 19 (= 23.5%) of 81 patients with undetectable (< 0.1 microU/ml) basal value. In particular: a) for subnormal but detectable basal TSH ranging between 0.1 and 0.2 microU/ml, TSH was always hyporesponsive (delta-TSH < or = 2.5 microU/ml), while between 0.2 and 0.3 microU/ml TSH was hyporesponsive in 72.2% and normoresponsive (delta-TSH > 2.5 and < or = 11.9 microU/ml) in the remaining 27.8%; b) for basal TSH values within the normal range (0.3-3.2 microU/ml). TSH was hyporesponsive in 13.7%, normoresponsive in 74.8% and hyperresponsive in 11.5%; c) for high basal TSH values TSH was always hyperresponsive. The analysis of R TSH showed relatively constant values in the range of euthyroidism and hypothyroidism (m +/- SD: 7.4 +/- 2.3 and 7.7 +/- 3.1, respectively), and a marked differentiation of hyperthyroid patients whose R-TSH values were significantly lower (4.2 +/- 3.4) but had a wide individual variability. Linear regression analysis of basal or stimulated TSH and circulating thyroid hormones showed a close negative relationship, being highly significant between delta-TSH and T4 (r = 0.57, p < 0.001) and delta-TSH and FT4 (r = 0.46, p < 0.001). In conclusion, after the introduction of current second generation TSH immunoradiometric assay, the diagnostic role of the TRH test is greatly limited but not to be excluded: it can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism and in the precise evaluation of the degree of TSH suppression in patients with a subnormal basal TSH, either for endogenous thyrotoxicosis or I.-thyroxine treatment.

The role of [131I]metaiodobenzylguanidine in the treatment of medullary thyroid carcinoma: results in five cases.

Therapeutic doses of [131I]metaiodobenzylguanidine (131I-MIBG) were administered to 5 patients, 3 men and 2 women aged from 33 to 66 years, with proven medullary thyroid carcinoma (one "intermediate" papillary/medullary tumor). The treatment procedure consisted of single doses (3.7-8.5 GBq) of 131I-MIBG given by slow i.v. infusion at 2-8 month intervals. In two advanced-stage patients the treatment played an important palliative role, ranging from an objective response (substantial, but not complete, regression of the tumor) to pain relief which was significant for these patients. In three other cases with residual/recurrent tumor, 131I-MIBG complemented conventional treatment in the attempt to effect a cure which actually was achieved in one case. The only side-effect observed was a transient, mild hematologic toxicity in some cases.

Early prenatal diagnosis and therapy of fetal hypothyroid goiter.

We report a case of early diagnosis of iodide-induced fetal hypothyroidism at 22 weeks of gestation, confirmed at 29 weeks by cordocentesis and successfully treated intra-amniotically. The ultrasonographic feature was the presence of two echogenic masses in the fetal neck; polyhydramnios was absent. Mild hypothyroidism was diagnosed based on fetal serum obtained by percutaneous umbilical blood sampling at 29 weeks of gestation. The persistence of fetal hypothyroidism in spite of maternal thyroid improvement was confirmed by a second cordocentesis at 35 weeks of gestation, and a single injection of intra-amniotic levothyroxine (250 micrograms) was performed. The serial ultrasonographic examinations showed disappearance of the fetal goiter. A healthy female baby (3,630 g) was delivered at term. At birth, the thyroid gland was not enlarged, and neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method to assess the fetal thyroid status; moreover a single injection of intra-amniotic thyroxine was effective in treating fetal hypothyroid goiter.

Radiolabeled somatostatin analog scintigraphy in medullary thyroid carcinoma and carcinoid tumor.

The aim of this study was to evaluate the effectiveness of a recently developed radiolabelled somatostatin analog (111In-pentetreotide) for the detection and localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and to compare the results obtained with the results of 99mTc(V)-DMSA, and radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9 patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9 patients with known lesions of carcinoid tumor. It gave a negative result in 2 MTC patients with high levels of calcitonin but with no evidence of disease at conventional diagnostic modalities. The scintigraphic results were comparable with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the modifications of calcitonin levels brought about by the acute administration of octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients studied.