Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

PURPOSE: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. METHODS: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. RESULTS: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response. CONCLUSIONS: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

Mental disorders in patients with metabolic syndrome. The key role of central obesity.

BACKGROUND: The Authors sought to evaluate current prevalence of mental disorders in patients affected by metabolic syndrome compared with patients affected by central obesity alone. METHODS: 186 (63.5%) patients affected by central obesity and 107 (36.5%) affected by metabolic syndrome according to ICF criteria were interviewed by means of SCID I. RESULTS: Axis I current prevalence was respectively 45.7% and 44.9% among patients with central obesity and patients with metabolic syndrome, differences which were not significant. No statistically significant differences were found between groups as far as each single axis I diagnostic category was concerned. Moreover, current prevalence of any axis I, anxiety and mood disorders were independent of the number of components of metabolic syndrome. CONCLUSION: metabolic syndrome is associated to an higher risk for current mental disorders, which seems to be mainly due to the strong association of central obesity to psychopathology.

Obesity, alexithymia and psychopathology: a case-control study.

OBJECTIVE: The relationship between psychopathology and alexithymia in obese patients is uncertain. The present study was performed to evaluate this relationship in a clinical sample of patients attending a centre for the diagnosis and treatment of obesity compared to a matched sample of non-obese subjects. METHODS: 293 consecutive obese patients (48 males, 245 females, mean age 45, 41±13.55 yrs; mean BMI 35.60±6.20) were compared with a control group made of 293 non-obese subjects (48 males, 245 females, mean age 45, 66±13.86 yrs; mean BMI 21.8±2.06); all subjects were interviewed by means of SCID I and SCID II together with several self-evaluation instruments including the TAS-20 (Toronto Alexithymia Scale) and SCL-90 (Symptom Check List, Revised). RESULTS: Alexithymia was significantly more frequent among obese patients compared to "normal" controls (12.9% vs 6.9%, p=0.010); moreover obese patients achieved significantly higher mean scores on subscales 1 and 2 and on overall scale of the Toronto Alexithymia Scale; comorbidity with axis I/II disorders, in particular Binge Eating Disorder, was associated with a significantly higher frequency of alexithymic traits and higher scores at TAS. CONCLUSIONS: Alexithymia and psychopathology are strongly correlated among obese patients seeking treatment. Routine evaluation of personality traits and comorbid psychopathology may be relevant in treatment of obesity.

Electrical Impedance to Easily Discover Undeclared Freeze-thaw Cycles in Slaughtered Bovine Meat.

A portable electrical impedance spectroscopy device was developed to monitor the bioimpedance resistive component of bovine meat by injecting a sinusoidal current of 1 mA at 65 kHz. Both right and left longissimus dorsi muscles were trimmed from 4 slaughtered cows. The left muscle portions were frozen to -18 °C for 7 days while the right ones were meantime maintained at 5 °C. Mean value of impedance per length (Ω/cm) of frozen and thawed left samples was 31% lower than that of right non-frozen one (P = 0.0001). It was concluded that the device is reliable for monitoring the maturation of beef meat in situ with the possibility of revealing undeclared freeze-thaw cycles.

Prevalence and trend of overweight and obesity among Sardinian conscripts (Italy) of 1969 and 1998.

This study evaluated the prevalence of overweight and obesity in the male Sardinian population (Italy), and verifies that it has increased over the last 30 years. Data were collected during 2003-2004 from military registers in the Archive of the Military District of Cagliari for the years 1969 and 1998. A total of 22,345 forms were analysed from all Sardinia. The conscripts were classified on the basis of their place of residence and socioeconomic status. The overall prevalence of overweight and obesity in Sardinia were 4.33% and 0.55%, respectively, for the conscripts of 1969 and 9.8% and 3% for 1998. Olbia-Tempio (northern Sardinia) was the province with the highest incidence of overweight and obesity in 1969, and Nuoro (central Sardinia) had the highest incidence in 1998. Distribution of body mass index, overweight and obesity across the island showed a statistically significant heterogeneity that strongly decreased from 1969 to 1998. Among the conscripts of 1969, the incidence of overweight and obesity were higher in rural than in urban regions. An opposite trend was observed for the 1998 prevalence, it being more frequent in urban than rural regions. Comparison with other Italian regions was made. The percentages of overweight and obese individuals in Sardinia have markedly increased during the last 30 years, but their low incidence with respect to other Italian populations could be explained by the genetic peculiarity of the island. The change in the internal distribution of obesity clearly reflects socioeconomic changes.

Fifteen-year follow-up of thyroid function in lithium patients.

OBJECTIVE: To study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. METHOD: Patients (no.=150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for thyroid circulating thyroid antibodies, hypothyroidism, hyperthyroidism, and thyroidectomy, during a further period of lithium exposure of up to 15 yr. RESULTS: Annual rates of newly developed circulating thyroid antibodies and hypothyroidism were 1.7 and 1.5%, respectively. Subjects with thyroid antibodies had a higher chance of requiring substitution treatment with levothyroxine for hypothyroidism compared with subjects with no evidence of thyroid antibodies (6.4% annual rate compared to 0.8%; relative risk: 8.4; 95% confidence interval: 2.9-24.0). One case of hyperthyroidism was observed over 976 patient-yr. Three patients underwent thyroidectomy during followup (two for multinodular goiter and one for multicentric papillary carcinoma). CONCLUSIONS: Lithium may be associated with hypothyroidism in particular in the presence of circulating thyroid antibodies. Incidence of thyroid antibodies is comparable with that reported for the general population. Hyperthyroidism and thyroid cancer are rare.

Prevalence of overweight and obesity in Sardinian adolescents.

BACKGROUND: To estimate the prevalence of overweight and obesity among adolescents in Sardinia and to examine the association with several biological and geographic factors. METHODOLOGY: A cross-sectional study was performed in 3,946 unselected adolescents (2,011 boys, 1,935 girls; aged 11-15 years) attending the public secondary schools in 33 Sardinian municipalities: 28 semi-rural, 5 urban, sub-grouped according to their geographic location (mountain, hillside and plain). Oversized children were measured and their BMI defined as being above normal values according to parameters provided by the International Obesity Task Force (IOFT) by Cole et al. (BMI for age > or = 95th percentile). Relative risk for overweight and obesity was calculated using Poisson regression analysis: risks associated to each covariate were reciprocally adjusted. The 95% confidence interval (CI) of the estimated risk was calculated using Wald's formula (RR, RR = log(n) beta +/- 1.96 se(beta)). MAIN FINDINGS: The overall prevalence rate found for overweight and obesity was 14.9% (95% C.I.: 13.7-16.1%) and 3.7% (95% C.I. 3.1-4.3%), respectively. Overweight rate showed no association with gender, whereas belonging to the female sex constituted a significant protection against obesity. Increasing age in the range 12-14 years was protective against both overweight and obesity in the whole sample. A similar finding however was not observed for obesity in girls or overweight in boys, when considered separately. Boys, but not girls, living in urban areas displayed a modest though significant 20% increase in overweight and a 40% decrease in obesity risk. Living in a mountainous area conveyed a 30% decrease in risk of overweight and a 50% decrease in risk of obesity, when compared to living on the plains and hillside combined. However, the small sample size of study subjects living in mountainous areas generated extremely wide 95% confidence intervals, thereby preventing the drawing of any significant conclusions. CONCLUSION: In comparison with other surveys performed by the IOFT, Sardinian adolescents show a low prevalence rate for oversize, emphasizing a marked discrepancy with the general north-south rising trend of oversize observed throughout Europe. Geographic location, aesthetic or other age related factors seem to exert a different gender-specific influence on overweight and obesity. SIGNIFICANCE: The present report is cross sectional and the consequences of overweight and obesity on individuals over time are not traceable. However, the outcome of the study suggests the need to implement suitable policies and public health programs leading to increased awareness.

Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease.

BACKGROUND: The iodine-rich antiarrhythmic drug, amiodarone, can induce both thyrotoxicosis and hypothyroidism, the former being more frequent in iodine-deficient areas, the latter in iodine-sufficient areas. In this study we evaluated prospectively thyroid function in amiodarone-treated patients with positive or negative baseline thyroid autoantibody test results who resided in a moderately iodine-deficient area of Italy. SUBJECTS: Two groups of patients received long-term amiodarone treatment: Group 1 included 13 patients with negative thyroid autoantibody test results. Group 2 consisted of seven patients with positive thyroid autoantibody test results and thyroid ultrasound patterns compatible with Hashimoto's thyroiditis. The control group (group 3) included 16 untreated euthyroid patients with Hashimoto's thyroiditis. All subjects resided in a mildly iodine-deficient area of Italy (Southern Sardinia) and had low urinary iodine values. Patients in groups 1 and 2 had markedly elevated urinary iodine excretion during treatment. The follow-up period ranged from 6 to 29 months in group 1, from 4 to 9 months in group 2, and from 12 to 55 months in group 3. RESULTS: Two (15%) of 13 patients in group 1 with nodular goiter developed thyrotoxicosis. No patient in this group developed circulating thyroid autoantibodies. Five (71%) of seven patients in group 2 became hypothyroid after 4 to 9 months of amiodarone treatment associated with a rise in serum thyroid autoantibody levels. No patient in group 3 became hypothyroid. CONCLUSIONS: (1) Amiodarone administration can cause both thyrotoxicosis and hypothyroidism. (2) Hypothyroidism is far more frequent in patients with preexisting thyroid autoimmune disease. (3) Amiodarone can modify the natural history of Hashimoto's thyroiditis. (4) Circulating thyroid autoantibodies do not appear in amiodarone-treated patients who have negative test results prior to therapy.

The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH-independent Cushing's syndrome.

TSH secretion was evaluated in 10 patients with ACTH-dependent (pituitary microadenoma, n = 5) or ACTH-independent [adrenal adenoma (n = 4) or carcinoma (n = 1)] Cushing's syndrome, and in 12 normal controls matched for age and sex. Serum TSH concentration was assayed at night, from 2200-0200 h, and in the morning, both basally and 30 min after iv injection of 200 micrograms synthetic TRH. Patients with hypercortisolism showed significantly reduced serum total T4 and T3 and free T3 concentrations and increased serum reverse T3 levels. Their mean baseline serum TSH concentration in the morning, albeit slightly lower, did not significantly differ from those of controls. The mean peak TSH value after TRH was significantly reduced, and a blunted TSH response to TRH was found in 4 out of 10 patients. At variance with normal controls, who showed nighttime TSH values 63-228% higher than morning values, 9 out of 10 patients had nighttime levels not different from or even lower than those in the morning; the remaining patient had nighttime TSH values marginally (33%) higher than in the morning. An inverse relationship (r = 0.80, P less than 0.001) was found between serum cortisol and TSH values both at night and in the morning. No differences were found either in the pattern of TSH secretion or in the TSH response to TRH between patients with ACTH-dependent and those with ACTH-independent Cushing's syndrome. These results show a substantial impairment of TSH secretion, and in particular the loss of the nocturnal surge of the hormone, in patients with Cushing's syndrome. Although the origin of the nocturnal TSH rise is probably multifactorial, cortisol, at least when secreted in excess, appears to play an important role in its regulation.

The lack of nocturnal serum thyrotropin surge in patients with nontoxic nodular goiter may predict the subsequent occurrence of hyperthyroidism.

TSH secretion, with particular regard to the nocturnal TSH surge, was evaluated in 115 subjects with non-toxic nodular goiter. All patients were clinically and biochemically euthyroid. After 18-36 months of follow-up (mean, 24 months), hyperthyroidism occurred in 21 (18%; group 1), while the remaining 94 remained euthyroid (82%; group II). The analysis of hormonal data at the time of first observation showed that the 2 groups had similar total and free T4 and T3 serum concentrations. Morning serum TSH values in group I were lower than those in group II patients (0.6 +/- 0.1 vs. 1.1 +/- 0.1 mU/L; P less than 0.001); this difference was even more striking for the nocturnal values (0.6 +/- 0.1 vs. 2.2 +/- 0.2 mU/L; P less than 0.0001); nocturnal values were significantly lower than morning values in group II, but not in group I. The mean peak TSH value after TRH was also significantly reduced in group I (5.5 +/- 0.4 vs. 9.2 +/- 0.7 mU/L; P less than 0.001). Morning TSH values in group II did not differ from those in controls (1.3 +/- 0.1 mU/L), whereas nocturnal and TRH stimulated peak TSH values were slightly but significantly lower. The nocturnal serum TSH values in control subjects were 62-390% higher than morning values. The nocturnal TSH surge was abolished in 18 of 21 (86%) group I patients and in 7 of 94 (8%) group II patients. TRH testing resulted in an absent or blunted TSH responses in 5 subjects in group I and 6 in group II. Analysis by the Galen and Gambino predictive model; comparing the abolition of the nocturnal TSH surge and the abnormal TRH test as predictors of the subsequent occurrence of hyperthyroidism, showed that the former had higher sensitivity (86% vs. 24%) and predictivity (72% vs. 45%). In conclusion, the results of the present study demonstrate that the evaluation of the nocturnal TSH surge may be useful in identifying patients with nontoxic nodular goiter in whom hyperthyroidism may eventually occur. Patients who lack the nocturnal serum TSH surge are more prone to develop thyroid hyperfunction; their thyroid status should, therefore, be more carefully and frequently monitored.

Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients.

Circadian variations in serum TSH, especially its nocturnal rise, are often blunted in nonthyroidal illness. We analyzed TSH secretion in 15 diabetic patients (7 with type I and 8 with type II diabetes mellitus). Patients were evaluated when diabetes was poorly controlled (fasting blood glucose ranging from 13.7-19.2 mmol/L with absence of ketoacidosis) and after achieving glycemic control. Before correction of hyperglycemia, the nocturnal serum TSH peak (2230-0200 h) was abolished in 11 of 15 patients (73%); the mean (+/- SE) night TSH/morning TSH x 100 was 109.0 +/- 9.5 (range, 66.7-166.7) vs. a mean of 216.5 +/- 27.0 (range, 139.8-462.5) in normal controls. The mean morning TSH value in diabetics (1.9 +/- 0.4 mU/L) did not differ from that in normal age- and sex-matched controls. The mean TSH increase after iv administration of TRH was only slightly reduced (8.4 +/- 1.2 mU/L pretreatment vs. 10.8 +/- 1.6 mU/L posttreatment), with the TRH test blunted in 3 cases. No differences were found between type I and type II patients. Correction of hyperglycemia was associated with the reappearance of a nocturnal TSH peak in all but 1 patient (mean TSH peak, 198.2 +/- 13.0; P = NS vs. controls). This change paralleled the normalization of serum total T3 and rT3, which were reduced and increased, respectively, when diabetes was poorly controlled. An inverse relationship was found between serum fructosamine levels and the nocturnal TSH peak, suggesting that metabolic decompensation accounts for the abolishment of the latter.

Thyroid volume measurement by ultrasound in children as a tool for the assessment of mild iodine deficiency.

Thyroid ultrasound was used to measure thyroid volume in children and compared with thyroid palpation for the assessment of the prevalence of goiter in an area of mild iodine deficiency. School children, 6-14 yr old, were from control areas (n = 2693; urinary iodine excretion, 110 micrograms/L) or from an area of mild iodine deficiency (IDA; n = 278; urinary iodine excretion, 72 micrograms/L). Thyroid volume determined by ultrasound in control children increased with age (r = 0.62; P < 0.0001) and was significantly correlated with height (r = 0.51; P < 0.0001) and body weight (r = 0.126; P < 0.0001). Both median and mean thyroid volumes were greater in IDA children than in controls. The prevalence of goiter determined by ultrasound was 68 of 268 children (25.3%) in IDA and 105 of 2693 children (3.9%) in the control area (chi 2 = 204; P < 0.0001). Thyroid enlargement, as assessed by palpation, was found in 59 of 268 children (22%) in the IDA group and in 165 of 2693 (6.1%) subjects in the control area (chi 2 = 88; P < 0.0001). Some subjects of the IDA who were judged goitrous by palpation (11.2%) had a normal thyroid volume at ultrasound, and 12.7% of subjects with an abnormal thyroid volume at ultrasound were judged nongoitrous by palpation. In conclusion, 1) thyroid volume in children, as assessed by ultrasound, increases with age and is closely related to the parameters of body growth; 2) in every age group, thyroid ultrasound shows greater thyroid volume in an IDA group than in controls; and 3) a discrepancy between palpation and ultrasound is found in 23.9% of children living in an IDA, confirming that palpation is relatively inaccurate for assessing the prevalence of goiter in mild iodine deficiency. These data indicate that thyroid volume measurement by ultrasound in children provides a useful tool for the assessment of goiter in mild iodine deficiency.

False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies.

OBJECTIVE: Anti-thyroid peroxidase autoantibody (anti-TPO) and anti-thyroid microsomal antibody (anti-M) are strictly related, but discrepancies are sometimes observed. The aim of this study was to assess the incidence and to identify the causes of these discrepancies. DESIGN AND ANTIBODY MEASUREMENTS: Anti-M by passive hemagglutination and anti-TPO by two competitive monoclonal antibody-assisted radioimmunoassays (RIA-1 and RIA-2) were measured in 10,103 sera from 4232 subjects (663 male, 3569 female) screened for thyroid disease. RESULTS: Anti-TPO and anti-M correlated quite well (r = 0.7 and p < 0.0001 by RIA-1: r = 0.74 and p < 0.0001 by RIA-2), with discrepancies mostly limited to sera with low antibody titers. After exclusion of the latter samples, anti-TPO were detected in only 79 (1.4%) out of 5317 anti-M negative sera, but were undetectable in a more consistent proportion (130/2880 = 4.5%) of sera from patients with autoimmune thyroid disease and positive anti-M. In 61 sera of the latter group, anti-TPO was measured by a non-competitive RIA (RIA-3). Forty-one (67.7%) were positive by RIA-3, suggesting the presence of anti-TPO not competing with the monoclonal antibodies of RIA-1 and RIA-2. The remaining 20 sera had undetectable anti-TPO also by RIA-3. Nineteen (95%) of these sera had positive anti-thyroglobulin (anti-Tg) autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of anti-M tests. CONCLUSION: Anti-TPO by competitive monoclonal antibody-assisted RIA is negative in a minority of sera of patients with autoimmune thyroid disease and positive anti-M. This could be accounted for by anti-Tg producing false positives in the anti-M assay and by a subset of anti-TPO not competing with the monoclonal antibodies in the RIA. When autoimmune thyroid disease is suspected on clinical grounds, a negative anti-TPO test with a competitive RIA should be confirmed always by a non-competitive assay.

Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders.

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous intranodular ethanol injection for treatment of autonomously functioning thyroid nodules.

BACKGROUND: The aim of the study is the assessment of percutaneous intranodular ethanol injection (PNEI) as an alternative therapeutic procedure to classic surgery and radioiodine administration in autonomously functioning thyroid nodule treatment. METHODS: Thirty-seven patients with hot nodules (18 pretoxic and 19 toxic) have been treated by means of PNEI under ultrasonographic guide. Ninety-five percent ethanol in a mean dose of 25 ml has been used. RESULTS: Nearly 80% of the patients showed normalization of thyroid-stimulating hormone levels and a complete recovery of extranodular tissue at scintiscan. All nodules decreased strikingly in size, many becoming undetectable. Mild and transient side effects were seen in 9% of the patients. CONCLUSIONS: PNEI seems to be a feasible procedure on outpatients. It is safe when performed by a well-trained staff using ultrasonographic control. It may be carried out at any age and in patients at risk for surgery. PNEI can be considered a useful alternative to surgery and radioiodine administration in all autonomously functioning thyroid nodules and particularly in pretoxic nodules.

Melanocortins and opioids modulate early postnatal growth in rats.

This study was undertaken to investigate the effects of melanocortins and opioids on rat early postnatal body and organ growth. Among melanocortins tested desacetyl-alpha-melanocyte-stimulating hormone (alpha-MSH) at dosages of 0.3 and 3 micrograms/g/day was effective in stimulating neonatal growth with a weight gain of 7 and 5.6%, respectively, after 2 weeks of treatment. Likewise, a weight rise of 4.2 and 3% was obtained with 3 micrograms/g/day of both alpha-MSH and Nle4-D-Phe7 alpha-MSH. As far as opioids were concerned, while N-acetyl-beta-endorphin (beta-End) was ineffective, the activity of beta-End was dependent on dosage. Indeed, newborns treated with 0.03 microgram/g/day showed a slight, but significant, increase in weight, whereas a marked decrease in growth followed treatment with 0.3 and, mainly, 3 micrograms/g/day, with a final weight loss of 3.4 and 5.5%, respectively. All melanocortins exerted a positive action on muscular and brain trophism and, in addition, desacetyl-alpha-MSH also induced a rise of fat deposits. On the contrary, while the 0.03 microgram/g/day beta-End dose caused an increase in muscular and brain weight, the higher dosages of the opioid were detrimental, not only for muscle and brain, but also for both liver and spleen weight. A slight, although significant (P < 0.05), enhancement of serum dehydroepiandrosterone sulfate (DHEAS) level was found after the injection of 0.3 microgram/g desacetyl-alpha-MSH, whereas both the 0.3 and 3 micrograms/g doses of desacetyl-alpha-MSH and the 3 micrograms/g dose of alpha-MSH determined the rise of plasma androstenedione (P < 0.05). All tested melanocortins and opioids failed to modify the concentrations of corticosterone. Our results suggest that melanocortins and opioids can modulate early postnatal growth in rats either by direct or indirect mechanisms.

Failure of ketamine to interact with opiate receptors.

Ketamine, an anesthetic agent endowed with several morphine-like effects, failed to displace 3H-dihydromorphine or 3H-methionine-enkephalin from opiate receptors in the rat brain synaptosomal-mitochondrial membrane preparations. Furthermore, ketamine-induced analgesia in rats was not antagonized by naloxone, suggesting that this effect is not mediated by opiate receptors.

Circulating telopeptide type I is a peripheral marker of thyroid hormone action in hyperthyroidism and during levothyroxine suppressive therapy.

The aim of the present investigation was to evaluate the clinical performance of serum carboxy-terminal-1-telopeptide (ICTP), a new marker of bone resorption, in identifying peripheral overexposure to thyroid hormones, as compared with serum osteocalcin (OC) and serum sex hormone binding globulin (SHBG). Serum ICTP, SHBG, and OC were assayed by specific radioassays in three study groups. Group 1: 50 perimenopausal women on long-term levothyroxine (LT4) suppressive treatment; group 2: 29 women with untreated hyperthyroidism; group 3: 36 normal euthyroid women matched with group 1 patients for age, alcohol, smoking habits, and lifestyle. Serum concentrations of SHBG, ICTP, and OC were markedly increased in hyperthyroid patients, whereas only serum ICTP was slightly but significantly increased in LT4 treated patients. Serum ICTP had higher diagnostic value for hyperthyroidism when compared with SHBG and to OC (sensitivity: 100%, 71%, 55%; accuracy: 97%, 88%, and 76%, respectively). In group 1, increased serum ICTP was observed in 30 of 50 patients, whereas increased SHBG and OC were found only in 11 of 50 (p < .001). Serum free thyroid hormone concentrations correlated with circulating ICTP and SHBG, and the correlation with serum OC was of lower significance. In conclusion, serum ICTP is a sensitive and reliable marker of peripheral thyroid hormone activity at the bone level; its clinical performance is higher than OC and even better than SHBG. Thus, serum ICTP is better than other peripheral markers in monitoring LT4 suppressive therapy in patients at increased risk for osteoporosis such as perimenopausal women.

The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid antibodies in Sardinian schoolchildren: relationship to goiter prevalence and thyroid function.

The relationship among iodine intake, goiter prevalence, and thyroid autoimmunity remains controversial. In the present article, we report the prevalence of antithyroid antibodies (ATA) in relation to iodine intake, frequency of goiter, and thyroid function in a large group of Sardinian schoolchildren living in areas with borderline iodine sufficiency, or mild to moderate iodine deficiency. A total of 8,040 schoolchildren (4,194 males, 3,846 females, ages 6-15 years) from 29 communities were examined between 1986-1994. Thyroid size was assessed by palpation, according to the Pan American Health Organization (PAHO) criteria. In all cases antimicrosomal (MAb) or antithyroid peroxidase antibodies (TPOAb) and thyrotropin (TSH) were assayed. Urinary iodine was determined in a subgroup of 820 children. ATA was detected in 235 (2.92%) sera (88 males, 2.12%; 147 females, 3.82%; chi2 = 20.41, p < 0.0001). ATA prevalence ranged between 0.0%-7.3% in the 29 communities without any geographical correlation with goiter prevalence and urinary iodine excretion. However, ATA was more frequently detected in goitrous children, especially in females. The presence of ATA was not age-dependent in males, whereas a significant increase of ATA was observed in females older than 11 years of age. Seventy-seven (0.96%) children showed borderline to slightly increased serum TSH (>5.2-32 mU/L). Increased serum TSH concentration was more frequently found in children with ATA, especially at higher titers. In summary, our study in Sardinian schoolchildren indicates: (1) ATA display geographical heterogeneity, which seems to be unrelated to goiter prevalence and/or to iodine supply; (2) ATA are more frequently detected in females older than 11 years of age, suggesting that puberty has a role in determining the predominance in females of thyroid autoimmunity; (3) although most goitrous children are ATA-negative, the prevalence of ATA is increased in children with enlarged glands; (4) ATA is associated with an increased prevalence of subclinical hypothyroidism.

[Low levels of dehydroepiandrosterone sulfate in adult males with insulin-dependent diabetes mellitus]. / Bassi livelli di deidroepiandosterone solfato in maschi adulti affetti da diabete insulino dipendente.

UNLABELLED: Studies on animals and humans have suggested that dehydroepiandrosterone sulphate (DHEAS) has antiatherogenic effects. It has been hypothesized that insulin may have an atherogenic role and it has been reported recently that, surprisingly, DHEAS levels decreased in normal men and women during the hyperinsulinemic-euglycemic technique. Since a hyperinsulinemia frequently occurs during insulin therapy in patients with insulin dependent diabetes mellitus (IDDM), the present work was undertaken to determine whether DHEAS serum concentrations were decreased in IDDM patients as compared to controls and if so, to discover the possible causes. To this, purpose, out of 805 outpatients afferent to our Diabetes Centre from 1989 to 1992, three groups were selected on the basis of the criteria described below. Known interferences with the DHEAS serum concentrations such as gender (all males), age (aged 20-40 years) and Body Mass Index (BMI < 30) were excluded. Group A (cross-sectional study) was made up of 15 IDDM patients on insulin treatment with good metabolic control (HbA1C < 8%); group B (control study) was made of 18 healthy subjects (these patients were selected also on the basis of their normal oral glucose tolerance test) and group C (longitudinal study) was made up of 7 IDDM patients who had been examined previously and who were on insulin treatment. METHODS: In all three groups serum concentrations of DHEAS, 17 OH progesterone (17 OHP), delta 4 androstenedione (A4) and cortisol (F) were measured. In 10 patients from group A and in 9 patients from group B the ACTH test (9.25 mg IM Synacthen) was administered and the same hormonal pattern was measured after 60 min. In group C the same hormonal evaluation was performed 5 +/- 2.8 months after commencement of insulin therapy. RESULTS: DHEAS serum concentrations were significantly decreased in group A (median 2.9; range 1.1-5.2 mumol/l) with respect to group B (median 5.7; range 3.0-9.5 mumol/l) (p < 0.0012). However, the serum concentrations of 17 OHP (median 3.9 nm/l; range 2.9-6.9 nm/l and A4 (median 5.2 nm/l; range 1.8-10.2 nm/l) were also significantly reduced, while cortisol levels and the 17 OHP/A4 ratio were comparable to group B. After administration of ACTH, the delta increment in cortisol percentage showed a frank increase (55.1%) in group A with respect to group B (33.1%) (p < 0.01). The rise in DHEAS showed a lower increase in group A (10.2%) with respect to group B (65.5%) even though not statistically significant, while the other hormones showed an overlap between the two groups. In group C the serum concentrations of hormones before insulin therapy did not show any statistical differences with respect to the values in group B. A second evaluation, which was performed during insulin therapy, showed that only the 17 OHP/A4 ratio tended towards higher values with respect to pretherapy values (1.1 and 0.6 respectively; p = 0.07). In conclusion our data confirm low DHEAS levels during chronic insulin administration therapy. The underlying mechanism could be a general aspecific reduction in the activity of P 450 C 21 SCC enzymes in contrast with the specific inhibition of 17.20-lyase obtained during insulin bolus. Whether the low serum concentrations of DHEAS can determine an atherogenic effect of insulin needs further investigation, but the hormone could constitute a new parameter for the follow-up of patients affected by diabetes mellitus.