Endurance training improves heart rate on-kinetics in women with subclinical hypothyroidism: a preliminary study.

PURPOSE: The aim of the study was to evaluate the effect of endurance training on heart rate (HR) on-kinetics in patients with subclinical hypothyroidism (SH). METHODS: Eighteen women were randomly assigned to trained group (TG) or control group (CG). Both groups performed three tests at 50 W in a cycle ergometer for 6 min. HR kinetics was obtained during the tests and the mean response time (MRT), which is equivalent to the time taken to reach 63% of the HR at steady state, was extracted. The TG was then submitted to 12 weeks of endurance training (50 min, 3x/week, intensity between 70 and 85% of the maximum HR predicted for the age). Statistical analysis was performed by the mixed analysis of variance. RESULTS: At baseline, TG and CG were similar for TSH (7.7 ± 3.1 vs. 6.9 ± 3.3 mUI/L, p = 0.602, respectively) and FT4 (12.31 ± 1.51 vs. 12.20 ± 1.89 pmol/L, p = 0.889, respectively). After adjustment for body mass index and age, interactions between moment (baseline or after 12 weeks) and group (trained or control) were only significant for MRT (TG: 39.6 ± 10 to 28.9 ± 8.4 s, CG: 53.6 ± 20.3 to 55 ± 19.7 s, p = 0.001) and physical activity level (CG: 7.3 ± 0.7 to 8 ± 0.9, CG: 6.8 ± 0.8 in both moments, p = 0.005). CONCLUSION: The preliminary results suggest that 12 weeks of endurance training improve HR on-kinetics and physical activity level in SH.

Military field training exercise with prolonged physical activity and sleep restriction causes hormonal imbalance in firefighter cadets.

PURPOSE: To evaluate the impact of the "Search and rescue" field military training exercise (SR_FTX) on hormonal modulation and identify their possible correlation with physical and cognitive performance. METHODS: An observational (before and after) study was carried out, with male firefighters cadets (n = 42; age = 23[22;27] years) undergoing a nine-day military exercise (SR_FTX). The Countermovement jump (physical performance), the Stroop test (cognitive alertness), and blood tests for testosterone, cortisol, GH, and IGF-1 were applied. Wilcoxon for paired samples and Spearman's correlation tests were used. RESULTS: Testosterone (751.10 [559.10;882.8] vs. 108.40 [80.12;156.40] ng/dL) and IGF-1 (217.5 [180;239.30] vs. 105 [93;129] ng/mL) significantly decreased while GH (0.10 [0.06;0.18] vs. 1.10 [0.58;2.28] ng/mL) and cortisol (9.60 [8.20;11.55] vs. 15.55 [12.28;18.98] ug/dL) significantly increased. Physical performance (31.2 [30.04;35.4] vs. 21.49 [19,02;23,59] cm) and cognitive alertness were significantly worse after SR_FTX (Congruent task: 1,78 (0183) vs. 1,56 (0185) response/s and incongruous task: 1,23 (0191) vs. 1,02 (0207) response/s). The physical performance showed a strong correlation with testosterone (rho = 0.694) and regular correlations with both IGF-1 (rho = 0.598) and cortisol (rho = - 0.580). The Stroop test presented weak correlations with GH (rho = - 0.350) and cortisol (rho = - 0.361). CONCLUSION: SR_FTX negatively impacted hormonal modulation, physical and cognitive performance. These findings could help commanders decide to replace the employed firefighters in a real mission more frequently. Also, if the real scenario allows, they could think about providing better work conditions, such as improving caloric intake and rest periods, to preserve the military performance and health.

MCT8 is Downregulated by Short Time Iodine Overload in the Thyroid Gland of Rats.

Wolff-Chaikoff effect is characterized by the blockade of thyroid hormone synthesis and secretion due to iodine overload. However, the regulation of monocarboxylate transporter 8 during Wolff-Chaikoff effect and its possible role in the rapid reduction of T4 secretion by the thyroid gland remains unclear. Patients with monocarboxylate transporter 8 gene loss-of-function mutations and monocarboxylate transporter 8 knockout mice were shown to have decreased serum T4 levels, indicating that monocarboxylate transporter 8 could be involved in the secretion of thyroid hormones from the thyroid gland. Herein, we aimed to evaluate the regulation of monocarboxylate transporter 8 during the Wolff-Chaikoff effect and the escape from iodine overload, besides the importance of iodine organification for this regulation. Monocarboxylate transporter 8 mRNA and protein levels significantly decreased after 1 day of NaI administration to rats, together with decreased serum T4; while no alteration was observed in LAT2 expression. Moreover, both monocarboxylate transporter 8 expression and serum T4 was restored after 6 days of NaI. The inhibition of thyroperoxidase activity by methimazole prevented the inhibitory effect of NaI on thyroid monocarboxylate transporter 8 expression, suggesting that an active thyroperoxidase is necessary for MCT8 downregulation by iodine overload, similarly to other thyroid markers, such as sodium iodide symporter. Therefore, we conclude that thyroid monocarboxylate transporter 8 expression is downregulated during iodine overload and that the normalization of its expression parallels the escape phenomenon. These data suggest a possible role for monocarboxylate transporter 8 in the changes of thyroid hormones secretion during the Wolff-Chaikoff effect and escape.

Evaluation of epicardial fat tissue thickness as a marker of cardiovascular risk in patients with subclinical hypothyroidism.

BACKGROUND: Epicardial fat thickness (EFT) has been evaluated as a marker of cardiovascular disease, with good correlation with classical cardiovascular risk factors in the general population. The aim of this study was to evaluate the EFT in subclinical hypothyroidism (SCH), in comparison to a group without thyroid dysfunction. METHODS: A cross-sectional study was performed with 100 participants, including 52 SCH patients and 48 individuals without any thyroid dysfunction (euthyroid group-EU). Transthoracic echocardiography (TE), thyroid hormone levels, lipid profile, and assessment of body composition by bioelectrical impedance (BIA) and anthropometry were measured in all subjects. RESULTS: The SCH and EU groups were comparable with respect to age, gender, and Framingham risk scores. Serum thyroid-stimulating hormone (TSH) was 6.7 ± 1.4 mIU/L in the SCH group and 2.0 ± 0.84 mIU/L in the control group. EFT was similar in both groups (SCH 3.5 ± 1.3 mm, EU 3.5 ± 1.1 mm, p = 0.43). EFT showed a slight trend for a positive correlation with serum TSH in the SCH group (r s = 0.263, p = 0.05). EFT correlated with the body fat percentage in the SCH group (r s = 0.350, p = 0.03) and EU group (r s = 0.033, p = 0.04). EFT in this cohort was not independently correlated to changes in TSH and Framingham risk score. CONCLUSIONS: EFT determination by TE does not seem to be a good marker of cardiovascular risk in SCH patients with serum TSH <10.0 mIU/L and no pre-existing cardiovascular morbidity.

Surgical approach and radioactive iodine therapy for small well-differentiated thyroid cancer.

BACKGROUND: Management of small well-differentiated thyroid cancer (DTC) has generated much debate regarding the surgical approach and radioactive iodine treatment (RAI). AIM: The aim of the study was to evaluate the impact of surgical extension and RAI on the outcome of DTC ≤2 cm. METHODS: A retrospective analysis of 176 cases of DTC ≤2 cm was performed. RESULTS: At diagnosis, tumor size was 1.38 ± 0.55 cm, age 40.2 ± 13.6 years. After a mean follow-up period of 14.1 ± 4.5 years, 15.9 % patients had recurrent/persistent structural disease, with cervical neck disease (thyroid gland area and/or cervical lymph nodes) in 11.9 % cases and distant metastasis in 5.1 %. Disease specific mortality was of 1.1 %. No difference in outcome was observed between patients submitted to total or subtotal thyroidectomy. After total and subtotal thyroidectomy, the rate of recurrent/persistent structural disease was 19.1 and 10.6 % (p = 1.00), respectively. Using the multivariate cox proportion hazards analysis, no difference in the clinical outcome was observed after total or subtotal thyroidectomy (p = 0.703) neither after RAI (p = 0.807). Similar results were observed after stratification by tumor size. Multifocal disease (p = 0.007), extra-thyroid extension (p = 0.007) and presence of lymph node metastasis (p = 0.000) were associated with unfavorable outcome. CONCLUSIONS: Total thyroidectomy and RAI did not improve clinical outcomes of DTC ≤2.0 cm when compared with less extensive surgery and no RAI in selected patients. Therefore, in carefully selected patients with DTC ≤2.0 cm and no unfavorable risk factors (multifocal disease, extra-thyroid extension, lymph node and/or distant metastasis), less extensive surgery and no RAI may be acceptable treatment options.

A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in graves' ophtalmopathy patients with different clinical activity score.

The present study describes the preliminary results of the use of 99mTc-anti-TNF-α scintigraphy as a new diagnostic approach to evaluate patients presenting with Graves' ophthalmopathy (GO). Patients (n=25) presenting at different inflammatory stages of GO and 10 healthy volunteers underwent 99mTc-anti-TNF-α scintigraphy. Images were obtained 15 min after the intravenous injection of 370 MBq (10 mCi) 99mTc-anti-TNF-α. Planar images were obtained in a 256×256 matrix (each lasting 5 min) and single photon emission computed tomography (SPECT) scan lasting 13 min. Regions of interest (ROI) were drawn on the orbit and cerebral hemispheres. The uptake of 99m Tc-anti-TNF-α in these regions was compared and positive scintigraphy established when the ROI was >2.5. In addition, uptake for each positive exam was scored as either slight (2.6-5.1), moderate (5.2-7.6), or high (>7.6). In this pilot study, 69 orbits were evaluated (1 patient had only 1 eye), and 27 had a positive CAS (≥3/7). Scintigraphies were positive in 38 orbits. Comparing the results of the exams with CAS, a high sensitivity and negative predictive values were determined for scintigraphy (96.3% and 96.7%, respectively). However, the specificity and the positive predictive values were 71.4% and 68.4%, respectively, with an accuracy of 81.2%. The exclusion of examinations that were slightly positive from the analysis resulted in an improvement in test accuracy (95.5%). The preliminary results suggest that 99mTc-anti-TNF-α scintigraphy is a promising procedure for the evaluation of active orbital inflammation in GO.

How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study.

BACKGROUND: Studies from every continent have shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range. However, to date, there are no consistent data about Brazil. OBJECTIVES: To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil. METHODS: Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro - UFRJ, Unicamp, Universidade Federal do Paraná - UFPR and Universidade Federal do Ceará-UFC) answered a questionnaire that inquired about clinical and biochemical conditions, social- economic status, life quality and clinicians' orientations as well as their understanding about the information given. Serum TSH was checked close to the interview. RESULTS: 2292 consecutive patients met the inclusion criteria. Mean age 51.2 yr and TSH values between 0.4 and 4.0 mUI/l were considered to be within the reference range. Among all patients taking thyroid medication, 42.7% had an abnormal serum TSH (28.3% were undertreated and 14.4% were overtreated). Approximately all patients (99%) took LT4 in the morning but less than 30 min before breakfast (85.4%). Regarding the clinicians' orientations: 97.5% of the patients were instructed to take the medication daily, and 92.6% to take 30 min before breakfast (92.6%). However, only 52.1% were told not to take LT4 along with other medication. CONCLUSIONS: Our study found that a significant number of patients taking thyroid hormones were not in the therapeutic range. Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.

Current recommendations for levothyroxine treatment of differentiated thyroid cancer patients are not properly implemented in clinical practice.

BACKGROUND: Levothyroxine (L-T4) treatment aims to minimize the risk of differentiated thyroid cancer (DTC) recurrence and should be tailored to patient risk stratification and potential morbidity from adverse effects. AIM: To evaluate the effectiveness of current recommendations on L-T4 treatment of DTC patients in clinical practice. MATERIAL AND METHODS: We submitted to in-person interviews and revised the charts of 139 low-risk (LR) and 57 not-low-risk (NLR) DTC patients. A second evaluation made 24-60 months after surgery reclassified 131 patients who maintained (thyroglobulin) Tg≤2 ng/dl with no evidence of relapse/recurrence as LR, whereas the remaining 65 cases were considered NLR. RESULTS: Only 27% LR patients were appropriately controlled; 18% were kept suppressed; 49% maintained serum TSH levels between 0.11-0.4 mU/l; 21% had TSH=2.5- 4.5 mU/l; and 12% TSH>4.5 mU/l. Among the NLR patients, 24 (37%) of the patients presented serum TSH levels above goal, including 13 (20%) patients with TSH>4.5 mU/l. There were 4 NLR elders whose TSH levels were kept between 0.41 and 4.5 for medical reasons; likewise, 28 NLR patients maintained with low but not undetectable serum TSH levels had cardiovascular and/or bone risk factors, but all the remaining 24 NLR patients were not adequately controlled because of poor treatment compliance. On the other hand, 45% of 152 inappropriately controlled patients presented risks for bone fractures, including 33 patients kept with low serum TSH levels without medical indication. CONCLUSION: We concluded that guidelines are not adequately applied and alternative strategies aiming to increase adherence are urgently needed for DTC patients.

Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism.

Although muscle metabolism and exercise capacity seem to be affected in patients with subclinical hypothyroidism, there is little evidence indicating improvement of the exercise tolerance due to levothyroxine (L-T(4)) replacement. The aim of the present study was to verify possible cardiopulmonary changes during exercise in patients with subclinical hypothyroidism on L-T(4) replacement with a normal serum TSH for six months. Twenty-three patients with subclinical hypothyroidism were randomized into treated (no.=11) and untreated (no.=12) patients. A cardiopulmonary test was performed with a treadmill, using the modified Balke protocol. Heart rate, oxygen uptake, minute ventilation and other cardiopulmonary parameters were assessed at the 5th minute of exercise. FT4 levels increased while TSH normalized after hormone replacement. Oxygen uptake decreased significantly after hormone replacement (24.1+/-6.3 vs 17.1+/-4.2 ml x kg x min(-1); p=0.03).Minute ventilation also showed an enhanced performance in treated patients (28.0+/-8.1 vs 23.5+/-5.6 l x min(-1); p=0.03), as did the heart rate (128+/-17 vs 121+/-17 bpm; p=0.03). There were no changes in the untreated group. The results demonstrate that submaximal cardiopulmonary exercise performance improved after six months of TSH normalization and this improvement can help enhance the ability to carry out daily life activities in patients with subclinical hypothyroidism.

Is there a relationship between spontaneous GH secretion, anthropometric parameters and exercise capacity in healthy men over 50 years?

BACKGROUND: The use of growth hormone (GH) in deficient adults has already been demonstrated to result in several benefits regarding metabolic parameters, body composition and quality of life. Due to the similarities between GH deficiency in adults and the aging process, the concept of somatopause has emerged. OBJECTIVES: Correlate the GH secretion profile in healthy men older than 50 years with anthropometric parameters and exercise capacity. PATIENTS AND METHODS: Twenty-nine healthy male were selected, with a mean age of 57.9+/-4.2 years (range 50-66). After hospital admission, body mass index (BMI), body composition (fat mass) and abdominal circumference, 24-h GH profile, GH peak and basal IGF-I were evaluated, and all the patients underwent a treadmill stress testing to estimate exercise capacity with the Bruce protocol, with evaluation of the maximum oxygen peak, maximum heart rate and METs. All the results are shown as mean+/-Std deviation: BMI -26.5+/-4.9kg/m2, percent fat mass -27.1+/-6.2%, abdominal circumference -92.1+/-10.1cm, 24h GH profile -0.3+/-0.2ng/dl, peak GH -2.5+/-2.0ng/dl, IGF-I -202.4+/-72.4ng/dl, maximum oxygen peak -31.9+/-6.8L, maximum heart rate - 161.4+/-7.5 bpm and METs - 9.1+/-1.9. After regression analysis using the GH secretion profile (mean GH in 24h, spontaneous peak GH and basal IGF-I) as dependent variable, no correlations were found between these and the other evaluated parameters.

Acute thyroiditis due to septic emboli derived from infective endocarditis.

Acute infectious thyroiditis is a rare condition of the thyroid gland, most often arising in children with congenital conditions connecting the thyroid directly to the oropharynx, such as a piriform fistula or thyroglossal duct. We report a case of acute thyroiditis due to septic emboli derived from infective endocarditis.

Association of insulin resistance and nocturnal fall of blood pressure in GH-deficient adults during GH replacement.

The GH deficiency syndrome in adults is characterized by changes in body composition, metabolic, cardiovascular and psychological profile. Such alterations fit the metabolic syndrome. Changes of blood pressure (BP) levels related to the presence of insulin resistance (IR) may be present in the GH-deficient adult prior to or after therapy with recombinant GH (hGH). The purpose of the study was to assess the relationship between BP and IR in GH-deficient adults after 24 months of replacement with hGH. Thirteen GH-deficient adults were studied [7 men and 6 women, with an average age of 38.6+/-14.14 yr body mass index (BMI) 25.83+/-2.26 kg/m2]. The BP was assessed by means of ambulatory monitoring of BP (AMBP), prior to the treatment and 12 and 24 months after replacement with hGH. Glucose metabolism was assessed by the homeostatic model assessment (HOMA), during the same periods. The average dosage of hGH utilized was 0.67+/-0.15 mg/day. In the analysis of BP levels, we observed a decrease of the diurnal systolic BP (SB P) (p=0.043) and a reduction of the diurnal systolic (p=0.002) and diastolic pressure loads (p=0.038). During the night there were no changes in BP levels. We observed an increase in the percentage of patients with a non-physiological nocturnal fall (non dippers) after replacement with hGH (61.53%). The mean HOMA, insulin and glucose in the fasting state did not present any statistically significant changes. Although the patients within the nondipper group had higher HOMA and insulin levels throughout the study, there were no changes in any of these parameters after GH replacement. All patients with HOMA >2.5 were within the non-dipper group, whereas all dippers had HOMA <2.5. In conclusion, 24 months of therapy with hGH do not seem to have affected glucose homeostasis, and since there is no relationship with the increase of the percentage of non-physiological nocturnal fall, we will need a longer observation time to discover the effects of this finding.

Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12.

The majority of somatotropinomas are sporadic, although a small number occur with a familial aggregation, either as a component of an endocrine neoplasia complex that includes multiple endocrine neoplasia type 1 (MEN-1) and Carney complex (CNC) or as isolated familial somatotropinomas (IFS). IFS is defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit MEN-1 or CNC. This rare disease is associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN-1 gene, although the MEN-1 sequence and expression appear normal. These data suggest the presence of another tumor suppressor gene located at 11q13 that is important in the control of somatotrope proliferation. To establish linkage of IFS to 11q13 and to define the candidate interval of the IFS gene, we performed haplotype and allelotype analyses on two families with IFS. Collectively, allelic retention in one tumor and a recombinant haplotype in an affected individual mapped the tumor suppressor gene involved in the pathogenesis of IFS to a region of 8.6 cM between polymorphic microsatellite markers D11S1335 and INT-2 located at chromosome 11q13.1-13.3. Maximum two-point LOD scores for five markers within this region were 3.0 or more at theta = 0.0. As somatotropinomas are the predominant pituitary tumor subtype associated with CNC and arise before 30 yr of age, which is strikingly similar to the age at diagnosis for IFS, we explored the possibility that the putative CNC genes might also contribute to the pathogenesis of IFS. Although the genetic defect responsible for the complex is unknown, CNC has been mapped by linkage analysis to chromosomes 2p15-16 and 17q23-24 in different kindreds. Two-point LOD scores less than -2.0 were obtained using marker D17S949 from chromosome 17q23-24, excluding linkage. However, LOD scores of 2.5 were obtained for markers within 2p16-12; therefore, linkage of IFS to chromosome 2p cannot be excluded. This report establishes linkage of the tumor suppressor gene involved in the pathogenesis of IFS to chromosome 11q13.1-13.3 and identifies a potential second locus at chromosome 2p16-12.

Ca(2+)/nicotinamide adenine dinucleotide phosphate-dependent H(2)O(2) generation is inhibited by iodide in human thyroids.

A calcium and NAD(P)H-dependent H(2)O(2)-generating activity has been studied in paranodular thyroid tissues from four patients with cold thyroid nodules and from nine diffuse toxic goiters. H(2)O(2) generation was detected both in the particulate (P 3,000 g) and in the microsomal (P 100,000 g) fractions of paranodular tissue surrounding cold thyroid nodules (PN), with the same biochemical properties described for NADPH oxidase found in porcine and human thyroids. In PN tissues, the particulate NADPH oxidase activity (224 +/- 38 nmol H(2)O(2) x h(-1) x mg(-1) protein) was similar to that described for the porcine thyroid enzyme. However, no NADPH oxidase activity was detectable in the particulate fractions from eight diffuse toxic goiter patients treated with iodine before surgery; all but one also received propylthiouracil or methimazole in the preoperative period. Thyroid cytochrome c reductase (diffuse toxic goiters = 438 +/- 104 nmol NADP(+) x h(-1) x mg(-1) protein; PN = 78 +/- 10 nmol NADP(+) x h(-1) x mg(-1) protein) and thyroperoxidase (diffuse toxic goiters = 621 +/- 179 U x g(-1) protein; PN = 232 +/- 121 U x g(-1) protein) activities were unaffected by iodide. Thus, the human NADPH oxidase seems to be inhibited by iodinated compounds in vivo and probably is an enzyme involved in the Wolff-Chaikoff effect. Our findings reinforce the hypothesis that thyroid NADPH oxidase is responsible for the production of H(2)O(2) necessary for thyroid hormone biosynthesis.

Goiter and hypothyroidism in two siblings due to impaired Ca(+2)/NAD(P)H-dependent H(2)O(2)-generating activity.

We report herein the study of two siblings (DESM and DSM) with hypothyroidism, goiter, and positive perchlorate discharge tests (50% and 70%) in a family (M) with no history of consanguinity. Thyroid gland histology showed a predominance of hyperactive follicles, with high epithelial cells and variable colloid content. Thyroid peroxidase iodide oxidation (DESM, 1034; DSM, 1064 U/g protein) and albumin iodination (DESM, 16; DSM, 8 nmol I/mg protein) activities were within the normal range. Tg content was normal in both glands compared with that in diffuse toxic goiter (DESM, 28; DSM, 17; diffuse toxic goiter, 19 mg/g tissue), and Tg could be normally iodinated by thyroid peroxidase in vitro (DESM, 3.4; DSM, 4.3; diffuse toxic goiter, 6.3 nmol I/mg Tg). Thyroid cytochrome c reductase activities in these goiters were higher than that in paranodular tissues (DESM, 473; DSM, 567; paranodular tissues, 78 nmol NADP(+)/h/mg protein). However, thyroid NADPH oxidase activities were very low both in the particulate 3,000 x g (DESM, 4.8; DSM, 44; paranodular tissues, 224 nmol H(2)O(2)/h/mg protein) and in the particulate 100,000 x g fractions (DESM, 40; DSM, 47; paranodular tissues, 200 nmol H(2)O(2)/h/mg protein). Thus, a decreased Ca(2+)/NAD(P)H-dependent H(2)O(2) generation is the probable cause of the organification defect in these goiters.

Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene.

Familial acromegaly/gigantism occurring in the absence of multiple endocrine neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families since the biochemical diagnosis of GH excess became available, and the genetic defect is unknown. In the present study we examined 2 unrelated families with isolated acromegaly/gigantism. In family A, 3 of 4 siblings were affected, with ages at diagnosis of 19, 21, and 23 yr. In family B, 5 of 13 siblings exhibited the phenotype and were diagnosed at 13, 15, 17, 17, and 24 yr of age. All 8 affected patients had elevated basal GH levels associated with high insulin-like growth factor I levels and/or nonsuppressible serum GH levels during an oral glucose tolerance test. GHRH levels were normal in affected members of family A. An invasive macroadenoma was found in 6 subjects, and a microadenoma was found in 1 subject from family B. The sequence of the GHRH receptor complementary DNA in 1 tumor from family A was normal. There was no history of consanguinity in either family, and the past medical history and laboratory results excluded MEN-1 and the Carney complex in all affected and unaffected screened subjects. Five of 8 subjects have undergone pituitary surgery to date, and paraffin-embedded pituitary blocks were available for analysis. Loss of heterozygosity on chromosome 11q13 was studied by comparing microsatellite polymorphisms of leukocyte and tumor DNA using PYGM (centromeric) and D11S527 (telomeric), markers closely linked to the MEN-1 tumor suppressor gene. All tumors exhibited a loss of heterozygosity at both markers. Sequencing of the MEN-1 gene revealed no germline mutations in either family, nor was a somatic mutation found in tumor DNA from one subject in family A. The integrity of the MEN-1 gene in this subject was further supported by demonstration of the presence of MEN-1 messenger ribonucleic acid, as assessed by RT-PCR. These data indicate that loss of heterozygosity in these affected family members appears independent of MEN-1 gene changes and suggest that a novel (tissue-specific?) tumor suppressor gene(s) linked to the PYGM marker and expressed in the pituitary is essential for regulation of somatotrope proliferation.

Computed tomography and ultrasonography of the adrenal glands in paracoccidioidomycosis. Comparison with cortisol and aldosterone responses to ACTH stimulation.

Fifteen patients with proven disseminated paracoccidioidomycosis (PCM) had computed tomography (CT) and ultrasonography (US) performed to evaluate the form, shape, density and size of their adrenal glands. Plasma and urinary cortisol were determined and adrenal reserve assessed by measuring the cortisol and aldosterone responses to synthetic ACTH. The adrenal CT showed unilateral lesions in two cases and bilateral in another four. The US study showed more frequent alterations, unilateral in seven and bilateral in three subjects. Combining both methods increased the sensitivity to 85% of the cases. All patients had normal plasma cortisol concentrations and normal or increased urinary cortisol excretion. Plasma aldosterone concentration was also normal except in one patient with hypokalemia. Seven patients showed diminished cortisol responses, five had subnormal aldosterone responses and in five plasma aldosterone concentration increased more than normally after stimulation by ACTH. There was an incidence of limited adrenal reserve in 53% of the patients on ACTH stimulation. No correlation was evident between the disorders in adrenal steroid responses to ACTH and changes in morphology revealed by CT and/or US.

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference.

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 +/- 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was lower in men than in women (p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.

Treatment of symptomatic retinal breaks.

Forty-three patients with symptomatic retinal breaks were treated with photocoagulation and a comparable group of 43 patients were treated with cryopexy. All patients had either a vitreous hemorrhage, or photopsia and floaters. Most of the breaks were of the horseshoe type. Of the patient eyes, 14% (six patients) in both groups developed new retinal tears without detachment during the long term postoperative observation. The new breaks were treated with the method used for the original breaks, and no scleral surgery was necessary. The incidence of retinal detachment was 7% in patients treated with photocoagulation and 11.6% in patients with cryocoagulation, but two cases that developed retinal detachment arising from new tears years after the initial procedure were included.

Skeletal muscle function and body composition of patients with hyperthyroidism.

The purpose of this study was to determine whether the improvement in muscle performance after treatment of hyperthyroidism is only a result of an increased muscle mass or if it also depends on the improvement of intrinsic contractile function. Nine patients with Graves' disease were evaluated 1) at the time of diagnosis, 2) after 1 wk of monotherapy with propranolol, and 3) after the euthyroid state had been achieved with antithyroid drugs. At each evaluation the patients were submitted, on the dominant side, to anthropometric measurements and to skeletal muscle function tests to determine the maximal static voluntary contraction (MAX) and endurance (END); "endurance" is defined as the time limit at maintaining 30% of MAX. Three movements were tested: hip flexion, ankle dorsiflexion, and handgrip. Body weight changed from 53.4 +/- 3.2 to 58.2 +/- 2.9 kg (P = 0.004) and the sum of skinfold-corrected limb circumferences changed from 90.7 +/- 3.1 to 94.4 +/- 3.1 cm (P = 0.017). MAX and END of all movements increased at the end of the study even if adjusted for the sum of skinfold-corrected limb circumferences: Hip flexion: MAX 20.60 +/- 3.32 to 31.26 +/- 5.07 g.cm-1, END 0.43 +/- 0.18 to 1.18 +/- 0.42 kg.s-1.cm-1. Ankle dorsiflexion: MAX 12.34 +/- 1.97 to 26.88 +/- 2.46 g.cm-1, END 0.97 +/- 0.28 to 2.50 +/- 0.58 kg.s-1.cm-1; Handgrip: MAX: 2.20 +/- 0.23 to 2.9 +/- 0.2 g.cm-1, END 0.13 +/- 0.01 to 0.20 +/- 0.02 kg.s-1.cm-1. In conclusion, improved muscle performance resulting from the treatment of hyperthyroidism is a consequence of an enhanced intrinsic muscle function as well as a greater muscle mass.