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.

Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter.

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 +/- 62.0 mL, 20 females, 2 males, 64 +/- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +/- 17.6%) and II (21.6 +/- 17.8%), but not in group III (2.7 +/- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +/- 18.1%) and II (37.4 +/- 27.1%), but not in group III (19.0 +/- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6 percent) and II (21.6 ± 17.8 percent), but not in group III (2.7 ± 15.3 percent). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1 percent) and II (37.4 ± 27.1 percent), but not in group III (19.0 ± 24.3 percent). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Wound healing in colonic anastomosis in hypothyroidism.

Colonic anastomosis healing in hypothyroidism was evaluated. Twenty Wistar rats were separated into two groups: the study group (n = 10), which underwent total thyroidectomy to induce hypothyroidism, and the control group (n = 10). After 10 weeks, hypothyroid status was confirmed by blood tests (p < 0.0001). Three days later, a colonic anastomosis was performed, and the animals were sacrificed 1 week later. The colon containing the anastomosis was resected for bursting strength tests and histological studies. The slides were stained with hematoxylin-eosin and with Sirius red to quantify and classify the collagen. Reduced values were found for the bursting strength test (p = 0.0006) and for collagen density in the experimental group. There was a prevalence of immature type III collagen (p < 0.0001) and a decrease in mature type I collagen (p < 0.0001) in the hypothyroid group.

Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre.

CONTEXT: High doses of (131)I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid-stimulating hormone (rhTSH) is an adjuvant to enhance (131)I uptake, allowing a decrease in radiation activity and enhancing (131)I efficacy. OBJECTIVE: To evaluate whether rhTSH increases the efficacy of a fixed activity of (131)I for the treatment of MNG. DESIGN: Two-year, observational, placebo-controlled study. SETTING: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B) or placebo (C). A fixed activity of 1.11 GBq of (131)I was administered 24 h after rhTSH or placebo. PATIENTS: A total of 28 outpatients (26 females and two males) with MNG. MEASUREMENTS: TSH, free T4, T3, thyroglobulin (Tg) and TV. RESULTS: Basal radioactive iodine uptake and TV values were comparable among all groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n = 2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three in B and three in C). TV reduction was similar between A and B (37.2 +/- 25.5% vs. 39.3 +/- 27.9%, p = 0.88), but different from the non-significant reduction in C (15.3 +/- 28.3%, p = 0.08). CONCLUSIONS: Followed by 1.11 GBq, a very low dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses increased the efficacy of radioiodine. Adverse events were mild, transient and readily treatable.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4 percent (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6 percent), painful thyroiditis (29.4 percent) and hypothyroidism (52.9 percent). Thyroid volume was reduced by 34.3 ± 14.3 percent after 6 months (P < 0.001) and by 46.0 ± 14.6 percent after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone.

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 +/- 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 +/- 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 +/- 9.7 to 49.6 +/- 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 +/- 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 +/- 0.48 ng/dL for free-T4, 204.61 +/- 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 +/- 14.3% after 6 months (P < 0.001) and by 46.0 +/- 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine.

The use of 131I in the treatment of multinodular goiters (MNG) is well established. We evaluated the effect of 30 microCi 131I (1.11 GBq) in 18 patients with MNG with the aid of two injections of 0.1 mg recombinant human TSH (rhTSH), given on d 1 and 2. A dose of 30 microCi 131I was given on d 3. TSH, T3, free T4, and thyroglobulin were measured on d 1, 2, 3, 5, 10, 30, 60, 90, and 180, and antithyroid antibodies were measured on d 1, 30, 90, and 180. Twenty-four-hour 131I uptake measured 1-3 months before rhTSH increased from 12.3 +/- 6.2 to 53.5 +/- 10.9% (P < 0.0001), free T4 from 1.3 +/- 0.2 to peak 3.2 +/- 1.1 ng/dl levels (P < 0.0001), T3 from 113.9 +/- 35.0 to peak 332.2 +/- 123.0 ng/dl levels (P < 0.0001), TSH from 0.76 +/- 0.71 to peak 18.9 +/- 5. 3 mU/liter levels (P < 0.0001), and thyroglobulin from 280.9 +/- 370.0 to peak 1838.5 +/- 1360.7 ng/dl levels (P = 0.001). Painful thyroiditis (33%) and mild thyrotoxicosis (39%) constituted minor side effects. There were no changes in echocardiographic parameters, done before and after rhTSH administration, on d 3. Hypothyroidism developed in 65%. Mean goiter size, measured by computed tomography, decreased from 97.9 +/- 45.4 to 65.5 +/- 47.3 ml (P < 0.0001; reduction: 39 +/- 19%) after 6 months. We conclude that rhTSH is a safe and efficient therapeutic tool in the treatment of MNG allowing the use of outpatient therapeutic 131I doses.

Aggressive behavior of papillary microcarcinoma in a patient with Graves' disease initially presenting as cystic neck mass.

Prognosis of papillary carcinoma of the thyroid associated with Graves' disease is controversial; nevertheless, tumors smaller than 1 cm (microcarcinoma) are usually considered to render a good prognosis. We describe a patient with Graves' disease who developed a lateral cystic neck mass that was later confirmed to be a metastatic lymph node from papillary thyroid microcarcinoma. Contrary to having a good prognosis with a microcarcinoma, our patient developed bilateral lung metastases. The possible role of thyroid stimulating immunoglobulins in the aggressive course of the tumor is discussed.

Amyloidotic muscle pseudohypertrophy: case report.

The authors report one case of amyloidosis associated with muscular pseudohypertrophy in a 46-year-old woman, who developed weakness, macroglossia and muscle hypertrophy associated with primary systemic amyloidosis. Electromyography showed a myopathic pattern and bilateral carpal tunnel syndrome. The muscle biopsy presented with a type I and II fiber hypertrophy and infiltration of amyloid material in the interstitious space and artery walls. She underwent bone marrow transplantation with stabilization and subjective improvement of the clinical picture.

Efficacy of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of complex thyroid nodules.

Cystic thyroid nodules are considered to be one of the major causes of nondiagnostic and false-negative results on conventional fine-needle aspiration biopsy, thus limiting the potential of this method for the evaluation of complex (solid-cystic) thyroid nodules. Although ultrasound-guided fine-needle aspiration biopsy has emerged as a highly effective diagnostic method for the assessment of nonpalpable and difficult to palpate nodules, its role in complex nodules has not yet been carefully evaluated. In this study, we report the efficacy of ultrasound-guided fine-needle aspiration biopsy in 124 complex nodules in 113 patients. This method proved to be highly effective, yielding a satisfactory specimen for cytological evaluation in 94% of the nodules, suggesting that it is an excellent modality for the evaluation of complex nodules and also for the reevaluation of those nodules with a nondiagnostic result on conventional fine-needle aspiration biopsy.

Concomitant presentation of Hashimoto's thyroiditis and maltoma of the thyroid in a twenty-year-old man with a rapidly growing mass in the neck.

We report an uncommon case of a 20-year-old man, who noted a painless, growing mass in his neck, which appeared in a weekend, associated with moderate dysphagia and weakness. Laboratory examination revealed an elevated serum thyrotropin of 25 mU/L, normal serum triiodothyronine and thyroxine levels, and high titers of antithyroglobulin and antithyroid peroxidase antibodies. The neck lesion showed a depressed iodine uptake in the left thyroid lobe, which had an asymmetrical pseudocystic pattern associated with poor vascularization in the ultrasound scan. Cytologic examination showed a lymphocyte thyroiditis in association with lymphoma of large cell arising from mucosa-associated lymphoid tissue (MALT-lymphoma or maltoma). The patient underwent a left thyroid lobectomy while being treated with levothyroxine for Hashimoto's thyroiditis, and the surgical treatment was further complemented with chemotherapy using fludarabine. The histologic examination confirmed the cytologic findings and the immunohistochemistry showed a B-cell type maltoma. Additional investigation provided no evidence of disease in other tissues. The clinical course has been favorable in the first 2 years of follow-up, with no evidence of local or systemic recurrence of the disease.

Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is associated with germline mutations in two genes: vasopressin receptor type 2 (V2(R)) in X-linked NDI, and the water channel aquaporin-2, in autosomal-recessive disease. Genetic heterogeneity is further emphasized by reports of phenotypically abnormal individuals with normal structural genes. We analyzed both genes in five Brazilian families and the aquaporin-2 gene in two Swedish families with clinical and laboratory diagnosis of NDI, by a combination of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing. A novel polymorphism in the aquaporin-2 gene (S167S), but no disease-associated mutations in any tested individual from all seven families, was detected. In two Brazilian families, frameshift mutations were detected in the V2(R) gene: one leading to a premature stop after codon 36 and the other to a longer peptide (462 aa instead of the 373 aa wild-type protein). In two other Brazilian families, probable disease-associated missense mutations were detected: an alanine to proline at codon 163 (A163P) and an asparagine to aspartic acid at codon 85 (D85N). In one Brazilian family, both genes were structurally normal and the aquaporin-2 gene was also normal in the two Swedish kindreds. This report further extends the mutational spectrum of NDI and suggests that there are other mutational or epigenetic events inactivating the two known genes or even novel genes that underlie NDI.

Description of a Brazilian patient bearing the R271W Pit-1 gene mutation.

The pituitary-specific transcription factor Pit-1/GHF-1 is responsible for pituitary development and expression of somatotrophs and lactotrophs as well as hormonal regulation of the prolactin (PRL) and thyrotropin (TSH) beta genes by thyrotropin-releasing hormone (TRH) and cyclic adenosine monophosphate (cAMP). Pit-1 gene mutations result in complete growth hormone (GH) and PRL deficiencies and variable degrees of TSH deficiency, producing the clinical syndrome of combined pituitary hormone deficiency (CPHD). Several cases of mutations in the Pit-1 gene have been reported; the most common one is a sporadic mutation altering an arginine (R) to a tryptophan (W) in codon 271, in one allele of the Pit-1 gene. We describe a case of a 38-year-old woman, born to consanguineous parents, presenting with growth failure and hypothyroidism. Growth failure was noted from early infancy, whereas hypothyroidism was only apparent from adolescence. She had almost undetectable GH and PRL levels and an inappropriate low TSH for very low triiodothyronine (T3) and thyroxine (T4) levels, while the remaining pituitary evaluation was normal. The pituitary gland was hypoplastic by magnetic resonance imaging. A point mutation in exon 6, monoallelic, causing a C to T substitution that changes amino acid 271 from Arg (R) to Trp (W) was identified. Children with Pit 1 mutations and delayed onset of hypothyroidism may be initially diagnosed as isolated GH deficiency.

Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis.

In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment.

Adrenal response to corticotrophin and testosterone during long-term therapy with itraconazole in patients with chromoblastomycosis

In order to establish whether long-term itraconazole therapy can affect adrenal or testicular function, the adrenal response to corticotrophin and testosterone was evaluated by radioimmunoassay in 15 patients undergoing treatment for chromoblastomycosis. Mean cortisol and testosterone concentrations were 12.4 microg/dL and 454 ng/dL respectively at baseline and 15.4 microg/dL and 480 ng/dL respectively after 12.4+/-5.2 months of treatment with itraconazole (200-400 mg daily). Results were analysed using Student's t-test. There was no clinical or laboratory evidence of steroidogenic or androgenic impairment.

Tomografia computadorizada das suprarenais. Analise de 15 casos. / Computerized tomography of the adrenal glands. Analysis of 15 cases

Sao apresentados 15 pacientes com patologia supra-renal, submetidos a tomografia computadorizada (TC). Com esta tecnica foram visualizados facilmente todos os 6 tumores da nossa serie. Nos casos de hiperplasia simples observou-se aumento evidente de ambas as supra-renais em 7 de 8 pacientes, e no ultimo a presenca de supra-renais de tamanho aparentemente normal.Em uma paciente, a TC foi capaz de revelar aumento nodular das glandulas. Desta forma, a TC confirmou ser um excelente metodo auxiliar no diagnostico etiologico e topografico das patologias das supra-renais