Low bone mineral density is associated with insulin resistance in bone marrow transplant subjects.

Post-BMT subjects have an increased bone fracture risk. Additionally, several factors were associated with osteopenia and osteoporosis in these individuals. We aimed to identify other factors associated with osteopenia and osteoporosis in allogeneic post-BMT subjects. We conducted a cross-sectional study with 47 allogeneic post- BMT subjects. Serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, ferritin, vitamin B(12), insulin, glucose, cholesterol and triglyceride levels were measured. Insulin resistance and secretion were estimated through the homeostatic model assessment for insulin resistance (HOMA-IR) and homeostatic model assessment for beta-cell function (HOMA-B), respectively. A bone densitometry (BMD) was also obtained. The median time after BMT was 47.7 (12-115) months. Osteoporosis was identified in 17.0% of the subjects and osteopenia in 19.7%. The mean serum ferritin (P=0.002), insulin (P<0.0001), glucose (P=0.003) and triglyceride (P=0.018) levels were higher in individuals with osteopenia/osteoporosis. HOMA-IR (P<0.0001) and HOMA-B (P<0.0001) were increased in post-BMT subjects with osteopenia/osteoporosis. There was no other factor associated with the outcome. After adjustments ferritin, serum 25(OH)D and HOMA-IR remained independently associated with osteopenia/osteoporosis; however triglycerides no longer were. In conclusion, in the present study, low serum 25(OH)D levels, high serum ferritin levels and insulin resistance were associated with osteopenia/osteoporosis in post-BMT subjects.

Thyroid volume is associated with family history of thyroid disease in pregnant women with adequate iodine intake: a cross-sectional study in southern Brazil.

UNLABELLED: Maternal euthyroidism is important for fetal neural development. For this reason, adequate iodine nutrition during pregnancy is an important public health objective and should be periodically revised. The objective of this study was to measure urinary iodine (UI) excretion and the factors associated with thyroid volume (TV), in a group of healthy pregnant women in southern Brazil, to evaluate iodine nutrition. The median UI of the 147 women was 224 microg/l (P25=164 microg/l and P75=286 microg/l). Serum levels of free T4 and thyroglobulin did not correlate with UI, but there was a weak inverse correlation between serum TSH levels and UI (r=-0.200; p=0.02). TV, calculated through ultrasound in 57 women, was significantly associated with family history of thyroid diseases (p=0.002) and BMI (p=0.03), but there was no association with UI, corrected or not for creatinine, serum free T4, TSH or thyroglobulin, current or past smoking, gestational age, parity or oral contraceptive. CONCLUSIONS: The healthy pregnant women studied had adequate iodine intake. In this situation, the main thyroid size determinants are probably genetic factors.

Hypovitaminosis D and secondary hyperparathyroidism in resident physicians of a general hospital in southern Brazil.

OBJECTIVES: To evaluate the prevalence of hypovitaminosis D and secondary hyperparathyroidism in resident physicians of a general hospital in southern Brazil and identify associated factors. DESIGN: Cross-sectional study. POPULATION: Resident physicians of Hospital de Clinicas de Porto Alegre, Porto Alegre, southern Brazil. PARTICIPANTS: Seventythree subjects age 26.4+/-1.9. MEASUREMENTS: Serum PTH, 25- hydroxyvitamin D [25(OH)D], total calcium, phosphorus, magnesium, creatinine, and alkaline phosphatase were measured. In addition calcium, creatinine, and magnesium were measured in urine. Fractional excretion of calcium and magnesium were calculated. Calcium intake was estimated by a food intake questionnaire. RESULTS: Mean serum levels of 25(OH)D were 17.9+/-8.0 ng/ml and 57.4% presented 25(OH)D below 20 ng/ml. Secondary hyperparathyroidism, defined as serum PTH > or =48 pg/ml and normal or low serum calcium, was identified in 39.7% of the individuals. Mean serum levels of magnesium were higher (p=0.02) and the fractional excretion of calcium was lower (p<0.001) in individuals with secondary hyperparathyroidism. Serum PTH levels were positively correlated with body mass index (r=0.33 and p=0.006) and serum magnesium levels (r=0.33 and p=0.02) and negatively correlated with serum 25(OH)D levels (r=-0.33 and p=0.008), estimated calcium intake (r=-0.25 and p=0.04), and fractional excretion of calcium (r=-0.34 and p=0.009). CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism was very common in resident physicians. Therefore, measures to prevent this situation should be recommended.

Ultrasonography: is it useful in the diagnosis of cancer in thyroid nodules?

The role of ultrasonography (US) in the diagnosis of cancer in thyroid nodules is not well-established. The aim of the present study was to evaluate US performance in predicting cancer in thyroid nodules using a novel approach. Two hundred and eighty-nine patients with thyroid nodular disease were evaluated with clinical, biochemical and cytopathological examinations. Eighty patients with palpable solitary thyroid nodules or multinodular goiters who were to undergo surgery were included, and had a US exam performed by one of us. Some US characteristics of thyroid nodules were associated to cancer: absent halo, hypoechogenicity and microcalcifications, with sensitivity, respectively, of 56, 44 and 56%, and specificity of, respectively, 80, 83 and 94%. These findings were considered positive and were studied in two different combinations: simultaneous, when two or more were positive, and parallel, when any positive finding was present. When positive findings were studied simultaneously, sensitivity ranged 25 to 38% and specificity ranged 89 to 97%. Microcalcifications, associated or not to other findings, were highly specific for thyroid cancer, but they were only present in half of the malignancies. When positive findings were studied in parallel, sensitivity ranged 69 to 81% and specificity ranged 70 to 81%. The parallel combination of hypoechogenicity or microcalcifications or absent halo improved US sensitivity to 81% with an acceptable specificity (70%). This method is potentially useful to help us select patients for surgery when fine-needle aspiration biopsy is repetitively non-diagnostic or select for biopsy incidentally discovered non-palpable nodules.

Low-dose adrenocorticotropin test in patients with the acquired immunodeficiency syndrome.

Adrenocortical insufficiency is a serious complication of AIDS. Usually, integrity of the hypothalamo-pituitary-adrenal (HPA) axis in AIDS patients is assessed by measuring basal cortisol levels and cortisol response to 250 microg of ACTH. Recent studies suggest that a lower ACTH dose increases the sensitivity of the procedure. In the present study, we investigated the prevalence of adrenal hypofunction in AIDS patients using a low-dose ACTH test (1 microg), evaluated the clinical characteristics that might suggest this diagnosis, and the diseases and/or drugs that could be associated with it. We prospectively evaluated 63 very ill AIDS patients and 16 normal controls. A standard examination assessed the presence of signs and symptoms of adrenal insufficiency. Blood samples were collected before and 30 and 40 minutes after an injection of 1 microg 1-24 ACTH. No opportunistic disease, signs, symptoms or drugs were associated with an abnormal cortisol response to ACTH. The lowest stimulated cortisol level in the control group was 18.5 microg/dL; cortisol levels > or = 18 microg/dL were taken to indicate a normal HPA axis. Test results revealed that 12/63 AIDS patients (19%) had an abnormal HPA axis. With these data in mind, we suggest a prospective adrenal function evaluation of all severely ill AIDS patients.

Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells.

Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 +/- 0.370 to 2.085 +/- 0.364 pmol I-/microg DNA at 1 ng/ml (P<0.02), to 1.970 +/- 0.302 pmol I-/microg DNA at 10 ng/ml (P<0.003), and to 2.038 +/- 0.389 pmol I-/microg DNA at 100 ng/ml (P<0.02). In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 +/- 0.408 to 7.312 +/- 0.506 pmol I-/microg DNA (P<0.02). A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 0.370 to 2.085 0.364 pmol I-/æg DNA at 1 ng/ml (P<0.02), to 1.970 0.302 pmol I-/æg DNA at 10 ng/ml (P<0.003), and to 2.038 0.389 pmol I-/æg DNA at 100 ng/ml (P<0.02). In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 0.408 to 7.312 0.506 pmol I-/æg DNA (P<0.02). A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis

Prevalência de nódulos de tireóide detectados por ecografia em mulheres após os 40 anos / Prevalence of thyroid nodules in 40 years-old or old women

Nódulos de tireóide säo uma condiçäo clínica comum e em seu diagnóstico diferencial inclui-se o câncer de tireóide. Como o câncer de tireóide é raro, é importante conhecer a prevalência de nódulos de tireóide em grupos fortemente pre-dispostos para dimensionar seu impacto e adequar estratégias diagnósticas. OBJETIVOS: O objetivo deste estudo foi verificar a prevalência de nódulos de tireóide diagnosticados por ecografia em mulheres na maturidade. MÉTODOS: Entre agosto de 1996 e dezembro de 1997 foram avaliadas, de forma consecutiva, pacientes do sexo feminino com idade de 40 anos ou mais que realizavam ecografia no Serviço de Radiologia do HCPA...

A novel mutation (M310L) in the thyroid hormone receptor beta causing resistance to thyroid hormone in a Brazilian kindred and a neonate.

Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone (T3) caused by mutations in the thyroid hormone receptor beta (TRbeta). The index patient of the family reported here, a 17-year-old woman, came to medical attention because of a diffuse goiter, short stature, and learning disabilities. Biochemical tests revealed an elevated free T4 of 5.2 ng/dl (0.8-2.1), a T3 of 270 ng/dl (80-220), and a nonsuppressed TSH of 1.79 mU/l (0.4-4). Administration of exogenous T4 or T3 did not result in the usual TSH suppression, prompting the clinical diagnosis of RTH. Her father and one of her brothers also had clinical and biochemical findings consistent with RTH. Direct sequence analysis of the TRbeta gene revealed a heterozygous transition 928A>G in exon 9 resulting in substitution of methionine 310 by leucine (M310L). This novel receptor mutant has a reduced affinity for T3 ( approximately 10% of normal) and dominant negative properties that are similar in comparison to other RTH mutations. The index patient had a normal pregnancy and delivery. At birth, the female neonate had no goiter, a significantly elevated T4, and increased TSH. The diagnosis of RTH was confirmed by sequencing the TRbeta gene. She was underweight at birth and her length was between the 5th and 10th percentile. At 26 months, her height remained at the 10th percentile but her bone age was 18 months, suggesting mild hypothyroidism at the level of the bone. In contrast, increased heart rate and restlessness are consistent with hyperthyroidism in other tissues, such as the heart and possibly the brain.

Post-partum thyroiditis in South Brazil presenting as thyrotoxicosis: prevalence and risk factors.

The prevalence of post-partum thyroiditis (PPT) has been reported in several countries (1.9 to 16.7%) but is not known in Brazil. Several factors have been associated to its development, such as a female sex of the newborn, PPT in a previous pregnancy, a family history of thyroid disease and cigarette smoking. To investigate the prevalence of PPT and its risk factors in a southern Brazilian city, a three-cross-sectional observation study was performed. PPT was diagnosed in 14/284 subjects (5.3%) and all cases had thyrotoxicosis (13 sub-clinical and one clinical). Serum total T4 and free T4 were higher and serum TSH was lower in PPT subjects. Anti-thyroid antibodies were positive in 16.7% of PPT subjects and in 4.5% of those with no thyroid dysfunction. Goiter was identified in 14.3% of PPT subjects and in 15% of no PPT subjects. Thyroid was hardened more frequently in PPT subjects (21.4%) than in others (5.2%). Male sex of the newborn was associated to PPT, increasing 11 times the risk of PPT. Cigarette smoking was associated to PPT in group II subjects. There was no clinical sign or symptom able to contribute to this diagnosis, except the presence of hardened thyroid. Based on these findings, PPT, manifesting itself as mild thyrotoxicosis, is a common problem in southern Brazil and is associated to male sex of the newborn.

[Prevalence of thyroid nodules in 40 years-old or old women]. / Prevalência de nódulos de tireóide detectados por ecografia em mulheres após os 40 anos.

OBJECTIVES: Thyroid nodules constitute a very common clinical problem and the differential diagnosis includes thyroid cancer. As thyroid cancer is rare, it is important to know the prevalence of thyroid nodules in cohorts strongly predisposed to this problem to be able to measure its impact on the health care system, and to devise appropriate diagnostic strategies. The aim of this study was to determine the prevalence of thyroid nodules in women 40 year-old or older by echography. METHODS: Between August 1996 and December 1997, 207 women, 40 year-old or older, were consecutively evaluated by thyroid echography in the Radiology Division of the Hospital de Clínicas de Porto Alegre. Patients who came to the Division to be submitted to thyroid echography were excluded. The mean age of patients studied was 54.7 years (median: 53, range: 40-86 years). One hundred and twenty three patients (54.9%) had a normal thyroid and eighty-two had an abnormal gland (39.6%). Thyroid nodules were detected in seventy-three women (35.3%) and these were larger than 1 cm in 35 women (16.9%). Women without thyroid nodules were younger (53.1 +/-10.7 years) than women with thyroid nodules (58.2 +/-10.6 years) p=0.001; and the prevalence of any thyroid nodule (p=0.001) or nodules larger than 1 cm (p=0.007) increased with age. CONCLUSIONS: Thyroid nodules are very common in women 40 year-old or older, their prevalence increases with age in this cohort and these nodules are potentially palpable (larger than one cm) in one of six women in this age group It is important to have these data in mind when ordering thyroid echographic studies in women 40 year-old or older.

Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells.

Goiter (increased thyroid gland size) is more prevalent in women than men, even in areas where iodine levels in the diet are sufficient. We investigated a possible role of estrogen on thyroid follicular cell growth using rat FRTL-5 thyroid follicular cells as a model. Estrogen receptor-alpha (ERalpha) messenger RNA was present in FRTL-5 cells using a RT-PCR assay and was confirmed by Western blot analysis. An estrogen-responsive reporter gene was transfected into FRTL-5 cells to test the functionality of the endogenous ERs. Estradiol increased the activity of the reporter gene, and the antagonist, ICI182780, inhibited ER-dependent transcription. To extend this analysis, we examined the effect of estradiol on FRTL-5 cell growth. Estradiol increased FRTL-5 cell growth in a time- and concentration-dependent manner in either the absence or presence of TSH. Because iodine is known to inhibit thyroid cell growth, the effect of estradiol on the expression of the sodium/iodide symporter (NIS) was assessed as a potential target of estrogen action. Estradiol blocked TSH-induced NIS expression, and treatment of cells with estradiol and ICI182780 restored TSH-induced NIS expression to normal levels. These data demonstrate that FRTL-5 cells contain functional ERs that enhance cell growth and inhibit expression of the NIS. The demonstration of a direct effect of estradiol on thyroid follicular cells raises the possibility that it may play a role in the sexually dimorphic prevalence of goiter.

Carbohydrate metabolism of rats with chronic renal failure.

1. Various aspects of carbohydrate metabolism were evaluated in rats exhibiting chronic uremia induced by the surgical removal of 5/6 of the kidneys (NX group). Operated rats developed moderate uremia and maintained a nutritional status similar to that of a sham-operated control group (C rats). 2. After a 12-h fast, the NX group showed a 32% decrease in plasma glucose vs 20% for the C group. 3. After intravenous glucose administration (75 mg/100 mg body weight), plasma glucose and insulin levels were similar in both NX and C rat groups. 4. The decrease in plasma glucose after insulin administration (0.025 U/100 g body weight) was larger in the NX group than in controls. 5. No significant difference was found between the hepatic glycogen levels of NX and C animals although diaphragm muscle glycogen levels in the NX group were nearly twice that of controls. 6. Carcass fatty acid levels in the NX group were 42% lower than in the C group, while total liver lipids were similar for both. 7. These findings suggest that nephrectomized rats exhibit increased sensitivity to exogenous insulin, are not intolerant to intravenous glucose and after a 12-h fast show hypoglycemia that could be related to higher glucose utilization by muscle tissue.

Hiperparatiroidismo e hipotiroidismo primario na gravidez: relato de um caso. / Hyperparathyroidism and primary hypothyroidism in pregnancy: a case report

O hiperparatiroidismo materno, durante a gravidez, acarreta aumento da morbidade e mortalidade materno-fetais. Os autores relatam um caso de hiperparatiroidismo primario durante a gestacao em uma paciente que apresentava hipotiroidismo primario.Durante a gravidez, observou-se acentuacao da hipercalcemia e hipofosfatemia. A paciente foi operada no inicio do 3o. trimestre com retirada de um adenoma da paratiroide, nao tendo havido complicacoes para a mae ou para o feto. E feita revisao da literatura sobre hiperparatiroidismo na gravidez e sobre a associacao de hiperparatiroidismo primario com doencas da tiroide

Caracteristicas clinicas e laboratoriais das doencas da tiroide. / Clinical and laboratorial characteristics of thyroid diseases

Os autores analisam prospectivamente caracteristicas clinicas e laboratoriais dos diferentes tipos de doencas da tiroide, observadas em 256 pacientes atendidos no Servico de Endocrinologia do Hospital de Clinicas de Porto Alegre, no periodo compreendido entre fevereiro de 1978 a marco de 1979. Constatam que as doencas de tiroide mais frequentemente encontradas foram o bocio atoxico e o hipertiroidismo, os quais ocorreram respectivamente em 50 e 26% dos pacientes. Com base nos resultados, afirmam que os bocios nodulares constituiram a causa mais frequente de hipertiroidismo, e que o carcinoma folicular foi a neoplasia mais prevalente, ressaltando que estes achados tem sido descritos em pacientes provenientes de areas deficientes de iodo. Sugerem que, em nosso meio, a deficiencia do iodo, alem de ter um papel preponderante na genese das doencas de tiroide, modifica significativamente as formas de apresentacao de algumas delas, em especial do hipertiroidismo e do carcinoma. Enfatizam, finalmente, a necessidade da realizacao de estudos futuros, de carater epidemiologico e mais abrangentes, atraves dos quais seja possivel determinar objetivamente o grau de deficiencia de iodo, a prevalencia de bocios e os diferentes tipos de doencas da tiroide, peculiares as diversas regioes do Estado do Rio Grande do Sul

Suprasellar germinoma: an unusual clinical presentation.

A case is described of suprasellar tumor with diabetes insipidus, diminishing visual acuity, inferior bitemporal quadrantanopia, and hypopituitarism in a 19-year-old man. Computerized tomographic scan of the brain after contrast injection demonstrated periventricular enhancement. Diagnosis of germinoma was made on the basis of clinical and radiographic information and a biopsy that revealed malignant cells. The tumor responded well to radiation therapy. Diagnostic difficulties were created by systemic manifestations unrelated to endocrinopathy. Pertinent literature is reviewed.