Alexandru Buescu

Retinoic acid in patients with radioiodine non-responsive thyroid carcinoma

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.

Lipid profile in different degrees of hypothyroidism and effects of levothyroxine replacement in mild thyroid failure

The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in subclinical hypothyroidism (SH). Initially, a cross-sectional study was performed with 226 participants [SH = 133 participants, manifest hypothyroidism (MH) = 23 participants, and euthyroidism (EU) = 70 participants]. The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU, although the differences between SH and EU did not reach statistical significance. The SH subgroup with greater serum thyrotropin (TSH) levels and that with positive antithyroperoxidase antibodies (TPO-Ab) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol (rs = 0.167; P = 0.006), triglycerides (rs = 0.219; P < 0.001), and ApoB levels (rs = 0.205; P < 0.001). Eleven patients who received levothyroxine (L-T4) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention. A fall in atherogenic variables was observed in the L-T4-treated group, with significance for total cholesterol (-20.0 vs +16.1 mg/dL in the placebo group) and LDL-c (-21.7 vs +17.2 mg/dL). We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy.

Influence of Thyroid Autoimmunity and Maternal Age on the Risk of Miscarriage

Objectives:  Recently, studies have shown an association between antiperoxidase for the detection of thyroid autoimmunity (TAI) and abortion. Another point to be considered is the association of high risk of abortion and maternal age. The aim of the present study was to evaluate if the association between TAI and miscarriage could also be verified whether a population of unselected pregnant young women who normally present a low risk of miscarriage.

Serum Leptin in Overt and Subclinical Hypothyroidism: Effect of Levothyroxine Treatment and Relationship to Menopausal Status and Body Composition

BACKGROUND The relationship between thyroid status, including subclinical hypothyroidism (SH) and serum leptin is controversial or uncertain. Therefore we evaluated serum leptin in SH and overt hypothyroidism (OH) and determined the effects of levothyroxine (LT(4)) replacement on serum leptin in these disorders. METHODS Serum leptin, thyrotropin (TSH), free thyroxine, insulin, glucose, and body composition parameters were compared in 55 SH, 20 OH, and 28 euthyroid (EU) pre- and postmenopausal women. In addition, the effect of LT(4) treatment on serum leptin in SH and OH was assessed. RESULTS The mean +/- SD (median) serum leptin concentrations in the OH and SH groups were higher than in the EU group (35.1 +/- 27.2 [33.0] and 36.6 +/- 21.9 [30.6] ng/mL, respectively, vs. 23.2 +/- 19.3 [17.9] ng/mL, p = 0.011), but the difference was only significant in postmenopausal women. The body mass index (BMI), fat mass index (FMI), and the homeostasis model assessment-insulin resistance (HOMA-IR) index values were not different among these groups. In premenopausal women there was no correlation between leptin, BMI, or FMI and serum TSH levels (r(s) = 0.009, p = 0.474; r(s) = 0.043, p = 0.367; r(s) = 0.092, p = 0.232). In the postmenopausal women, the partial correlation coefficient between TSH and leptin was present, even when controlling for BMI (r(s) = 0.297, p = 0.042) and FMI (r(s) = 0.275, p = 0.050). LT(4) treatment was associated with a reduction of serum leptin concentrations in the OH group (p = 0.008). In SH group there were no differences between LT(4) replacement or no treatment, since a fall in serum leptin levels was detected in both SH subgroups, despite a more pronounced fall with LT(4) use. Treatment of the SH and OH groups with LT(4) did not influence HOMA-IR index or body composition. CONCLUSIONS Serum leptin concentrations are elevated in postmenopausal women with SH or OH. A relationship between thyroid status and serum leptin is further supported by the fact that LT(4) treatment, to restore the EU status, reduced serum leptin levels in OH in the absence of significant effects on BMI. In women, hypothyroidism influences either leptin secretion or degradation and this effect is more pronounced in postmenopausal than in premenopausal women.

Impact of subclinical hypothyroidism treatment in systolic and diastolic cardiac function

OBJECTIVE To evaluate the effects of levothyroxine (L-T4) replacement in echocardiographic parameters of middle-aged women with subclinical hypothyroidism (SH). SUBJECTS AND METHODS This was a randomized, double-blind, placebo-controlled study. Echocardiographic evaluation was carried out at baseline and one year after restoration of euthyroidism. Thirty-three women with SH were assigned to one of two groups (L-T4 or placebo). RESULTS The two groups had similar basal characteristics. There was a significant deterioration of left ventricular Tei index after one year of placebo use, which differed from the effect of L-T4 replacement (+0.086 ± 0.092 vs. -0.014 ± 0.012; p = 0.047). There was also a slight reduction in cardiac output and cardiac index with placebo use, which was not different from L-T4 effect. CONCLUSION Results suggest a positive impact of L-T4 replacement in cardiac function of middle-aged women with SH.

Value of combined clinical information and thyroid peroxidase antibodies in pregnancy for the prediction of postpartum thyroid dysfunction.

To investigate the utility of thyroid peroxidase antibodies (TPOAb) in early pregnancy combined with clinical information for prediction of postpartum thyroid dysfunction (PPTD) within 1 year postpartum.

Prevalence of thyroid diseases in patients with acromegaly: experience of a Brazilian center

OBJECTIVES Acromegaly is frequently associated with thyroid diseases. In this study, we evaluated the frequency of thyroid disorders in a series of acromegalic patients. SUBJECTS AND METHODS We evaluated 106 acromegalic patients using thyroid ultrasonography (US) and measurements of GH, IGF-I, free T4, TSH and anti-thyroperoxidase antibody levels. IGF-I was expressed in mass units and age-related standard deviation scores (SD-scores). Fine-needle aspiration biopsy (FNAB) was performed on thyroid nodules with a diameter greater than one centimeter or with suspicious characteristics. RESULTS Thyroid disorders were found in 75 patients. Eleven patients had diffuse goiter, 42 patients had nodular goiter, and 22 patients had unspecific morphological abnormalities. Four patients (3.8%) had thyroid carcinoma. Considering the patients with diffuse or nodular goiter, thyroid volume was greater in patients with active acromegaly, and was positively correlated with GH, IGF-I, and IGF-I SD-score. CONCLUSIONS Our study confirmed that benign thyroid diseases are frequent in acromegalic patients. The prevalence of thyroid cancer was higher than in the overall population. We suggest that thyroid US should be routinely performed in patients with acromegaly.

Altered cardiovascular vagal responses in nonelderly female patients with subclinical hyperthyroidism and no apparent cardiovascular disease.

Objective  Subclinical hyperthyroidism (SH) has been associated with exercise intolerance, changes in cardiac morphology, atrial arrhythmias and sympathovagal imbalance. The aim of this study was to evaluate the vagal reserve and modulation by a sympathetic stimulus in nonelderly patients with SH without cardiovascular problems.

Estudo longitudinal do eixo hipófise-tireóide durante a gravidez

The thyroid undergoes important changes during pregnancy. In order to evaluate changes of the hypophyseal-thyroid axis during this period we studied the thyroid function in 587 pregnants by determining serum TSH, free T4, TPO antibodies and betahCG in the 1st trimester and serum TSH, free T4 and TPOAb in to 2nd and 3rd. We observed a progressive rise in average serum TSH in the 2nd (2.14 mU/L) and 3rd (2.96 mU/L) trimesters when compared to the 1st (1.39 mU/L). Serum TSH values in the 1st trimester were inversely correlated with betahCG levels in as much as TSH levels below 0.4 mU/L corresponded to average betahCG levels of 129,000 UI/L whereas these were 34,200 UI/L in the normal TSH group. A slight decrease in free T4 levels was also observed in the 2nd and 3rd trimesters (averages 1st: 1.15; 2nd: 0.99; 3rd: 0.94 ng/dl). Thyroid autoimmunity defined as positive TPOAb occurred in 13.9% of our patients during pregnancy. No significant differences in TSH and free T4 medium values were found between patients with positive TPOAb and those without. However, a significantly higher proportion of pregnants had abnormal hormonal values throughout the trimesters. We conclude that thyroid function is affected by pregnancy with a tendency for decline as it progresses, a feature more easily observed in positive TPOAb group.

Avaliação clínica e da função muscular em pacientes com hipotireoidismo subclínico

Some symptoms and signs of hypothyroidism, as well as some laboratory abnormalities, may be present in subclinical hypothyroidism (SH). This study evaluates the prevalence of signs and symptoms of hypothyroidism and skeletal muscle dysfunction in 57 patients with SH compared to 37 euthyroid controls. The participants received a clinical score based on signs and symptoms of hypothyroidism. The muscle strength was estimated by manual testing and chair dynamometer and inspiratory force by manuvacuometer. Thyroid hormones and muscle enzymes were measured. The SH group presented with higher score (p< 0.01), complained about mialgia and weakness more frequently (p< 0.05), and showed strength disability in scapular and pelvic girdles (p< 0.05). The median free T4 serum levels were lower in SH (p< 0.001). These findings suggest that signs and symptoms of thyroid dysfunction may be related to lower levels of FT4 in SH and should be taken into account in the decision of beginning LT4 therapy.