Relationship Type and Use of the Vaginal Ring for HIV-1 Prevention in the MTN 020/ASPIRE Trial.

Gender roles and imbalances in sexual power contribute to the heightened HIV-1 risk faced by women in Sub-Saharan Africa. This has led prevention research to focus on the development of female controlled methods. Despite the design of products such as vaginal rings to be used autonomously by women, male partners and women's perceptions of relationships influence HIV prevention choices. To understand the influences that male partners and dyadic dynamics had on the use of the Dapivirine Vaginal Ring in the ASPIRE trial, this analysis of qualitative data explored the types of intimate partner relationships that women engaged in. This paper describes how partners facilitated or challenged women's ring use and how women dealt with these challenges within six different types of relationships characterized by power dynamics and commitment levels. We offer insights into how future use of female-initiated HIV prevention products can be promoted through recognition of different relationship types.

Misreporting of Product Adherence in the MTN-003/VOICE Trial for HIV Prevention in Africa: Participants' Explanations for Dishonesty.

Consistent over-reporting of product use limits researchers' ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting.

Relationship between thyroid stimulating hormone and thyroid stimulating immunoglobulin in Graves' hyperthyroidism.

BACKGROUND AND AIM: In Graves' hyperthyroidism, suppression of serum TSH after restoration of normal serum T4 and T3 with treatment has been attributed to binding of TSH-receptor antibodies to TSH receptors in the pituitary. Accordingly, the relationship between TSH and serum thyroid stimulating immunoglobulin (TSI) was examined during follow-up of patients with Graves' hyperthyroidism. SUBJECTS AND METHODS: 23 patients with Graves' hyperthyroidism were identified who met the inclusion criteria of at least 24 months follow-up after initiation of methimazole and availability of concurrent measurements of serum TSH and TSI. RESULTS: TSI disappeared in 12 patients (Group A) and persisted in 11 patients (Group B). Initial T4 was not significantly different between the 2 groups. However, TSI was significantly lower in Group A than Group B [median (interquartile range) 179 (152-212)% vs 255 (208-369)%, p=0.0009]. In Group A, TSH normalized during treatment, and this anteceded disappearance of TSI by a significant time interval [median (interquartile range) 6 (3-8) months vs 15 (11-20) months, p=0.005]. In Group B, TSI persisted in all patients during follow-up ranging from 24 to 73 months. No correlation was found to exist between serum TSH and TSI, and for Group B TSI at final follow-up was not significantly different from the initial value [median (interquartile range) 255 (208-369)% vs 236 (160-310)%, p=0.4]. CONCLUSIONS: These findings do not support the suggestion that TSI has a direct suppressive effect on TSH secretion.

Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations.

Although the normal thyroid gland secretes both levothyroxine (L-T4) and levotriiodothyronine (L-T3), normalization of serum TSH with L-T4-replacement therapy alone in hypothyroidism is generally believed to result in a normal serum L-T3 and to reflect a euthyroid state. However several recent studies suggest that this may not be the case. Accordingly, the relationship between serum free L-T4 and free L-T3 was examined in 20 normal individuals (group A) and in 53 patients with chronic autoimmune thyroiditis, 18 with normal TSH on no L-T4-replacement (group B), and 35 with normal TSH on L-T4-replacement therapy for hypothyroidism (group C). Data were analyzed by applying a one-way analysis of variance with correction for multiple comparisons. Serum TSH values were very similar among the 3 groups. In groups A and B, mean serum free T4 and free T3 were very similar. In group C, the mean free T4 (16+/-2 pmol/l) was significantly higher than the values in groups A (14+/-1) and B (14+/-2) (p<0.001) and the mean free T3 lower (4.0+/-0.5 pmol/l vs 4.2+/-0.5, NS and 4.4+/-0.5, p<0.02). Consequently, the mean molar ratio of free T4 to free T3 was significantly higher in group C than the ratios in groups A and B (p<0.0001), despite very similar TSH values. These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.

Update on the management of hyperthyroidism and hypothyroidism.

Clinical aspects, laboratory investigation, and treatment of hyperthyroidism and hypothyroidism are reviewed in light of recent information. Special circumstances, such as hyperthyroidism during pregnancy, Graves ophthalmopathy, iodine-induced hyperthyroidism, and subclinical hypothyroidism, are also considered.

The year in review: the thyroid.

Several studies that have important implications for the management of patients with various thyroid disorders were recently published. These studies concern screening for thyroid disease, thyroid eye disease and treatment with iodine-131, antithyroid drug treatment, treatment of hypothyroidism, and management of thyroid nodules. For each topic, the results of the studies are presented and recommendations for their translation into clinical practice are offered.

Subclinical thyroid dysfunction.

Subclinical thyroid dysfunction may be defined as an abnormal serum thyrotropin concentration in an asymptomatic patient with a normal serum free thyroxine concentration. This article addresses the prevalence, natural history, and potential pathophysiological consequences of subclinical hypothyroidism and subclinical thyrotoxicosis. Subclinical hypothyroidism, which occurs in more than 10% of women older than 60 years, may be accompanied by an unfavorable serum lipid profile and may lower the threshold for the development of major depressive disorder. Subclinical thyrotoxicosis, which is most commonly due to thyrotropin-suppressive levothyroxine sodium therapy, may be associated with reduced bone mineral density in postmenopausal women and confers a 3-fold relative risk for the development of atrial fibrillation. While there are no outcome data to support therapeutic intervention in subclinical thyroid dysfunction, some screening and management recommendations are offered.

Cost-effective evaluation of the patient with a thyroid nodule.

Although thyroid nodules are common, less than 5% prove to be malignant. Because of its accuracy, simplicity, and low cost, FNAC has virtually replaced ultrasonography and radionuclide scintigraphy as the primary diagnostic procedure in the evaluation of the patient with a thyroid nodule. In studies comparing preoperative cytodiagnosis with histopathologic diagnosis, the predictive values of benign, malignant, and indeterminate cytodiagnoses averaged 94%, 96%, and 73%, respectively. Guidelines for a cost-effective approach to management of the patient with a thyroid nodule are presented. With a benign cytodiagnosis, follow-up with repeat FNAC in about 1 year is recommended. For the nodule with malignant or indeterminate cytology, surgical resection is indicated. Surgical resection is also indicated for the cyst that recurs after aspiration, as FNAC is less reliable owing to the paucity of cells. FNAC has less diagnostic utility in the evaluation of a nodule with clinical features suggesting malignancy, a nodule that is present in the diffuse toxic goiter of Graves' disease, or a nodule that is found in a patient with a history of radiation to the head, neck, or chest. In these circumstances, surgery is indicated irrespective of the cytologic findings.

Thyrotoxicosis and the heart.

Many patients with thyrotoxicosis have clinical features that reflect the effects of excess thyroid hormone on the cardiovascular system. Thyrotoxicosis can aggravate preexisting cardiac disease and can also lead to atrial fibrillation, congestive heart failure, or worsening of angina pectoris. In elderly patients, these cardiac manifestations may dominate the clinical picture and warrant the measurement of the serum thyrotropin concentration. In the absence of preexisting cardiac disease, treatment of thyrotoxicosis usually results in a return of normal cardiac function.

Iodine and thyroid disease.

Iodine is a requisite substrate for the synthesis of the thyroid hormones, the minimum daily requirement being about 50 micrograms. An autoregulatory mechanism within the thyroid serves as the first line of defense against fluctuations in the supply of iodine and also permits escape from the inhibition of hormone synthesis that a very large quantity of iodine induces (Wolff-Chaikoff effect and escape therefrom). Environmental iodine deficiency continues to be a significant public health problem worldwide, compounded in some geographic regions by the presence of other goitrogens in some staple foods. The pathologic consequences of severe iodine deficiency include endemic goiter, endemic cretinism, increased fetal and infant mortality, and an increased prevalence in the community of cognitive and neuromotor disabilities. The implementation of an iodization program prevents endemic cretinism and reduces the frequency of the other pathologic consequences of iodine deficiency. Iodine excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. The pathologic consequences of iodine excess will ensue only when thyroid autoregulation is defective, in that escape from the Wolff-Chaikoff effect cannot occur, or when autoregulation is absent. Defective autoregulation characterizes the fetal and neonatal thyroid, Hashimoto's thyroiditis, radioiodine or surgically treated Graves' hyperthyroidism, the thyroid of patients with cystic fibrosis, and the thyroid that has been exposed to weak inhibitors of the organic binding of iodine. In these circumstances, the provision of excess iodine may lead to iodide goiter with or without hypothyroidism. Absent autoregulation may be a feature of longstanding multinodular goiter, and the provision of excess iodine in this circumstance may induce thyrotoxicosis (Jod-Basedow disease). The pathologic consequences of iodine excess will resolve when the source of iodine has been dissipated. In addition to its role in reversing iodine deficiency, iodine is used as adjunctive therapy for hyperthyroidism. By inhibiting the proteolytic release of iodothyronines from thyroglobulin, it induces a prompt slowing of thyroid hormone secretion. This effect is exploited in the treatment of thyrotoxic crisis or severe thyrocardiac disease. Iodine also reduces thyroid cellularity and vascularity and therefore is used in the preparation of the patient for thyroidectomy. Finally, by exploiting the failure of escape from the Wolff-Chaikoff effect, iodine may also be used in the early management of radioiodine-treated Graves' hyperthyroidism.

Effect of amiodarone on L-triiodothyronine stimulation of [3H] thymidine incorporation into GH3 cells.

The antiarrhythmic agent amiodarone was found to inhibit the stimulatory effects of L-triiodothyronine on [3H] thymidine incorporation into GH3 rat pituitary tumor cells. This inhibitory effect of amiodarone was detected at concentrations as low as 0.5 microM; at 2 microM greater than 50% of the stimulatory effect of L-triiodothyronine was inhibited. The effect of amiodarone was present at all concentrations of L-triiodothyronine tested (50 pM to 10 nM), suggesting that amiodarone acted as a non-competitive antagonist. These studies raise the possibility, therefore, that the effect of amiodarone on thyroid hormone metabolism may be mediated in part by an inhibition of thyroid hormone action at the cellular level.