Llanyee Liwanpo

Bio: Llanyee Liwanpo is an academic researcher from Veterans Health Administration. The author has contributed to research in topics: Thyroid peroxidase & Levothyroxine. The author has an hindex of 3, co-authored 3 publications receiving 198 citations.

How Does Sunitinib Cause Hypothyroidism

Abstract: In this issue of Thyroid, there are two case reports (1,2) that provide important clinical data on the mechanism by which the tyrosine kinase inhibitor, sunitinib (Sutent , Pfizer Inc., New York, NY), causes hypothyroidism. Sunitinib is approved for treatment of renal cell cancer and gastrointestinal stromal tumor. Initial retrospective studies showed that the incidence of hypothyroidism in patients treated with sunitinib varied from 18% to 35% (3–5). Several excellent prospective studies showed a similar incidence, 27% to 46% (6–8). In addition to causing hypothyroidism, sunitinib has another effect on the thyroid—in several patients, it has caused thyrotoxicosis secondary to painless thyroiditis that often results in hypothyroidism (6,9–11). Tests for thyroid autoimmunity have been negative in these patients. An additional effect of sunitinib is an increased requirement for levothyroxine in patients with preexistent hypothyroidism taking levothyroxine (3). This effect is shared by other tyrosine kinase inhibitors that do not have direct effects on the thyroid gland (12,13). The mechanism by which sunitinib induces hypothyroidism is unclear. Based on clinical studies of thyroid radioiodine uptake, Mannavola et al. (7) proposed that hypothyroidism was due to inhibition of iodide uptake, but in vitro studies with rat thyroid cells showed that cells incubated with sunitinib had no impairment of iodide transport or down-regulation of the sodium-iodide symporter (14). Inhibition of thyroid peroxidase is another proposed mechanism for hypothyroidism. Sunitinib impairs peroxidase activity in vitro, but this has not yet been confirmed in vivo (3). Several case reports have reported destructive thyroiditis as the principal mechanism for sunitinib-induced hypothyroidism (6,9,11). However, careful prospective studies show that thyrotropin (TSH) increases during the 4-week treatment period with sunitinib, then falls back to the normal range after 2 weeks off the drug in most patients. Eventually there may be sustained elevation of TSH and subnormal thyroxine levels, usually without an observed suppression of TSH (8,11). These data do not support the hypothesis of destructive thyroiditis causing hypothyroidism. Sunitinib inhibits vascular endothelial growth factor receptors as a principal mechanism of its action on tumors. Studies with a small-molecule tyrosine kinase inhibitor in mice showed that endothelial cells in the thyroid were much more affected by this mechanism than those in other tissues (15). The article by Rogiers et al. (1) shows that sunitinib therapy caused marked diminution of thyroid size in two patients with multinodular goiter, resulting in hypothyroidism. Makita et al. (2) report a patient who developed hypothyroidism during her first cycle of therapy. Measurements of thyroid volume and blood flow were both reduced on sunitinib compared to values obtained when sunitinib was stopped. Interestingly, the patient’s thyroid volume nearly doubled in the short period off sunitinib, a mechanism that may not be solely explained by revascularization of the thyroid bed. These authors propose the unifying hypothesis that sunitinib causes regression of the thyroid vascular bed resulting in impaired thyroid function. Vasoconstriction of thyroid vessels could reduce glandular uptake of radioiodine. Severe reduction in thyroid cell perfusion could cause apoptosis of thyroid cells, resulting in thyroiditis in some patients. This is an appealing unifying mechanism and needs to be substantiated by additional quantitative studies of thyroid gland vascularity. Mannavola et al. (7) performed systematic ultrasound studies of 11 patients both before and during sunitinib treatment and did not detect changes in thyroid volume or vascularity. Although their findings do not support the hypothesis that regression of thyroid endothelial function and capillary blood flow is the main mechanism for impaired thyroid function, it is possible that some patients are very susceptible to this mechanism of action of sunitinib. Further studies should be performed to support or refute this hypothesis.

2013 ETA Guideline: Management of Subclinical Hypothyroidism

Abstract: Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroidstimulating hormone (TSH) level: mildly increased TSH levels (4.0–10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT 4 within reference range, should be investigated with a repeat measurement of both serum TSH and FT 4 , along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with L -thyroxine is recommended for younger patients ( 10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of L -thyroxine replacement therapy should be considered. For such patients who have been started on L -thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, L -thyroxine therapy should generally be

Soy, Soy Foods and Their Role in Vegetarian Diets.

Abstract: Soy is a basic food ingredient of traditional Asian cuisine used for thousands of years. In Western countries, soybeans have been introduced about a hundred years ago and recently they are mainly used for surrogate foods production. Soy and soy foods are common nutritional solutions for vegetarians, due to their high protein content and versatility in the production of meat analogues and milk substitutes. However, there are some doubts about the potential effects on health, such as the effectiveness on cardiovascular risk reduction or, conversely, on the possible disruption of thyroid function and sexual hormones. The soy components that have stimulated the most research interest are isoflavones, which are polyphenols with estrogenic properties highly contained in soybeans. In this review, we discuss the characteristics of soy and soy foods, focusing on their nutrient content, including phytoestrogens and other bioactive substances that are noteworthy for vegetarians, the largest soy consumers in the Western countries. The safety of use will also be discussed, given the growing trend in adoption of vegetarian styles and the new soy-based foods availability.

Sunitinib Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer: A Phase III Trial

Abstract: Purpose Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non–small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. Patients and Methods Patients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results In all, 960 patients were randomly assigned, and baseline characteristics wer...

Treatment with thyroid hormone.

Abstract: Thyroid hormone deficiency can have important repercussions. Treatment with thyroid hormone in replacement doses is essential in patients with hypothyroidism. In this review, we critically discuss the thyroid hormone formulations that are available and approaches to correct replacement therapy with thyroid hormone in primary and central hypothyroidism in different periods of life such as pregnancy, birth, infancy, childhood, and adolescence as well as in adult patients, the elderly, and in patients with comorbidities. Despite the frequent and long term use of l-T4, several studies have documented frequent under- and overtreatment during replacement therapy in hypothyroid patients. We assess the factors determining l-T4 requirements (sex, age, gender, menstrual status, body weight, and lean body mass), the major causes of failure to achieve optimal serum TSH levels in undertreated patients (poor patient compliance, timing of l-T4 administration, interferences with absorption, gastrointestinal diseases, and drugs), and the adverse consequences of unintentional TSH suppression in overtreated patients. Opinions differ regarding the treatment of mild thyroid hormone deficiency, and we examine the recent evidence favoring treatment of this condition. New data suggesting that combined therapy with T3 and T4 could be indicated in some patients with hypothyroidism are assessed, and the indications for TSH suppression with l-T4 in patients with euthyroid multinodular goiter and in those with differentiated thyroid cancer are reviewed. Lastly, we address the potential use of thyroid hormones or their analogs in obese patients and in severe cardiac diseases, dyslipidemia, and nonthyroidal illnesses.