Orally Induced Hyperthyroidism Regulates Hypothalamic AMP-Activated Protein Kinase.

Besides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribution of the central vs. peripheral effects in physiologic conditions of peripheral release (or administration) of TH remains unclear. In this study we used two different models of peripherally induced hyperthyroidism (i.e., T4 and T3 oral administration) to assess and compare the serum and hypothalamic TH status and relate them to the metabolic effects of the treatment. Peripheral TH treatment affected feeding behavior, overall growth, core body temperature, body composition, brown adipose tissue (BAT) morphology and uncoupling protein 1 (UCP1) levels and metabolic activity, white adipose tissue (WAT) browning and liver metabolism. This resulted in an increased overall uncoupling capacity and a shift of the lipid metabolism from WAT accumulation to BAT fueling. Both peripheral treatment protocols induced significant changes in TH concentrations within the hypothalamus, with T3 eliciting a downregulation of hypothalamic AMP-activated protein kinase (AMPK), supporting the existence of a central action of peripheral TH. Altogether, these data suggest that peripherally administered TH modulate energy balance by various mechanisms; they also provide a unifying vision of the centrally mediated and the direct local metabolic effect of TH in the context of hyperthyroidism.

Current surgical treatment of intermediate risk differentiated thyroid cancer: a systematic review.

Introduction: Surgical treatment of thyroid cancer has become less aggressive but for many patients, the threshold for performing total thyroidectomy (TT), as opposed to thyroid lobectomy (TL), has remained unclear. Current American Thyroid Association (ATA) guidelines encourage more individualization of treatment options, which necessitates explicit review of the pros and cons of the different options with patients.Areas covered: This review focuses on the extent of surgery for treatment of intermediate-risk differentiated thyroid cancer, restricted to relevant literature available after publication of the 2015 ATA guidelines.Expert opinion: Dynamic risk-stratification facilitates a tailored approach when deciding on the extent of surgery for thyroid cancer. Treatment with TT allows for a lower recurrence risk, a simpler follow-up regimen, and treatment with adjuvant post-operative radioactive iodine. Treatment with TL has a lower associated risk of complications and avoidance of lifelong thyroid hormone replacement but has a significant risk of requiring a completion thyroid lobectomy (CT). Overall, treatment with TL and TT have comparable survival outcomes, but TL is the more cost-effective option. Larger cancer size is correlated with worse clinical outcomes, and numerous subgroup analyses have shown poorer outcomes for cancers with a diameter that is 2-4 cm compared to 1-2 cm.

Thyroid Hormone Supplementation Therapy for Differentiated Thyroid Cancer After Lobectomy: 5 Years of Follow-Up.

Background: Lobectomy with preservation of the contralateral lobe has already become the most preferred surgical method for patients with low-risk thyroid cancer. The incidence of and risk factors for the development of hypothyroidism after lobectomy for thyroid cancer remains unclear. The previous practice of levothyroxine supplementation post-thyroidectomy, to bring about thyroid stimulating hormone (TSH) suppression, had some serious side effects. This study aimed to evaluate the incidence of hypothyroidism and to identify the factors associated with hypothyroidism requiring thyroid hormone replacement. Methods: We retrospectively reviewed the charts of 256 consecutive patients with differentiated thyroid cancer treated with lobectomy at the Gangnam Severance Hospital between April and December 2014 who were followed-up for more than 5 years. Patients were evaluated using a thyroid function test at the time of outpatient visit every 6 months for the 1st year, with an annual follow-up thereafter. Results: After 5 years, 66.0% (169) of the patients needed levothyroxine supplementation to maintain euthyroid status. The incidence of hypothyroidism requiring levothyroxine supplementation increased until 3 years but showed no significant change in the 4 and 5th year. Recurrence showed no difference between the group with and without levothyroxine supplementation. The presence of thyroiditis and preoperative TSH levels were correlated with postoperative levothyroxine supplementation to maintain euthyroid status, in univariate and multivariate analyses. Conclusion: High preoperative TSH levels and/or thyroiditis indicate a significantly increased likelihood of developing hypothyroidism requiring thyroid hormone supplementation after a thyroid lobectomy. Patients with an increased risk of postoperative hypothyroidism must be aware of their risk factors and should undergo more intensive follow-ups.

Expression profiles of types 2 and 3 iodothyronine deiodinase genes in relation to vitellogenesis in a tropical damselfish, Chrysiptera cyanea.

Thyroid hormone (TH) is involved in regulating the reproduction of vertebrates. Its physiological action in the target tissues is due to the conversion of TH by iodothyronine deiodinases. In this study, we aimed to clone and characterize type 2 (sdDio2) and type 3 (sdDio3) of the sapphire devil Chrysiptera cyanea, a tropical damselfish that undergoes active reproduction under long-day conditions, and to study the involvement of THs in the ovarian development of this species. When the cDNAs of sdDio2 and sdDio3 were partially cloned, they had deduced amino acid sequences of lengths 271 and 267, respectively, both of which were characterized by one selenocysteine residue. Real-time quantitative PCR (qPCR) revealed that both genes are highly expressed in the whole brain, and sdDio2 and sdDio3 are highly transcribed in the liver and ovary, respectively. In situ hybridization analyses showed positive signals of sdDio2 and sdDio3 transcripts in the hypothalamic area of the brain. Little change in mRNA abundance of sdDio2 and sdDio3 in the brain was observed during the vitellogenic phases. It is assumed that simultaneous activation and inactivation of THs occur in this area because oral administration of triiodothyronine (T3), but not of thyroxine (T4), upregulated mRNA abundance of both genes in the brain. The transcript levels of sdDio2 in the liver and sdDio3 in the ovary increased as vitellogenesis progressed, suggesting that, through the metabolism of THs, sdDio2 and sdDio3 play a role in vitellogenin synthesis in the liver and yolk accumulation/E2 synthesis in the ovary. Taken together, these results suggest that iodothyronine deiodinases act as a driver for vitellogenesis in tropical damselfish by conversion of THs in certain peripheral tissues.

Successful Management of Hypothyroidism in Gastric Outlet Obstruction Using Levothyroxine Rectal Enemas: A Case Report.

BACKGROUND Hypothyroidism is the second most common endocrine disorder following diabetes. Appropriate hormone replacement therapy is the cornerstone of its management and is typically in the form of oral preparations of levothyroxine. Intravenous replacement is a well-known alternative in patients who are unable to take medication orally for long periods. However, effective and safe alternatives to oral preparations of levothyroxine should be sought in the absence of the parenteral alternative. The aim of this report is to describe an alternative route for levothyroxine supplementation when the oral and parenteral routes are not available. CASE REPORT This study reports a hypothyroid patient with symptomatic malignant gastric outlet obstruction requiring surgery. However, the patient's surgical condition precluded oral administration of levothyroxine and the parenteral alternative was unavailable. Hormone replacement therapy was administered rectally in the form of enemas in preparing the patient for surgery. CONCLUSIONS Rectal administration of levothyroxine using enemas can be a safe and effective alternative for patients in whom administration via the oral route is not feasible, especially when parenteral formulas are unavailable.

Terminal or truncal ligation of the inferior thyroid artery during thyroidectomy? A prospective randomized trial.

INTRODUCTION: Thyroidectomy is a common procedure in general and endocrine surgery. The technique of ligation of inferior thyroid artery (ITA) has been invoked as a possible cause of appearance of postoperative hypocalcemia. METHODS: We performed a prospective randomized study involving 184 patients undergoing total thyroidectomy to evaluate the differences of truncal ligation versus distal ligation of ITA in terms of postoperative hypocalcemia, vocal fold palsy, voice and swallowing impairment. The patients were divided into group A (trunk ligation of ITA) and group B (terminal branches ligation of ITA). RESULTS: We evaluated postoperative PTH and calcemia (immediate, 6 and 12 months after thyroidectomy), postoperative day of discontinuation of calcium and vitamin D supplementation, voice and swallowing complaints, evaluated by mean of two specific tests available in literature, day of hospital discharge. CONCLUSION: The only significant differences between the two groups were a higher immediate postoperative calcemia and a greater number of patients discharged without calcium and vitamin-D supplementation in the group B. In conclusion, no substantial differences were found between the two groups. The choice depends on the experience of the surgeon.

A Case of Capgras Syndrome Related to Hypothyroidism.

Hypothyroidism is commonly associated with a variety of psychiatric conditions, most commonly depression and cognitive impairment, but up to 5% to 15% of symptomatically hypothyroid patients may develop a nonaffective psychosis, classically referred to as "myxedema madness." We report the case of a woman who developed Capgras syndrome in the context of hypothyroidism, and whose psychosis rapidly resolved with levothyroxine supplementation. To date, very few cases of Capgras syndrome related to hypothyroidism have been reported. The pathophysiology of this condition remains unclear but it may be related to global cerebral hypometabolism or possibly to increased cerebral dopamine. Given the robust response of "myxedema madness" to thyroid replacement, psychiatrists should remain vigilant for covert hypothyroidism in patients with psychosis and atypical histories or presentations.

Preoperative hypothyroidism is a risk factor for postoperative atrial fibrillation in cardiac surgical patients.

BACKGROUND AND AIM: Although studies analyzing the effect of thyroid supplementation on postoperative morbidity and mortality from cardiac surgery have been inconclusive, they suggest a role in the prevention of postoperative atrial fibrillation. To further explore this relationship we conducted a retrospective study to determine whether abnormalities in routine preoperative thyroid function studies correlate with the incidence of postoperative atrial fibrillation. METHODS: From May 2004 until July 2011, 821 patients with complete thyroid function testing performed preoperatively underwent cardiac surgery. Preoperative, intraoperative, and postoperative laboratory, clinical and hemodynamic data including postoperative electrocardiogram monitoring were retrospectively evaluated. RESULTS: Mean age was 65.7 years and 36% (294) of patients were female. Mean preoperative ejection fraction was 48.6% and 18% (100) had clinical heart failure. Ninety percent (682) of patients were euthyroid and 10% (77) were hypothyroid. Atrial fibrillation occurred significantly more frequently in hypothyroid patients (33.4% vs. 22.5%; p = .033). In multivariable analysis, increasing thyroid stimulating hormone (TSH) level (OR: 1.11; CI: 1.01 to 1.22; p = .030) was an independent predictor of postoperative atrial fibrillation. Beta blocker use within 24 hours prior to operation was protective (OR: .54; CI: .35 to .83; p = .005). Length of stay was significantly longer in patients with postoperative atrial fibrillation (9.1 vs. 6.5 days; p < .001). CONCLUSIONS: In the current study, preoperative hypothyroidism was associated with postoperative atrial fibrillation. Further studies are warranted to delineate whether preoperative hypothyroidism is a useful biomarker for selecting patients most likely to benefit from preoperative thyroid supplementation in the prevention of postoperative atrial fibrillation.

Recombinant human thyrotropin versus thyroid hormone withdrawal in radioiodine remnant ablation for differentiated thyroid cancer: a meta-analysis.

AIM: We aim to assess the effects of recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal (THW), and rhTSH-aided low doses (1.11 GBq and 1.85 GBq) versus high dose (3.7 GBq) of radioiodine in the residual ablation for differentiated thyroid cancer (DTC). METHODS: Studies were obtained from computerized searches of MEDLINE, EMBASE, the Cochrane Library (all until September 2012). Randomized controlled trials were included. RESULTS: Altogether 1325 patients with DTC participated in seven trials for residual ablation. Overall, studies had a low risk of bias. We found no statistically significant differences between rhTSH and THW treatment in terms of successful ablation rate (OR 0.87, 95% CI 0.56 to 1.37, P=0.56) but significant benefits in health-related quality of life (mean difference 3.59, 95% CI 2.81 to 4.37, P<0.00001), adverse events during and after ablation (OR 0.57, 95% CI 0.44 to 0.73, P<0.00001), radiation exposure to blood and bone marrow (mean difference -0.01, 95% CI -0.02 to -0.01, P<0.00001). In addition, no significant difference was found in the successful ablation rate between the low dose (1.11 GBq and 1.85 GBq) and high dose (3.7 GBq) of radioiodine aided by rhTSH (OR 0.85, 95% CI 0.49 to 1.47, P=0.56). There were no deaths and no serious adverse effects in DTC patients treated with either rhTSH or THW, maximum follow-up was 12 months. None of the included trials investigated secondary malignancies or economic outcomes. CONCLUSION: rhTSH is as effective as THW on radioiodine thyroid remnant ablation with significant benefits on health-related quality of life, adverse effects during and after ablation, decreased whole body radiation exposure. The lower radioiodine doses are as effective as high doses for remnant ablation under rhTSH stimulation.

[Hormonal deficiencies in the elderly: is there a role for replacement therapy?]. / Déficiences hormonales du sujet âgé: faut-il les traiter?

Biological aging is characterized by a progressive loss of the secretion of various hormones, a phenomenon that leads some physicians to propose an anti-aging hormonal therapy. It is mandatory to differentiate: 1) the physiological functional loss, which is a natural phenomenon without clear deleterious consequences on health and should not be compensated by the administration of hormones only to restore plasma levels similar to those measured in young people and 2) a pathological defect that deserves a replacement therapy to correct the endocrine deficiency and improve the health status of older individuals. This article considers the deficiencies in insulin, thyroid hormones, growth hormone, dehydroepiandrosterone (DHEA) and testosterone. For each hormone, a benefit/risk ratio of a so-called replacement therapy will be analyzed.

Thyroid hormone supplementation in preterm infants born before 28 weeks gestational age and neurodevelopmental outcome at age 36 months.

BACKGROUND: Thyroid hormones are required for normal brain maturation, and neonatal plasma thyroid hormone concentrations are low in infants less than 28 weeks gestation. It is not known whether treatment of such infants with thyroid hormone improves neurodevelopmental outcome. METHODS: At three years corrected age, mental, motor, and neurological development was assessed in infants born at less than 28 weeks gestational age who had participated in a phase 1 trial of differing doses and modes of administration of thyroid hormone. The trial's endpoints were thyroid hormone (thyroxine, T4) and thyotropin plasma concentrations in eight study arms: six treated with T4 [4, 8, and 16 µg/(kg · day)], bolus or continuous], one treated with iodine only, and one treated with placebo. Follow-up at three years was not part of the original study goals. Developmental index scores, rates of cerebral palsy (CP), and rates of adverse outcome (death or moderate to severe delay in development and/or disabling CP) were compared between the eight study groups and between groups combined by dosage level, and between infants with and without T4 supplementation. RESULTS: Of 166 randomized infants, 32 (19%) died in the neonatal period. Of the 134 survivors, follow-up results were available for 89 children (66%). Mental and motor development and rates of cerebral palsy did not differ in any of the comparisons made. CONCLUSION: In this study, no differences in neurodevelopment were found in relation to thyroid hormone treatment, but power was insufficient to detect any but very large differences.

Thiamine and Hashimoto's thyroiditis: a report of three cases.

OBJECTIVES: In a previous study on fatigue and related disorders in inflammatory bowel disease (IBD), we observed that IBD patients improved after treatment with high-dose thiamine. We hypothesized that the chronic fatigue accompanying inflammatory and autoimmune diseases is the clinical manifestation of a mild thiamine deficiency that is probably due to a dysfunction of the intracellular transport or to enzymatic abnormalities. Hashimoto's thyroiditis is both a common automimmune disease and cause of hypothyroidism. Although levothyroxine, a thyroid hormone, is the treatment of choice for hypothyroidism, a significant number of patients on thyroid hormone replacement therapy report not feeling well despite having thyroid function tests within the healthy range. Based on our hypothesis, we started treating the fatigue in patients affected by Hashimoto's thyroiditis and taking a thyroid hormone with thiamine. This is a report of the outcomes of three cases in which the fatigue component reported by patients with Hashimoto's thyroiditis was treated with thiamine. DESIGN: Three patients on thyroid hormone replacement because of Hashimoto's thyroiditis were treated for the fatigue component of the disease from May to July 2011. Fatigue was measured using the Fatigue Severity Scale. Free thiamine in the serum and thiamine pyrophosphate in red cells were tested before and after the therapy. All three patients received oral (600 mg/day) or parenteral (100 mg/ml every four days) doses of thiamine. RESULTS: Treatment with thiamine led to partial or complete regression of the fatigue within a few hours or days. CONCLUSION: As the administration of thiamine led to a partial or complete regression of the fatigue and related disorders, it is reasonable to infer that the administration of large quantities of thiamine restores thiamine-dependent processes. The mild thiamine deficiency suggested by fatigue and related disorders may be due a dysfunction of the intracellular transport of thiamine or to enzymatic abnormalities most likely related to the autoimmune process of the disease.

Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 µg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.

Thyroid hormone reverses aging-induced myocardial fatty acid oxidation defects and improves the response to acutely increased afterload.

BACKGROUND: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to the development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone supplementation reverses these defects. METHODS: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with (13)C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. RESULTS: Old mice maintained cardiac function under standard workload conditions, despite a marked decrease in unlabeled (presumably palmitate) Fc and relatively similar individual carbohydrate contributions. However, old mice exhibited reduced palmitate oxidation with diastolic dysfunction exemplified by lower -dP/dT. Thyroid hormone abrogated the functional and substrate flux abnormalities in aged mice. CONCLUSION: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

Involvement of thyroid hormones in the alterations of T-cell immunity and tumor progression induced by chronic stress.

BACKGROUND: Stress alters the neuroendocrine system, immunity, and cancer. Although the classic stress hormones are glucocorticoids and catecholamines, thyroid hormones have also been related to stress. We recently reported that chronic restraint stress impairs T-cell mediated immunity and enhances tumor growth in mice. METHODS: To study the participation of these hormones on the stress-induced alterations of the immune function and lymphoma growth, mice were subjected to acute or chronic stress, with or without thyroxin supplementation. Hormone levels, immune status, and cancer progression were evaluated. RESULTS: Differential endocrine alterations were observed in response to acute and chronic stress. Although corticosterone and noradrenaline levels were increased by acute stress, they were restored after prolonged exposure to the stressor. Instead, thyroid hormone levels were only reduced in chronically stressed animals in comparison with control subjects. Correlating, chronic but not acute stress impaired T-cell reactivity. Thyroxin replacement treatment of chronic restraint stress-exposed mice, which restored the euthyroid status, reversed the observed reduction of T-cell lymphoproliferative responses. Moreover, therapeutic thyroid replacement also reversed the alterations of lymphoma growth induced by chronic stress in syngeneic mice bearing tumors as well as Interleukin-2 production and specific cytotoxic response against tumor cells. Finally, we found that the isoforms theta and alpha of the protein kinase C are involved in these events. CONCLUSIONS: These results show for the first time that thyroid hormones are important neuroendocrine regulators of tumor evolution, most probably acting through the modulation of T-cell mediated immunity affected by chronic stress.

Effects of substitution and high-dose thyroid hormone therapy on deiodination, sulfoconjugation, and tissue thyroid hormone levels in prolonged critically ill rabbits.

To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3'-diiodothyronine (T(2)) and T(4)S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T(4) and T(3), either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T(3) (P=0.006), hepatic T(3) (P=0.02), and hepatic D1 activity (P=0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P=0.0006) and tissue T(4) (P=0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T(3) and tissue T(3)/reverse T(3) ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T(2). Plasma T(4)S was increased only by T(4) in high dose. We conclude that in prolonged critically ill rabbits, low plasma T(3) levels were associated with low liver and kidney T(3) levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism.

The present study was conducted to evaluate the serum copper, zinc, magnesium, and selenium levels in patients with subclinical hypothyroidism in the iodine-rich region of Ankara, Turkey. The effects of hormone replacement therapy on these elements were also studied in these patients. Basal levels of selenium and iron in patients were significantly lower than control group (67.7 +/- 10.4 vs. 83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03 microg/dl). Serum magnesium levels were significantly higher in patient group (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in patients with selenium levels <80 microg/l (n = 31) was significantly higher than hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0; 1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace elements have changed after euthyroidism in patients with SH when compared to pretreatment levels. Selenium deficiency may contribute to cardiovascular disease risk in these patients.

Repigmentación del pelo canoso tras tratamiento con hormona tiroidea / Repigmentation of gray hair after thyroid hormone treatment

Introducción y objetivos. Basándonos en dos pacientes con oscurecimiento de sus canas que sufrieron una elevación exógena de T3, debida a un coma mixedematoso y a una descompensación de su enfermedad, sugerimos que la hormona tiroidea puede tener un efecto en la homeostasis del folículo piloso. Para ello se utilizan un modelo animal de ratón y un modelo de cultivo in vitro de unidades foliculares, con el objeto de valorar la influencia de la hormona tiroidea en el ciclo capilar. Métodos. Sobre un modelo de ratón estandarizado para el estudio del ciclo capilar (C57BL/6), aplicamos tópicamente T3 (0,5 g) disuelta en etanol una vez al día durante 10 días en el dorso de ratones depilados en fase de telogen. Cultivamos in vitro unidades foliculares, obtenidas de cirugía capilar, con diferentes concentraciones de T3. Resultados. In vivo, al quinto día del tratamiento el 100 % de los ratones estudiados entraron en anagen, mientras que en el grupo control se apreció un inicio del anagen el día 9, que no se completó en todos los ratones hasta el día 15. In vitro, las unidades foliculares tratadas con 100 nM de T3 crecieron de forma significativa respecto al grupo control. Conclusiones. Estos datos sugieren que los folículos en telogen pueden estimularse para entrar en anagen tras la aplicación tópica de T3. Esta hormona puede revertir el encanecimiento del pelo terminal. En cultivo, la administración de T3 estimula el crecimiento del tallo piloso. Los melanocitos foliculares podrían ser la célula diana para estas acciones

Background and objectives. Darkening of gray and white hairs occurred in 2 patients with increased exogenous triiodothyronine (T3) due to treatment of myxedema coma in one case and iatrogenic hyperthyroidism in the other. We hypothesized that thyroid hormone may affect the homeostasis of hair follicles. To test our hypothesis and investigate the influence of thyroid hormone on the hair cycle, we used an in vivo murine model and an in vitro model based on culture of follicular units. Methods.We used the standard C57BL/6 murine model of the hair cycle. T3 (0.5 g) dissolved in ethanol was applied topically once daily for 10 days to a depilated area in the telogen phase on the backs of the mice. Follicular units, obtained from hair transplant interventions, were cultured in vitro with different concentrations of T3. Results. On day 5, all T3-treated mice entered the anagen phase, whereas the anagen phase started spontaneously in control mice on day 9, and not until day 15 had all controls entered this phase. In the in vitro experiment, follicular units treated with 100 nmol/L T3 grew significantly larger compared to the control group. Conclusions. These data suggest that follicles in the telogen phase can be induced to enter the anagen phase by the topical application of T3. This thyroid hormone may reverse graying of the terminal hair. In the in vitro experiments, T3 stimulated hair shaft growth. Follicular melanocytes may be the target cell for these actions

Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis.

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T(3) results in a serum T(3) level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T(3) and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.

Effects of thyroid hormone on food intake, hypothalamic Na/K ATPase activity and ATP content.

The effects of thyroid hormone on whole body energy metabolism and compensatory effects on food intake are well established. However, the hypothalamic mechanisms that translate perceived whole body energy demands into subsequent appetitive behavior are incompletely understood. In order to address this question, we tested the effects of T3 on food intake and body weight in rats and measured neuronal Na/K ATPase activity and ATP content in the hypothalamus. Intraperitoneal T3 (100 microg/kg BW) administered for 6 consecutive days increased 24-h rat food intake from control, 26.6+/-1.2, to T3-treated 33.2+/-1.6 g (P<0.01). In T3-treated rats, rubidium-86 (86Rb) uptake (measured as a marker of Na/K ATPase activity) in ex vivo hypothalamic tissue increased (P<0.01) while the content of ATP in the ventral hypothalamus declined following T3 treatment (P<0.01). In another model of energy deficit, which was induced by a very low calorie diet, ATP content was also reduced in the hypothalamus compared to rats fed ad libitum. In summary, increased food intake in response to T3 may be secondary to decreased hypothalamic ATP content, perhaps resulting from both increased Na/K ATPase activity in the hypothalamus and metabolic signaling induced by whole body caloric deficit.