Affect Thyroid Hormone Metabolism Research Articles

FRI511 Bexarotene: A Deceptive Cause Of Iatrogenic Hypothyroidism

Abstract Disclosure: S. Ghaith: None. A. Ramachandran: None. C. Alcorn: None. F. Amer: None. A. Thompson: None. A. Ramachandran: None. Background: Bexarotene, an antineoplastic agent used for the treatment of cutaneous T cell lymphoma, is associated with a rapid and profound suppression of thyrotropin, which may lead to central hypothyroidism. Case: A Seventy-four-year-old female with a recent diagnosis of Cutaneous T cell lymphoma presented with a 1-week history of progressive fatigue, lightheadedness, and night sweats. She was found to have hypotension and hypothermia. She was started on oral Bexarotene chemotherapy 225 mg daily five days prior to admission. The physical exam was unremarkable except for sinus bradycardia and hypothermia. Labs were significant for TSH 0.48 [0.4-4.2 uIU/mL] dropped from 3.3 uIU/mL one week prior, FT4 0.5 [0.8-1.7 ng/dL] and Total T3 111 ng/dL [87- 187 ng/dL] consistent with central hypothyroidism. Bexarotene was held during her hospitalization per hematology recommendations. The patient was started on Levothyroxine 50 mcg, which was later advanced to 75 mcg daily based on free T4 levels. At one month follow up, free T4 level normalized while on Levothyroxine and Bexarotene was restarted again by her hematologist. Discussion: Bexarotene, an antineoplastic agent approved for treating cutaneous T cell lymphoma, can rapidly suppress TSH levels by directly inhibiting its secretion and affect thyroid hormone metabolism, leading to central hypothyroidism. The degree of suppression of TSH increases with higher doses of Bexarotene while reduction in free T4 and TSH are reversible. Patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels. If bexarotene is permanently discontinued, levothyroxine can either be stopped or can be resumed to doses used prior to bexarotene therapy. Recovery of thyroid function usually occurs within weeks of Bexarotene discontinuation. Conclusion: Oral Bexarotene can cause central hypothyroidism therefore, thyroid function tests should be measured at baseline and treatment. Thyroid hormone replacement should be considered if central hypothyroidism is suspected. Presentation: Friday, June 16, 2023

Does Arsenic Exposure Have a Role in Development of Thyroid Disease?

Abstract Background: Several animal studies indicate arsenic toxicity can affect thyroid hormone metabolism. There is no study in the English scientific literature of the relationship between thyroid disease and arsenic exposure in human population. The Indian state of West Bengal is affected by arsenic contamination of ground water. According to the World Health Organisation 6 of the 23 districts of West Bengal are higher affected areas. Objectives: To study the role of arsenic in development of thyroid disease. Methods: Arsenic exposure in seven patients with thyroid disease was estimated by Inductive Coupled Plasma Mass Spectroscopy (ICP-MS) of hair and nail samples. Results: Of the seven patients 2 were male and 5 were female. Two patients had thyroid malignancy (papillary carcinoma) while the rest had benign thyroid disease. Six out of the seven were residents of higher arsenic affected districts of West Bengal. One patient with a thyroid adenoma had elevated concentration of arsenic in hair (1.19 mg/kg). A second patient with of follicular adenoma had sub-clinical hypothyroidism at the time of the survey. Conclusion: This small study suggests that arsenic exposure may be associated with the development of thyroid disease. A larger study with adequate controls is warranted to establish the true role of arsenic in the aetio-pathogenesis of thyroid disorders.

Administration of silver nanoparticles affects ovarian steroidogenesis and may influence thyroid hormone metabolism in hens (Gallus domesticus)

This study aimed to determine the in vivo effect of silver nanoparticles (AgNPs) on the concentration of sex steroids (progesterone – P4, estradiol – E2, testosterone – T) and thyroid hormones (thyroxine – T4, triiodothyronine – T3) in the blood plasma as well as the messenger ribonucleic acid (mRNA) and protein expression of HSD3β, CYP17A1 and CYP19A1 enzymes and steroid hormone concentrations in chicken ovarian follicles. AgNPs did not affect serum steroid hormone levels, but increased T3 levels depending on the size and concentration of AgNPs. At the level of ovarian tissues, AgNPs: (i) affected the levels of E2 and T in prehierachical follicles; (ii) reduced the expression of CYP19A1 mRNA and protein and consequently diminished E2 concentration in small white follicles; and (iii) increased the expression of CYP17A1 mRNA in large white follicles, without changing its protein expression. The results indicate that AgNPs affect chicken ovarian steroidogenesis. The effects of AgNPs depend on exposure time, the type of follicle and the degree of its development and are associated with the modulation of steroidogenic gene expression and E2 and T synthesis. Prehierachical follicles seem to be more susceptible to AgNPs than preovulatory ones. In conclusion, AgNPs by targeting the chicken ovary may indirectly influence the selection processes of prehierarchical follicles to the pre-ovulatory hierarchy and disturb the ovarian steroidogenesis. Furthermore, AgNPs may affect thyroid hormone metabolism in different ways by size which in turn may influence energy homeostasis of the target cells.

Effects of concomitant selenium and vitamin E administration on thyroid hormone metabolism in broilers

A total of 400, as hatched, broilers were used to investigate the effect of selenium (Se) and vitamin E supplementation on thyroid hormones metabolism. There were 5 replicates of 4 dietary treatments namely: control (C), a soybean meal maize basal diet with adequate Se and vitamin E (0.3 mg Se per kg diet and 80 mg vitamin E per kg diet), control diet with Se added (Se+, with an additional 1 mg of Se per kg of diet), control diet with vitamin E added (E+, with an additional 350 mg of vitamin E per kg of diet) and Se+E+ (with additional 1 mg of Se and 350 mg of vitamin E per kg of diet). Diets were isonitrogenous and isocaloric. Zinc L-selenomethionine complex was used to increase Se content and dl-α-tocopheryl acetate to increase vitamin E content. The experiment lasted 42 days. Plasma Se concentration increased in Se+ groups, while whole blood glutathione peroxidase (GPx) activity increased in Se+, E+ and Se+E+ groups compared to control. Hepatic type I iodothyronine deiodinase (ID-I) and thyroid hormone concentrations were unaffected by any dietary treatment. It is concluded that supplementation with Se or vitamin Ε alone or in combination above animal’s requirements does not affect thyroid hormone metabolism and liver ID-I activity under the conditions examined.

Polychlorinated biphenyl exposure and deiodinase activity in young infants

BackgroundSeveral studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct influence on the thyroid gland, binding to thyroid binding proteins, increased excretion or metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well known whether the effect on thyroid hormone levels is caused by PCBs themselves, or by their hydroxylated metabolites (OH-PCBs). ObjectiveTo determine the effects of perinatal exposure to PCBs and OH-PCBs on thyroid hormone levels in cord blood and in serum of newborn infants. MethodsIn a Dutch cohort of 100 mother-infant pairs, exposed to background PCB levels, correlations were assessed between 10 PCBs and 6 OH-PCBs in maternal blood during pregnancy and serum thyroxine (T4), T4 sulfate (T4S), triiodothyronine (T3), reverse T3 (rT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) levels in cord blood and in serum of three- and 18-month-old infants. We corrected for age of the mother, gestational age, gender and type of feeding. ResultsAfter correction, prenatal levels of three of 10 measured PCBs showed a positive correlation with cord serum T3, and four PCBs showed a negative correlation with cord serum rT3. After correction, two PCBs and the sum of the 10 measured PCBs were positively correlated with the cord serum T3/rT3 ratio, an indicator of deiodinase 3 activity. No correlations were found between PCBs and T4, TSH and TBG in cord blood. 4-OH-PCB-107 was correlated with T4 at 3months and T4, T4S and T3 at 18months. ConclusionOur results suggest that PCBs have a negative effect on deiodinase type 3 activity, as reflected by a positive correlation with the T3/rT3 ratio. We identified a potential mechanism by which PCBs may affect thyroid hormone metabolism during human development.

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis.

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end-stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty-one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid-stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.

Exposure to oxidative by-products during metamorphosis affects pigmentation patterns in flounder, Paralichthys olivaceus

Hatcheries often employ disinfection by electrolysis for water; however, this produces free oxidants that pose practical problems in the production of flounder, Paralichthys olivaceus. Rearing juvenile flounder in electrolyzed seawater (EL-SW) causes pseudo-albinism. To elucidate the mechanism of the onset of EL-SW-induced pseudo-albinism, we compared thyroid hormone (TH) metabolism, melanoblasts, and skin differentiation in flounder reared in normal seawater (normal SW) and EL-SW and determined the critical period for the onset of pseudo-albinism. The number of thyroxin (T4)-positive thyroid follicles increased toward the metamorphic climax. The expression of deiodinase 1 (dio1), which converts plasma T4 to triiodothyronine (T3), in the liver peaked synchronously with the increase in T4-positive thyroid follicles. EL-SW exposure had no effect on TH metabolism. Instead, EL-SW inhibited differentiation of adult-type melanoblasts in the skin of the ocular side together with a loss of structural asymmetry in the bilateral skins. Although EL-SW does not affect TH metabolism, our data indicate that it does inhibit the signaling system that controls differentiation of the blind and ocular lateral halves during the establishment of metamorphic asymmetry. The early-metamorphic stage, E- and F-stages, was demonstrated to be the critical period for the onset of pseudo-albinism in EL-SW-reared larvae. These results suggest that long-term exposure to free oxidants, even at low levels, acts as a chronic stressor on flatfish metamorphosis.

Food deprivation induces chronic stress and affects thyroid hormone metabolism in Senegalese sole (Solea senegalensis) post-larvae

In vertebrates, stress and thyroid systems interact closely, most likely because of the involvement of both systems in energy metabolism. However, studies on these interactions, especially during larval development, are scarce. Recently, cDNAs coding for corticotropin-releasing hormone (CRH) and CRH-binding protein (CRH-BP), two key players in the regulation of the neuroendocrine stress response, were characterized for the flatfish Senegalese sole (Solea senegalensis). To investigate the involvement of stress and thyroid systems in this species, the effects of food deprivation during early development of S. senegalensis were assessed. Growth was arrested in food-deprived post-larvae, which was also reflected by decreased carbon and nitrogen contents, indicating increased catabolism. Food deprivation induces chronic stress, as illustrated by enhanced whole-body cortisol levels, as well as an up regulation of crh and a decrease of crh-bp expression levels. Furthermore, whole-body total T3 concentrations of food-deprived post-larvae were reduced, although tshβ subunit expression levels remained unaffected. Our results show that food deprivation is a chronic stressor that induces energy-releasing catabolic processes that compensate for the reduced energy intake, and inhibits anabolic processes via the peripheral thyroid system.

Drugs Affecting Thyroid Function

Over the years, several drugs used in the treatment of nonthyroidal conditions have been shown to affect thyroid function. As novel drugs are introduced, novel interactions are described. The aim of this review is to summarize clinically relevant thyroidal side effects of drugs used for nonthyroidal conditions. Special focus is given to recent developments and to drugs with the largest clinical relevance. Thyrosine kinase inhibitors are novel drugs used in the treatment of several neoplasias, including thyroid cancer. Thyroidal side effects are being increasingly detected with these drugs. Some drugs in this category affect thyroid hormone metabolism and therefore only affect patients on thyroid replacement. Others affect the thyroid directly profoundly, causing primary hypothyroidism. Immune modulators used in infectious, inflammatory, and neoplastic conditions also cause hyper- and hypothyroidism, through poorly understood immune or nonimmune mechanisms. The effects of amiodarone on the thyroid have been long recognized. However, given the complexity of these effects, several areas in this field remain problematic, such as the identification of subtypes of hyperthyroidism and the best treatment strategies. Lithium also has important antithyroid effects and it is a commonly prescribed medication. Its antithyroid effects may have clinical utility in selected clinical situations. Other drugs known to affect thyroid hormone absorption, metabolism, and transport are also briefly reviewed. Several drugs are known to alter thyroid function as a side effect of their primary pharmacological action. Some of these effects have been recognized for decades, but novel thyroid-drug interactions are being recognized as new drugs are developed. It is important for the clinician to be familiar with thyroid-drug interactions, as enhanced surveillance may be necessary in patients undergoing therapies known to affect thyroid function.

The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism

Although most hypothyroid patients do well with one single tablet of thyroxine daily, approximately 10% are dissatisfied and another important group of patients is difficult to control. We reviewed the most common causes for frequent-dose adjustment or high-dose requirement, including poor compliance with therapy and inadequate medication. Since these two causes have been ruled out, drug interaction and other concomitant diseases need to be investigated. Requirements of thyroxine increase in all conditions characterized by impaired gastric acid secretion. Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption. In addition, a series of diseases including celiac disease and chronic inflammatory intestinal diseases, as well as nutritional habits may be important in patient control. Finally, we mention the effects of a growing list of drugs and thyroid disruptors that may also affect thyroid hormone metabolism at many levels.

Circulating adiponectin concentrations were related to free thyroxine levels in thyroid cancer patients after thyroid hormone withdrawal

Because it is unclear whether adipose-derived hormones are related to thyroid hormone metabolism, this study evaluated the relationship between adiponectin concentrations and changes in the thyroid hormones in athyreotic patients after thyroid hormone withdrawal. Twenty-eight athyreotic thyroid cancer patients (4 male and 24 female; mean age, 52.2 ± 11.3 years) were analyzed on the final day of levothyroxine treatment and 1 day before serum thyroglobulin and radioiodine scanning examinations after an average of 4 weeks of thyroid hormone withdrawal. Evaluations included analysis of thyroid function test, serum adiponectin, body composition by bioimpedance analysis, and insulin sensitivity index as determined by the homeostasis model assessment of insulin resistance (HOMA-IR). Discontinuation of thyroid hormone treatment resulted in a significant change in thyroid-stimulating hormone (82.1 ± 9.8 vs 1.0 ± 0.4 mL/L, P < .05), free thyroxine (FT4) (5.7 ± 0.4 vs 18.7 ± 2.3 pmol/L, P < .05), and free triiodothyronine levels (1.8 ± 0.2 vs 3.4 ± 0.2 pmol/L, P < .05) as compared with the prewithdrawal values, whereas circulating adiponectin levels (5.7 ± 0.6 vs 5.4 ± 0.6 mg/L), body fat mass (20.3 ± 1.2 vs 19.4 ± 1.2 kg), and insulin sensitivity index (1.8 ± 0.2 vs 2.2 ± 0.3) remained unaltered. A positive correlation between adiponectin and FT4 ( r = 0.61, P < .01) independent of age, sex, fat body mass, HOMA-IR, and other potential covariates known to affect thyroid hormone metabolism, such as renal and liver functions, was observed after thyroid hormone withdrawal. In addition, baseline circulating adiponectin levels were correlated with a diminished postwithdrawal reduction of FT4 concentrations after adjusting for baseline FT4 levels and changes in body mass index, fat body mass, and HOMA-IR ( r = 0.71, P < .01). In conclusion, adiponectin concentrations were associated with FT4 levels in the athyreotic patients after thyroid hormone withdrawal. The relevant roles of adiponectin in the regulation of thyroid hormone metabolism require further investigation.

Oxidative stress and thyroid hormones in patients with liver diseases

Background The liver metabolizes the thyroid hormones and regulates their systemic endocrine effects so liver disease could affect thyroid hormone metabolism. Oxidative stress could play a role in the pathogenesis and progression of liver diseases. The objective of this study was to investigate serum levels of oxidative stress and antioxidant in liver diseases as prognostic markers and know the importance of these antioxidants level in relation to thyroid hormones. Methods Serum nitric oxide (NO), malondialdehyde (MDA) and triiodothyronine (T 3), thyroxine (T 4), thyroid stimulating hormone (TSH), apolipoprotein-1 (APOA1) levels and erythrocyte reduced glutathione (GSH) level and glutathione peroxidase (GSHPx) and glutathione reductase (GR) activities were determined in 20 control subjects, 13 patients with non-alcoholic steatohepatitis (NASH), 18 patients with chronic HCV, 17 patients with compensated cirrhotic HCV and 42 patients with decompensated cirrhotic HCV. Results Cirrhotic patients with HCV had higher NO and MDA levels while lower T 3 and erythrocyte GSH levels, and GSHPx activity than the chronic. Serum T 3 showed negative correlation with serum NO and MDA whereas positive correlation with APOA1, GSH, and GSHPx in cirrhotic patients with HCV. Conclusion The measurement of the total T 3, NO, MDA, GSH reduced and GSHPx as biomarkers for liver diseases might be a beneficial tool, helping in monitoring the state of liver disease patients.

Thyroid Hormone Receptor β Mediates Acute Illness‐Induced Alterations in Central Thyroid Hormone Metabolism

Acute illness in mice profoundly affects thyroid hormone metabolism in the hypothalamus and pituitary gland. It remains unknown whether the thyroid hormone receptor (TR)-β is involved in these changes. In the present study, we investigated central thyroid hormone metabolism during lipopolysaccharide (LPS)-induced illness in TRβ(-/-) mice compared to wild-type (WT) mice. We administered a sublethal dose of LPS or saline to TRβ(-/-) and WT mice. TRβ(-/-) mice displayed higher basal levels of serum triiodothyronine (T(3)) and thyroxine (T(4)) compared to WT, reflecting thyroid hormone resistance. In the periventricular area of the hypothalamus, we observed a marked decrease in thyrotrophin-releasing hormone (TRH) mRNA expression in TRβ(-/-) and WT mice at t = 4 h, coinciding with the peak in plasma corticosterone. The decrease in TRH mRNA persisted in WT, but not in TRβ(-/-) mice at t = 24 h. By contrast, the increase of type 2 deiodinase (D2) mRNA already present at 4 h after LPS remained significant at 24 h in TRβ(-/-), but not in WT mice. LPS decreased pituitary thyroid-stimulating hormone β mRNA expression in WT at 24 h but not in TRβ(-/-) mice. The peak in pituitary D2 expression at t = 4 h in WT was absent in TRβ(-/-) mice. The relative decrease in plasma T(3) and T(4) upon LPS treatment was similar in both strains, although, at t = 24 h, plasma T(3) tended to be restored in TRβ(-/-) mice. Our results suggest that TRβ is involved in suppression of the central component of the hypothalamic-pituitary-thyroid axis in acute illness.

4MBC and OMC, components of UV-sunscreens, exert organ specific alterations on type I 5'-Deiodinase activity and expression in female rats

Endocrine disrupting compounds (EDC) of natural or synthetic origin were originally found to impair development and endocrine regulation of the reproductive system. Here, we assessed whether they also exert effects on the thyroid hormone axis. Female ovariectomized rats were treated for 12 weeks with two substances used as UV absorbers in sunscreens: Octyl-methoxycinnamate (OMC; 66 and 310mg/day) and 4-methylbenzylidene-camphor (4-MBC; 0.4 and 1.74mg/day) alone or in combination with soy-containing food. These substances are known to be resorbed by the skin, circulating in the blood (Janjua et al. 2004J Invest Dermatol 123:57–61) and suspected to have endocrine disrupting effects. The soy isoflavone genistein has estrogenic and anti-estrogenic effects and is known to inhibit thyroid hormone biosynthesis. As type I 5'-deiodinase (5'DI) is a well known T3-regulated endpoint, 5'DI activity was measured by deiodination of 125I--reverse T3, and 5'DI gene expression was determined by real time RT-PCR. Treatment with OMC caused a significant reduction of 5'DI activity from a basal level of 6.6 to 3.0 and 3.1 pmol iodide released x mg–1 x min–1 in the liver in the absence and presence of soy in the diet, respectively, while 4MBC did not show any effects. A similar decrease was also observed for 5'DI mRNA levels. In the kidney OMC as well as 4MBC led to a marked decline of 5'DI activity from 8.4 to 3.0 pmol iodide released x mg–1 x min–1, independent of the diet. Additionally, higher 5'DI activities were found in the kidney of animals consuming soy containing diet, while no such effect was obtained in liver. This data indicates that 4MBC and OMC affect thyroid hormone metabolism via tissue-specific inhibition of 5'DI activity and gene expression. Thus, 4MBC and OMC do not only interfere with steroid-hormone dependent regulation, but may also disturb endocrine regulation via the thyroid hormone axis.

Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) levels and thyroid function in Air Force veterans of the Vietnam War.

We assessed potential health effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentration in serum on thyroid function in US Air Force veterans involved in Operation Ranch Hand, the unit responsible for the aerial spraying of herbicides, including TCDD-contaminated Agent Orange, during the Vietnam War from 1962 to 1971. Other Air Force veterans who were not involved with spraying herbicides were included as Comparisons. We analyzed thyroxine (total T4), thyroid stimulating hormone (TSH), triiodothyronin percent uptake (T3% uptake), the free thyroxine index (FTI), and thyroid diseases against serum TCDD levels. Data was available for 1,009 Ranch Hand and 1,429 Comparison veterans compliant to any of five examinations in 1982, 1985, 1987, 1992, and 1997. Each veteran was assigned to one of four exposure categories based on serum TCDD levels, named Comparison, Ranch Hand Background, Ranch Hand Low Elevated, and Ranch Hand High Elevated. Cross-sectional analyses found statistically significantly increased TSH means at the 1985 and 1987 examinations in the High category and a significant increasing trend across the three Ranch Hand TCDD categories in 1982, 1985, 1987 and 1992. A repeated-measures analysis found significantly increased TSH means in the High TCDD category. We found no significant relation between the occurrence of thyroid disease and TCDD category. These findings suggest that TCDD affects thyroid hormone metabolism and function in Ranch Hand veterans. Further follow-up will be necessary to understand the relation, if any, between thyroid disease and TCDD levels.

Is the low tri-iodothyronine state a crucial factor in determining the outcome of coronary artery bypass patients? Evidence from a clinical pilot study.

The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.

Effects of starvation on gonadotropin and thyrotropin subunit mRNA levels and plasma hormone levels in the male Japanese quail (Coturnix coturnix japonica).

Contents of mRNAs encoding LHbeta-, FSHbeta-, TSHbeta- and common a-subunit precursor molecules were measured in male Japanese quail deprived of food for three days. Plasma LH, FSH, thyroxine and triiodothyronine levels were also measured in the same birds. Plasma LH levels declined during the period of food deprivation. Levels in starved birds were not different from those in control birds after one day of starvation but were significantly lower after three days. Plasma FSH levels showed a similar decline, although the changes were not significant. Plasma thyroxine levels did not decrease during starvation, whilst plasma triiodothyronine levels decreased drastically and significantly soon after the start of starvation. All the hormone subunit mRNA contents in starved birds also decreased, with differences from control birds significant 3 days after the start of starvation. Plasma FSH levels showed a strong positive correlation with pituitary FSHbeta mRNA levels, while plasma LH levels had a strong positive correlation with common a mRNA levels and practically no correlation or even a negative correlation with LHbeta mRNA levels. These results suggest that starvation suppresses not only gonadotropin and thyrotropin secretion but also their synthesis in the pituitary gland. Furthermore, these results showed that FSH and LH have different synthesis and secretion dynamics in the Japanese quail. Contradicting results with TSHbeta mRNA and thyroid hormones lead us to assume that starvation affects thyroid hormone metabolism in peripheral tissue, presumably in the liver.

Oral Cholecystographic Agents and the Thyroid

Oral cholecystographic agents (OCAs) are known to affect thyroid hormone metabolism by acting as potent inhibitors of type I and type II deiodinases, blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine released from the drug blocks thyroid gland secretion of thyroid hormone. These properties make OCAs a potentially useful drug therapy in patients with hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are not useful for long-term treatment, which is usually followed by exacerbation of hyperthyroidism with continued use. The lack of significant side effects makes these drugs an excellent short-term option in situations where a rapid clinical improvement is critical.

The hypothalamic–pituitary–thyroid axis in patients with schizophrenia

Serum concentrations of thyroxine (T 4), triiodothyronine (T 3), reverse triiodothyronine (rT 3) and thyrotropine (TSH) were measured in 31 acutely ill in-patients with schizophrenia before and after four weeks of treatment with the phenothiazine derivative perazine. The serum levels of all the above hormones were also determined in 19 schizophrenic patients in remission who were receiving no medication, 20 schizophrenic patients in remission taking neuroleptic drugs, and 24 patients with residual-type schizophrenia. The serum levels of T 4 of acutely ill schizophrenic patients were elevated, while those of T 3, rT 3 and TSH were normal. Their T 4 levels showed a positive correlation with the severity of illness and the degree of clinical response to neuroleptic treatment. There was a significant fall in serum concentrations of T 4 and rT 3 during four weeks of drug treatment and the decrease was significantly correlated to clinical response. No abnormalities in the serum concentrations of any of the hormones measured were found in schizophrenic patients in remission or in residual-type schizophrenia. In conclusion, our results indicate that the elevated serum levels of T 4 may be specific for acutely ill schizophrenic patients and that neuroleptic medication may affect thyroid hormone metabolism, this interaction being involved in the mechanism of action of these drugs.

Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells.

Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.