Role Of Thyroxine Research Articles

Role of thyroxine in reducing the size of benign thyroid swellings and pre-treatment thyroid stimulating hormone as a predictor of response to therapy

Background: Conservative management for benign thyroid swellings which do not require surgery is a matter of controversy. There has been studies and trials on the role TSH suppression in reducing thyroid volume, but low dose thyroxine was never been properly studied. Being such a common disorder, more studies have to be undertaken to have an idea on managing the goitres conservatively.Methods: Patients with benign thyroid goitres without indications for surgery and who were on 50-100 µg of thyroxine per day was included in the study. Their initial thyroid hormone levels, volume on ultrasonogram, and fine needle aspiration cytology were collected along with biodata. They were reassessed after 6 months and 1 year for change in volume of thyroid.Results: Majority of patients showed a decreasing trend in volume of thyroid after 1 year of thyroxine therapy, even though the amount of reduction was not statistically significant. Rate of decrease in thyroid volume was significantly higher in patients with higher TSH values.Conclusions: Thyroxine therapy has got a role in reducing and arresting further growth of benign thyroid swellings which doesn’t require surgical management. Pre-treatment TSH can be used a predictor of response to thyroxine therapy.

Protective Effect of Thyroxine on Minocycline Induced Thyroid Gland Damage

Background: Thyroxine has shown beneficial effects on intelligence, learning, and memory process in patients of congenital hypothyroidism. Minocycline has been used in clinical practice for various indications and reported to have anti-thyroid effects. This study was specifically designed to observe the role of thyroxine on minocycline induced damage to thyroid gland. Methods: This experimental study was undertaken at Anatomy department of BMSI, JPMC, Karachi, for eight weeks, from October to November 2019. Thirty adult (10-12 months) male guinea pigs, weighing from 450-650 gm were obtained and divided into 3 groups. Group A served as control, group B was given Minocycline 0.02mg/gram/day once daily and group C was administered Minocycline in similar amount as group B along with thyroxine 0.5µg/gram/day for the same duration. Dosing was continued for 8 weeks, at the completion of which all the animals were sacrificed. Thyroid gland was processed and tissue sections were stained with Haematoxylin and Eosin for morphology. Results: The absolute weight of thyroid gland was significantly increased (p<0.001) in minocycline treated group B animals compared to the control animals, whereas substantial decrease (p<0.01) in absolute weight of thyroid gland was witnessed in group C in comparison to group B animals. The follicular cells showed hypertrophy and shrinkage of colloid in the thyroid follicles. These changes were prevented when animals were co-administered with thyroxine and minocycline in Group C. Conclusion: Concomitant administration of thyroxine with the antimicrobial drug minocycline showed protective effects of thyroxine on Minocycline induced damage to thyroid gland of animals.

Role of Thyroxine in the Development of Keratoconus.

Keratoconus (KC) is a corneal ectasia whose pathophysiology is still mostly unknown. We investigated whether thyroid gland dysfunction (TGD) is associated with the development of KC. We first conducted an epidemiological study, examining the prevalence of TGD among patients with KC. Then, we compared tear thyroxine (T4) in TGD and immunohistochemical staining of its receptors (T4Rs) between patients with KC and controls. The significance of T4 for corneal metabolism was studied in organotypic tissue cultures from monkey corneas. We found that TGD prevalence among patients with KC is 13.6%, which is higher than its prevalence in the general population (about 2%). Tear T4 was higher in KC, and keratocyte T4Rs were elevated in KC compared with controls. Furthermore, core proteins such as collagen and cytokeratins were equally altered both in KC and in the cultured corneas substituted with T4. Our data implicate a crucial role of T4 in KC pathophysiology, which is most likely mediated by T4Rs.

Regulation of vernal migration in Gambel's white-crowned sparrows: Role of thyroxine and triiodothyronine

Appropriate timing of migratory behavior is critical for migrant species. For many temperate zone birds in the spring, lengthening photoperiod is the initial cue leading to morphological, physiological and behavior changes that are necessary for vernal migration and breeding. Strong evidence has emerged in recent years linking thyroid hormone signaling to the photoinduction of breeding in birds while more limited information suggest a potential role in the regulation of vernal migration in photoperiodic songbirds. Here we investigate the development and expression of the vernal migratory life history stage in captive Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) in a hypothyroidic state, induced by chemical inhibition of thyroid hormone production. To explore possible variations in the effects of the two thyroid hormones, triiodothyronine and thyroxine, we subsequently performed a thyroid inhibition coupled with replacement therapy. We found that chemical inhibition of thyroid hormones resulted in complete abolishment of mass gain, fattening, and muscle hypertrophy associated with migratory preparation as well as resulting in failure to display nocturnal restlessness behavior. Replacement of thyroxine rescued all of these elements to near control levels while triiodothyronine replacement displayed partial or delayed rescue. Our findings support thyroid hormones as being necessary for the expression of changes in morphology and physiology associated with migration as well as migratory behavior itself.

HYPOTHYROXINAEMIA AND BRAIN DEVELOPMENT.

The aim of this review is to indicate the current position on the role of thyroxine (T4) and fetal brain development with particular relevance to the human situation. Adequate maternal iodine nutrition and maternal circulating thyroxine (T4) concentrations are essential to ensure optimum T4 placental passage which in turn will ensure transport of T4 into fetal brain cells. These processes are discussed and the role of thyroid hormone transporters is considered. The emphasis on isolated maternal hypothyroxinaemia (IH) as an important factor affecting brain development is discussed from the animal experimental point of view as well as in the clinical setting. There is evidence of neurocognitive impairment as assessed by different modalities in children up to the age of 8 years and some suggestion of increased psychiatric disorder in older persons whose mothers had IH during gestation. Although international guidelines have not in general recommended thyroxine therapy for IH the recent demonstration of adverse obstetric outcomes in women with isolated maternal hypothyroxinaemia may warrant a revision of this strategy.

Role of nitric oxide and endogenous antioxidants in thyroxine facilitated healing of ischemia-reperfusion induced gastric ulcers

Background: Studies have revealed the role of thyroxine during healing of gastric ulcers with information lacking on the mechanism involved hence the focus of this study.Materials and Methods: Adult male Wistar rats (150 – 200g) were randomly divided into 4 groups (n=5 per group): Normal control (NC), Sham ulcerated (SU), Thyroidectomised ulcerated untreated (ThU) and Thyroidectomised ulcerated + Levo-thyroxine (100μg/kg/day) (ThU + T4). Animals were stabilised for 35 days following thyroidectomy and treated accordingly to experimental groupings. Weekly body weight changes were recorded, gastric ulcer was induced by ischemia-reperfusion and gastric acid secretion evaluated. They were sacrificed 1 hour, 3 and 7 days post ulcer induction, blood samples collected for haematological indices through cardiac puncture and their stomachs prepared for gross and microscopic examinations to assess gastric healing. Gastric tissue protein, malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), and Nitric oxide (NO) were assessed as biomarkers of healing. Data were analysed using one way ANOVA and Student’s t test with p< 0.05 considered statistically significant.Results: Thyroxine treated rats showed significant weight loss compared with NC and ThU groups. Percentage healing rate was significantly increased in thyroxine treated group compared with ThU animals by 1 hour (42.45% and -42.81%), days 3 (35.14% and -59.36%), and 7 (64.29% and -115.7%). Hematological indices significantly increased in thyroxine treated group compared with other groups. Thyroxine treatment significantly reduced Neutrophil/Lymphocyte; Platelet/NO as well as lipid peroxidation index in this study. Superoxide dismutase, CAT and NO increased significantly in thyroxine treated rats compared with other groups.Conclusion: Thyroxine treatment facilitates the healing of ischeamic-reperfused gastric ulcers possibly by increasing NO activity which in turn causes increased vasodilatation and enhanced endogenous antioxidants at the ulcer sites.Keywords: Nitric Oxide, Antioxidants, Thyroidectomy, Levo-thyroxine, Ulcer healing.

English

English

The adjuvant role of thyroxine in the treatment of chronic hepatitis C infection

Thyroid disease (TD) is the commonest extra-hepatic complication in patients with chronic hepatitis C undergoing combination interferon-α and ribavirin treatment. About 5–10% develops TD of various aetiologies during the course of treatment.1,2 It had been suggested that patients who developed thyroid diseases tend to achieve sustained virological response more readily3 although a meta-analysis did not support this contention.4 Furthermore, the underlying pathogenetic mechanisms are poorly understood. The following 2 cases are presented to support this observation. In both cases, initial therapies were unsuccessful with normal thyroid function, whereas re-treatment with interferon-α (and ribavirin) in the presence of overt TD resulted in successful sustained viral clearance. Although anecdotal, these cases lend further evidence to the potential synergistic effect of thyroid hormone and interferon therapy. Further research is required to support this hypothesis. ### Case 1 A 48-year-old woman presented for ongoing management of her TD after her first course of interferon therapy. She had chronic hepatitis C of genotype 1 with cirrhosis. She underwent a first course of treatment with combination interferon-α (IFN-α) and ribavirin (RBV) for 48 weeks and did not achieve sustained virological response (SVR) at the end of treatment despite good compliance. She had regular monthly thyroid function tests throughout and they were entirely normal. Four weeks after completion, she developed Graves’ disease (GD) with hyperdynamic cardiovascular activity in the presence of a confirmed diffuse goitre. Her thyrotropin (TSH) was undetectable [reference range (RR), 0.4–4.0 mU/l]; free tetra-iodothyronine (fT4) was 28.7 (RR, 10.1–24.5 pmol/l), free tri-iodothyronine (fT3) was 6.9 (RR, 3.3–5.8 pmol/l). Her anti-thyroglobulin (anti-Tg) antibody was normal at 1:64 (RR, < 1 : 400), anti-thyroperoxidase (anti-TPO) titre 1 : 640 (RR, 1: 400), and thyrotropin stimulating immunoglobulin (TSI) titre 14 (RR, < 10 U/ml). The thyroid pertechnetate uptake scan showed diffuse uptake at 11%, (RR: 3–8%). The endocrinology team confirmed the diagnosis and began treatment …

Renal dysfunction manifesting in subclinical hypothyroidism-a possible role for thyroxine.

Renal dysfunction, both acute and chronic, is a recognized association of overt hypothyroidism. We describe a patient who developed renal dysfunction at the stage of subclinical hypothyroidism. We emphasize that renal dysfunction is a reflection of tissue hypothyroidism, dissociated with the severity of biochemical hypothyroidism and can manifest in patients with subclinical hypothyroidism. This report also makes a case for thyroxine therapy if an alternative cause of renal dysfunction is not found in a patient with subclinical hypothyroidism.

Thyroid function in chronic urticaria and angio-oedema

In a case report (August 2003, JRSM1) Dr Edwards and colleagues discuss the relation between subacute thyroiditis and chronic urticaria and angio-oedema (CUA).1 Here we describe a case that illustrates the possible role of thyroxine in suppressing CUA, as previously postulated. A woman of 52 was seen at another department in August 2002 with widespread arthralgia (large joints), shoulder girdle stiffness and early morning stiffness. In September 2002 she also noticed dry eyes and mouth, associated with sweatiness. Her previous history included CUA diagnosed in 1988, and hypothyroidism requiring thyroxine 150 μg daily since the age of 17. Her menstrual periods had stopped eleven months earlier. The relevant findings were: Schirmer's tear test normal (wet); erythrocyte sedimentation rate 22 mm/h, C-reactive protein 11 mg/L, autoimmune screen negative, alkaline phosphatase 136 U/L (normal 39-117), TSH <0.06 mU/L (0.5-4.7), fT4 28.3 pmol/L (9.1-23.9), fT3 1.91 nmol/L (1.20-2.20). She was started on prednisolone 5 mg twice daily and diclofenac/misoprostol 50 mg/200 mg twice daily in October 2002 for a presumed inflammatory musculoskeletal condition. On review in February 2003 her symptoms had not resolved. Thyroid peroxidase antibodies were absent. As the TSH was persistently suppressed (<0.01 mU/L) and fT4 was raised (18-30 pmol/L), the thyroxine dose was reduced from 150 μg to 125 μg daily in February, then to 100 μg in April and 75 μg in May 2003. The prednisolone dose was also reduced every 2-3 weeks by 1 mg/day between March and May to a maintenance dose of 5 mg/day. In late April, having been urticaria-free for 15 years, the patient developed generalized urticaria and angio-oedema which persisted for 6 weeks and required antihistamine treatment. There was a further episode of CUA in June. The dose of diclofenac/misoprostol was not changed from October 2002 until May 2003 when it was stopped because of an abnormal liver function test. At the time of writing (September) the patient has had no further episodes of urticaria/angio-oedema and her daily dose of thyroxine has been 75 μg since mid-May. Current TSH is 2.0 mU/L, fT4 16.4 pmol/L. We propose that this patient's flare of CUA was related to the reduction in thyroxine dose. Previously the condition may have been suppressed by the excessive dosage. However, we cannot exclude the possibility that the reduction of her prednisolone dose was an aetiological factor, though this was very gradual. Furthermore, the treatment with diclofenac, well known to precipitate urticaria, may be relevant—though she took this drug for seven months before the return of CUA and had not taken it for 4 weeks before the second episode. If we postulate that each reduction in thyroxine dose is followed by a 3-4 week latent period before reactivation of CUA, then the final episode of urticaria in June could be explained by the dosage alteration in May, and the April/May flare by the dosage alteration in mid-March and early April. The possible role of thyroxine in suppressing CUA requires further investigation.

Regulation of adipose cell development in utero.

The condition of obesity is impacted by increases in fat cell number, fat cell size, or a combination of the two. It is generally believed that fat cell number is dependent on the age of onset and the degree of obesity. This review provides an update on intrauterine growth of fetal adipose tissue, the earliest period of proliferation onset, and the factors that interact to enhance or suppress development. Fetal adipose tissue development is regulated by the complex interaction of maternal, endocrine, and paracrine influences that initiate specific changes in angiogenesis, adipogenesis, and metabolism. Developmental stages and metabolic processes influenced by specific hormones and paracrine factors have been identified through examination of the offspring of obese and diabetic pregnancies, hormonal manipulation during late pregnancy in animal models, and the use of cell culture. Collectively, the results of the studies cited herein delineate the basis for imprinting or conditioning of fetal preadipocytes at the paracrine/autocrine level and a role of thyroxine, glucocorticoids, and other hormones in fetal adipose tissue development and metabolism.

Protective Role of Thyroxine in Methylparathion Intoxicated Chick Embryos

ABSTRACTThe efficacy of thyroxine against methylparathion poisoning in chick embryos was studied. the mortality rate and survival rate, frequency of abnormalities, growth rate and size of embryos, and also the change in cholinesterase activity were determined to evaluate the protective effect of thyroxine and atropine. It was observed that the survival rate, growth rate and size, and the cholinesterase activity significantly declined in the methylparathion treated group while the mortality rate and the frequency of abnormalities increased. When thyroxine was given, a significant reversal in these parameters was seen, indicating an effective protective action of thyroxine against methylparathion intoxication in chick embryos. the results also showed that the therapeutic treatment of the combination of thyroxine and atropine did not further improve the effects. Since in many respects, chick embryo development parallels that of mammalian embryos, a short term use of thyroxine as an effective protective agent against organophosphate methylparathion (perhaps other compounds) poisoning may have important implications.

Thyroidal regulation of lingual lipase development in suckling rats.

Rat lingual lipase undergoes maturational increases during postnatal development. The role of thyroxine (T4) in the control of lingual lipase during development was evaluated. T4 given at an early suckling stage (starting day 4 or 5) moderately increased lingual lipase (20-30%) compared to age-matched controls. A similar dose of T4 given later (age > 2 weeks) was ineffective. The T4-sensitive period coincides with a time of low circulating T4, suggesting a role of T4 in modulating the development of lingual lipase in rat pups. Since simultaneous treatment with U486, a type II glucocorticoid receptor antagonist only partially blocked the T4 induction of lingual lipase, T4 appeared to have a direct action on the lingual gland. Pups of propylthiouracil (PTU)-treated dams (previously found to be hypothyroid) showed a delay in the maturation of lingual lipase compared to age-matched pups whose dam was not given PTU. Pups were most sensitive to PTU in the early suckling stage. PTU-induced delayed maturation of lingual lipase was a result of hypothyroidism, since T4 replacement when given early (at the age of 5 days) abolished most of the effect of PTU. When T4 was given later (at the age of 10 days), recovery was much less. This suggests the presence of an early period that is critically dependent on T4 for the full expression of lingual lipase in the rat tongue serous glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory activity of isolated liver mitochondria following Trypanosoma congolense infection in rabbits: The role of thyroxine

1. 1. The effect of trypanosome infection on rabbit liver mitochondrial oxidative phosphorylation was investigated, with and without thyroxine replacement. 2. 2. State 3 respiration, respiratory control ratio (RCR) and ADP/O ratio were significantly reduced in mitochondria from trypanosome-infected animals whereas there was no change in state 4 respiration. 3. 3. State 3 respiration, RCR and ADP/O ratio were not significantly altered in trypanosome-infected animals given thyroxine replacement therapy. 4. 4. Trypanosome infection leads to impairment of mitochondrial integrity, apparently through lowered thyroxine levels. Replacement of thyroxine therefore sustains optimal mitochondrial respiratory activity.

Influence of Thyroxine in the Regulation of Rat Parotid Salivary Protein Composition

This study tested the role of thyroxine in the regulation of the protein composition of rat parotid saliva. Thyro-parathyroidectomy was performed on two groups of rats, one of which subsequently received thyroxine replacement; the third group was sham-operated. Parotid saliva was collected on the eighth day after surgery, with pilocarpine and isoproterenol used as a secretory stimulus. The volume of saliva collected in 30 min from the thyro-parathyroidectomized rats was 55% less than that collected from sham-operated rats. In the thyro-parathyroidectomized rats, the protein concentration as measured by absorption at 215 nm was unaltered, but that measured by the Lowry procedure was 43% higher. Spectrophotometric scans of Coomassie Blue-stained gels following sodium dodecylsulfate polyacrylamide gel electrophoresis of the secreted proteins showed an 18% reduction in the proportion of protein attributable to amylase and a 43% reduction in proportion of acidic and basic proline-rich proteins following thyro-parathyroidectomy; deoxyribonuclease and two other major secretory proteins (Fraction I and Fraction V) were increased (38%, 20%, and 46%, respectively). These changes in flow rate, protein concentration by the Lowry assay, and protein composition were prevented by treatment of thyro-parathyroidectomized rats with thyroxine replacement and are in opposition to those changes we reported earlier for hyperthyroid rats. The results indicate that the flow of saliva as well as the synthesis of the various salivary proteins are influenced by thyroxine.

The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses.

We studied the effects of various concentrations of oleic acid (0.1-3.3 mM), such as are often found in the serum of patients with nonthyroidal illness, on the dialyzable (free) fraction of T4 (DFT4) in three types of serum samples: pooled normal serum (PNS), pooled pregnancy serum (PPS), and pooled serum of hospitalized patients (PSHP). The samples were extracted with diethyl ether to remove endogenous fatty acids before being tested in the DFT4 assay. Oleic acid caused only a moderate increase in DFT4 in PNS; a significant (greater than 2 SD above control) increase (15%) was found with 2.0 mM oleic acid, and the maximal dose of oleic acid (3.3 mM) caused a 33% increase in DFT4. However, the DFT4-increasing effect of oleic acid was enhanced (increase in DFT4 of 33% caused by 0.9-1.2 mM oleic acid) when the serum tested had low (0.5 times normal) albumin and prealbumin concentrations with either normal (50% PPS) or half-normal TBG (50% PNS). The effect of oleic acid in 100% PSHP was significantly (P less than 0.005) greater than that in 100% PNS, and it was close to that in 50% PNS (increase in DFT4 with 3.3 mM oleic acid, 118% in PSHP vs. 98% in 50% PNS). Normalization of serum albumin in PSHP by adding exogenous albumin markedly reduced the DFT4-increasing effect of oleic acid; the maximal increase in DFT4 of 64% with 3.3 mM oleic acid in albumin-normalized PSHP was equalled with 1.3 mM oleic acid in unmodified PSHP. The data suggest that the serum concentrations of albumin and other T4-binding proteins are important in modulating the DFT4-increasing effect of oleic acid and that oleic acid may contribute to the reduced serum binding of T4 in nonthyroidal illness.

Role of thyroxine and insulin on the development of the fetal mouse duodenum in organ culture.

The role of thyroxine and insulin in the regulation of proliferation and differentiation of the immature duodenal epithelium of the fetal mouse was investigated using an organ culture method with a serum-free medium. Thyroxine (10 nM) stimulates specifically the activity of maltase. Insulin (125 mU/mL) remains without effect on the maturation of all hydrolytic functions studied. Each hormone significantly increases the percentages of brush border enzyme activities liberated in the medium and reduces the amount of glucose released in the medium. In the presence of dexamethasone (76 nM) the effect of thyroxine on maltase activity is still observed. Finally, thyroxine and insulin do not modify the labelling index in the duodenal crypts of the explants in the presence or absence of dexamethasone. These findings indicate that thyroxine and insulin can act directly on the development of the fetal mouse duodenum at the end of gestation. Nevertheless, their implication in prenatal development of the gut functions appears to be of minor importance.

Role of thyroxine on postnatal development of ileal active bile salt transport.

The role of thyroid hormone on the postnatal development of ileal active taurocholate transport uptake was measured by an in vitro incubation technique in Sprague-Dawley rats. In 16-day-old rats treated with pharmacological doses of L-thyroxine (50 micrograms X 100 g body wt-1 X day-1 on days 10-13), ileal active transport appeared precociously whose Km was 1.60 +/- 0.48 mM and Vapp (apparent maximal velocity) was 8.09 +/- 1.14 nmol X min-1 X mg dry wt-1, while age-matched shams had only passive diffusion of taurocholate. To determine whether enhanced endogenous secretion of thyroxine was capable of stimulating development of ileal active taurocholate transport, thyrotrophic stimulating hormone (TSH) (0.5 U/100 g body wt twice daily) was given on days 10-13, with uptake measured on day 16. Following TSH treatment, only passive transport for taurocholate was observed in the ileum; uptake rates were consistently higher than those for untreated controls at each study concentration. Thyroidectomy performed at age 14 days with uptake measured at age 21 days did not ablate development of ileal active transport but resulted in a significant reduction (P less than 0.001) in the Vapp (7.39 +/- 1.10 nmol X min-1 X mg dry wt-1) and a significant increase (P less than 0.014) in Km (1.72 +/- 0.53 mM) compared with age-matched controls. Thyroid hormone does not appear to be obligatory for the postnatal development of ileal active taurocholate transport.

Role of thyroxine in functional gastric development.

The role of thyroxine (T4) on the functional development of chief and parietal cells was studied in the rat. Daily injection of thyroxine (0.1 microgram/g body wt) resulted in the precocious appearance of pepsinogen in the oxyntic gland mucosa and an increase in basal acid output. Thyroxine had no effect in adrenalectomized rats. In propylthiouracil-induced hypothyroid pups, pepsinogen content and basal acid secretion were low. Corticosterone acetate (200 micrograms/g body wt) injection increased pepsinogen content and basal acid secretion in the absence of normal levels of thyroid hormones. We conclude that the effect of thyroxine on the development of chief and parietal cells is primarily due to accompanying changes in serum corticosterone.

Role of thyroxine in the postnatal development of rat hepatic tryptophan oxygenase and ornithine aminotransferase.

The activities of tryptophan oxygenase and ornithine aminotransferase are known to increase markedly in rat liver during the postnatal period. The aim of this study was to determine whether thyroxine regulates the development of these two enzymes. It was found that hyperthyroidism had no effect on the activity of tryptophan oxygenase, but caused a modest increase of ornithine aminotransferase activity at 10 days of age. The latter effect persisted in adrenalectomized animals, indicating that it was not secondary to elevation of plasma corticosterone. When thyroxine was administered together with cortisone acetate, elevation of ornithine aminotransferase activity was substantially greater than that observed with cortisone acetate alone. It is concluded that the postnatal development of hepatic ornithine aminotransferase is primarily controlled by glucocorticoids, but that the effect of these hormones may be potentiated by thyroxine.