Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on the pituitary-thyroid axis in rats

Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid gland by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary's response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T3 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5'-deiodinase activity. These data demonstrate that dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine's effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary's TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.     

The effects of delta 9-tetrahydrocannabinol on serum thyrotropin levels in the rat

The effects of acute treatment with delta 9-tetrahydrocannabinol (delta 9-THC) on serum levels of thyrotropin (TSH) and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) were determined in the rat. Intraperitoneal doses of delta 9-THC greater than 3 mg/kg reduced serum TSH levels to less than 10% of control. The ED50 for delta 9-THC was approximately 0.3 mg/kg. After a 10 mg/kg dose of delta 9-THC, the maximum decrease in serum TSH occurred at one hour. Both serum T3 and serum T4 levels were decreased by a single 10 mg/kg delta 9-THC injection with maximal decreases at 6 hr post-injection. The effects of delta 9-THC on the ability of thyrotropin releasing hormone (TRH) to increase serum TSH and T3 were determined. TRH produced a 10-fold increase in serum TSH levels and this increase was unaffected by delta 9-THC pretreatment. Serum T3 levels were slightly increased by TRH and this increase was also unaffected by delta 9-THC. These findings indicate that acute treatment with delta 9-THC results in a decrease in circulating TSH, T3 and T4 levels but has no effect on the pituitary or thyroid response to exogenous TRH.     

A biologically based dose-response model for dietary iodide and the hypothalamic-pituitary-thyroid axis in the adult rat: evaluation of iodide deficiency.

A biologically based dose-response (BBDR) model was developed for dietary iodide and the hypothalamic-pituitary-thyroid (HPT) axis in adult rats. This BBDR-HPT axis model includes submodels for dietary iodide, thyroid-stimulating hormone (TSH), and the thyroid hormones, T(4) and T(3). The submodels are linked together via key biological processes, including (1) the influence of T(4) on TSH production (the HPT axis negative feedback loop), (2) stimulation of thyroidal T(4) and T(3) production by TSH, (3) TSH upregulation of the thyroid sodium (Na(+))/iodide symporter, and (4) recycling of iodide from metabolism of thyroid hormones. The BBDR-HPT axis model was calibrated to predict steady-state concentrations of iodide, T(4), T(3), and TSH for the euthyroid rat whose dietary intake of iodide was 20 mug/day. Then the BBDR-HPT axis model was used to predict perturbations in the HPT axis caused by insufficient dietary iodide intake, and simulation results were compared to experimental findings. The BBDR-HPT axis model was successful in simulating perturbations in serum T(4), TSH, and thyroid iodide stores for low-iodide diets of 0.33-1.14 mug/day. Model predictions of serum T(3) concentrations were inconsistent with observations in some cases. BBDR-HPT axis model simulations show a steep dose-response relationship between dietary intake of iodide and serum T(4) and TSH when dietary iodide intake becomes insufficient (less than 2 mug/day) to sustain the HPT axis. This BBDR-HPT axis model can be linked with physiologically based pharmacokinetic models for thyroid-active chemicals to evaluate and predict dose-dependent HPT axis alterations based on hypothesized modes of action. To support continued development of this model, future studies should include time course data after perturbation of the HPT axis to capture changes in endogenous iodide, serum TSH, T(4), and T(3).     

Aspects of chronic oral treatment with thyrotropin-releasing hormone: the hypothalamic-pituitary-thyroid axis in rats. A study with a pharmacological dose of thyrotropin-releasing hormone.

The effects of 16 days of oral treatment with thyrotropin-releasing hormone (TRH, 1 mg/24 h) on serum levels of thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3) and the kinetics of TRH in the blood were studied in normal rats. A second group of animals served as controls. TRH was dissolved by sonification (10 mg/l) and was stable in tap water. TRH was measured by a radioimmunoassay procedure (normal range: 20-80 pmol/l, antiserum K2B9 1:120,000 final dilution). An increase in basal TSH (7,200 +/- 440 ng/l, mean +/- SD) was found after 2 days of treatment (11,420 +/- 810 ng/l), but a significant increase was observed after 5 days of treatment (12,530 +/- 640 ng/l, p less than 0.001). T4 serum concentrations remained in the normal range during the entire period of study, whereas T3 serum concentrations (0.76 +/- 0.1 micrograms/l) were increased to 1.22 +/- 0.2 micrograms/l on day 5 (p less than 0.001). A subsequent decline of TSH, T4 and T3 up to the end of the study was observed. TRHmax concentrations were registered on day 5 (790 +/- 24 pmol/l). The mean value of TRHmax was 723 +/- 34 pmol/l. To improve the stability of TRH in tap water, 1-ml samples of drinking water with dissolved TRH were measured. The mean TRH concentration in drinking water was 73 +/- 1.5% (SD). No significant correlations were found between the area under the curve of TSH (184,340 ng.l-1.24 h) and that of TRH (14,954 pmol.l-1.24 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of the pituitary and thyroid to tropic hormones in Sprague-Dawley versus Fischer 344 male rats.

Modulation of endocrine function is frequently a confounding factor in the interpretation of chronic rodent toxicology studies. Of particular interest are agents that cause deviation of thyroid hormone homeostasis and result in thyroid cancer for rodents. An endocrine challenge test (ECT), commonly used to study endocrine organ health in human and veterinary medicine, quantifies the response of the thyroid to tropic hormones. This study compared the response of Fischer (F344) and Sprague-Dawley (SD) rats to a thyrotropin-releasing hormone (TRH) ECT and a thyroid-stimulating hormone (TSH) ECT and characterized the dose-response curve. TSH, thyroxine (T4), triiodothyronine (T3), and prolactin responses were characterized for several doses of TRH over a 4-h time period. Animals were equipped with intra-atrial cannulae and were free moving at all times during blood sampling. Both strains of rats responded to intravenous TRH by releasing TSH into their blood in a dose-responsive fashion. At doses of > or = 100 ng, TSH concentrations were increased by more than 2-fold at 2 min. Concentrations reached a maximum at 15 min for doses of 100 ng/100 g body weight (bw) to 5000 ng/100g bw. The effective dose 50 (ED50) of TRH (that dose causing release of half maximal TSH concentrations) was 61 ng in F344 rats and 78 ng in SD rats. The ED75 was 173 ng and 217 ng/100 g bw, respectively. The response of T4 and T3 after TRH ECT and TSH ECT was highly variable. F344 rats responded with an increase in levels of both hormones, starting at 60 min and continuing through 240 min. In SD rats, the presence of a thyroid hormone response (T4) was present, although that of T3 was not clear. These data provide essential information for design of toxicology studies focused on the effects of toxicants and drugs on the pituitary-thyroid axis.     

Unusual characteristics of the dose-dependent uptake of propylthiouracil by thyroid gland in vivo. Effects of thyrotropin, iodide or phenobarbital pretreatment.

Dose dependency of propylthiouracil (PTU) uptake by the thyroid gland was investigated in intact, adult male rats after a single intraperitoneal dose of PTU. PTU pharmacokinetics in rat serum, liver and lung were independent of the size of this single dose of PTU. However, in the thyroid gland, PTU concentrations corrected for dose were disproportionately high at low doses. At low PTU doses, a transport mechanism contributes substantially to thyroidal PTU uptake, but at high PTU doses this transport system becomes saturated. Thus, at serum PTU concentrations of 5 μg/ml or above, thyroid to serum (T/S) PTU ratios are independent of PTU dose and serum concentration. Alteration in the functional status of the thyroid changed the relationship between serum and thyroidal PTU concentrations. Thyroxine administration prior to an intraperitoneal PTU dose of 5 mg/kg reduced ratios of T/S PTU concentrations. However, thyrotropic hormone (TSH) preadministration had little effect on early thyroidal PTU concentration, but appeared to exert an effect at later times. Chronic administration of either potassium iodide or phenobarbital prior to PTU increased T/S PTU ratios, again suggesting an effect of TSH on PTU metabolism in the thyroid.     

The effects of chronic ingestion of spironolactone on serum thyrotropin and thyroid hormones in the male rat

Male rats were fed spironolactone admixed with feed at doses of 6, 50, and 200 mg/kg/day for up to 13 weeks. After 13 weeks of treatment, there were dose-related increases in thyroid weight and follicular hypertrophy. Serum thyrotropin (TSH) concentrations were significantly increased throughout the treatment period. Serum thyroxine (T4) and triiodothyronine (T3) were significantly decreased at Weeks 2 and 4, but returned to control concentrations by Week 13. The TSH increase and transient T4 decrease suggested that the thyroid hypertrophy was a compensatory reaction to lowered thyroid hormone levels. To determine the effect of spironolactone ingestion on T4 synthesis and metabolism, male rats were fed spironolactone admixed with feed at 200 mg/kg for 2 weeks. The decrease in T4 was not due to decreased synthesis, since iodide uptake and organification were significantly increased by spironolactone treatment. Since uridine diphosphate glucuronosyl transferase activity was significantly increased by spironolactone treatment, it appears that, by increasing hepatic clearance of T4, spironolactone causes a decrease in the serum concentration of this hormone. The lower T4 level causes a release of feedback inhibition and an increase in TSH resulting in the increase in thyroid gland size and activity.     

The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that is neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor alpha and beta, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk assessments for AA.     

TRH testing, T4-thyrotoxicosis and the aging thyroid gland

Secondary thyroid function tests were compared in 41 mildly thyrotoxic and 36 euthyroid patients with an elevated free thyroxine index (FT4I). A serum TSH measurement 20 minutes after intravenous TRH (delta TSH) most reliably separates these two groups. A significant delta TSH response (greater than 0.5 microU/ml) is also helpful in excluding clinical thyrotoxicosis in patients with nodular goitre. The free T3 index was normal in one-third of mildly thyrotoxic patients and in all euthyroid patients with a falsely elevated FT4I. Blunted delta TSH responses to TRH in elderly New Zealand women were associated with nodular goitre or occult thyroid nodularity revealed only by thyroid scan. The reduced TRH responses are more likely due to partial thyroid autonomy than reduced synthetic capacity of thyrotrophs in old age.     

Determination of thyroxine release in vivo: a simple, specific and sensitive method in mice

When thyroid hormone secretion in vivo was studied by the release of 125I from thyroid to blood after TSH in mice preloaded with the isotope, only 54.4 +/- 2.0% (+/- SE) of plasma 125I was butanol extractable, indicating low specificity for thyroid hormones. To improve specificity plasma 125I was bound to anti-T4 rabbit antibodies and precipitated with goat antirabbit serum. The intraassay coefficient of variation was 2.5%, and anti-T4 bound radioactivity correlated well with that extractable with butanol (r = 0.95, P less than 0.001). The effect of 40-1000 microU TSH intravenously in mice pretreated with 1 microgram T3 3 times during 2 days to suppress endogenous TSH was evaluated 2 hrs after the injection of TSH by 1) conventional radioimmunoassays of total and free stable T4 in plasma (no preloading with 125I), 2) total blood 125I in mice preloaded with 125I, and 3) anti-T4 bound 125I in plasma in mice preloaded with 125I. Stable T4 increased with TSH doses of 70 microU or higher, but the slope was low and the relation between error variance and slope did not permit a useful bioassay. Total blood 125I responded significantly to 40 microU TSH and showed a favourable relation between error variance and slope, but the specificity may be questioned. Anti-T4 bound 125I in plasma also responded significantly to 40 microU TSH and showed a very good relation between error variance and slope. The new technique of measuring anti-T4 bound radioactivity seems to combine the specificity of radioimmunoassay with a precision and sensitivity well comparable to that of the conventional radioiodine release technique.     

Ophthalmic Graves's disease: natural history and detailed thyroid function studies

Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.     

Subacute toxicity of celecoxib on thyroid and testis of rats: Hormonal and histopathological changes

Celecoxib is an effective agent in the treatment of signs and symptoms of inflammation, rheumatoid arthritis and osteoarthritis. The purpose of this study is to assess the effects of two different doses of celecoxib on some hormones and endocrine glands of male rats. In this study, the doses of 10 and 50mg/kg/day of celecoxib were given to male rats orally for 28 days. At the end of the study, serum total triiodothyronine (T(3)), total thyroxine (T(4)), thyroid stimulating hormone (TSH), testosterone and luteinizing hormone (LH) levels of rats were analyzed by radioimmunoassay technique using RIA kits. Thyroid and testis tissues of male rats were examined histopathologically. While there was no a change in serum T(3), T(4) and LH levels of celecoxib-treated rats, there were differences in serum TSH and testosterone levels of rats treated with 50mg/kg/day celecoxib for 28 days compared with those of control rats. In histopathological examinations, celecoxib-related changes were found in thyroid glands of the rats.     

Changes in cross-fostered Sprague-Dawley rat litters exposed to perchlorate

Ammonium perchlorate is used as an oxidizer in rocket fuel. It has become a groundwater contaminant, dissociating to ammonium cation and perchlorate anion. The perchlorate ion competes with iodide for uptake into the thyroid, reducing thyroid hormone production. Pregnant Sprague-Dawley rats were given either untreated or perchlorate (1 mg/kg-day) treated drinking water beginning on gestation day 2. One set of control and exposed dams was sacrificed on gestation day 20. The litters from the second set of control and exposed dams were crossed immediately after parturition and were sacrificed at postnatal day 10. Dam serum and thyroid, pooled fetal sera, and male and female pup sera were collected and analyzed for perchlorate, thyroid-stimulating hormone (TSH), triiodothyronine (T(3)), and thyroxine (T(4)). Control pups receiving perchlorate through lactation had serum levels at postnatal day 10 of 0.54 microg/ml and 0.56 microg/ml for male and female pups, respectively, whereas exposed fetuses had serum perchlorate levels of 0.38 +/- 0.04 microg/ml. Female pups receiving perchlorate lactationally had significantly lower levels of serum T(4) than control pups and prenatally exposed pups. Serum T(4) levels in male pups were not affected by perchlorate. Serum thyroid hormone levels from gestational perchlorate exposure were restored to control values by postnatal day 10. In utero perchlorate-exposure decreased serum T(4) levels in the fetus. Gestational studies in conjunction with a cross-fostering study design helped discern thyroid hormonal changes caused by perchlorate exposure during the perinatal period.     

Goitre and thyroid dysfunction during chronic amiodarone treatment

We measured thyroid function in a cross-sectional survey of 37 unselected patients receiving chronic amiodarone treatment. Palpable goitre was presented in 17 patients and was a new finding in ten. Despite frequent elevations of serum free T4 (67%) or free T4 index (43%), all 37 patients were clinically euthyroid with a normal or decreased serum free T3 or free T3 index. Mean urine iodide/creatinine excretion was increased 13-fold. Three patterns of thyroid function were seen; in 21 patients with normal TRH responses, the mean basal serum TSH was significantly elevated. Five patients had biochemical hypothyroidism which did not require treatment. Eleven patients had evidence of thyroid autonomy and the three patients with absent TRH responses each gave a past history of goitre or thyrotoxicosis; a trial of carbimazole treatment in these three was without clinical benefit. The observed spectrum of subclinical goitre and thyroid dysfunction may result from an unpredictable thyroid response to excessive free iodide combined with a weak goitrogenic effect of amiodarone mediated by increased TSH secretion.     

Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants, are ubiquitous environmental contaminants. PBDEs act as endocrine disruptors via alterations in thyroid hormone homeostasis. We examined thyroid hormone concentrations and hepatic enzyme activity in weanling rats exposed to three commercial PBDE mixtures: DE-71, DE-79, and DE-83R. Female Long-Evans rats, 28 days old, were orally administered various doses of DE-71, DE-79, or DE-83R for 4 days. Serum and liver samples were collected 24 h after the last dose and analyzed for serum total thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone (TSH), hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridinediphosphate-glucuronosyltransferase (UDPGT) activities. The PBDE-treated groups did not exhibit significant changes in body weight; however, increased liver weights, as well as 10- to 20-fold induction in EROD and 30- to 40-fold induction in PROD were found in the DE-71-- and DE-79--treated animals. DE-71 and DE-79 caused dose-dependent depletion of T(4), accompanied by up to 3- to 4-fold induction in UDPGT activities. Serum total T(4) was decreased a maximum of 80% for DE-71 and 70% for DE-79 in the highest dose, with benchmark doses (BMDs) of approximately 12.74 mg/kg/day for DE-71 and 9.25 mg/kg/day for DE-79. Dose-related effects in serum T(3) levels were less apparent, with maximal reductions of 25-30% at the highest dose for both DE-71 and DE-79. The two mixtures showed no effect on serum TSH levels. Benchmark dose analysis revealed that the two mixtures were comparable in altering thyroid hormone levels and hepatic enzyme activity. DE-83R was not effective in altering any of the measured parameters. The present study suggests that short-term exposure to some commercial PBDE mixtures interferes with the thyroid hormone system via upregulation of UDPGTS:     

Subacute toxicity of p,p'-DDT on rat thyroid: Hormonal and histopathological changes

The purpose of this study is to assess the effect of p,p'-DDT on thyroid activity of male Wistar rats. Pesticide was administered intraperitoneally (i.p.) for 10 consecutive days at doses of 50 and 100mg/kg/day. At the end of the treatment, the endpoints examined included serum total levels of triiodothyronine (T(3)), total thyroxine (T(4)), and thyroid stimulating hormone (TSH). Thyroid gland histopathology and tissue metabolism of thyroid hormone (T(4) UDP-glucuronyltransferase UDP-GT and 5'-deiodinases) were determined. DDT treatment altered thyroid function namely by increasing hepatic excretion of T(4) glucuronide. At the dose of 50mg/kg it decreased T(4) circulating levels and increased thyroid 5'-deiodinase type I (5'-D-I) and brown adipose tissue (BAT) 5'-deiodinase type II (5'-D-II) activities but it did not affect liver 5'-D-I activity which might contribute to the maintenance of the serum T(3) level. Treatment with 100mgDDT/kg decreased serum thyroid hormone concentration and tissue 5'-D-I activity without affecting BAT 5'-D-II activity. Gland histomorphological analysis showed hyperplasia and squamous metaplasia with abundant colloid. These observations associated to the elevated serum TSH levels and gland hypertrophy suggest that DDT exposure induced an hypothyroidism state with a colloid goiter in rats.     

Effects of carbendazim on rat thyroid,parathyroid, pituitary and adrenal glands and their hormones

The purpose of this study is to determine the effects of low and high dose of carbendazim on the level of certain hormones and endocrine glands (thyroid, parathyroid, adrenal and pituitary glands) of male rats. Carbendazim is a systemic fungicide with activity against a number of plant pathogens. In this study, daily doses of 0, 150, 300 and 600 mg/kg per day carbendazim were applied to male rats by gavage for 15 weeks. At the end of the experiment, T3, T4, TSH, ACTH and GH levels in rat serum were analysed. Thyroid, parathyroid, adrenal and pituitary glands of rats were taken. A significant increase was observed in serum T3 levels of the rats, which were exposed to 300 mg/kg per day carbendazim doses, compared to the serum T3 levels of the control group. There were no differences between the control and carbendazim-treated group of rats regarding serum TSH, T4, ACTH and growth hormone levels. This showed us that carbendazim caused histopathological damages in thyroid, parathyroid and adrenal glands of rats. No changes were observed in pituitary glands of treated rats. These results suggest that a high quantity of subchronic carbendazim exposure affects thyroid, parathyroid and adrenal glands.     

Effects of recombinant growth hormone therapy on thyroid hormone concentrations

BACKGROUND AND OBJECTIVE: There are numerous, often contradictory reports on the effects of growth hormone (GH) therapy on thyroid function. The aim of this study was to assess the effect of such therapy on serum concentrations of thyroid hormones in GH-deficient children euthyroid prior to the treatment, and to determine the necessity of thyroid hormone administration in these patients. MATERIAL AND METHODS: The study included 32 GH-deficient patients in the first stage of sexual development, in whom disorders of thyroid function could be excluded. The inclusion criteria were based on clinical examination and levels of thyroxine (T4), triiodothyronine (T3), free thyroxine (fT4), free triiodothyronine (fT3), reverse triiodothyronine (rT3), thyrotropin (TSH) before and after stimulation with thyrotropin-releasing hormone (TRH). Recombinant growth hormone (rGH) (Genotropin 16U, Pharmacia) was administered at a dose of 0.7 U/kg/week. Fasting blood samples were drawn before treatment and after 3, 6, 9 and 12 months of therapy. Thyroid hormones were measured using RIA and IRMA methods. RESULTS: There were no physical signs of hypothyroidism in the patients examined during 12 months of rGH administration, and the satisfactory growth rate was achieved. T4 levels decreased in the first 3 months but remained within the normal range, and then returned to the values prior to the treatment. A similar trend was observed for fF4, with 28.5% of patients exhibiting fF4 levels below the normal in the 3rd month. An increase during the first 3 months of therapy was observed in the cases of T3 (statistically non-significant) and fT3, and these values then fell to levels within the normal range of patients' age. During treatment, TSH levels decreased but remained within the normal range. CONCLUSIONS: A transient decrease in T4 concentrations in the 3rd month with unchanged T3 and an increase in fT3 concentrations probably result from the effect of rGH on the peripheral metabolism of thyroid hormones. The results obtained do not support the use of thyroid hormone therapy with levothyroxine during the first year of rGH therapy in patients who are initially euthyroid.     

COMPARISON OF THE EFFECTS OF IODINE AND IODIDE ON THYROID FUNCTION IN HUMANS

Concerns have been raised over the use of iodine for disinfecting drinking water on extended space flights. Most fears revolve around effects of iodide on thyroid function. Iodine (I2) is the form used in drinking-water disinfection. Risk assessments have treated the various forms of iodine as if they were toxicologically equivalent. Recent experiments conducted in rats found that administration of iodine as I- (iodide) versus I2 had opposite effects on plasma thyroid hormone levels. I2-treated animals displayed elevated thyroxine (T4) and thyroxine/triiodothyronine (T4/T3) ratios, whereas those treated with I- displayed no change or reduced plasma concentrations of T4 at concentrations in drinking water of 30 or 100 mg/L. The study herein was designed to assess whether similar effects would be seen in humans as were observed in rats. A 14-d repeated-dose study utilizing total doses of iodine in the two forms at either 0.3 or 1 mg/kg body weight was conducted with 33 male volunteers. Thyroid hormones evaluated included T4, T3, and thyroid-stimulating hormone (TSH). TSH was significantly increased by the high dose of both I and I-2, as compared to the control. Decreases in T were observed with dose schedules with I-4 and I2, but none were statistically significant compared to each other, or compared to the control. This human experiment failed to confirm the differential effect of I2 on maintenance of serum T4 concentrations relative to the effect of I- that was observed in prior experiments in rats. However, based on the elevations in TSH, there should be some concern over the potential impacts of chronic consumption of iodine in drinking water.