Increased Serum T4 Levels Research Articles

SUN-520 Graves Disease and T3 Thyrotoxicosis: A Case Report

Introduction: Hyperthyroidism is one of the common problems in the world of endocrinology. Identifying the type of thyrotoxicosis is crucial before starting treatment. We present a case of a 37-year-old woman presented with hyperthyroidism and was started on methimazole. Her symptoms persisted and further workup showed T3 thyrotoxicosis. Her symptoms improved after switching her to PTU. She eventually underwent thyroidectomy.Case description: Thirty-seven-year old African American woman presented to her primary care physician(PCP) with symptoms suggestive of hyperthyroidism for three months. Her past medical history is significant for recent delivery one year ago. Her Physical exam is pertinent for hypertension of 160/80 with a heart rate of 120. Her neck is diffusely enlarged with bilateral bruits. Bilateral lid retraction with lid lag was noted along with left lid proptosis. There were no tremors or leg swelling noted. Her Initial workup showed sinus tachycardia in the electrocardiogram. Her TSH level was <0.010 and a free T4 level of 3.48. Ultrasound showed diffuse enlargement of the thyroid gland with no focal nodule. She was started on methimazole 10mg twice daily and metoprolol 25mg twice daily.Three months later, she presented to the emergency room(ER) with tachycardia of 130 and hypertension of 170/85. Work up showed a TSH level of <0.010 and a free T4 level of 3.94. She was compliant with medications. When free T3 levels were checked it turned out to be >30. She was diagnosed with T3 Thyrotoxicosis and was started on propylthiouracil 150mg every 8 hours. Her metoprolol was increased to 50mg every 12 hours. Her symptoms improved and she finally underwent surgery for thyroidectomy.Discussion: Hyperthyroidism is seen in about 1 in 5000 with a strong female predominance. Graves disease, the most common cause of hyperthyroidism is due to excess production of TSH receptor stimulating antibodies. Hyperthyroid patients with graves disease sometimes have a disproportionate increase in serum T3 levels when compared to serum T4. This is thought to be due to increased T3 production or extrathyroidal conversion of T4 to T3. It is very crucial to identify the free hormone levels in a new patient with hyperthyroidism because of the difference in management. Antithyroid drugs are traditionally the first-line treatment option along with beta-blockers prior to definitive therapy like radioactive iodine or thyroidectomy. The main drugs used are methimazole and propylthiouracil(PTU). Methimazole is more commonly used than PTU because of its rapid efficacy, longer duration of action and less adverse effects. For patients with T3 thyrotoxicosis, PTU is preferred as it is known to reduce the peripheral conversion of T4 to T3. Our patient medication was changed from methimazole to PTU, after which she started to notice improvement. She eventually underwent definitive treatment with thyroidectomy.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium–iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen®). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.

Effect of Monosodium Glutamate and Sodium Nitrite on Some Biochemical Parameters in Japanese Quails

ABSTRACT This study was conducted to investigate the effect of monosodium glutamate and sodium nitrite on some biochemical parameters in Japanese quails. Forty birds were randomly divided into equal four groups for 60 days. In comparison with the normal group we have found a significant increase in serum levels of AST, ALT, GGT, urea, BUN, creatinine uric acid, glucose and calcium in all treated groups while, there is a decrease in serum total protein, albumin, globulin, protein electrophoresis fractions, iron, phosphorus and zinc in all treated groups. In our view of lipid profile there is an increased level of total cholesterol and TAG concentration in MSG and mixed group while, there is an increase in total cholesterol level and a decreased level in TAG in NaNO2 treated group. In our view of thyroid hormones there is a significant increase in serum T3 level in all treated ones and a significant increase in serum T4 in all treated groups except the MSG-treated group.

TAS2R bitter taste receptors regulate thyroid function.

Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca(2+) increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca(2+) release in Nthy-Ori 3-1 cells, but not basal Ca(2+) levels, in a dose-dependent manner. Ca(2+) responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.

Serum Thyroid Hormone Levels in Epileptic Children Receiving Anticonvulsive Drugs

How to Cite this Article: Mahyar A, Ayazi P, Dalirani R, Hosseini SM, Daneshi Kohan MM. Serum Thyroid Hormone Levels in Epileptic Children Receiving AnticonvulsiveDrugs. Iranian Journal of Child Neurology 2011;5(4):21-24.ObjectiveThe aim of this study was to investigate serum thyroid hormone levels in epileptic children receiving anticonvulsive drugs.Materials & MethodsIn this case- control study, 30 epileptic children who were receiving anticonvulsive drugs (case group) were compared with 30 healthy children (control group). This study was carried out in the Qazvin Children's Hospital (Qazvin, Iran) from October to December 2007. Both groups were matched for age and sex. Thyroid hormone levels were measured using a radioimmunoassay and immunoradiometric assay. Data were analyzed using Chi-square and Student's t-tests.ResultsThe mean serum T3 and T4 levels in the case group were 2.36 ± 0.73 nmol/L and 95.96 ± 27.01 nmol/L, respectively, and the corresponding values in the control group were 1.88 ± 0.93 nmol/L and 147.46 ± 35.77 nmol/L, respectively. The mean serum thyroid-stimulating hormone (TSH) levels in the case and control groups were 2.73±0.73 mIU/mL and 2.49 ± 2.17mIU/mL, respectively.ConclusionThis study revealed that long-term consumption of anticonvulsive drugs resulted in a decline in serum T4 levels and an increase in serum T3 levels, but had no effect on TSH levels. 1. Johnston M. Neurodegenerative disorders of childhood;Spingolipidoses. Nelson textbook of pediatrics, 17th edPhiladelphia: Saunders; 2004.P.2031-2.2. Sankar R, Koh S, Wu J, Menkes J. Paroxysmal disorders.In(eds): Menkes JH, Sarnat HB, Maria BL. ChildNeurology; 2006.P.7:877.3. Shiva S, Ashrafi M, Mostafavi F, Abasi F, RahbariA, Shabanian R. Effects of anticonvulsant drugs onthyroid function tests. Iranian Journal of pediatrics2003;13(02):101.4. Kimura M, Yoshino K, Suzuki N, Maeoka Y. Effect ofantiepileptic drugs on thyroid function. Psychiatry andclinical neurosciences. 1995;49(4):227-9.5. Eris Pural J, Delrio-Garma M, Delrio - Castro – GagoM. Long Term treatment of children with epilepsy withvalprovats or carbamazepin, may cause subclinicalhypothyroidism. Epilepsia 1999;40(12):1961.6. Isojarvi JIT, Turkka J, Pakarinen AJ, Kotila M,Rattya J, Myllyla VV. Thyroid function in men takingcarbamazepine, oxcarbazepine, or valproate for epilepsy.Epilepsia 2001;42(7):930-4.7. Vainionpaa LK, Mikkonen K, Rattya J, Knip M,Pakarinen AJ, Myllyla VV, et al. Thyroid function ingirls with epilepsy with carbamazepine, oxcarbazepine,or valproate monotherapy and after withdrawal ofmedication. Epilepsia 2004;45(3):197-203.8. Verrotti A, Basciani F, Morresi S, Morgese G, ChiarelliF. Thyroid hormones in epileptic children receivingcarbamazepine and valproic acid. Pediatric neurology2001;25(1):43-6.9. Kantrowitz L, Peterson M, Trepanier L, Melian C,Nichols R. Serum total thyroxine, total triiodothyronine,free thyroxine, and thyrotropin concentrations in epilepticdogs treated with anticonvulsants. Journal of the AmericanVeterinary Medical Association 1999;214(12):1804.10. Schroder-van der Elst J, Van der Heide D, Van der BentC, Kaptein E, Visser T, DiStefano J. Effects of 5, 5 -diphenylhydantoin on the thyroid status in rats. Europeanjournal of endocrinology 1996;134(2):221.11. Schonberger W, Grimm W, Schonberger G, SinterhaufK, Scheidt E, Ziegler R. [The influence of primidone onthyroid function (author’s transl)]. Dtsch Med Wochenschr1979;104(25):915-7.12. Tiihonen M, Liewendahl K, Waltimo O, Ojala M,Valimaki M. Thyroid status of patients receiving longtermanticonvulsant therapy assessed by peripheralparameters: a placebo-controlled thyroxine therapy trial.Epilepsia 1995;36(11):1118-25.13. Benedetti MS, Whomsley R, Baltes E, Tonner F. Alterationof thyroid hormone homeostasis by antiepileptic drugsin humans: involvement of glucuronosyltransferaseinduction. Eur J Clin Pharmacol 2005;61(12):863-72.

Acute Experimental Hyperthyroidism Does Not Affect Basal and Volume-Induced Atrial Natriuretic Peptide Secretion in Healthy Subjects

Background. Excess circulating thyroid hormones are associated with increased cardiac atrial natriuretic peptide (ANP) secretion but the exact mechanisms involved have not been fully elucidated in vivo. Methods. To examine whether thyroid hormone regulation of ANP secretion is the result of a direct action on the myocardium and/or of an indirect action through alterations in the peripheral circulation, plasma ANP levels (baseline and volume expansion-induced) were evaluated in 14 healthy men, before and after triiodothyronine (T3) administration. Results. T3 administration was followed by a significant increase in serum T3 levels and a significant decrease in serum TSH levels, without significantly affecting ANP levels. Systemic vascular resistance, plasma rennin activity (PRA), and aldosterone (ALDO) levels, as well as indices of left atrial function, were not significantly altered, despite a significant increase in cardiac output. Plasma volume expansion, induced by a 1500 ml normal saline (NSal) infusion, both before and after T3 administration, was followed by a significant decrease in PRA and ALDO and a significant increase in plasma ANP levels, without significantly affecting the mean blood pressure (BP) and heart rate (HR) in each study period. The NSal-induced response, measured as the integrated area under the curve corrected for baseline values (-AUC), was not different after T3 administration for ANP, ALDO, PRA, HR, and mean BP. Conclusion. In vivo thyroid hormone-induced myocardial ANP secretion is the result of an indirect action mainly through hemodynamic changes that increase atrial stretch.

The effects of fertiliser iodine application on herbage iodine concentration and animal blood levels

Two experiments were conducted to evaluate surface applications of potassium iodide and potassium iodate as alternatives to direct treatment of ewes where iodine (I) deficiency may be a problem. In Experiment 1, the hypothesis that grazing of pasture which had been sprayed with a potassium iodide and oil mixture results in increased blood iodine (serum T4) levels in ewes was tested over two years on five farms in Southland and West Otago, New Zealand. The results show that spraying elevated pasture I levels from March to pre lambing. The increased pasture I levels increased serum T4 levels by only 1.5% in late winter, an increase which was not significant (P > 0.05). There were small increases in lambing percentages (1–5%) due to the spraying in both years, but these were not significant (P > 0.05). In Experiment 2, the hypothesis that surface applications of potassium iodide and potassium iodate fertiliser can result in increased herbage I levels was tested on two farms in Southland and West Otago in 1996 and one farm in Central Otago in 1997. The trials ran from mid autumn (March/ April) to late winter (August/September) each year. There was a significant (P < 0.01) increase in pasture I levels after 6 weeks with both forms of iodine fertiliser, and this increase was still significant for the top application rates at the 19‐week measurement (P < 0.05 for Southland and West Otago, P < 0.01 for Central Otago). The iodide fertiliser was slightly more effective at increasing herbage I levels than was the iodate. However, despite the efficiency of I uptake being low (4.25% of the applied I taken up by the herbage), herbage I concentrations were lifted to acceptable levels and maintained at such for the duration of the study.

The influence of hyperthyroidism on pharmacologically induced contractions of isolated resistance arteries

We investigated the effect of hyperthyroidism on the responses of small mesenteric resistance arteries to several contractile and dilator agents. Hyperthyroidism was established by feeding rats for 28 days with 5 mg/kg l-thyroxine-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by the increased serum T4 levels (236 ± 7 mvs. 60 ± 2; T4-treated vs. control). Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for K +, Ca 2+, methoxamine, phenylephrine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-11α,9α-epoxymethano-prostaglandin F 2α (U46619), methacholine and nitroprusside. Our results indicate that hyperthyroidism does not induce major changes in the sensitivity of isolated resistance vessels to K +, Ca +, the α-adrenoceptor agonists, methacholine and nitroprusside. Furthermore, neither the affinity of α-receptors for methoxamine, nor the α-receptor reserve was influenced by the hyperthyroid state of the animal. A clearly sensitizing influence of hyperthyroidism was found for the vasoconstrictor effects of both 5-HT (6.57 ± 0.04 vs. 6.29 ± 0.06; hyperthyroid vs. control) and the thromboxane A 2 receptor agonist U46619 (6.78 ± 0.13 vs. 6.30 ± 0.09; hyperthyroid vs. control). Sensitization to both 5-HT and U46619 was abolished in the presence of N ω-nitro- l-arginine methylester HCl (L-NAME, 0.1 mM). 5-HT-induced contractions in vessels from hyperthyroid rats were diminished by prior incubation with indomethacin (10 μM). The present results indicate that during hyperthyroidism resistance vessels are sensitized to both 5-HT and U46619. This sensitization involves the nitric oxide/ l-arginine pathway and probably also certain steps in the cyclooxygenase pathway.

The Influence of Human Growth Hormone (GH) and Thyroxine (T4) on the Differentiation of Adipose Tissue in the Fetus

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T4 levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T4 increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T4 (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a "critical" or "sensitive" period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitment/replication during this period. Furthermore, T4 but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T4 may have a major role in preadipocyte recruitment/replication during late fetal life.

Selenium deficiency and type II 5'-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine.

Selenium deficiency in rats is characterized by elevated serum T4 and decreased serum T3 concentrations, and low liver type I (5'D-I) and brain type II (5'D-II) iodothyronine 5'-deiodinase activities. These findings are partially explained by the demonstration that type I 5'D is a selenoprotein; however, 5'D-II does not contain selenium. Since 5'D-II varies inversely with serum T4 concentrations, and serum T4 is elevated in selenium deficiency, the decreased cerebrocortical 5'D-II activity may be secondary to the increased serum T4 levels. To determine the mechanism(s) by which selenium influences 5'D-II activity, we examined the effects of altered selenium intake on brain 5'D-II levels and enzyme turnover in euthyroid and thyroidectomized rats. Rats were fed a selenium-supplemented or selenium-deficient diet for 5 weeks from weaning; half of the animals were also thyroidectomized 3 weeks before death. Selenium deficiency was confirmed by decreased liver and brain glutathione peroxidase activities. In euthyroid rats, selenium deficiency caused a 38% increase in serum T4, and 91% and 39% decreases in 5'D-I and 5'D-II, respectively, compared to those in selenium-supplemented rats. In the thyroidectomized hypothyroid rats, selenium deficiency caused a 60% decrease in 5'D-I, but had no effect on 5'D-II activity, fractional turnover of the enzyme, or the calculated enzyme synthesis rate. The lack of effect of selenium deficiency on 5'D-II levels in hypothyroid rats is consistent with the finding that 5'D-II is not a seleno-enzyme. Thus, the decrease in brain and pituitary 5'D-II activity in selenium-deficient euthyroid rats is due to the T4-dependent increase in the turnover of the enzyme polypeptide.

Increased production of thyroxine and inappropriately elevated serum thyrotropin in levels in endogenous depression

The increased serum thyroxine (T4) levels in endogenous depression (ED) might be due to an increased production or a reduced degradation of T4. We therefore performed turnover studies of radiolabeled T4 and 3,5,3′-triiodothyronine (T3) in 6 patients with ED and 8 age-matched healthy controls. In ED, the median daily production of T4 was 130 nmol/day/70 kg, (range 100–186 nmol/day/70 kg) and elevated compared to control values which were 99 nmol/day/70 kg (range 85–142 nmol/day/70 kg) ( p < 0.05), whereas that of T3 was similar in the two groups. Serum thyrotropin (TSH) levels (0.90 mU/liter, 0.18–2.15 mU/liter) were elevated in ED compared to a group of 7 L-T4-treated hypothyroid subjects with similar production and serum levels of T4 and T3 (0.11 mU/liter, 0.07–1.10 mU/liter) ( p < 0.02). The data show that increased serum T4 levels in ED are secondary to an increased thyroidal production of T4, which is at least partly due to inappropriately high serum TSH levels.

Thyroidectomy and central catecholamine neurons of the male rat. Evidence for the existence of an inhibitory dopaminergic mechanism in the external layer of the median eminence and for a facilitatory noradrenergic mechanism in the paraventricular hypothalamic nucleus regulating TSH secretion.

Using the Falck-Hillarp methodology in combination with quantitative microfluorimetry, catecholamine (CA) levels and utilization in discrete hypothalamic CA nerve terminal systems in the male rat have been analyzed 24 h, 1, 2 and 4 weeks following thyroidectomy as well as after T3 or T4 restitution therapy 4 weeks after thyroidectomy. By means of high pressure liquid chromatography (HPLC), dopamine (DA) and noradrenaline (NA) levels and utilization 4 weeks after thyroidectomy have been analyzed in various brain regions. Triiodothyronine treatment (10 micrograms/kg, s.c., twice daily during 10 days) of 4-week athyroidic rats increased serum T3 levels, but not T4 serum levels. Thyroxine treatment (36 micrograms/kg, s.c., twice daily during 10 days) of 4-week athyroidic rats increased serum T4 levels and the T3 levels were found to be even slightly higher than those found in normal animals. Triiodothyronine or T4 restitution therapy reversed the changes induced by thyroidectomy on the anterior pituitary hormones (TSH, prolactin and growth hormone) and corticosterone secretion. It is suggested that removal of thyroid hormones may be responsible for the changes in the anterior pituitary hormones and corticosterone secretions. In the quantitative microfluorimetrical analysis 24 h, 1, 2 and 4 weeks after thyroidectomy, decreases in DA levels and utilization and increases in NA levels and utilization were found in the lateral palisade zone (LPZ) of the median eminence and in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus (PA), respectively. In addition, 1-,2- and 4-week decreases were found in DA levels and turnover in the medial palisade zone (MPZ) as well as in NA turnover in the dorsomedial hypothalamic nucleus (DM) and in the 'border zone' (BZ) between the medial and lateral hypothalamus ventral to the fornix. In the HPLC analysis it could be demonstrated that 4 weeks after thyroidectomy decreases in DA levels and utilization in the mediobasal hypothalamus and increases in DA levels as well as NA levels and utilization in the hypothalamus had developed. The T3 or T4 restitution therapies after 4 weeks of thyroidectomy counteracted the effects on CA levels and utilization in all hypothalamic CA nerve terminal systems except for the reduced NA utilization found in the DM following 4 weeks after thyroidectomy.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroid function in gestational trophoblastic neoplasia: Evidence that the thyrotropic activity of chorionic gonadotropin mediates the thyrotoxicosis of choriocarcinoma

An investigation was made of thyroid function in 20 patients with gestational trophoblastic neoplasia. Two patients were judged to be overtly thyrotoxic on the basis of the symptoms and physical findings; both patients had widely metastatic choriocarcinoma, markedly increased serum T4 levels (21.4 and 27.7 μg/100 ml), and extremely high levels of serum human chorionic gonadotropin (hCG) (3,220 and 6,720 IU/ml) relative to those of normal gestation (<100 IU/ml). Three other patients had moderately increased serum T4 levels (13 to 17.1 μg/100 ml), moderately increased serum hCG levels (110 to 310 IU/ml), and findings on clinical examination which suggested euthyroidism. Using the mouse thyroid bioassay, we found that the biologic characteristics of the thyroid-stimulating factor were those of purified hCG, and that the levels of thyroid-stimulating activity in both serum and urine correlated closely with the levels of hCG. These results provide evidence that the thyroid-stimulating activity intrinsic to the hCG molecule plays the central pathophysiologic role in choriocarcinoma-associated thyrotoxicosis.

Abnormal Thyroid Regulation in Chickens with Autoimmune Thyroiditis*

The obese strain of chicken (OS) in which virtually all individuals spontaneously develop autoimmune thyroiditis was developed by selection from the Cornell strain (CS). Lymphocytes start infiltrating the thyroid gland 1 week after hatching. One possibility explaining this infiltration postulates preexisting abnormalities or defects of the target organ. The present study examines one parameter of thyroid function, uptake of 131I- under conditions in which TSH secretion is minimized. This was accomplished by supplementation of feed with T4 from hatching until sacrifice. Serum T4 levels were monitored by RIA. Twenty-hour thyroidal iodide uptakes were determined at autopsy by counting the radioactivity in the extirpated thyroid lobes. Dietary T4 supplementation increased serum T4 levels many times above normal. This drastically decreased thyroid function in four normal chicken strains; thyroidal uptake of 131I- was suppressed 97.5-99.2%. OS chickens were incompletely suppressed; mean values ranged between 80...

Effect of parturition on serum iodothyronine concentrations in fetal sheep.

T4, T3, and rT3 were determined by RIA on daily serum samples collected from five catheterized fetal sheep during the 2-week period before spontaneous vaginal delivery (PTD). Samples were also available from three newborn lambs during the first 4 h of life. T3 concentrations began to increase 4-6 days before spontaneous vaginal delivery, from a stable geometric mean concentration of 30 ng/dl to a mean concentration of 131 ng/dl on the day of delivery (day 0). T4 concentrations decreased in four of the animals and remained unchanged in one during this time interval. rT3 concentrations decreased from a stable mean of 472 to 249 ng/dl on day 0. The prenatal increase in serum T3 levels correlated temporally with increasing fetal serum cortisol concentrations. The mean T3 concentration increased further after delivery to a level of 487 ng/dl at 1 h of age without significant changes in T4 or rT3 levels. The following conclusions were reached: 1) fetal serum T3 concentrations increase while T4 and rT3 concentrations decrease during the 4-6 days preceding spontaneous labor, and 2) T3 concentrations increase further after delivery. Available evidence suggests that the prenatal increase in fetal serum T3 levels is mediated by a cortisol-induced increase in T4 to T3 conversion in fetal tissues. The mechanism(s) of the postnatal increase in serum T3 concentrations in the newborn is not clear.

Serum Levels of Thyrotropin, Thyroid Hormones and Their Response to Thyrotropin Releasing Hormone in Infective Febrile Illnesses

In 25 patients suffering from fever of infection, serum levels of thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), and thyroxine binding globulin (TBG) were estimated on two consecutive days during the febrile period and again 3 to 10 days after the fever had subsided. The serum TSH and T3 responses to 100 mug iv TRH were also studied during fever. Hormones were estimated by specific radioimmunoassays and TBG by radioligand binding assay. As compared with age and sex matched normal controls, patients with fever of infection had significantly lowered levels of total serum T3 and TBG. The serum TSH and total T4 concentrations were not significantly altered. During fever both % FT4 and absolute FT4 were significantly elevated, whereas only % FT3 was significantly increased and due to lowered serum total T3 levels the absolute FT3 were not significantly altered as compared to that in normal subjects. After the fever had subsided, the serum T3 levels returned to normal and the serum TBG levels increased. There was no correlation between basal serum levels of T3 and TSH during fever. Although in response to iv TRH the mean rise in serum TSH during fever was comparable to that in normal subjects, the overall TSH response showed an inverse correlation with serum TT3 levels. Following iv TRH there was a significant increase in serum T3 levels and the T3 response in fever was comparable to that in normal subjects. These data suggest that hormone secretion by the thyroid and its responsiveness to endogenous TSH are maintained during fever. The lowered T3 levels are not suggestive of a hypothyroid state, but perhaps could be due to decreased peripheral conversion of T4 to T3 and to decreased binding of T3 to serum proteins. The exact mechanism or significance of these alterations in thyroid function during febrile illness remains to be elucidated.

The effect of food deprivation of the peripheral metabolism of thyroxine in rats.

Starvation depresses thyroid gland function. In addition, the peripheral turnover of thyroxine (T4) is reduced, in part due to decreased fecal elimination of T4. The present studies were performed to determine if starvation also affects the deiodinative pathway for T4 degradation. Rats were isotopically equilibrated with daily injections of exogenous [131-I]T4 while endogenous thyroidal T4 secretion and concentration of iodide were blocked with KCl04. Following a period of equilibration, either complete or 50% food deprivation was imposed on half the animals. Within 48 h of starvation, the serum T4 concentration of the fully starved rats doubled and remained high throughout. A marked decrease in fecal excretion of T4 was partially responsible for the increase. In spite of variability in the quantity of urinary 131-I excreted, the dieodinative clearance was consistently reduced. These effects were readily reversible upon resumption of normal feeding. Similar though less severe changes were observed in the half-fed rats. In both fully and partially-starved animals, the decreased dieodinative clearance in the face of increased serum T4 levels indicates a significant impairment of peripheral deiodination by some as yet unknown mechanism. In contrast, normal rats equilibrated with doses of T4 sufficient to increase serum T4 levels exhibit increased urinary clearance of iodide derived from T4. Thus the increased serum T4 levels are a consequence of impairment of the deiodinative pathway by starvation as well as decreased fecal T4 excretion. Clearly, voluntary alterations in food consumption must be controlled for differences between groups during experimental studies of T4 utilization.