Effects of hyper-and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5\s=deg\C)and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU-treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine \g=b\-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P <0.01 vs controls). T4-treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and[3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, 1) thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and 2) the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency.The calorigenic action of thyroid hormone and catecholamine (CA) is well established. Both arise from the common precursor, tyrosine, and play a pivotal role in the homeotherm. Thyroid hor¬ mone controls the basal metabolic rate (BMR) by stimulating oxydative phosphorylation of the mitochondrial respiratory chain. Thyroid hor¬ mone-induced changes in BMR usually occur slowly and tend to persist. On the other hand, CA increases heat production above BMR by enhanc¬ ing lipolysis and glycolysis in response to various metabolic demands, which are rapidly switched on and off. On exposure to cold, an elevation of heat pro¬ duction is brought about by the enhanced nore¬ pinephrine (NE) secretion from the sympathetic nervous system (Hsieh et al. 1957b), which is the underlying mechanism of non-shivering thermo¬ genesis. Recently, the major site of non-shivering thermogenesis is recognized to be brown adipose tissue (BAT) (Foster & Frydman 1978). Although a line of evidence indicates that cold exposure evokes a rapid rise in plasma thyrotropin (TSH) (Knigge 1960;Itoh et al. 1966) and a stimulation of thyroid secretion, the interrelationship be¬ tween thyroid hormone and CA still remains to be elucidated. In our study, we examined effects of altered thyroid states on the CA metabolism in the central nervous system (CNS), adrenal glands, liver, and BAT during cold acclimation. We show that there is a close metabolic interrelationship between thyroid hormone and CA.

The echo patterns of diffuse thyroid lesions in children are not yet well known. We present here the ultrasound findings of 32 children aged 5 to 15 years with a newly diagnosed diffuse thyroid disease. 23 patients had thyromegaly by palpation, 9 had hypothyroidism but no goiter. Of the 23 goitrous patients 9 were hypo-, 3 hyper-and 11 euthyroid. The 9 with hypothyroidism had all autoimmune thyroiditis as judged by antithyroid antibodies, and confirmed cytologically in 5. They had all 9 a hypoechogenic patchy, partly nodular thyroid by ultrasound.2 of the 3 with Graves disease had initially a similar pattern than in thyroiditis, the 3rd showed hypoechogenity later. Of the 11 euthyroid patients 8 had antithyroid antibodies and the ultrasound suggested thyroiditis in 5 of them, 3 were judged normal (2 and 1 became later hypothyroid). Of the 3 patients with euthyroid goiter but without antithyroid antibodies the ultrasound finding was normal in 1, showed multicystic thyroid in 1 and suggested thyroiditis in 1 who later had antithyroid antibodies. Of the 9 hypothyroid patients without thyromegaly one had an unusually small hit otherwise normal thyroid by ultrasound. The others had an echopoor thyroid, but the patchy and nodular pattern was often less marked than in goitrous hypothyroidism. We conclude that autoimmune thyroiditis gives a typical ultrasound pattern, and ultrasonography gives useful information especially of euthyroid goiter and nongoitrous hypothyroidism. PERICARDIAL EFFUSION IN CONGENITAL HYPOTHYROID/ ; A 1NFANTS:AN AETIOLOGICAL CORRELATION. Gianfili~po -" ...~e h children positive at the newborn screen'ing program for congenital hypothyroidism were studied. Confirmlng diagnosis was made in 8/10 infants,while 2/10 were false positive. Moreover we have considered in the study a patient clinically diagnosed at 19 months (he did not undergo the screening prograrn),in which was demonstrated an ectopic g1and.A complete thyroid function evaluation (FT3,FT4,T3,T4,TBG,TRH test),scintlgraphy (TC99),echocardiography (B-mode)were carried out in all the babies (scintigraphy was not performed in the 2 false positive children). Pericardial effusion was demonstrated in 4/9 patients (44%); complete resolution occurred after a variable period of L-T4 therapy (15 days to 5 months).None of the patients showed clinical symptoms nor electrocardiographrc signs of cardiac failure. Data collected in Zaire suggested that severe iodine deficiency resulted in neonatal hypothyroidism and its longterm consequence, endemic cretinism. In order to further evaluate this possibility, we initiated neonatal thyroid screening in an endemic goiter area in Algeria (area A) with a high prevalence of goiter (51.3 %) and cretinism (1.1 %) and a low dietary supply of iodine (I)(Mean urinary I : 16.2 uglg creatinine) and in a non goitrous area (B) with no cretinism and a normal iodine supply (urinary 1:73.9 ug/g creat.). Serum TSH levels in 3135 newborn infants of area A were shifted towards high values as compared to the results obtained in a...

Abstract. To elucidate the mechanism by which TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro)), act on the maturation of homoiothermy, the chronic effects of intrathecal administration of the peptides on body temperature, serum thyroid hormone levels, and mitochondrial energy-producing enzyme activities were examined in neonatal rats. The two peptides or an equimolar mixture of both were injected intrathecally at a dose of 3, 6 and 9 nmol for 7 consecutive days during the 1st, 2nd or 3rd week of life, respectively. Control rats were treated with saline and they were sacrificed at 6 weeks of age. Although food and water intake were not decreased, body weight gain was slightly reduced in the rats treated with TRH or cyclo(His-Pro) during the 1st and 2nd week of life, whereas the mixturetreated rats showed normal weight gain. Body temperature at 25°C was not different in the TRH- and cyclo(HisPro)-treated groups, whereas after cold exposure (5°C for 3 h), the groups treated with TRH during the 1st and 2nd week of life had an impaired thermoregulation at 5 weeks of age. Serum T4 and T3 concentrations were similar in all groups, except in the rats treated with TRH during the 2nd week of life; their thyroid hormone levels were slightly reduced. The TRH treatment suppressed mitochondrial cytochrome c reductase and glucose-6-phosphatase activities, whereas cyclo(His-Pro) reduced cytochrome c reductase and malic enzyme activities. In contrast, α-glycerophosphate dehydrogenase was enhanced by both treatments. These results suggest that TRH and cyclo(His-Pro) modulate the central thermoregulatory mechanism and produce particular changes in the mitochondrial respiratory chains in peripheral thermogenic tissues.

The effects of TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro] on catecholamine metabolism in the central nervous system, peripheral tissues and plasma were examined in adult and young Wistar rats aged 3 weeks. The intravenous administration of 50 micrograms of TRH produced an increase in plasma epinephrine, cerebral dopamine and a reciprocal decrease in norepinephrine and dopamine in diencephalon and midbrain. In contrast, 50 micrograms of cyclo(His-Pro) induced a rise in plasma dopamine and a decrease of dopamine in cerebellum, pons and medulla oblongata. After intraperitoneal injection of 3 mg of alpha-methyl-p-tyrosine, which blocked re-uptake of catecholamines in synapses, intrathecal administration of 30 ng TRH accelerated 2 times metabolic turnover of norepinephrine and dopamine in cerebral hemisphere, diencephalon and midbrain as well as norepinephrine turnover in cerebellum, pons, medulla oblongata, heart and brown adipose tissue. Consecutive intrathecal administration of TRH for 6 days enhanced cerebral catecholamine content. These results indicate that (1) TRH accelerates metabolic rate of catecholamine in the central nervous system as well as peripheral tissues, and (2) TRH acts on both noradrenergic and dopaminergic neurons in cerebral hemisphere, diencephalon and midbrain, whereas cyclo(His-Pro) acts mainly on dopaminergic neurons in cerebellum, pons and medulla oblongata.

Abstract. The effects of thyrotropin-releasing hormone (TRH) and its putative metabolite, cyclo-histidine-proline (cHP), on the homeothermic development of neonatal rats were studied. The daily intrathecal administration of 10−11–10−9 moles of TRH during the second week of age produced a significant rise in body temperature by 3 weeks of age and was followed by a transient period of hypothermia. This effect, which could not be produced by an intraperitoneal injection of 10−7 moles of TRH, was abolished by the simultaneous administration of 6-hydroxydopamine (6OHD). In contrast, intrathecally administered cHP decreased thermogenesis. During TRH treatment, brain norepinephrine (NE) and dopamine (DA) release was accelerated 2- to 4-fold. Two weeks after either TRH or cHP treatment, brain NE and DA were significantly reduced; adrenal NE in cHP-treated rats increased. The weight of the interscapular brown adipose tissue (BAT) was decreased by both cHP and 6OHD. At 3 weeks of age, [3H]guanosine diphosphate binding capacity in BAT mitochondria was reduced by 60% in TRH-treated rats and was associated with reduced mitochondrial levels of α-glycerophosphate dehydrogenase and liver cytochrome C reductase. These results indicate that 1) TRH stimulates central NE release thereby enhancing thermogenesis, 2) cHP decreases heat production, and 3) TRH-induced hyperthermia is associated with changes in mitochondrial exothermic processes. The central TRH-cHP system may modulate the maturation of homeothermic mechanism in neonatal rats.