Pituitary-thyroid responsiveness to thyrotropin-releasing hormone in preterm and small-for-gestational age newborns.

A dose of 40 microgram TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T4) and serum-triiodothyronine (T3) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T3 increase about 46% and median serum-T4 increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced that later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Endocrine reactivity (T3, T4, cortisol) during cold exposure in preterm and full-term lambs

The endocrine reactivity to a short-term cold exposure (+ 4 degrees C during 1 h 30 min) was studied in 8 full-term (FT) and 12 preterm (PT) Limousin x Romanov lambs, obtained by oestrogen injections to the ewes; 4 PT animals died (PTD) during the observation period and 8 remained alive (PTA). The plasma cortisol, T4 and T3 levels were lower in PT lambs (particularly in PTD for T4 and T3) during the first hours of life. Moreover, rectal temperature decreased sharply between birth and 30 min postpartum in the PT group; at this time, plasma T3 levels and rectal temperature were positively related. During cold exposure, the plasma cortisol levels increased in FT lambs, but did not change in the PT group. Moreover, the plasma T4 levels rose slightly in FT animals (+ 12%), increased sharply in PTA lambs (+ 137%), or showed a small decrease in the PTD group (-5%) in which a marked hypothermia occurred; the relative changes in the circulating T4 levels were positively related to the algebraic variations of rectal temperature in PT lambs. However, the changes in the plasma T3 levels did not parallel that of T4 in the three groups of animals, but a positive relationship was observed, in all lambs, between the circulating T3 levels and the rectal temperatures at the end of the cold exposure. These results suggest a reduced sensitivity of the adrenal cortex to stressful conditions in PT lambs. Moreover, they underline the importance of thyroid function for thermoregulation in the newborn lamb, particularly in PT animals.     

TSH and PRL response to thyrotrophin-releasing hormone in children with chronic renal failure undergoing haemodialysis.

Eight children (aged between 8 1/2 and 15 1/2 years) with chronic renal failure receiving intermittent haemodialysis, and 2 children with renal transplants were studied. The response of TSH and prolactin (PRL), and basal T4 and T3 values was measured. Basal TSH was normal, and rose only slightly after TRH stimulation. Plasma T4 and T3 were below normal levels in 6 children. Mean basal PRL was raised and could not be stimulated by TRH. This study demonstrates the involvement of the hypothalamus and pituitary in chronic renal disease. The cause of the abnormal secretion of TSH and PRL in chronic renal failure is discussed in the light of clinical importance.     

Thyrotropin and prolactin response to thyrotropin-releasing hormone in healthy and asphyxiated full-term neonates

To evaluate the effect of perinatal asphyxia on the pituitary response to thyrotropin-releasing hormone (TRH) in full-term newborn infants, serum thyrotropin (TSH) and prolactin (PRL) levels were measured before and 30 and 180 min after i.v. administration of 40 micrograms TRH. Birth weight, gestational and postnatal age were similar in the healthy (group NA) and in the asphyxiated (group A) babies. Hormone levels were determined by radioimmunoassay using commercial kits. It was demonstrated that the basal TSH level was slightly higher and the basal PRL level significantly (p less than 0.05) higher in group A than in group NA. In response to TRH administration in group A a marked increase in PRL occurred from 6781 +/- 887 to 11 072 +/- 1318 and 9636 +/- 1024 mU/l at 0, 30 and 180 min, respectively. A similar response was seen in group NA; the values, however, remained significantly lower during the TRH-test. The respective PRL values at 0, 30 and 180 min were 4672 +/- 411, 7945 +/- 343 (p less than 0.05) and 5963 +/- 372 mU/l (p less than 0.05). TRH administration also resulted in a significant elevation of the serum TSH level from 6.20 +/- 1.30 to 49.02 +/- 7.25 (p less than 0.01) and 18.72 +/- 6.35 mU/l (p less than 0.05) in group A, and from 3.90 +/- 0.57 to 24.01 +/- 3.81 (p less than 0.01) mU/l in group NA, but in group NA the 180 min TSH value of 6.07 +/- 1.25 mU/l did not differ statistically from the basal level (p greater than 0.1). It is concluded that the pituitary PRL and TSH reserves are maintained in full-term newborn infants recovering from perinatal asphyxia whose biochemical findings are indicative of subclinical hypothyroidism.     

Increased risk of primary hypothyroidism in preterm infants

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.     

Response of the maternal, fetal, and neonatal pituitary-thyroid axis to thyrotropin-releasing hormone

Thyrotropin releasing hormone (TRH) readily crosses the placenta and stimulates the fetal pituitary. We studied the response of the maternal and fetal pituitary-thyroid axes to TRH and the influence of prenatal exposure to TRH on the physiological postnatal increase in thyrotropin (TSH) and triiodothyronine (T3) in the neonate. Twenty-six pregnant women received TRH (400 or 600 micrograms) intravenous or saline (controls) either 2 or 12 h before elective cesarean section at term. Administration of 400 micrograms of TRH resulted in significant elevations of maternal TSH (15.7 +/- 2.9 versus 3.2 +/- 0.4 microU/ml, p less than 0.01) and prolactin (416 +/- 94 versus 223 +/- 41 ng/ml, p less than 0.05) 2 h later. Maternal T3 remained unchanged. A higher dose of TRH (600 micrograms) produced comparable results. Maternal administration of TRH (400 micrograms) 2 h before delivery resulted in significant increases in fetal TSH and T3 over controls (21.1 +/- 3.7 versus 4.8 +/- 1.0 microU/ml, and 132 +/- 12 versus 64 +/- 9 ng/dl, p less than 0.01, respectively). Cord blood hormone levels 12 hours after TRH administration were similar to controls. Higher doses of TRH did not produce further increases in fetal TSH or T3. Control and treated neonates demonstrated similar physiological postnatal increases in TSH and T3, suggesting that prior exposure to TRH did not blunt this response. These data suggest that maternal administration of TRH is an effective way of increasing fetal T3 levels, and that this treatment does not inhibit the postnatal surge in TSH and T3.     

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.     

Prolactin response to thyrotropin-releasing hormone in children with Turner's syndrome and hyperthyroidism

Plasma prolactin (PRL) response to synthetic thyrotropin-releasing hormone (TRH) was studied in 26 prepubertal and 19 pubertal children with constitutional short stature, 7 patients with Turner's syndrome and 10 patients with hyperthyroidism. The mean basal concentrations of plasma PRL did not differ among groups. In prepubertal children PRL responses to TRH were comparable in both sexes, while pubertal children plasma PRL levels after TRH in females were significantly higher (P<0.05) than those in age-matched males. Plasma PRL levels after TRH in patients with Turner's syndrome were significantly higher (P<0.05) than those in age-matched males, but were not significantly different from those in age-matched females. Plasma PRL response to TRH was markedly suppressed in patients with hyperthyroidism before treatment, but it returned to normal after treatment when patients became euthyroid. A significant correlation (P<0.05) between peak concentrations of plasma PRL after TRH stimulation and plasma T₃ but not T₄ levels was observed.These data suggest that a sex difference in TRH-stimulated PRL secretion appears around puberty and that plasma PRL response to TRH is suppressed in children with hyperthyroidism. The magnitude of plasma PRL response to TRH is closely correlated with the severity of hyperthyroidism when judged by plasma T₃ but not T₄ concentrations.     

McCune-Albright syndrome in a male child: a clinical and endocrinologic enigma.

A 6 5/12-year-old boy with polyostotic fibrous dysplasia, café-au-lait pigmentation of the skin, and precocious pubertal development was studied for two years. Parathormone, calcium, phosphorus, testosterone, cortisol, and growth hormone levels were within normal limits. Urinary 17-ketosteroids, 17-ketogenic steroids, and estrogens were at the upper limits of normal. After GnRH stimulation, there was only a very slight increase in LH and no increase in FSH. There was no increase in TSH after TRH, and plasma levels of T4 and T3 were normal. The plasma prolactin level was within normal limits, and increased after TRH stimulation (with a second, delayed upsurge). Abnormal distribution of 131I in the thyroid was evident, without clearcut evidence of hyperfunctioning areas after TSH stimulation and T3 suppression tests followed by conventional scanning and gamma camera scintiphotography. Our findings do not support the claimed, single, hypothalamic origin of the disease that is presumed to result in overproduction of releasing hormones; they are more in keeping with a pleiotropic, scattered peripheral lesion, possibly of embryonal origin.     

Thyrotropin, prolactin and growth hormone response to synthetic thyrotropin-releasing hormone in newborn infants.

The effects of 50 microgram synthetic thyrotropin-releasing hormone (TRH) intravenously on thyrotropin (TSH), prolactin (PRL) and growth hormone (GH) levels were studied in 8 normal male newborns during the first hours of life. Mean plasma GH concentrations were similar to baseline values during the period of study; on the contrary, plasma PRL and TSH values increased in all infants after TRH administration. These data demonstrate a normal pituitary reserve of PRL and TSH in the early period of human life.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

Thyroid function in thalassaemia major.

Serum concentrations of T4, T3, rT3, and TSH were measured by radioimmunoassay in 45 patients suffering from beta-thalassaemia. A TRH stimulation test was performed and the binding capacity of TBG and TBPA for T3 and T4 measured by reverse flow zone electrophoresis in a group of these patients. Mean T4 serum concentration was lower in thalassaemic patients than controls; T3, rT3, TSH levels, and the pituitary response to TRH were normal. TBPA binding capacity for thyroxine was greatly decreased, probably due to iron overload impairing the liver function. The decreased circulating total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration values being normal. It is concluded that thalassaemic children are euthyroid, despite often having low-normal or subnormal thyroxine levels.     

Thyroid hormone concentrations in preterm infants born to pre-eclamptic women with placental insufficiency

The aim of this study was to compare thyroid function in preterm infants born to women with placental insufficiency (n = 15) and those born to women without placental insufficiency (n = 13). Gestational ages ranged between 28 and 33 weeks. Concentrations of free thyroxine (FT4), thyrotropin (TSH), triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmmunoassays in cord blood and on d 1, 3, 5, 7, 14 and 21. Infants born to the women with placental insufficiency had significantly lower mean FT4 (p = 0.001), TSH (p = 0.002) and rT3 values (p = 0.025) in cord blood, and higher rT3 values on d 5 (p = 0.019) and d 7 (p = 0.025). The following conclusions were reached: (i) preterm infants born to pre-eclamptic women with placental insufficiency have intact hypothalamic-pituitary-thyroid axes; (ii) compared to preterm infants born to healthy women, preterm infants born to pre-eclamptic women with placental insufficiency have lower FT4 and TSH concentrations before birth and (iii) elevated rT3 concentrations after birth, suggesting a temporarily impaired hepatic type 1 deiodination process.     

Disorders of thyroid gland function--hypothyroidism in childhood. An ambulatory follow-up study

42 children with different kinds of hypothyroidism, who had been treated with thyroid hormones during several years, were thoroughly follow-up examined in 1988. Apart from few exceptions, patients in therapy attained standard data in length. Concerning skeleton maturation, clear differences between boys and girls were found. While male patients, with one exception, showed a retardation of bone-age, in females both, retardation and acceleration of bone-development were found. Serum concentration of FT4 and FT3 were chosen as hormonal parameter, and TSH was taken basal and after stimulation with TRH. Normal FT4 levels were found in 29 patients. In 5 children FT4 was significantly lower, in 8 cases an elevation of this serum-parameter was observed. Measurement of serum FT3 in 27 patients showed normal levels in 18 children. In 4 cases low and in 5 elevated FT4 levels were found. 29 patients had basal TSH concentrations within normal range, in 13 the estimated levels were elevated. TRH-stimulation carried out on 40 children showed normal serum TSH response for 13 of them. In 14 children an exaggerated TSH response to TRH occur, in 13 TSH still remain low after stimulation with TRH. Serum-GOT, -GPT, -Gamma GT and -CK were determined as encymic parameters. In 5 patients a typical hypothyroidism-associated GOT- and CK-elevation was found. 3 children showed an isolated rise of GOT-, 8 an isolated CK-elevation.     

Thyroid function in preterm infants with respiratory distress syndrome.

Thyroid function was evaluated in premature infants 30 to 35 weeks EGA with severe RDS and was compared to that of healthy control subjects of similar EGA. The infants with RDS had significantly lower serum levels of T3, T4, and FT4I during the first 60, 90, and 30 days, respectively, and had elevated T3UR during the first 10 days. The mean (+/- SD) postdelivery TSH peak was lower in the RDS group (32.8 +/- 9.6 muU/ml) than in the control group (60.9 +/- 21.8 muU/ml; P less than 0.005). After TRH injection the increment in serum TSH was inversely related to the basal FT4I in the control infants but not in the infants with RDS.     

Decreased antihaemophilic globulin and leucocyte response to epinephrine in preterm infants.

Twenty-one preterm and 23 term neonates, 13 splenectomized children and one with congenital asplenia, and 20 normal children were examined for plasma antihaemophilic activity and for blood leucocyte levels before and 30 minutes after a subcutaneous injection of epinephrine 0-01 mg/kg. The basal values for antihaemophilic activity were similar for the 4 groups. The response to epinephrine was a trivial rise in antihaemophilic activity in the preterm group, while the rise in the term newborns was comparable to that of the normal children. The asplenic children all showed a trivial rise. The leucocyte response was also negligible in both the preterm neonates and asplenic groups, while in the term infants it was comparable to that seen in the normal children. These results may indicate an incapacity of the preterm newborn infant''s reticuloendothelial system and spleen to react to other challenges, such as bacterial infection.     

PITUITARY-THYROID RESPONSIVENESS TO THYROTROPIN-RELEASING HORMONE IN PRETERM AND SMALL-FOR-GESTATIONAL AGE NEWBORNS

Abstract. A dose of 40 μg TRH was injected intravenously in 12 preterm (PT) and 15 small-for-gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum-thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum-thyroxine (T₄) and serum-triiodothyronine (T₃) were measured prior to and 180 min after TRH. The percentage increase in serum-TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum-TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH-test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum-T₃ increase about 46% and median serum-T₄ increase about 14%. It is concluded that in low-birth-weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced than later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.     

Hyperfunctioning thyroid nodules in children

We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.     

The effects of intranasally sprayed synthetic TRH on TSH and on PRL secretion in children

The effects of intranasally applied TRH on serum TSH and PRL were investigated in ten healthy, prepubertal children. Serum levels of T4, T3, TSH, and PRL were all in the normal range. Synthetic TRH, 500 micrograms, in water was insufflated in one nostril. Intranasal TRH induced a prompt rise of TSH and PRL in all children with peak values at 30 min. TSH: 10.29 +/- 1.24 microU/ml; PRL: 25.12 +/- 3.53 ng/ml (mean +/- SEM). TSH values were still significant raised 120 min after the insufflation (P less than 0.025) whereas the PRL values did not differ significantly. A dose-dependent TSH release following intranasal sprayed TRH was shown. delta TSH and TSH values at 120 min were significantly higher in children receiving greater than 10 micrograms/kg TRH than in children receiving less than 10 micrograms/kg (P less than 0.025; P less than 0.05). Dose dependent differences in PRL release following intranasal TRH were not shown. Any side effects of intranasally applied TRH were not observed. Intranasal insufflation of synthetic TRH seems to be a valuable and harmless tool for the evaluation of pituitary TSH and PRL secretory reserve.     

Role of thyrotropin-releasing hormone in thyroid-stimulating hormone and growth hormone regulation during postnatal maturation in female Wistar rats

The role of endogenous thyrotropin-releasing hormone (TRH) in the control of pituitary thyroid-stimulating hormone (TSH) and growth hormone (GH) secretion was studied during postnatal maturation in female Wistar rats. Half of the sucklings in each litter was treated intraperitoneally with either specific rabbit antiserum against TRH or normal rabbit serum (0.1-0.3 ml according to age). All animals were decapitated after 2 h. The presence of anti-TRH activity was checked as a binding of labelled TRH with plasma of the experimental animals. Immunoneutralization of endogenous TRH resulted in a decrease of plasma TSH in 3- to 15-day-old female pups as compared to control littermates. No effect of TRH antibody injection was seen at the ages of 1, 21, 30 and 70 days despite the presence of excess antibody in the plasma. A profound effect of TRH antibody on plasma TSH was seen again at the age of 100 days. Plasma GH in the same animals exhibited a paradoxical increase after TRH immunoneutralization at the age of 5 and 8 days, a decrease was found at the age of 21 days. It was concluded that hypothalamic TRH control of TSH secretion matures early in Wistar rats. Hypothalamic secretion of TRH at the ages of 1, 21, 30, and 70 days is low and(or) its role in TSH regulation is masked by other regulating factors. TRH may play a dual role in the regulation of GH secretion during the postnatal period.