Pseudohypoparathyroidism with hypothyroidism (author's transl)

This is a report about three children suffering from pseudo-hypoparathyroidism type I and moderate primary hypothyroidism. The thyroid dysfunction was characterised by slightly low plasma thyroxine and high basal TSH showing an increased response to TRH. T3 and rT3 were within normal limits, the size of the thyroid glands and also bone age were normal. The plasma concentrations of T4 and TSH and the response of TSH to TRH were no different during hypocalcemia from those obtained in normocalcemia during vitamin D treatment. Thyroxine treatment could normalize T4 and TSH. Moderate hypothyroidism is frequently present in pseudohypoparathyroidism. It has to be assumed that the same genetical defect of the second messenger, already proved to exist in the kidneys of patients with pseudohypoparathyroidism may also exist in the thyroid gland.     

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.     

Familial growth retardation with isolated thyroid-stimulating hormone deficiency

Three brothers with isolated thyroid-stimulating hormone (TSH) deficiency were observed at ages 17, 15, and 10 years. They suffered from severely retarded growth, with a marked retardation in bone maturation. Their serum T4, T3, and TSH levels were low. Serum thyrotropin-releasing hormone (TRH) concentration was normal. No increases in TSH levels were elicited during the TRH test. The other pituitary hormones, adrenocorticotropic hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin hormone, responded normally to stimulation. Thyroxin treatment triggered a growth acceleration. Genetic investigation revealed several instances of small stature on the father's side.     

Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings

Female patients with anorexia nervosa (a.n.) are characterized by distinct endocrine features probably due to hypothalamic pituitary dysfunctions. There is only a limited number of case reports available on patients with a.n.; mostly with few data on hormones. In six male patients with a.n. we examined basal and stimulation values of several hormones performing three pituitary function tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle stimulating hormone (FSH) after LHRH were low comparable to results in prepuberal boys. Similarly, testosterone levels in serum were also markedly reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in one patient and at the lower limit in two patients; concentration of free T4 was in the normal range, while five of six subjects had reduced total T3 concentration and two of six patients showed increased reversed T3 levels; TBG concentration was always in the normal range. Basal TSH was normal, while in two patients the TSH stimulation levels after TRH were diminished; in all patients the TSH stimulation levels were found to be delayed. The basal levels of growth hormone were normal, but the growth hormone response after insulin was diminished in four patients. In all six patients basal prolactin (PRL) and PRL concentration after TRH stimulation was in the normal range. The neuroendocrine results in the six patients with a.n. confirm in males a similar hypothalamic-pituitary dysfunction as it is already known for female patients.     

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 RESPONSE TO THYROTROPIN-RELEASING HORMONE IN FULLTERM, EUTHYROID AND HYPOTHYROID NEWBORNS

Abstract. The serum concentration of thyrotropin (TSH) and the TSH response following thyrotropin-releasing hormone (TRH) were studied in 16 euthyroid babies from 16 to 172 hours after birth and in 2 primary hypothyroid babies, 3 and 28 days of age. Serum-TSH was measured before an intravenous injection of 40 μug TRH and after 30 and 180 min. In the euthyroid babies increased basal levels of TSH were seen shortly after birth, followed by a pronounced decline. The extent of TSH increase after TRH could be correlated with the basal levels, and the relative increase was comparable to that which occurs in adults. In the hypothyroid babies very high basal levels of serum-TSH were seen, 125 and 400 μ/ml respectively, with no further increase following TRH stimulation. It was concluded that in euthyroid fullterm newborn, the relative response of serum-TSH to TRH was equal to that of adults, in spite of elevated thyroid hormone concentrations. In the hypothyroid newborn very high levels of serum-TSH were seen and a supplementary TRH-test seems without diagnostic value in congenital hypothyroidism.     

Endocrine activity in preterm and full-term lambs. 1. Adrenal response to synacthen. 2. Thyroid response to ovine thyroid-stimulating hormone or thyrotropin-releasing hormone

Neonatal endocrine status was studied in 14 lambs born 7 days before term, after estrogen injection into the ewes, and in 15 full-term animals. Plasma cortisol and triiodothyronine (T3) levels were depressed during the first hours of life in preterm lambs and plasma reverse T3 levels were significantly higher than in controls. The rise in plasma cortisol levels after Synacthen injection was significantly lowered by prematurity, suggesting reduced sensitivity of the adrenal cortex to ACTH. After ovine TSH injection, plasma thyroxine (T4) levels increased during a shorter period of time in preterm lambs, resulting in a lowered T4 rise; the T3 response was not affected by prematurity. After TRH injection, the rises in plasma T3 and T4 levels were significantly higher in preterm than in full-term lambs, suggesting a pituitary hypersensitivity to TRH linked to prematurity. Moreover it appeared that the response of reverse T3 to TSH or TRH was very weak.     

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.     

Normal values for circulating thyroid hormones, T3 uptake and thyrotropin before and after TRH. Radioimmunoassay determinations on 182 euthyroid children (author's transl)

Measurements of T4, T3, rT3, T3U, and TSH (before and after TRH stimulation) were performed by RIA. 182 children, apparently euthyroid, age 2/12--14 years, were investigated in a cross sectional study. Free T4RIA and free T3RIA Indices and the ratio rT3/T3 and T4/T3 were calculated. Statistical analysis showed the following results: 1. Geometric mean serum concentrations of T4, T3, rT3 and TSH (basal) show no age related differences; T4 showed a not significant negative slope with age.--2. The ratio rT3/T3 and T4/T3 remains constant.--3. TRH induced TSH release (indicating the activity of the regulatory system) is unchanged from 2/12 to 14 years. Geometric means values, standard deviations and normal ranges are given.     

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.     

Transient infantile hyperthyrotropinaemia. Report of a case.

A case of transient hyperthyrotropinaemia was found by mass screening for neonatal hypothyroidism using the paired TSH assay method. The patient was a baby boy born at term after a normal pregnancy who grew without any abnormal signs or symptoms. For the first 7 months after birth, his serum TSH was abnormally high while his total serum T4, T3, and free T4, T3 were within normal limits, exept for slightly low free T4 level at 7 months. The raised serum TSH decreased spontaneously to within normal limits after he was 9 months old.     

Pituitary function in 8 patients with familial pituitary dwarfism

Pituitary function was evaluated in four pairs of familial pituitary dwarfs (two sisters, 28 and 20 years old, two brothers 15 and 10 years old, one girl 19 years old and her brother 7 years old, and one girl 9 years old and her brother 3 6/12 years old), who all proved to have multiple pituitary hormone deficiency (MPHD), in order to find out whether a distinct intrafamilial or interfamilial pattern of deficiency existed. The response of FSH and LH to LRH, of TSH to TRH, of growth hormone (GH) to L-dopa, and of prolactin to sulpiride administration was studied. Basal levels of ACTH and cortisol (F) were also measured on two consecutive days. Basal FSH, LH and GH concentrations were below the sensitivity of the assay in all patients (except one who had measurable levels of LH) and showed no change after the appropriate stimulation. Basal TSH was normal in 6 patients and slightly increased in two members of the same family. Both these patients presented an exaggerated response to TRH. Three of the remainder patients showed a small and the other three no response to TRH. Basal prolactin values ranged within the normal limits, but prolactin was not increased during the sulpiride provocative rest. Mean basal ACTH was normal in 5 and low in 3 patients. Mean cortisol levels were normal in 5, near the lower normal limit in 2, and low in one patient. This patient had also a low ACTH concentration. It is concluded that the lack of a common pattern of hormone deficiency in all families indicates a variability in the expression of the hypothalamo-pituitary defect, which suggests that the familial MPHD dwarfism constitutes a genetically and pathogenetically heterogenous group.     

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.     

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.     

Peripheral insensitivity to thyroid hormones in a euthyroid girl with goitre.

A 9-year-old girl was euthyroid with a small goitre, exophthalmos, scaphocephalic skull, minor sketelal abnormalities, and raised serum thyroid hormone concentrations. Other members of the family did not have goitres and their thyroid hormone levels were normal. From age 3 years the patient was treated for Graves''s disease, but after 4 years treatment was stopped because of enlargement of the goitre. Despite increased serum thyroxine (T4), free T4 (FT4), and triiodothyronine (T3), basal serum TSH, and the TSH response to thyrotropin-releasing hormone (TRH) were normal. Pituitary refractoriness was present because full suppression of the TSH response to TRH was achieved only after daily administration of 500 micrograms thyroxine. Urinary excretion of hydroxyproline, and the activity of red cell glucose-6-phosphate dehydrogenase remained normal when excess T4 was administered, demonstrating the tissue resistance to thyroid hormones. Peripheral lymphocytes were found to have nuclear receptors for T3 with normal affinity, but the relatively low binding capacity indicated that the biochemical defect might be a deficiency of nuclear receptor protein. The findings in this patient differ somewhat from previously reported cases of peripheral resistance to thyroid hormones.     

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.     

Effect of long-term GH administration on pituitary-thyroid function in idiopathic hypopituitarism.

Twenty-four euthyroid children with idiopathic pituitary dwarfism were studied. The euthyroid state for seven of these patients was determined by negative physical examinations, normal plasma T4 assays and normal 131I uptakes. For the other children, thyroid function was evaluated with T3 and T4 assays and on the basis of the TRH test. Each of the children was treated with HGH in one of three different ways. The first group (five cases) was given a HGH dose, ranging from 12.4 to 17.2 IU/m2//week. The second and third groups (nine and ten cases, respectively) were treated with 10 and 20 IU/m2/week, respectively. Treatment was carried out for periods ranging from 6 months to 6 years. After no less than 6 months of treatment, and at intervals of 6 months (or some multiple of 6 months) plasma T3 and T4 assays, as well as a TRH test were performed in each patient. In some patients one of the indices was once beyond the upper or lower limit of the normal range (none of the children presented simultaneous abnormal levels of more than one index during the controls). This value, however, returned to within normal limits at the following control. There was no correlation between T3, T4 and TSH with the duration of HGH therapy. There was no significant difference between the groups of children treated with the different HGH doses. These data seem to demonstrate that the risk of inducing an alteration in thyroid function in hypopituitary patients during HGH treatment is very slight, and that the irregularly abnormal thyroid indices observed in some of the children during one of the controls might be an expression of their metabolic status at that moment.     

Pituitary function and growth in children under treatment for leukemia (author's transl)

The effect of cranial irradiation with doses of 2,400 and 4,800 rad on the pituitary function of children with acute lymphoblastic leukaemia was studied. The plasma growth hormone level after arginine simulations was normal in 13 out of 15 children. The rise of TSH after TRH stimulation and the metyrapone test were also normal. The growth of 40 children during an observation period of 3 or more years was also normal.     

Significance of transient postnatal hypothyroxinemia in premature infants with and without respiratory distress syndrome

The significance of relatively low thyroxine (T4) levels in preterm infants with and without respiratory distress syndrome (RDS) was assessed by evaluating the free T4 level, the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH), and intellectual development in infants less than or equal to 35 weeks with cord blood T4 concentrations less than 6.5 microgram/100 ml. Fifty-four (19 well, 28 with RDS, and seven without RDS and sick) of 215 premature infants (25%) and 27 of 8,831 term infants (0.3%) had cord T4 levels less than 6.5 microgram/100 ml. Serum T4 levels were measured in 39 surviving preterm infants (20 RDS and 19 well) during the first 5 days of life and at 2, 4, 24, and 52 weeks postnatally. Serum total T4 level during the first week was 4.5 +/- 0.3 microgram/100 ml (mean +/- SEM). Free T4 levels ranged from 1.1 to 2.2 ng/100 ml (normal adult range 0.8 to 2.3 ng/100 ml). Administration of TRH resulted in a clear increase in both TSH and T4 levels in all infants. T4 levels increased significantly (r = .70, P less than .01) with increasing postnatal age, reaching stable levels by 6 to 7 weeks. Developmental quotients obtained in the infants with low T4 levels were no different from those found in a matched control population at 12 months of age. The low T4, free T4, and TSH concentrations and normal TSH responses to TRH found in these infants are characteristic of hypothalamic (tertiary) hypothyroidism, but differ from classic tertiary hypothyroidism in that the disorder was transient. The normal intellectual development at 12 months of age and the spontaneous increase in T4 levels that occurs over the first six weeks of life suggest that the low T4 levels in these infants reflect a benign relative delay in maturation of hypothalamic-pituitary-thyroid control.     

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.