Effect of perinatal factors on cord blood thyroid stimulating hormone levels

OBJECTIVE: To study the influence of perinatal factors on cord blood (CB) TSH levels. INFANTS AND METHODS: In a prospective cross-sectional study, CB TSH levels were measured in 1,590 live-born infants using IRMA. The effect of various perinatal factors on the CB TSH levels was analyzed statistically. RESULTS: The mean TSH level in the study group was 10.6 +/- 6.7 microU/ml (range 0.01-66.4 microU/ml). A significant fall in CB TSH levels was noted with increasing gestational age. A similar decline was noted in TSH levels with increase in birth weight. No significant difference in TSH levels was noted between males and females, or AGA and SGA (n = 296) infants. Infants with birth asphyxia (Apgar score < 4 at 5 min) had significantly higher CB TSH levels (mean 31 microU/ml, n = 18) as compared to those without (mean 10.4 microU/ml) (p < 0.01). The highest TSH levels were noted in neonates delivered by forceps extraction (mean 29.4 microU/ml, n = 17) and lowest levels in infants born by elective Caesarian section (mean 8.7 microU/ml, n = 149). CONCLUSION: CB TSH levels fall with increase in gestational age while birth asphyxia and difficult deliveries tend to elevate them.     

Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism.     

A mutation in thyroid hormone receptor beta causing "resistance to thyroid hormone" in a neonate

Resistance to thyroid hormone (RTH) is an inherited syndrome characterized by reduced tissue responsiveness to thyroid hormones. The main defects are due to mutations in thyroid hormone receptor beta (TRbeta). A male, term neonate was admitted because of indirect hyperbilirubinemia and polycythemia. Physical examination revealed ophtalmopathy. High serum T? with unsupressed thyroid stimulating hormone (TSH) levels suggested RTH. In this presented case, A317T mutation was detected on exon 9 of the TRb-1 gene and precise diagnosis had been confirmed with genetic testing. In neonates and infants exhibiting hypo or hyperthyroidism features with increased circulating levels of thyroid hormones with a normal or increased serum TSH concentration should raise the suspicion of RTH.     

标准化脐血筛选方法在脐血库中的应用

目的对广州脐血库脐血筛选结果进行回顾性分析,建立脐血筛选的标准化方法和探讨其在脐血库建立中的意义。方法对脐血供者从产妇或其旁系亲属医学病史到新生儿随访实行四步筛选程序,筛选内容包括遗传、血液病等病史、脐血采集量、总有核细胞数、细胞活率、凝块和病原学感染等。结果1998年6月至2004年12月共分娩27404例、采集脐血8350份,占总分娩量比率为30.47%。合格4085份,合格率为48.92%;废弃脐血4265份(占51.08%),废弃的主要原因依次为脐血采集量<60ml、血凝块、总有核细胞数、活率低。检疫期共废弃脐血46份(占1.11%);其中检出细菌阳性19例(占41.30%),巨细胞病毒抗体(CMV-lgM)阳性20例(占43.48%)。新生儿随访共发现15例异常,占0.37%。4085份脐血总有核细胞数平均为1.21×109,根据脐血有核细胞输入量3.7×107/kg体重计算,平均能适合32.7kg的受者移植;而按2.0×107/kg体重计算平均能适合60.5kg的受者移植。104例脐血移植中72例获得植入(69.2%)。结论脐血供者的标准化筛选方法可以排除可能存在的血液性、遗传性和传染性等疾病,确保移植用脐血的安全;并能为脐血库的建立节约采集、处理、冻存等费用,提高库存脐血的有效利用率。     

Growth and development in a child with resistance to thyroid hormone and ectopic thyroid gland

Resistance to thyroid hormone is an uncommon problem, which has rarely been associated with thyroid dysgenesis. We report a case with both thyroid gland ectopy and resistance to thyroid hormone and, thus, a reduced capacity to produce and respond to thyroid hormone. The patient presented at 2 years of age with developmental delay, dysmorphic features, and elevation in both thyroxine and thyrotropin. We document her response to therapy with thyroxine, with particular regard to her growth and development. Persistent elevation of thyrotropin is commonly recognized during treatment of congenital hypothyroidism. Resistance to thyroid hormone may be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated.     

Resetting the detection level of cord blood thyroid stimulating hormone (TSH) for the diagnosis of congenital hypothyroidism

An appraisal of a 17-year primary thyroid stimulating hormone (TSH) screening programme for the detection of congenital hypothyroidism was carried out to establish the reference interval of cord blood TSH in unaffected infants; the mean cord blood TSH concentration of affected infants and the incidence of congenital hypothyroidism in the Najran province of Saudi Arabia. Our findings show a reference interval of cord blood TSH of 2.0-16.8 mU/l in unaffected infants; a mean cord blood TSH concentration of 399 mU/l in affected infants; a false positive rate for the diagnosis of at-risk infants of 1.02% and a congenital hypothyroidism incidence rate of 34/100 000 (1 : 2931) live births. These findings suggest that there is a need to reset the cord blood TSH concentration for the detection of at-risk infants. We suggest that the detection level of cord blood TSH for the recognition of at-risk infants can be set at 90 mU/l rather than the recommended level of 30 mU/l. This should reduce the false positive rate for detection of infants at risk of congenital hypothyroidism.     

Levels of growth hormone and growth-hormone-releasing factor in cord blood

In order to evaluate the mechanism of high growth hormone (GH) secretion in perinatal life, the levels of GH and growth-hormone-releasing factor (GRF) in cord blood were determined. Plasma-immunoreactive GRF was measured by a double antibody RIA method. The levels (mean +/- SD) of GH, GRF and somatostatin (SRIF) were 23.4 +/- 10.2 ng/ml, 49.5 +/- 11.7 and 41.5 +/- 10.4 pg/ml, respectively; they were remarkably higher than those of healthy adults. In statistical analysis, there were no significant relationships among the levels of GH, GRF or SRIF. We speculate that a high GRF release from the hypothalamus might increase the secretion of GH in the perinatal period.     

Case report: thyroid hormone resistance and its therapeutic challenges

Thyroid hormone resistance occurs when a genetic mutation in the thyroid hormone receptor leads to reduced hormone binding affinity; the concentration of free thyroid hormone in the circulation is inversely correlated with the hormone binding affinity of the mutant receptor. Thyroid hormone resistance mutations are associated with a wide variety of phenotypes and subsequent treatment challenges. Among the more common symptoms are hyperactivity, emotional lability, a below average intelligence quotient, and short stature. We report here a patient who presented with thyroid hormone resistance at an early age, providing an opportunity to optimize her overall growth and development. We review the limited information currently available in the literature addressing the treatment of thyroid hormone resistance in children and describe the approach used to determine the treatment plan in this young child.     

Treatment of pituitary resistance to thyroid hormone (PRTH) in an 8-year-old boy

We report on an 8-year-old boy with pituitary resistance to thyroid hormone (PRTH) having a cysteine for arginine substitution at codon 320 in the TR-β gene who was presented because of thyrotoxicosis. Due to its suppressive effect on the pituitary thyrotropin secretion, treatment with u-thyroxine (D-T4) was started. After a few days, clinical euthyroidism was achieved but thyroid stimulating hormone secretion was not suppressed. Symptoms of thyrotoxicosis relapsed when therapy was interrupted so that therapy with D-T4 was reinstituted and continued to date. Symptoms did not recur, and the psychomotor development proceeded normally. D-T4 should therefore be considered in the treatment of thyrotoxicosis in PRTH.     

Effect of thyroid hormone level on temperament in infants with congenital hypothyroidism detected by screening of neonates

To determine the effect of congenital hypothyroidism and its treatment on infant behavior, we assessed temperament in 50 six-month-old infants with congenital hypothyroidism detected by means of screening of neonates. Intelligence and temperament were also evaluated at 12, 18, 24, and 36 months. More of these children were classified as "difficult" than children in the nonhypothyroid standardization sample. Temperamental difficulty was associated with increased nervous system sensitivity, reflecting more intense responses and a lower threshold of response to external stimulation. Greater temperamental difficulty was found to persist until at least age 2 years of age and to be associated with higher circulating triiodothyronine and thyroxine levels between 1 and 3 months of age. Our results suggest that behavioral features should be considered, as well as circulating hormone levels, in determining the proper dose of thyroid hormone replacement in infants with congenital hypothyroidism.     

Thyroid dyshormonogenesis: severe hypothyroidism after normal neonatal thyroid stimulating hormone screening

We report four children who presented no evidence of primary hypothyroidism in the neonatal period, either clinically (normal growth velocity) or biochemically (normal plasma levels of thyroid stimulating hormone and/or thyroid hormone). However, in early childhood, these children developed severe hypothyroidism due to dyshormonogenesis. We conclude that apparently normal thyroid function in the neonatal period does not preclude the development of severe hypothyroidism due to thyroid dyshormonogenesis later in childhood.     

Familial partial peripheral and pituitary resistance to thyroid hormone: a frequently missed diagnosis?

The diagnosis of partial peripheral and pituitary resistance to thyroid hormone was ultimately made in two boys, 7 and 9 years of age, and a 10-year-old girl who had goiters and hyperthyroxinemia. The boys were treated with propythiouracil and/or thyroidectomy or iodine 131 for suspected thyrotoxicosis but had poorly suppressible serum thyroid-stimulating hormone (TSH) post treatment in spite of the usual L-thyroxine replacement. The girl had increasing goiter size while receiving propylthiouracil, 100 mg every eight hours. These findings led to reevaluation of thyroid hormone dynamics in these children and their families. Twelve additional family members, 3 to 38 years of age, compatible with an autosomal dominant inheritance, were also found to have peripheral and pituitary resistance to thyroid hormone. All affected individuals had elevated serum thyroxine and triiodothyronine levels, normal to slightly elevated triiodothyronine resin uptakes, and a nonsuppressed serum TSH. The five individuals who were given thyrotropin-releasing hormone showed exaggerated TSH responses, which normalized on L-thyroxine therapy. Misdiagnosis in six of 15 family members led to significant morbidity (hypothyroidism, delayed growth, and therapy risk). A nonsuppressed serum TSH in a patient with suspected thyrotoxicosis should lead to suspicion of this disorder. Appropriate management for this condition includes L-thyroxine therapy to decrease goiter size and normalize TSH responses to thyrotropin-releasing hormone.     

Cytochemical bioassay of parathyroid hormone in maternal and cord blood.

Parathyroid hormone and calcium were measured in plasma taken from pregnant women at term and from the umbilical veins of their infants at birth. Three assays were used to measure parathyroid hormone, a cytochemical bioassay of bioactivity and two immunoradiometric assays, one specific for the amino terminus, the other specific for the carboxy terminus of the parathyroid hormone molecule. Plasma calcium was significantly higher in the infants than in the mothers. Maternal parathyroid hormone bioactivity and the amino terminus were both slightly raised, but the carboxy terminus value was normal; these findings supported the view that late pregnancy is a time of mild physiological hyperparathyroidism. In the infants, the amino terminus was undetectable and the carboxy terminus was either undetectable or towards the lower end of the normal range: bioactivity of parathyroid hormone was considerably raised and was related to the gradient of calcium across the placenta. This suggests that the parathyroid glands are not suppressed during fetal life and that they may play an important part in the maintenance of high fetal plasma calcium concentrations.     

Multihormonal resistance to parathyroid hormone, thyroid stimulating hormone, and other hormonal and neurosensory stimuli in patients with pseudohypoparathyroidism

In patients with pseudohypoparathyroidism, hormonal resistance first affects parathyroid hormone (PTH), which leads to calcipenia, a decrease in renal vitamin D activation, and a tendency to bone receptor remodeling. However, because G proteins are ubiquitously distributed, multiple hormonal resistance occurs in pseudohypoparathyroidism type Ia and type Ic, impairing responses to other calciotropic hormones (PTHrP, calcitonin), TSH, and also pituitary and hypothalamic hormones, and to neurosensory stimuli. The diversity of multihormonal resistance contributes to the various phenotypes of the disease. Some clinical discomfort and medical consequences of the disease can be treated or prevented with hormone supplementation or modulation.     

Regional mucoviscidosis screening using immunoreactive trypsin in umbilical cord blood]

In all neonates delivered at the Steyr Landeskrankenhaus from 1987 to 1989, immunreactive trypsin (IRT) in the umbilical cord blood was determined to enable early diagnosis of mucoviscidosis (cystic fibrosis, CF). Amongst 4,507 neonates 75 were found in whom the IRT was over the cut-off value of 1,204 ng/ml. Of these babies, 69 were presented at the age of six weeks for determination of elecrolytes in their sweat. Mucoviscidosis could be diagnosed in two patients. The sensitivity of our test is likely to be 100%. There is no question that the specificity (98.38%) requires improvement. The incidence of mucoviscidosis in our catchment area is 1: 2,254. The hypertrypsinemia detected was probably transient in 73 babies. Ten of these patients showed a one-minute Apgar score of less than seven.     

Immunoreactive ghrelin in human cord blood: relation to anthropometry,leptin, and growth hormone

BACKGROUND: Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone-secreting and orexigenic properties. Leptin is secreted mainly by the adipocyte, plays a major role in energy balance, and reflects fat mass in infants as well as adults. Leptin and ghrelin central effects are mediated, at least partly, through the neuropeptide Y/Y1 receptor pathway in the hypothalamus. METHODS: We determined whether ghrelin is also present in the fetus and investigated its relationship to leptin, growth hormone, birth weight, and calf and abdominal circumferences in 90 full-term neonates. RESULTS: Immunoreactive ghrelin was detected in all cord samples (mean +/- SD, 187 +/- 88 pmol/L; range, 66-594 pmol/L). In contrast to leptin, ghrelin concentrations of boys and girls were not statistically different. In female neonates, ghrelin is inversely correlated with anthropometric measures. In male neonates, ghrelin is positively correlated with leptin and negatively with growth hormone. CONCLUSION: The presence of significant ghrelin concentrations in all neonates before the first feeding is intriguing. Unlike the fairly constant concentrations and effects of leptin over the short term, the wide variability of ghrelin concentrations observed in newborns raises the possibility that ghrelin secretion causes short-term changes in feeding behavior. We suggest that ghrelin may play a physiologic role in the initiation of feeding.     

Growth hormone-releasing hormone. Studies in cord blood from term human newborns

Plasma growth hormone-releasing hormone (GHRH) was measured by radioimmunoassay in the cord blood from 32 healthy human newborns after 38-41 weeks of gestation. All were born by uncomplicated vaginal delivery. The GHRH levels in cord blood were 78.33 +/- 8.35 pg/ml at 40 weeks of gestation, approximately threefold higher than the levels at 38 weeks of gestation (27.00 +/- 2.55 pg/ml). No significant differences were found between girls and boys. The rise of plasma GHRH levels in cord blood of the full-term newborns between 38 and 40 weeks of gestation suggests a role of this peptide in the neonatal growth regulation.     

Metabolic and cardiovascular responses to exogenous triiodothyronine favour nontreatment of a girl with familial receptor-positive thyroid hormone resistance

A father and daughter with inappropriate TSH secretion due to generalized relative receptor-positive thyroid hormone resistance are described. Minor variations of tissue peripheral resistance were observed in the adolescent girl. Shortened ankle reflex relaxation time and other clinical signs were consistent with a mild hyperthyroid state of the neuromuscular unit. The response of sex hormone-binding globulin concentration, 24 hour-ECG data and left ventricular echocardiographic parameters to increasing doses of triiodothyronine confirmed an euthyroid state of heart and liver tissue in the presence of excess thyroid hormone. Based on these findings and the benign course of the disease, treatment was withheld. Careful assessment, including echocardiography and 24 hour-ECG, of the functional state of thyroid hormone target tissues during triiodothyronine administration is recommended in these patients. No treatment is required when the functional state of the target tissues is eumetabolic.