Neonatal hyperthyroidism in a premature infant born to a mother with Grave's disease]

BACKGROUND: Neonatal thyrotoxicosis is most commonly due to transplacental transfer of maternal thyroid-stimulating hormone receptor antibodies (TRAb). Bioassay of thyrotropin receptor antibodies may help to determine the risk for neonatal hyperthyroidism. CASE REPORT: Thyrotoxicosis developed in a premature infant born to a mother with Graves' disease, with a low level of TRAb by bioassay. The infant was treated with carbimazole for two months, until TRAb had disappeared. CONCLUSION: Bioassay TRAb is not always reliable for predicting the development of neonatal hyperthyroidism in infants born to mothers with Graves' disease. Thyroid function should be measured in all these neonates.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.     

Elevated thyroid-stimulating hormone level in a euthyroid neonate caused by macro thyrotropin-IgG complex

Elevated thyroid-stimulating hormone (TSH) was discovered by routine neonatal screening in a newborn with no clinical symptoms. Thyroid function tests were repeated and confirmed a high TSH value but normal total thyroxine (T4) and triiodothyronine (T3). However, the mother also had elevated serum TSH with normal levels of T4 and T3. The results suggested a transmitted maternal interfering factor, and no treatment was started while further investigation was performed. Gel filtration chromatography of serum from both the infant and the mother showed a peak TSH with molecular mass consistent with a TSH-IgG complex (macro-TSH). TSH in the infant decreased to a normal level within 8 months in accordance with a normal rate of elimination of maternal IgG, whereas the TSH level of the mother remained high. CONCLUSION: This case suggests that interfering macro-TSH should be considered in a euthyroid neonate with elevated serum TSH and normal T4 and T3 levels to avoid unnecessary treatment.     

母亲干燥综合征致新生儿自身免疫性溶血性贫血一例

患儿男,出生12h,于2004年3月18日以“反复呕吐12小时、皮肤黄染5h”为主述入院。患儿系第四胎,第一产,孕38^ 3周,剖宫产儿。Apgar评分：1min9分。5min10分,出生体重2700g,羊水清,脐带无异常。生后反复呕吐数次,生后7h皮肤开始出现黄染。其母亲为干燥综合征(Sjogren’s syndrome,SS)患者,前三胎均流产。     

Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery

Appropriate methimazole dosing for initial treatment of childhood Graves' disease is uncertain. A retrospective chart review was performed on 5 to 17 year-old children treated for Graves' disease. Patients were divided into two groups depending on initial methimazole dosing: low-dose and high-dose regimens using <0.5 mg/kg/day and >0.5 mg/kg/day, respectively. The low-dose regimen was effective in 5/12 (42%) of patients and the high-dose regimen was effective in 27/33 (82%) of patients (p = 0.016). There was also a statistically significant dose/time interaction for levels of free thyroxine (T4) (p = 0.025). During treatment, 63.3% of diagnosable samples showed unambiguous hyperthyroidism or triiodothyronine (T3) toxicosis, 16.7% elevated free T3 with normal free T4 and T3 levels, indicating borderline hyperthyroidism, and 20% showed thyroid-stimulating hormone (TSH) suppression with normal or low levels of free T4 and free T3, indicating delayed recovery of pituitary TSH secretion. Free T3 levels combined with concurrent TSH levels permit differentiation of mild hyperthyroidism from delayed pituitary recovery.     

Progressive hypogammaglobulinaemia in a child born to a mother with Hodgkin's disease.

A young woman developed Hodgkin's disease (nodular sclerosis) in pregnancy and gave birth to a boy who developed common variable immunodeficiency. Initially there was normal IgG with low IgA and IgM, and antibody deficiency. IgG levels fell progressively over 4 years. Cellular immunity was normal. We suggest that this is a further family with immune deficiency presenting with common variable immunodeficiency and lymphoid malignancy.     

Neonatal hyperthyroidism: neonatal clinical course of two brothers born to a mother with Graves-Basedow disease, before and after total thyroidectomy

BACKGROUND: About 1-2% of infants born to mothers with Graves' disease or Hashimoto's thyroiditis develop neonatal hyperthyroidism because of transplacental passage of IgG stimulating TSH receptors (TRAb). OBJECTIVE: To evaluate the effect of maternal total thyroidectomy on neonatal clinical course. METHODS: We describe two brothers born to a mother with Graves' disease, before and after total thyroidectomy. RESULTS: The first child showed persistent tachycardia, the presence of TRAb and a laboratory pattern of hyperthyroidism. Lugol's solution was started and then propylthiouracil was added. Digitalis, furosemide and diazepam were necessary for treatment of heart failure, hypertension and irritability. On the 70th day of life, hormone serum levels normalized and treatment was interrupted. TRAb normalized by the third month of life. The second infant was born 2 years after the mother underwent total thyroidectomy. In spite of a laboratory pattern of hyperthyroidism and positivity to TRAb, he showed only considerable weight loss, and no therapy was required. CONCLUSIONS: TRAb may persist after total thyroidectomy: clinical and instrumental follow-up of the newborn is recommended.     

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.     

Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura

Abstract Neonatal thrombocytopenia related to maternal idiopathic thrombocytopenic purpura (ITP) is reportedly uncommon but may have severe complications. The present report reviews records of 15 infants born to mothers with ITP during a 10-year period, and the incidence of neonatal thrombocytopenia and the risk of hematological complications is examined. Severe thrombocytopenia (platelets < 50 000/μL) was seen in three infants despite successful therapy with high-dose gamma globulin prior to delivery, which elevated maternal platelet counts. Although the platelet counts of these three infants fell to < 10 000/μL, none had severe complications. Moreover, no infants required treatment such as adrenocorticosteroids, platelets transfusion, or high doses of gamma globulin. No maternal markers predicted the degree of neonatal thrombocytopenia. The risk of complications arising from neonatal thrombocytopenia is low, but careful observation is required for the thrombocytopenic newborn of ITP mothers even when the infant has no bleeding complications at delivery.     

Features of Antley-Bixler syndrome in an infant born to a mother with pregnancy luteoma

We report a female newborn with characteristic signs of Antley-Bixler syndrome (ABS) such as midface hypoplasia, radiohumeral synostosis and multiple joint contractures. The newborn also presented ambiguous genitalia, stage Prader V, and congenital adrenal hyperplasia. The mother experienced midterm virilization due to a pregnancy luteoma. Her elevated androgen levels and virilization symptoms normalized post partum without treatment. The newborn had elevated serum testosterone and 17-OH-progesterone levels which remained elevated because of a 21-hydroxylase deficiency. The child's treatment in order of priority was: hydrocortisone substitution, craniofacial/skeletal anomaly management and surgical correction of the external genitalia. Mutations in the genes for fibroblast growth factor (FGF) 8 and receptors FGFR1, FGFR2, and FGFR3 were not detected. Conclusion A newborn girl with manifestations of the Antley-Bixler syndrome showed severe virilization probably caused by the association of a mild 21-hydroxylase deficiency and maternal hyperandrogenism due to a pregnancy luteoma. Abnormalities of androgen metabolism may be responsible for virilization reported in other cases of the Antley-Bixler syndrome. Received: 14 May 1999 / Accepted: 3 August 1999     

Immunoglobulin levels and lymphocyte response to mitogenic stimulation in children with malignant disease during treatment and follow-up

Intensification of chemotherapeutic regimens has improved survival in childhood malignant disease. To characterize the impact of this intensified therapy on some aspects of the immune system, we have, in an unselected material of 220 children with malignant disease, investigated serum immunoglobulin levels and lymphocyte response at diagnosis and then subsequently during and up to 4 years after cessation of therapy. In leukemia and Hodgkin's disease, all immunoglobulin isotypes decreased during therapy. A profound depression of immunoglobulin M levels, lasting well after completion of therapy, was seen in all tumor types. The mitogenic response was attenuated in patients with leukemia at diagnosis but was rapidly restored after institution of therapy. Patients with solid tumors, particularly Hodgkin's disease, had a reduced mitogenic response during therapy. Thus these patients exhibit multiple immunological disturbances. The basis of the pronounced immunoglobulin M deficiency remains unclear.     

Successful treatment of MYCN amplified, progressive stage 4S neuroblastoma in a neonate with hepatic artery embolization in addition to multimodality treatment

Stage 4S metastatic neuroblastoma (NB) has a favorable prognosis due to a high rate of spontaneous regression. Young infants risk lethal complications arising from hepatomegaly, which can develop rapidly despite treatment. MYCN oncogene amplification confers a significantly worse prognosis. We describe a 4-week-old neonate with MYCN-amplified stage 4S NB complicated by gross hepatomegaly causing rapidly progressive respiratory, hepatic, and renal failure. The child remains in remission 3 years after hepatic artery embolization, radiotherapy, standard, and high-dose chemotherapy. Embolization of the hepatic artery, with classical treatment, is feasible and safe at this age and may contribute substantially to the management of high-risk patients.     

Arm span, serum IGF-1 and IGFBP-3 levels as screening parameters for the diagnosis of growth hormone deficiency in patients with myelomeningocele – preliminary data

Short stature is a common problem in patients with myelomeningocele (MMC) and hydrocephalus. We evaluated auxological and laboratory parameters to differentiate short stature due to neurological defect from short stature additionally caused by growth hormone deficiency (GHD). In a group of 38 prepubertal patients with MMC and hydrocephalus aged 3.8–11.0 years, auxological parameters, including arm span and bone age, and serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Patients with normal supine length (n = 15) had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal (≥ 10th percentile) in 14/15 patients. Twenty-three MMC patients had short stature (height SDS < −2), 11/23 patients had reduced arm span (SDS < −2), and 12/23 had normal arm span. Serum IGF-1 and IGFBP-3 levels were normal in 10/12 of short statured patients with normal arm span, but low (<10th percentile) in those patients with reduced arm span (IGF-1: 8/11 patients, P<0.05; IGFBP-3: 9/11 patients, P<0.005). In 7/11 short statured MMC patients with reduced arm span and low serum IGF-1 and IGFBP-3 levels, growth hormone secretion was investigated. All had a disturbed growth hormone secretion (GHD: n = 4; neurosecretory dysfunction: n = 3). Conclusion Arm span, serum IGF-1 and IGFBP-3 levels are estimated to be appropriate screening parameters for GHD in patients with MMC. Initiating growth hormone therapy should be considered not only according to endocrine findings but also with respect to neurological and orthopaedic anomalies. Received: 27 March 1997 / Accepted: revised form 18 September 1997     

Growth hormone and insulin-like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

OBJECTIVES: Despite improved supportive care, the mortality of sepsis and septic shock is still high. Multiple changes in the neuroendocrine systems, at least in part, are responsible for the high morbidity and mortality. A reduced circulating level of insulin-like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and septic shock in adults. The aim of this study was to evaluate the changes of growth hormone/insulin-like growth factor 1 axis in sepsis and septic shock and investigate the relationship between these hormones and survival. METHODS: Fifty-one children with sepsis (S), 21 children with septic shock (SS) and 30 healthy, age- and sex-matched children (C) were enrolled in this study. Growth hormone, insulin-like growth factor 1 and cortisol levels of the sepsis and septic shock groups were obtained before administration of any inotropic agent. RESULTS: Growth hormone levels were 32.3 +/- 1.5 microIU/mL (range 4-56), 15.9 +/- 0.6 microIU/mL (range 11-28) and 55.7 +/- 2.7 microIU/mL (range 20-70) in S, C and SS groups, respectively. The difference between the growth hormone levels of the S and C groups, S and SS groups, and C and SS groups were significant (P < 0.001). Non-survivors (54.7 +/- 1.6 microIU/mL) had significantly higher growth hormone levels than survivors (29.4 +/- 1.5 microIU/mL) (P < 0.001). Insulin-like growth factor 1 levels were 38.1 +/- 2.1 ng/mL (range 19-100), 122.9 +/- 9.6 ng/mL (range 48-250) and 22.2 +/- 1.9 ng/mL (range 10-46) in the S, C and SS groups, respectively, and the difference between the insulin-like growth factor 1 levels of the S and C, S and SS, and C and SS groups were significant (P < 0.001). Non-survivors (8.8 +/- 1.1 micro g/dL) had significantly lower cortisol levels than survivors (40.9 +/- 2.1 microg/dL) (P < 0.001). We detected a significant difference between the levels of cortisol in non-survivors (19.7 +/- 1.8 microg/dL) and survivors (33.9 +/- 0.9 microg/dL) (P < 0.01). CONCLUSIONS: There were elevated levels of growth hormone with decreased levels of insulin-like growth factor 1 in children during sepsis and septic shock compared to healthy subjects. In addition, there were even higher levels of growth hormone and lower levels of insulin-like growth factor 1 in non-survivors than in survivors. We think that both growth hormone and insulin-like growth factor 1 may have potential prognostic value to serve as a marker in bacterial sepsis and septic shock in children. As there is insufficient data in the paediatric age group, more studies including large numbers of patients and additionally evaluating cytokines and insulin-like growth factor binding proteins are needed.     

川崎病患儿血清中基质金属蛋白酶-9及其组织抑制物-1的变化

目的评价基质金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)在川崎病(KD)发病机制中的作用。方法采用酶联免疫吸附法(ELISA)检测33例KD患儿治疗前后血清MMP-9及TIMP-1的含量,并设置无热、发热对照组;同时检测KD患儿外周血中性粒细胞计数、C反应蛋白(CRP)等指标。结果KD组患儿急性期MMP-9血清水平较对照组升高,合并冠脉损害(CAL)者尤甚,治疗后降至正常;MMP-9的升高与外周血中性粒细胞计数、CRP呈正相关;KD患儿无论是否合并CAL,其急性期TIMP-1血清水平均高于对照组,治疗后虽有所下降,仍较对照组高;MMP-9/TIMP-1比值在KD组急性期与对照组差异无统计学意义,治疗后较无热对照组降低,与发热对照组差异无统计学意义。结论MMP-9作为一种损害因素参与了川崎病的病理生理过程,而TIMP-1可抑制其作用;MMP-9的水平可反映KD的严重程度。     

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-IL serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance. Finally, IGF-I administration suppresses GH secretion.