Pseudohypoparathyroidism in a mother and son: Phenotypic variability and associated disorder

A 2-month-old infant with clinical features of hypothyroidism presented with hypocalcemic seizures. The maternal phenotypic features aroused the suspicion of pseudohypoparathyroidism which was confirmed in both by biochemical and endocrinological investigations. Though the child had clinical and radiological features to suggest hypothyroidism he had normal free thyroxine and only slightly elevated thyroid stimulating hormone levels. Special note is made of the intra and interpatient variability of this rare inherited disorder.     

Thyroid function and dysfunction in premature infants

During the past four decades major advances in the management of premature infants have led to progressive reduction in mortality. During this period mortality in very low birth weight infants (VLBW, <1500 grams and <30 weeks gestation age) has decreased, and more than 50% of infants less than 24 weeks gestation age now survive, increasing the population of VLBW infants in intensive care nursery environments. Thyroid function in these infants is characterized by decreased TSH and T4 responses to parturition, low serum total T4 and TSH levels and variable free T4 concentrations during the first 2-4 postnatal weeks of life. These features reflect a state of transient hypothalamic-pituitary or central hypothyroidism. There is a high prevalence of morbidity in these infants, as well, often associated with further reductions in serum total T4, T3, TBG and TSH concentrations and variable levels of free T4 and reverse T3, resembling the non-thyroidal illness (NTI) syndrome in adults. The etiologic roles of thyroid system immaturity and NTI in the transient hypothyroxinemia of prematurity (THOP) and the impact of THOP on the subsequent neurological deficits in VLBW infants remains unclear. Several thyroxine supplementation trials have been conducted with inconclusive results. Further studies are planned or in progress.     

Hyperthyroxinämie mit kardialer Symptomatik

Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited disease, which is usually caused by mutations in the TRβ-gene. The clinical presentation of RTH is highly variable and patients can show signs of euthyroidism, hypothyroidism and/or hyperthyroidism. We report on a 12¹¹/₁₂ year old girl who was admitted to hospital with tachycardia. Laboratory tests showed high levels of serum free T3 and free T4 in the presence of non-suppressed TSH concentrations. Further investigations, including molecular genetic tests, were then performed and revealed a rare case of thyroid hormone resistance. Our case report demonstrates that patients with RTH may manifest only cardiovascular symptoms.     

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.     

Thyroid function and serum prolactin levels in patients with juvenile systemic lupus erythematosus

OBJECTIVE: To evaluate both thyroid function and serum prolactin levels in patients with juvenile systemic lupus erythematosus (JSLE) and to detect possible correlation with disease activity. METHODS: Forty-two JSLE patients (3-15 years old at disease onset), twenty-two pubertal. All patients were evaluated according their clinical manifestations and disease activity. We determined serum prolactin, thyroid-stimulating hormone (TSH), T4, free T4, T3, thyroid peroxidasis and thyreoglobulin antibodies in all patients and controls. Thyroid ultrasonography was performed in the patients. RESULTS: We did not observe any difference in thyroid hormone and prolactin levels between patients and controls. One patient with JSLE presented with hyperthyroidism and six had thyroid antibodies. We observed abnormalities by ultrasonography in four patients (9.3%), specially heterogeneity of the gland echotexture. We did not find any correlation between prolactin levels, clinical manifestations or disease activity. CONCLUSIONS: Evaluation of thyroid function should not be routine for JSLE patients. Thyroid hormones and prolactin should be measured only in patients with clinical manifestations of hypo- or hyperthyroidism.     

Endocrine function in thai children infected with human immunodeficiency virus

Most children infected by HIV show manifestations which mimic the clinical features of endocrine dysfunction, such as failure to thrive and hyperpigmentation. Our cross-sectional study was designed to assess the endocrine function of Thai children infected with HIV and to determine any relationship between disease severity, height and endocrine function. Thirty-six prepubertal children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/- 2 years), were tested for thyroid function (serum T4, T3, TSH and free T4), morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T-lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five patients had euthyroid sick syndrome. Thyroid function tests indicated another five patients had a condition compatible with compensated hypothyroidism. Most patients had normal morning serum cortisol levels. Two-thirds and one-third of the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS), respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were classified as severely immune suppressed. A weak linear relationship was indicated between disease severity and endocrine function (r = -0.03 to 0.41). Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3 SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively. Nearly half (44%) the patients were below the third percentile for height of Thai children. There was also a weak correlation between height SDS and endocrine function (r = -0.03 to 0.41). Statistical significance was observed between height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01, respectively). We conclude that HIV-infected children with demonstrated growth failure and greater disease severity tend to have abnormal endocrine function, particularly disordered IGF-I levels.     

Thyroid Hormone Resistance in children

Thyroid Hormone Resistance (RTH) is characterized by the diminished response of thyroid hormone-responsive tissues in varying degrees in association with elevated serum levels of total and free T4 and T3 and inappropriately normal or elevated TSH levels. In almost all cases it is due to different mutations in only one allele of the thyroid hormone receptor beta gene which blocks the action of normal allele thus producing dominantly inherited RTH. In RTH, varying degrees of target tissue responsiveness result in a heterogenous clinical presentation. Resistance in the thyrotrophs and the peripheral tissues is assessed by the evaluation of TSH secretion and changes in peripheral markers of thyroid hormone action after administration of L-T3, respectively. The treatment decision depends on the individual characteristics of each patient. Patients with hypothyroid and hyperthyroid symptoms may require treatment with thyroid hormone and with agents such as beta blockers, antithyroid drugs and thyroid hormone analogues.     

Congenital nephrotic syndrome with clinical hypothyroidism

A 15 month old boy with typical features of congenital nephrotic syndrome (CNS) is reported, who in addition to the renal pathology had an associated clinical hypothyroidism with low levels of total and free thyroxine and triiodothyronine and an elevated serum TSH. Improvement in the physical parameters and mental status from thyroid hormone replacement therapy is documented.     

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.     

Thyroid function tests and their interpretation

For general screening of children who are in fairly good health and in whom CNS or pituitary disease is not strongly suspected, the newer THS assays are very useful in assessing the action of both endogenous and exogenous thyroid hormone. Those children in whom primary hypothyroidism is strongly suspected or who are already on thyroid hormone supplementation, the free T4 assay provides a useful adjunct to the TSH. If Grave's disease or factious hyperthyroidism is suspected, the total T3 assay is a useful adjunct to the TSH and the free T4. The screening of possible hypothyroidism as a result of hypothalamic or pituitary disease, the free T4 is relied on heavily, along with the response of TSH to TRH stimulation. Measurement of the nocturnal TSH surge may also be useful in this situation.     

Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000–2004): It’s Prevalence and Clinical Characteristics

In Sapporo, Japan, a neonatal screening program for congenital hypothyroidism (CH) has employed measurement of free thyroxine (T4) and TSH in the same filter-paper blood spot. This system has enabled us to identify primary CH and central CH during the neonatal period. The aim of this study was to clarify the prevalence and clinical characteristics of central CH. For this purpose, the screening program requested serum from infants with free T4 concentrations below the cut off value regardless of the TSH levels. Between January 2000 and December 2004, 83,232 newborns were screened and six central CH patients were detected as a result of follow-up of low free T4 and non-elevated TSH screening (1:13,872). This frequency is higher than in other studies. Four patients showed multiple pituitary hormone deficiency with pituitary malformations on magnetic resonance imaging. One patient was diagnosed as having Prader-Willie syndrome. The remaining patient was considered to have isolated central CH. Our study demonstrated that the frequency of central CH is 1:13,872. Free T4 measurement would also be advantageous in early recognition of multiple pituitary hormone deficiency.     

1型糖尿病并低三碘甲状腺氨酸综合征201例

目的探讨1型糖尿病(T1DM)及糖尿病酮症酸中毒(DKA)患儿并低三碘甲状腺氨酸(T3)综合征的临床特点。方法采用放射免疫分析法检测91例T1DM并DKA患儿(DKA组)及110例单纯T1DM患儿(非DKA组)血清T3、甲状腺素(T4)、促甲状腺激素(TSH)水平,观察2组T3、T4下降例数及水平,并将DKA组分为轻、中、重3个亚组,观察不同组别中甲状腺激素变化特点。结果 DKA组易发生T3、T4下降,DKA组T3[(0.54±0.51)μg.L-1]、T4[(5.65±2.80)μg.L-1]与非DKA组T3[(1.02±0.38)μg.L-1]、T4[(9.28±2.85)μg.L-1]比较,差异均有统计学意义(Pa<0.000 1)。中、重度DKA组与非DKA组T3比较,差异有统计学意义(Pa<0.000 1),轻、中、重度DKA组与非DKA组T4比较,差异均有统计学意义(Pa<0.000 4,0.000 1)。DKA组与非DKA组TSH比较,差异无统计学意义(P>0.05)。结论 T1DM患儿甲状腺激素检测的结果主要表现为T3降低,部分伴T4降低,其疾病的严重程度与甲状腺激素降低程度一致,T1DM并DKA患儿的T3、T4水平均有明显下降,提示T1DM患儿需重视甲状腺激素的检测,利于早期防治。     

Persistently raised thyroid stimulating hormone in adequately treated congenital hypothyroidism on long-term follow-up

AIM: To determine the percentage of patients with inappropriate secretion of TSH (ISTSH) in a large cohort of patients with congenital hypothyroidism (CH), and to examine a probable influence of the pretreatment T4 or TSH levels and the etiology of CH on ISTSH by describing the clinical features of these patients. PATIENTS AND METHODS: We retrospectively examined the records, including anthropometric data, clinical findings, and thyroid function tests (TFT), of 500 children diagnosed with CH. Inclusion criteria of ISTSH were appropriate doses of L-T4, improvement of clinical findings, normalization of serum total T4 levels and persistently high TSH concentrations. A group of patients who demonstrated adequate suppression of TSH (<6 mU/l) with therapy among 500 CH patients were chosen randomly as a control group. Both groups were compared with regard to the etiology of CH, and TFT at baseline and during the treatment period. RESULTS: Overall, 27 (5.4%) out of the 500 patients with CH had ISTSH. Nine patients (1.8%) with ISTHS did not show TSH normalization during the follow-up period. Four out of 27 patients with ISTSH had organic lesions (three empty sella, one corpus callosum agenesis) on cranial imaging. No statistically significant difference was found between the groups for etiological classification. The pretreatment T4 and TSH levels in ISTHS and control groups were not significantly different. CONCLUSIONS: Our results suggest that a minority (5.4%) of adequately treated children with CH have persistently raised TSH levels. The delay in normalization of TSH is not related to pretreatment T4 and TSH values or the etiology of CH.     

Growth and thyroid function in children treated with growth hormone.

We examined the effect of growth hormone (GH) therapy on thyroid function in 57 children with isolated GH deficiency and whether this effect could influence their growth response. Thyroid function and insulin-like growth factor I levels were measured before and after 3, 6, and 12 months of recombinant-GH therapy (20 U/m2 per week, given subcutaneously), after a 1-month withdrawal from therapy, and after a further 6 months of GH administration. The serum concentration of triiodothyronine (T3) and the T3/T4 (thyroxine) ratio increased after 12 months of GH treatment, whereas total T4 and free T4 levels decreased; thyrotropin levels did not change significantly during treatment but increased after a 1-month withdrawal. After a further 6 months of GH therapy, an increase in T3 levels and in the T3/T4 ratio and a decrease in total T4 and free T4 levels were found again, and thyrotropin levels decreased. The increment in growth velocity after 12 months of therapy correlated positively with the T3/T4 ratio and negatively with total T4 and free T4 values. These data confirm in children a GH-induced enhancement of peripheral conversion of T4 to T3. This effect appears to be more evident in children who are most sensitive to GH in terms of growth-promoting activity.     

Kawasaki disease: Are we missing the diagnosis ?

We report 6 cases of Kawasaki disease (KD) diagnosed over a period of one year and review of all the cases reported from India. The diagnosis of KD was based on clinical criteria The mean age of patients was 6.83 years and mean duration of symptoms before diagnosis was 7.5 days. Apart from classical clinical features, elevated transaminases and blood urea along with free fluid in abdomen was present in one case each. Two patients had dilated coronaries that returned to normal on follow up. One patient developed headache and neck stiffness following treatment with intravenous gamma globulins. The outcome was excellent in all the cases.     

Reevaluation of thyroid function in low birth weight infants based on free triiodothyronine and triiodothyronine

We attempted to analyze the physiological meaning of abnormally low thyroid hormones in low birth weight (LBW) infants on the basis of cross-sectional data on free triiodothyronine (free T3) and T3 in addition to the other thyroid hormones. In LBW infants, the levels of free T3 and T3 were lower than those of normal infants, similar to the relation between free thyroxine (free T4) and T4. The ratio of free T3/T3 or free T4/T4, however, was not different between the groups. The levels of thyroid-stimulating hormone, thyroid hormone-binding globulin and reversed T3 in LBW infants were not significantly different from those of normal infants.     

Characteristic MR spectroscopy in fucosidosis: in vitro investigation

Fucosidosis is a rare lysosomal storage disorder that results in the deposition of the sugar fucose within various organs, including the central nervous system. Neuroimaging abnormalities on MR, specifically T2 shortening in the basal ganglia, have been reported as suggestive of fucosidosis. A more recent report of MR spectroscopy (MRS) of one patient provided evidence that MRS is specific for fucosidosis. We present another confirmed case with nearly identical MR spectroscopic findings along with in vitro data that support the contention that MR spectroscopy, in the setting of typical clinical and imaging features, is characteristic for this rare disorder.     

非自身免疫性甲状腺功能亢进症1例临床和基因变异分析

目的 分析非自身免疫性甲状腺功能亢进症的临床及遗传学特征.方法 回顾分析1例非自身免疫性甲状腺功能亢进症患儿的临床资料和基因检测结果.结果 患儿,男,9月龄,以心率增快为主要表现,合并全面性发育迟缓、先天性心脏病等.实验室检测提示促甲状腺激素降低,游离三碘甲状腺原氨酸及游离甲状腺素均升高,相关抗体检查全部阴性.基因检测...     

Thrombotic thrombocytopenic purpura in a child with systemic lupus erythematosus

We report a child with thrombotic thrombocytopenic purpura (TTP) secondary to systemic lupus erythematosus. The diagnosis was confirmed by low ADAMTS13 activity (<5%) along with the presence of a low titer inhibitor. Her clinical course was complicated by systemic lupus erythematosus, immunosuppressant therapy, and septic shock. She responded to plasma exchange and ADAMTS13 activity levels recovered. This case illustrates the heterogeneity of TTP and the difficulty of making a diagnosis of TTP. ADAMTS13 activity assay can be useful in the differential diagnosis of diseases with clinical features of thrombotic microangiopathy in pediatric patients. However, treatment needs to be decided carefully case-by-case.     

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.