Thyroglossal duct cyst: an infrequently considered diagnosis in pediatric patients with anterior neck masses.

OBJECTIVE: To describe a pediatric patient with an anterior neck mass and discuss the evaluation and treatment. METHODS: We present a case report and a discussion of the differential diagnosis of anterior cervical masses. The workup and therapy for an anterior neck mass, which was a thyroglossal duct cyst, are reviewed. RESULTS: A thyroglossal duct cyst in pediatric patients is an uncommon finding. For establishing a correct diagnosis, surgical confirmation is necessary. Identification is important because of the high incidence of misdiagnosis, recurrent infections, inadequate treatment, and possible neoplastic change. CONCLUSION: A thyroglossal duct cyst should be included in the differential diagnosis of an anterior neck mass. Recommended treatment consists of surgical removal of the cyst, the entire thyroglossal duct tract, and the central portion of the hyoid bone.

Growth and normal puberty.

We reviewed the growth characteristics of American boys and girls from published studies, including age at takeoff, age at peak height velocity, peak height velocity, duration of puberty, and the magnitude of the pubertal contribution to adult height. Age at takeoff is highly variable and sex-dependent. The mean takeoff age in children growing at an average rate is approximately 11 years in boys and 9 years in girls, and peak height velocity occurs at a mean age of 13.5 years and 11.5 years, respectively, in these children. Whole-year peak height velocity is 9.5 cm/y in boys and 8.3 cm/y in girls, with slight variations in the different studies. The contribution of pubertal growth to final height is approximately 30 to 31 cm in boys, accounting for 17% to 18% of the final height, and 27.5 to 29 cm in girls, accounting for 17% of the final height. The magnitude of pubertal growth has a negative correlation with age at takeoff, but no correlation with final height. Age at takeoff, however, correlates highly with pubertal stage, but correlates negatively with duration of puberty.

Dideoxyfingerprinting (ddF) analysis of the type X collagen gene (COL10A1) and identification of a novel mutation (S671P) in a kindred with Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (SMCD; MIM 156500) is an autosomal dominant disorder of the skeleton that is manifested in early childhood by short stature, coxa vara, and a waddling gait. Patients with SMCD have mutations in the gene that codes for the alpha-1 chain of collagen X (COL10A1); however, mutation analysis of this gene is hampered by its size. We studied a family with SMCD: the mother, a 36-year-old woman with a height of 149 cm, had mild bilateral coxa vara. Her two sons presented with short stature, bowed legs, and coxa vara in early childhood. DNA was extracted from peripheral lymphocytes from the three patients and subjected to PCR amplification by COL10A1 gene-specific primers. In addition to single-strand conformational polymorphism (SSCP) analysis of the COL10A1 gene, we used a novel method, dideoxy fingerprinting (ddF). The genetic defect in this family was found to be a previously unreported missense mutation (T-to-C transition) at nucleotide 2011. This change resulted in a Ser-to-Pro substitution at position 671 of the carboxy-terminus of the COL10A1 protein. In addition, the two boys, but not the mother, were found to carry a trinucleotide (CCC) deletion at position 2048 of the 3' untranslated region, a polymorphism of the COL10A1 gene. We conclude that ddF can be used in the analysis of the COL10A1 gene along with SSCP. The S671P substitution is novel, but located in the same region with the other reported COL10A1 mutations, confirming type X collagen as the locus for this disease.

The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat.

The development of insulin dependent diabetes mellitus (IDDM) and diabetes in the diabetes prone (DP) BB rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have been implicated but not proven to play a pathogenetic role in BB rats due to the increased NK cell number and activity found in these animals. We have recently reported that poly I:C, an inducer of cytokines and a potent enhancer of NK cell function, accelerates the development of diabetes in DP BB rats and induces diabetes in diabetes resistant (DR) BB rats. Since we have further demonstrated that poly I:C administration to BB rats increases NK cell number and levels of inducers of NK cell activity, interferon-alpha and IL-6 which is described therein, we tested the hypothesis that NK cell activity plays an important role in poly I:C accelerated disease. The role of NK cells in poly I:C accelerated diabetes and spontaneous diabetes was examined by determining whether selective depletion of NK cells using a rat NK cell specific antibody (anti-NKR-P1 antibody) alters the development of diabetes. The treatment of BB rats with anti-NKR-P1 antibody resulted in a significantly lower mean NK cell activity of splenic mononuclear cells than that found in control animals. However, the development of diabetes and degree of insulitis was not significantly different between treatment groups. BB rats administered anti-NKR-P1 antibody with poly I:C had a lower mean splenocyte NK cell activity and lower mean NK cell number within the peripheral blood and inflamed islets than rats administered poly I:C alone. However, anti-NKR-P1 antibody administration did not alter the accelerated development of diabetes or the degree of insulitis in poly I:C treated animals. These data document that NK cells do not play a major role in the pathogenesis of poly I:C accelerated diabetes or spontaneous diabetes in the DP BB rat.

Poly I:C induction of alpha-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships.

Although the administration of a fixed dose of the alpha-interferon (alpha-IFN) inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly I:C with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly I:C with the induction of serum alpha-IFN and the development of diabetes in DP-BB and normal Wistar rats. Also tested in this study is the hypothesis that the lack of development of diabetes in poly I:C-treated normal Wistar rats is attributable to a deficient alpha-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10 micrograms/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum alpha-IFN response. Moreover, all doses of poly I:C accelerated the onset of diabetes in BB rats. Serum alpha-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum alpha-IFN were associated with earlier onset of diabetes (P < 0.001). Poly I:C-induced serum alpha-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly I:C significantly increased serum alpha-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum alpha-IFN and accelerates the development of diabetes in BB rats at even very low doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Poly I:C induces development of diabetes mellitus in BB rat.

Polyinosinic polycytidilic acid (poly I:C), an inducer of alpha-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10-treated DR and poly-5-treated DP rats. A significant degree of insulitis occurred in all the poly I:C-treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C- and saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of fructosamine test in diabetic children.

OBJECTIVE: The goal of this study was to assess the effect of glucose and the contribution of the aldimine component on the measurement of fructosamine, the relationship of serum fructosamine with glycosylated plasma proteins, as measured by a new high-performance liquid chromatography methodology (Glyc PP-HPLC) and by an affinity chromatography (Glyc PP), and the ability of serum fructosamine to assess acute, short-term (1-2 wk), and long-term (2-3 mo) glycemic control. RESEARCH DESIGN AND METHODS: The measurement of fructosamine was unaltered by the addition of up to 27.5 mM glucose or by the elimination of the aldimine component of serum specimens by dialysis. Fructosamine was generated in vitro by incubating serum aliquots. This generation was dependent on time, glucose concentration, and temperature. RESULTS: Fructosamine (n = 27) correlated well with Glyc PP (r = 0.76, P less than 0.01) and significantly less with Glyc PP-HPLC (r = 0.46, P less than 0.01). Although oral glucose ingestion increased serum glucose acutely by 200%, fructosamine was unchanged at each time interval. Improving glycemic control decreased the mean serum fructosamine concentration from 3.68 (baseline) to 3.28 mM (P less than 0.01) at 1 wk and to 3.13 mM (P less than 0.01) at 2 wk. HbA1c correlated with fructosamine (r = 0.59) and Glyc PP-HPLC (r = 0.47) but correlated best with Glyc PP (r = 0.83). CONCLUSIONS: These results indicate the fructosamine assay is unaltered by serum glucose, solely measures the ketoamine component, correlates well with glycosylated plasma proteins measured by aminophenylboronic acid column chromatography, is unaffected by acute changes of serum glucose, and may be used to monitor changes in glycemic control over a 1-wk interval.

Female pseudohermaphroditism in a neonate born to a mother with polycystic ovarian disease.

A newborn with female pseudohermaphroditism (profound masculinization of the external genitalia and preservation of the internal female genitalia) is presented. During pregnancy progressive hirsutism was noted in the mother, and polycystic ovaries were found at cesarean section. The serum testosterone level in the cord blood was elevated markedly (1,232 ng./dl). After birth the serum testosterone levels of the mother and newborn decreased dramatically. Over-all it appears that the polycystic ovaries were the source of the excessive androgen secretion that caused maternal and fetal masculinization during the pregnancy.

Humoral and cell-mediated immunity in growth hormone-deficient children: effect of therapy with human growth hormone.

To delineate the role of growth hormone (GH) in the development and function of the immune system, immunological parameters including quantitative immunoglobulins, T and B lymphocytes, phytohemagglutinin lymphoproliferative response and delayed hypersensitivity skin tests were studied in nine GH-deficient children prior to GH therapy and at 2 months and 9 to 12 months following therapy. The phytohemagglutinin response (74.1 +/- 37.6, mean +/- SD), and the T rosette (58.3% +/- 9.4), B rosette (21.1% +/- 6.1), IgG (810 +/- 241 mg/dl), (IgA 140 +/- 85), and IgM (176 +/- 70) levels in GH-deficient children were comparable to age adjusted values in normal children. Following GH therapy the phytohemagglutinin response increased significantly at 9 to 12 months post-therapy, 123.2 +/- 51.9 versus 74.1 +/- 37.6, p less than 0.05. T and B rosettes, immunoglobulin concentrations, and hypersensitivity skin tests were not affected by GH therapy. Although an effect of GH was not demonstrable by these studies, a positive role of GH cannot be entirely excluded since total GH deficiency did not exist in all children.

Prenatal thyroid function abnormalities in infants with idiopathic respiratory distress syndrome.

Thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were measured on cord sera of 21 preterm infants with idiopathic respiratory distress syndrome (IRDS) and were compared to the values obtained from 15 healthy preterm infants. When log T3, log T4, and log TSH were considered as the dependent variables in the multivariate test Hotelling-Lawley-Trace, there was an overall difference between the two groups: F = 3.94, p = 0.03. When log T3 and log T4 were considered separately in an analysis of covariance, there was a significant difference between the two groups for log T3 after adjusting for birth weight and gestational age (F = 7.98, p = 0.008). However, for log T4 and TSH, there was no difference between the IRDS and control infants. These findings exclude the possibility of antenatal thyroid dysfunction in babies with IRDS. An explanation for reduced cord blood T3 concentration in infants with IRDS is lacking at present. Extrathyroidal factors that predispose to IRDS may also affect peripheral T3 generation. Alternatively, one might postulate that there is relative immaturity of both peripheral T3 generating pathway and lung development in infants who develop IRDS.

Benign elevation of serum alkaline phosphatase, transient and persistent variety.

Markedly increased serum concentration of alkaline phosphatase (AP) was discovered in seven children. Investigation showed the finding to be benign in each case. Family survey and follow-up studies revealed a familial pattern in four children and a transient, idiopathic origin in the other three. Awareness of these benign forms of hyperphosphatasemia will aid the physician in the interpretation of elevated AP.

Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.

The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.

Virilizing hepatoblastoma: precocious sexual development and partial response of pulmonary metastases to cis-platinum.

A 42/3 year old boy with hepatoblastoma presented with precocious sexual development and an abdominal mass. During the course of disease, serial endocrinologic laboratory investigations were done, along with alpha-fetoprotein levels. A significant correlation is noted in these values at diagnosis, postsurgery, and later during a relapse. Ectopic production of chorionic gonadotropins by the tumor is evident. After extensive surgical resection, chemotherapy was started because of metastases. Although the primary tumor failed to respond, the pulmonary metastatic disease showed a greater than 50 percent response rate with cis-platinum.

Clinical recognition of juvenile hypothyroidism in the early stage.

The clinical manifestations of biochemically-confirmed acquired hypothyroidism in nineteen children and adolescents were reviewed to evaluate the symptoms and signs in the early stage of the disease. The group consisted of 14 girls and 5 boys ranging in age from 4 to 15 years. In 13 of the 19 patients with profound biochemical hypothyroidism, classical symptoms were often absent and clinical signs limited. In these patients, hypothyroidism was presumed to have been short in duration and consequence of chronic lymphocytic thyroiditis. In the remaining 6 patients, hypothyroidism was long-standing and clinical presentation classical, including disproportionate weight gain, fatigue, cold intolerance, myxedematous feature, growth retardation and constipation. Goiter was the most consistent finding in both groups and was present in all instances of spontaneously acquired primary hypothyroidism. These observations emphasize the importance of routine examination of the thyroid gland, particularly in preadolescent and adolescent girls. The finding of goiter may be the only detectable sign of hypothyroidism in the early stage of the disease. Biochemical evaluation should not be deferred because of a clinically euthyroid presentation. Replacement therapy must be instituted when findings indicate a hypothyroid state. Failure to recognize and treat hypothyroidism in these pubertal patients may compromise the adult height, since skeletal maturation will proceed under the influence of sex hormones despite the presence of hypothyroidism.

Triiodothyronine (T3) concentration and therapy in autistic children.

The clinical and biochemical status of thyroid function of patients with an autistic syndrome was investigated. The study consisted of 13 patients between the ages of 7 and 21 years. There was no clinical evidence for hypothyroidism in any patient, and T3, T4, and TSH concentrations were within the normal range. Two patients who had retarded bone ages were treated with triiodothyronine for 6 months. Hyperthyroidism developed when T3 levels exceeded physiologic concentrations in these patients. The concept that the clinical response to triiodothyronine in autistic patients results from correction of thyroid dysfunction is not supported by these findings.