Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome.

UNLABELLED: In order to delineate the spectrum of thyroid abnormalities in children with Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and antiperoxidase antibodies concentrations were retrospectively evaluated in 137 children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism was detected in 2.9% of patients. Thyroid disease occurred in 9%: four hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l). According to TSH levels, they were divided into two groups: G1 (n = 68) with normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not different. CONCLUSIONS: Thyroid disorders are frequent in children with DS. Subtle thyroid abnormalities found in patients with DS with no evidence of clinical dysfunction need further investigation to demonstrate whether there is a need for therapeutic intervention.

Intermittent hyperaldosteronism in a child due to an adrenal adenoma.

UNLABELLED: Aldosterone producing adenoma (APA) is a rare but potentially curable form of paediatric hypertension. We report a case of APA in a 9-year-old boy, suspected due to persistent hypokalaemia. Neither BP nor initial laboratory investigations disclosed the diagnosis and the presence of an APA was suggested by functional tests and radiological findings. Histologically, a cortical tumour was found associated with a marked medullary hyperplasia of both chromaffin and ganglion cells. CONCLUSION: This case reinforces the need for further investigations in patients with misleading clinical and laboratory data.

Estrogen priming effect on growth hormone (GH) provocative test: a useful tool for the diagnosis of GH deficiency.

We have studied the effect of estradiol (E2) on the GH-insulin-like growth factor (GH-IGF) axis in 15 prepubertal GH deficiency (GHD) children and 44 prepubertal or early pubertal children with idiopathic short stature (SS). All of them received a daily dose of micronized E2 (1 or 2 mg) or placebo, for 3 days, before a sequential arginine-clonidine test. In SS children, GH maximal responses were 17.8+/-10.9 on placebo and 27.9+/-14.5 microg/L on estrogen (P < 0.0001). The lower 95% confidence limits for GH maximal response changed from 3.7 microg/L (without E2) to 8.3 microg/L (on E2). In GHD children, no significant stimulatory effect of estrogen on GH levels was observed. After placebo, a cut-off limit of 3.7 microg/L (the lower 95% confidence interval limit) resulted in 73% sensitivity, 95% specificity, and an overall 90% diagnostic efficiency. After E2, a cut-off limit of 8.3 microg/L resulted in a sensitivity of 87%, a specificity of 98%, and a diagnostic efficiency of 95%. After placebo, 68% of SS showed normal IGF-I levels, and the mean did not change on E2 (13.7+/-6.3 vs. 14.3+/-6.8 nmol/L, not significant). In 93% of SS, IGF binding protein (IGFBP)-3 levels were normal during placebo. On E2, mean IGFBP-3 did not change (2.63+/-0.70 vs. 2.70+/-0.70 mg/L, not significant). In 14 of 15 GHD patients, IGF-I values were below normal on placebo, and the mean of the group did not change after E2. During placebo, 13 of 15 GHD children presented low IGFBP-3 values. During E2, there was a small significant increase in IGFBP-3 values (1.06+/-0.58 vs. 1.20+/-0.69 mg/L, P < 0.02). The highest diagnostic efficiencies for IGF-I and IGFBP-3 were observed during placebo (75% and 91%, respectively). We conclude that GH stimulation tests after E2 priming had the highest diagnostic efficiency. Our findings suggest that the effect of estrogen priming on GH stimulated levels, by reducing the number of false nonresponders, might be useful to better discriminate between normal and abnormal GH status in SS children.

[Magnetic resonance imaging in central diabetes insipidus in children and adolescents. findings at diagnosis and during follow-up]. / Resonancia magnética en niños y adolescentes con diabetes insípida central: hallazgos al diagnóstico y durante su seguimiento.

AIM: The absence of the hyperintense signal of the posterior pituitary in magnetic resonance imaging (MRI) is considered by some authors to be evidence of neurohypophyseal dysfunction. To evaluate the utility of MRI as a complementary diagnostic aid in patients with central diabetes insipidus (CDI), we studied the MR images of pediatric patients at diagnosis and during follow-up. METHODS: MR images from 14 patients (4 females, 10 males; mean age 8.5 years) who were referred for polyuria and polydipsia and whose diagnosis was central diabetes insipidus (CDI) were analyzed. Mean time of evolution from onset of polyuria until the first MRI was 1.5 years. In 11 patients more than one MR image was obtained during follow-up. Mean time of follow-up was 2.8 years. RESULTS: In 10 patients CDI was idiopathic, in 3 it was secondary to a hypothalamic tumor and in 1 it was secondary to histiocytosis. In one patient with idiopathic CDI, the hyperintense signal was present at diagnosis but disappeared during the following 15 months. Four of the patients with idiopathic CDI developed thickening of the pituitary stalk, some at their diagnosis and others during follow-up. Of the three patients in whom CDI was secondary to a germinoma, the hyperintense signal was absent in two of them, while in one the signal was ectopic and associated with a thickened pituitary stalk. In the patient with histiocytosis, the hyperintense signal was absent at diagnosis. CONCLUSIONS: 1. In most of the patients with CDI the hyperintense signal of the posterior pituitary was absent at diagnosis; however in one patient this signal disappeared during follow-up and consequently its presence does not rule out a diagnosis of CDI. 2. Although a thickened pituitary stalk could reflect only a non-specific, transient inflammatory process, its presence makes ruling out tumoral or infiltrative disease obligatory.

Psychosocial outcome in growth hormone deficient patients diagnosed during childhood.

Social disabilities have been described in GHD patients. The aim of this study was to evaluate the social outcome of a group of adult hypopituitary patients diagnosed and treated during childhood. Seventy patients were interviewed at a mean age of 25.6 years (range 18-50 yr). They answered a semistructured questionnaire and the Beck Depression Inventory test. Patients were compared for academic achievement, marital status and employment with the nearest age sibling. We found high levels of school repeaters, school was often not completed, and around 50% were overprotected by teachers and teased by peers. 32% were unemployed, while 58% of those employed work with their families. 80% still live with their parents; only 16% are married and 9% have children. 44% had no dating experience and 52% had never had sexual intercourse. Depression was common, especially in hypogonadic subjects. Juvenilization was the most common complaint. We did not found differences in maximal educational achievements and levels of employment between patients and siblings, but significantly more married siblings were found. Depression, social isolation and dependent life style were found in GHD patients. Appropriate medical and psychological counseling should be included for patients and their families as part of treatment.

A novel E153X point mutation in the androgen receptor gene in a patient with complete androgen insensitivity syndrome.

AIM: To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome to confirm an anomaly in the AR gene. METHODS: Genomic DNA from leukocytes was isolated in order to analyze SRY gene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursors from the testis was performed in order to study testosterone production and response to hCG stimulation in culture. RESULTS: Surgical exploration disclosed two testes, no Wolffian structures and important Müllerian derivatives. The SRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported G to T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell cultures produced sizable amounts of testosterone and were responsive to hCG stimulation. CONCLUSION: This E153X nonsense point mutation has not been described previously in cases of AIS, and could lead to the synthesis of a short truncated (153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivity syndrome (CAIS).

The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess.

In the kidney, the 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11betaHSD2) inactivates glucocorticoids to their inactive ketoforms and thus prevents endogenous glucocorticoids from occupying the nonselective mineralocorticoid receptor in epithelial tissues. Several mutations have been described in the 11betaHSD2 gene in the congenital syndrome of apparent mineralocorticoid excess. These mutations generate partially or completely inactive 11betaHSD2 enzymes. In the present work, we describe an already known mutation in a new patient affected by apparent mineralocorticoid excess, which results in an arginine-to-cysteine mutation (R213C) in the 11betaHSD2 enzyme. This mutation has been found in two other independent families. In vitro expression studies of this mutant provide evidence that the mutant protein is normally expressed, but its activity is abolished. The CGC-to-TGC (C-toT) transition at codon 213 can be considered a typical CpG-consequence mutation. The present finding suggests that the codon R213 of 11betaHSD2 is a hot spot for mutations in this gene, as shown by the occurrence of an R213C point-mutation in several families unrelated to each other.

Determining the current roles of physical and occupational therapists in burn care.

The team approach has enjoyed great success in the care of patients with burns, and it has been shown to decrease morbidity and mortality in these cases. Although the concept of the team approach is well-defined, the delineation of roles within this approach remains unclear. This study was designed to better explain the roles of physical therapists (PTs) and occupational therapists (OTs) in burn care. With the use of a questionnaire, PT and OT responsibilities were reviewed. The results showed that OTs perform the majority of activities of daily living training, PTs perform the majority of functional mobility training, both professions are involved in scar management, and neither profession has significant responsibility for care of the burn wound itself. Role delineation occurs to help avoid role confusion and the duplication of services. The title burn therapist offers an example of unclear role definition when a physical therapy assistant uses that title to identify himself or herself. Communication is critical to define these roles within individual burn centers.

Final height in long-term primary hypothyroid children.

OBJECTIVE: We studied retrospectively the statural growth and bone maturation of 32 children with primary hypothyroidism in order to relate their final heights to their chronological ages, height deficits and bone ages at the beginning of treatment. Patients were grouped according to age when treatment was started: Group 1 (G1) (n = 17): (15 girls, 1 boy) 3.09 +/- 0.8 yr; Group 2 (G2) (n = 9): (7 girls, 2 boys) 9.1 +/- 1.2 yr, and Group 3 (G3) (n = 6): (5 girls, 1 boy) 13.58 +/- 1.13 yr. At diagnosis G1 and G2 were prepubertal and G3 children were in puberty. In 10 patients of G1, 7 of G2 and 6 (all) of G3 final height was compared with target height. RESULTS: (SDS) Initial height: G1: -3.74 +/- 1.2; G2: -3.94 +/- 1.32; G3 -3.65 +/- 1. Height at onset of puberty: G1: -1.06 +/- 1.1; G2: -2.5 +/- 1.4. Height menarche stage 5: G1: -0.63 +/- 1.1; G2: -1.76 +/- 1.2; G3: -2.6 +/- 1.7. Final height: (whole group) G1: -0.85 +/- 0.91; G2: -1.6 +/- 1.3; G3: -2 +/- 1.5. Final height G1 (n = 10): -1.05 +/- 0.89; G2 (n = 7) 1.2 +/- 1. Target height G1 (n = 10): -1.22 +/- 0.78; G2 (n = 7): -0.8 +/- 1.2; G3 (n = 6): -1.07 +/- 1.5. Initial bone age: G1: -4.9 +/- 0.85; G2: -7.2 +/- 2.6; G3: -4.5 +/- 1.9. Bone age (onset of puberty) G1: -0.26 +/- 1.74; G2: -2 +/- 1.7; Bone age (menarche) G1: 0.09 +/- 0.6; G2: -0.5 +/- 0.6; G3: -0.76 +/- 0.82. CONCLUSION: G1 and G2, prepubertal at diagnosis, reached a normal adult height with respect to target height; G3 did not, the difference being statistically significant (p < 0.04). Puberty plays a decisive role in the incomplete catch-up growth of longstanding hypothyroid patients.

Nocturnal TSH surge and TRH test response in the evaluation of thyroid axis in hypothalamic pituitary disorders in childhood.

We studied, by means of TSH nocturnal secretion and TRH test, 42 children (4.2-19.9 years) with hypothalamic pituitary disorders and 24 healthy euthyroid children (5.7-15.4 years) as control group. Patients were divided according to their serum values of FT4 in group 1 (n = 27) with FT4 >/=10.3 pmol/l and group 2 (n = 15) with FT4 <10.3 pmol/l. TSH was measured by immunoradiometric assay. TSH nadir, TSH peak and TSH surge were calculated. Both groups differed significantly from control group in TSH surge values: group 1 (p < 0. 05), group 2 (p < 0.01). TRH test was abnormal in 11/27 patients of group 1 and 10/15 patients of group 2. In group 1, 7 patients had normal tests, 2 had abnormalities in both tests, 9 had only TSH nocturnal surge altered and 9 showed only TRH alterations. All patients of group 2 presented thyroid axis abnormalities. In conclusion, in patients with hypothalamic pituitary disorders with low FT4, no further investigation is required to demonstrate thyroid axis alterations, however in patients with normal FT4, nocturnal TSH secretion and TRH test may be required to evidence thyroid abnormalities.

Oral desmopressin treatment of central diabetes insipidus in children.

To assess the efficacy of treatment with oral desmopressin (DDAVP), 20 patients, aged 5-20 y, with central diabetes insipidus were studied during 3 d of hospitalization and for 3 months at the outpatient clinic. At baseline the median rate of diuresis was 12.7 ml kg-1 h-1. Urinary output decreased significantly under treatment with an increase in urinary osmolality, normalization of plasma osmolality and absence of nocturia. Patients were discharged from hospital with a median dose of 500 micrograms d-1 (100-1200 micrograms d-1). An adjustment in dosage was necessary in seven patients during follow-up, resulting in a final dose of 600 micrograms d-1. Body weight and DDAVP doses (r = 0.75, p = 0.001) and body surface and DDAVP doses (r = 0.72, p < 0.001) were significantly correlated. The average dosage was 474 +/- 222 micrograms m-2 d-1 (mean +/- SD). The oral DDAVP treatment remained effective during the 3 months of follow-up. This therapy offers an alternative for the treatment of central diabetes insipidus in children.

The burn camp experience: variables that influence the enhancement of self-esteem.

Since 1982, there have been summer camps for children and adolescent burn survivors. Although the primary focus of camp is to have "fun," the principal goal is psychosocial readjustment through peer interactions and the resulting enhancement of self-esteem (SE). This study was initiated to test the hypothesis that the burn camp experience enhances the SE of campers. Forty-three campers at the Connecticut Burns Care Foundation Summer Camp were invited to participate in this study with the Rosenberg Self-Esteem Scale. The age range was 8 to 18 years (mean 12 years). The extent of previous burn injury ranged from 10% to 98% total body surface area (mean 40%). The interval between hospital discharge and camp experience was 4 to 144 months (mean 54 months). Thirty-seven percent of the children demonstrated an increase in SE to varying degrees, whereas 30% showed no change, and 3% exhibited a decrease in SE. This study failed to support the working hypothesis.

Reproducibility and comparison of growth hormone secretion tests.

To assess the degree of reproducibility of spontaneous GH secretion and pharmacological tests we studied 15 prepubertal children with short stature and abnormal growth rate. In all children, spontaneous overnight GH secretion was measured followed by a clonidine test in 8 children and an arginine test in the remaining 7. The same protocol was repeated a week later. Intra-individual variability of GH secretion in both physiological and pharmacological tests was expressed as the coefficient of variation (CV%). No significant difference was found between the first and second value of parameters of spontaneous GH secretion. Maximum spontaneous GH peak (MS) and mean 12-h GH concentration (MGH) correlated significantly (r = 0.78, p < 0.001). Mean CV% of all parameters of repeated GH profiles (around 30%) were lower than those of provocative tests (around 70%) (p < 0.05). No significant difference was found between CV% of clonidine and arginine tests. There was no correlation between MGH or MS and GH response to provocative test in the same child. We found a significant correlation between the log transformed maximum provocative GH response to the arginine test and the length of the time interval (in min) from the end of the last GH peak in the previous profile to the time zero of the provocative test (r = 0.60, p < 0.05). This relationship was not found for the clonidine test. We conclude that spontaneous GH secretion in children with short stature is more reproducible than stimulated GH response with a week's difference. Perhaps the higher variability of provocative GH secretion may be related to the state of the endogenous hypothalamic rhythm of both GHRH and somatostatin release at the time of the test.

Growth of Argentinian girls with Turner syndrome.

Growth data on 254 patients with Turner syndrome from Argentina-120 with XO karyotype and 134 with other chromosomal abnormalities-were analysed. Birth weight and height were significantly reduced. Ninety patients had received oestrogen treatment from a mean age of 14-0 years (SD 1.2) and 17 patients had spontaneous menarche. Patients who underwent spontaneous menarche had a small growth spurt. Final height was slightly higher (139.8 cm SD 5.6), though not significantly different from the mean adult height of the whole sample (137.9 cm SD 5.7). Mean adult height was 3.73 SD below mean of the normal local population. Mean height velocities from birth to maturity are very similar to those found in other samples. Distance standards were prepared by fitting a fifth-degree polynomial to the interpolated mean heights at each 0.5 year of age, and to the raw SD. Selected centiles were then calculated from the smoothed values. Differences between adult height in local Turner syndrome girls and local normal population are very similar to the same Turner-normal differences described in other communities. Standards presented here are useful for evaluating Turner syndrome patients from Argentina, and may also be used by those with similar growth pattern in their normal population.

Bone age at discontinuation of medroxyprogesterone acetate therapy in girls with precocious puberty: effect on final height.

To determine the final height of patients with precocious puberty treated with medroxyprogesterone acetate (MPA; 150 mg every week) for a period > 1 year (mean +/- SD = 3.24 +/- 1.85 years), data from a group of 26 girls were analyzed. The attained final height was 155.6 +/- 8.06 cm (-1.1 SD of the normal population). In a group of 8 untreated girls with precocious puberty, adult height was 149.2 +/- 5.07 (-2.16 SD, p < 0.02). In 9 patients in whom treatment was stopped at a bone age < or = 12 years, final height was 159.2 +/- 10.05 cm, while in 16 girls who had a bone age > 12 years at the end of treatment, the final height was 153.03 +/- 6.28 cm. Our data demonstrate the effectiveness of MPA treatment on ultimate height. The better height observed in those patients who stopped treatment with a bone age < 12 years suggests the advantage of discontinuing therapy before reaching a more advanced degree of skeletal maturation.

Growth follow-up in 100 children with congenital hypothyroidism before and during treatment.

In order to assess the influence of age at onset of treatment on subsequent growth, height, weight, head circumference (HC) and bone age as estimated by Greulich-Pyle and TW2-RUS methods, 100 children with congenital hypothyroidism (CH) were studied before and during adequate treatment up to 5 years of age. The patients were divided into five groups according to age at the start of treatment: Group 1: < 2 months (n = 26); Group 2: 2-3 months (n = 13); Group 3: 3-6 months (n = 21); Group 4: 6-12 months (n = 20); Group 5: 12-24 months (n = 20). Before treatment, groups 1 and 2 differed significantly from the others in height (p < 0.001). With hormone therapy, catch-up growth was observed in groups 3 to 5, but at age 5 years no differences were found between groups. In all groups, height at 5 years of age correlated significantly with children's midparental height (p < 0.002). Bone age was initially retarded in groups 3 to 5, but approximated the chronological age by age 5 years. Initially, HC was less affected than height and remained relatively larger up to age 5 years in all groups. These findings show that thyroid hormone replacement in CH as late as 24 months corrects the short stature and delayed bone age by age 5 years.

Heterologous humoral immune response in patients treated with human growth hormone from different sources.

The existence of homologous anti-human growth hormone (anti-hGH) and heterologous anti-bovine growth hormone (anti-bGH) humoral immune responses in hypopituitary patients under hGH therapy has been reported previously. In order to study the influence of the hormone source, both responses were compared by radiobinding assays performed with [125I]hGH or [125I]bGH as tracers. Fifty-seven hypopituitary patients treated with extractive hGH, recombinant methionyl hGH or authentic recombinant hGH were studied. A very low incidence of heterologous antibodies was found in patients under recombinant hGH therapy, contrary to the high incidence observed in patients treated with extractive hGH preparations. In addition, immunochemical studies performed with a synthetic peptide (hGH 44-128) indicated that this peptide exhibited, in the anti-bGH/[125]bGH radioimmunoassay system, higher reactivity than the native hGH, suggesting that such a fragment resembled an altered conformation of the hormone. The high heterologous response elicited only by the extractive hGH along with the behaviour of the hGH 44-128 fragment supports the fact that the extraction and purification procedures in extractive preparations may alter slightly the structure of the hGH molecule and trigger a heterologous immune response.