Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration measurement in GH deficiency diagnosis.

The diagnosis of growth hormone (GH) deficiency (GHD) is still problematic for the clinician. There is no gold standard for estimating GH secretion. The aim of this study was to compare the diagnostic usefulness of spontaneous GH secretion test, pharmacological tests with insulin, clonidine, L-dopa, and glucagon, and IGF-I measurement in GHD. We studied 180 prepubertal, short children. Predictive values were calculated for different GH cutoff levels for each diagnostic test. ROC curves were used to estimate the diagnostic usefulness of the tests. The results show that sleep is the strongest stimulatory agent for GH secretion. The estimation of GH secretion after onset of sleep can be used as a screening test in GHD diagnosis. The insulin test has the highest discrimination. A combination of insulin test with another provocative test allows high discrimination and accuracy for standard cut-off GH level. Measurement of IGF-I is characterized by low predictive values. IGF-I level below the mean according to age indicates high probability of GHD. Auxological parameters should be the most important factor in diagnosing GHD.

[Molecular analysis of the corticotropin-releasing hormone receptor type 2 gene fragment in anorexia nervosa]. / Analiza molekularna fragmentu genu dla drugiego typu receptora kortykoliberyny w jadlowstrecie psychicznym.

INTRODUCTION: There is strong evidence for the importance of genetic factors in the aetiology of anorexia nervosa (AN). Stress factors can be also associated with the clinical manifestation of AN. The hypothalamic-pituitary-adrenal axis plays an important role in stress control. The increased activity of the hypothalamic-pituitary-adrenal axis in AN is caused by corticotropin-releasing hormone hypersecretion. CRH concentration in cerebrospinal fluid is increased in patients with AN. Intracerebral administration of CRH suppresses appetite. CRH receptor type 2 (CRHR 2) is involved in the appetite suppression effects of CRH. Thus CRHR 2 gene can be a candidate gene for AN. Three CRHR 2 splicing isoforms are known: alpha, b and g. In the hypothalamus, the main appetite control centre, only the isoform CRHR 2alpha is expressed, whose mRNA is characterised by one unique exon 1alpha. AIM: The aim of the study was the screening for mutations in exon 1alpha of the CRHR 2 gene in patients with AN, which could play a role in the pathogenesis of the disease. METHODS: The molecular analysis has been performed in 20 patients with AN and 10 healthy controls. DNA was isolated from peripheral blood leukocytes. DNA fragments were amplified by polymerase chain reaction (PCR) and sequencing was performed. RESULTS: After screening, no genetic variants have been found in the analysed region, including exon 1alpha and the untranslated region, both in anorectic patients as in controls. CONCLUSION: The results do not confirm the hypothesis that the analysed region of the CRHR 2 gene is involved in the pathogenesis of AN.

[Diagnosis and treatment of thyroid cancer in children in the multicenter analysis in Poland for PPGGL]. / Diagnostyka i leczenie raka tarczycy u dzieci w Polscew analizie wieloosrodkowej dla PPGGL.

INTRODUCTION: Differentiated thyroid carcinoma (DTC) in children presents different biological behavior in comparison to adults. Authors presents preliminary results of multicenter analysis concerning incidence, diagnostics and treatment of DTC in children. MATERIAL AND METHODS: The study is a retrospective analysis of 107 pediatric patients from 14 academic centers based on the data from 2000 to 2005 obtained by questionnaire in hospitals involved in the treatment of DTC in children. RESULTS: Papillary thyroid cancer was diagnosed in 83 children, follicular thyroid cancer in 10 children and medullary thyroid cancer in 14 children. Incidence of DTC in children was estimated between 18 and 23 cases per year. The biggest group of patients consisted of children between 11 and 15 years of age, with girls to boys ratio 3.3 : 1. Clinically DTC in children presented most often as solitary thyroid nodule. Cervical lymphadenopathy was observed in 42% of patients. Intraoperative verification indicated metastatic nodes in 50% of children. Low stage DTC predominated (T1 in 36% and T2 in 26% of children). One step surgery was performed in 65% of children with DTC, two step surgery in 25% of patients. I131 therapy was undertaken in 80% of children. Lung metastases were indicated in post therapeutic studies in 14% of children with DTC. Prophylactic thyroidectomies were performed in 79% of children in the group of patients with MTC and RET gene mutations. CONCLUSIONS: The necessity of introduction of unified therapeutic standard in children with DTC in Poland is underlined.

[Estimation of growth hormone secretion during sleep as a screening test in the diagnosis of GH deficiency]. / Ocena wydzielania hormonu wzrostu po zasnieciu jako badanie przesiewowe w diagnostyce somatotropinowej niedoczynnosci przysadki.

BACKGROUND: Because of many disadvantages of growth hormone (GH) stimulation tests the diagnosis of growth hormone deficiency (GHD) is still problematic for the clinician. THE AIM of the study was the estimation of diagnostic usefulness of the GH provocation tests and basal IGF-I concentration measurement in the diagnosis of GHD. MATERIAL AND METHODS: The study group consisted of 180 children with short stature diagnosed in the Department of Pediatric Endocrinology and Diabetes in the years 1998-2003. Pharmacological stimulation test with insulin, clonidine, glucagon and L-dopa were used. GH concentration in physiological test after the onset of sleep was also measured. In 60 patients IGF-I concentration was estimated. For statistical analysis Spearman test was used. RESULTS: The highest mean GH concentrations (19.18 microl U/ml) and GH peaks (26.39 microl U/ml) were observed in sleep test. IGF-I concentration was correlated with GH concentration levels in physiological test after onset of sleep (r=0.4; p<0.05). CONCLUSIONS: Sleep is the strongest stimulatory agent for GH secretion. The estimation of GH secretion after the onset of sleep can be used as a screening test in the diagnosis of GHD. Because of many diagnostic problems in estimation of pituitary function the auxologic parameters should be considered as the most important part in the diagnostic work-up of children with short stature due to GHD.

The effects of growth hormone treatment in patients with somatotropin deficiency during their developmental age.

INTRODUCTION: In Poland treatment with growth hormone of adolescent patients dates back to 1964. Till 1993 the therapy was conducted in an interrupted manner, depending on the periodic availability of the drug. The data form such forms of therapy suggested that the end height within 3rd centile was achieved only by a portion of treated patients. Since 1995 the growth hormone is used in continuous therapy, which allows to sum up the effects of the therapy, including the growth rate and end height. MATERIAL AND METHODS: A total of 117 children and adolescent of both sexes, aged 4.6 to 18.1 years, with diagnosed somatotropic or multihormonal pituitary insufficiency were included in the study. All of them were treated with growth hormone and had an analysis of growth rate and end height. RESULTS: In the first 6 months of growth hormone treatment the growth rate achieved 10.4 cm/year in boys and 10.0 in girls and showed no correlation with maturation status. In the second half of the year the growth rate declined slightly. During the remainder of the therapy the growth rate markedly declined, and this effect was most notable in girls. In 93% of patients after the end of therapy the final height was no different than the expected height. CONCLUSIONS: 1. The growth rate in first half a year of the treatment was 3 times higher than before the beginning of therapy. 2. In the second half of the first year the growth rate slightly declined. 3. In following years the growth rate declined notably. 4. The final achieved height in most of the patients does not differ from the prognosed height.

A prospective study of thyroid nodular disease in children and adolescents in western Poland from 1996 to 2000 and the incidence of thyroid carcinoma relative to iodine deficiency and the Chernobyl disaster.

BACKGROUND: In Poland, where soil is deficient in iodine, supplementation of iodine was introduced in 1935, discontinued in 1980, and then re-introduced in 1997. One of the effects of inadequate iodine intake, prior to 1997, was an increase in the prevalence of thyroid nodular disease (TND) in children. Chernobyl, located in the neighbouring country of Ukraine, suffered a catastrophic nuclear explosion in April 1986. PROCEDURE: A total of 411 children with TND (an incidence of 7.53/100,000) were diagnosed and registered in western Poland between 1996 and 2000 and further evaluated as a population-based study. RESULTS: Based on the patient's clinical status, ultrasound examination, scintiscan, laboratory tests, cytology and the family history, many of the patients qualified for surgery and, as a result, histopathologic data were obtained from 155 of the 411 patients operated on to date (37.7% of all TND). Thyroid carcinoma was detected in 37 of the operated children, i.e. 23.9% or 9.0% of all children with TND with a median incidence of 0.68/100,000. Papillary carcinoma was the predominant histologic type (26-70.3%) compared to follicular carcinoma (10-27.0%) and medullary carcinoma (1-2.7%). Retrospective analysis of the figures for the 23 years (1972-1995) showed that in that period a total of 23 thyroid carcinomas were registered. However, only 12 of these were detected in the 20-year period between 1972 and 1991, none in the years 1992-1993 and, significantly, 11 from 1994 to 1995. CONCLUSIONS: Thyroid carcinoma appears to be an ongoing and increasing problem in the children and adolescents of our region, and it is developing more intensively when compared, both to other parts of Poland and to previous statistics (2000 vs. 1985; P<0.002). Iodine deficiency and radiation resulting from the Chernobyl disaster might be important risk factors in the development of thyroid carcinoma in the young population analysed in our region in the period since 1994. The high percentage of follicular carcinoma and follicular adenoma with an undetermined prognosis (19 out of 46) indicates that the long-term iodine deficiency in our region may be more significant in the pathogenesis of malignant transformation than has previously been postulated.

[Influence of Eqb 761 on the function of the retina in children and adolescent with long lasting diabetes mellitus--preliminary report]. / (146)Wplyw preparatu Egb 761 na czynnosc siatkówki u dzieci i mlodziezy z dlugo trwajaca cukrzyca insulinozalezna--doniesienie wstepne.

PURPOSE: Early detection of patological function of the retina, before anatomical changes, plays very important role in monitoring of visual complications in patients with diabetes mellitus. The aim of the study was the evaluation of anatomical and functional changes in visual organ in children and adolescents with long lasting diabetes mellitus type 1 and taking Egb 761 (Tanakan Beaufour Ipsen) as an adjuvant. MATERIALS AND METHODS: Group consists of 15 patients, age between 11 and 19 years, with diabetes mellitus lasting 6-12 years. All patients had full ophthalmologic examination and color vision tests (Panel D 15 saturated and desaturated). The examination was done 3 times, every 3 months. Egb 761 was given: 1 tablet - 3 times a day, during 3 months. RESULTS: No diabetic retinopathy was found. The results of color vision test were better after therapy (25% of pathological results) and 3 months later (only 4 % of patients). CONCLUSIONS: 1. Egb 761 seems to be good adjuvant in patient with long lasting diabetes mellitus. 2. Color vision tests are sensitive tests of the retinal function and are easy to perform.

Analysis of the human growth hormone receptor and IGF-I coding sequences in children with growth disorders.

Analysis of GHR and IGF-I coding sequences in 47 children with normal serum levels of GH, low IGF-I and growth disorders generally did not show mutation in the genes studied. Only one boy had a mutation located in the fifth exon of the GHR gene (C-->T in codon 88). This suggests that the growth disorders in this group of children might be due to a defect in a DNA region regulating expression of the GHR and IGF1 genes or genes involved in their regulation.

[Thyroid function and lipid metabolism in patients with anorexia nervosa]. / Czynnosc tarczycy a metabolizm tluszczów u osób z jadlowstretem psychicznym.

AIM: There are clinical similarities between anorexia nervosa (AN) and hypothyroidism. Previous reports have shown decrease FT3, increase rT3, sporadically decrease FT4 and normal levels of serum TSH. METHOD: To assess thyroid function in 36 patients with AN (4 males, 32 females the subjects ages ranged from 12 to 18 yrs) serum levels of FT4, FT3, rT3, TSH were measured. Out of this group, 24 patients have been singled out to examine the lipid metabolism by measuring the level of cholesterol, HDL, LDL, triglycerides. RESULTS: 67% (24) of the examined group resulted in low level of FT4 (0.75-0.97 ng/dcl), but decrease FT3 (= 0.67 pg/ml) was only found with 1 patient. The level of rT3 (measured in 94% (34) patients) were normal. The level of TSH were low (0.87-0.97 muIU/ml) in 25% (9) of patients, but 6 of them also manifested decrease FT4 (0.87-0.97 ng/dcl). At the same time, we found higher level of cholesterol in 63% of patients, decrease HDL in 71%. It is interesting to notice that in 80% of cases with a lipid metabolism disorder we found decrease FT4. CONCLUSIONS: Thyroid dysfunctions may be one of the essential reasons for lipid metabolism disorder in AN.

Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in children and adolescents.

Current methods of research into thyroid nodular disease (TND) based on the polymerase chain reaction (PCR) and reverse-transcription (RT) permit the detection of some markers, even in poorly cellular biological material. The findings from fine-needle aspiration biopsy (FNAB), the most commonly used procedure in TND, do not always correlate with the postoperative histopathological diagnosis, sometimes giving a false negative result. The aim of this present study was to improve the classical cytological evaluation of the material obtained with ultrasound-guided biopsy with a RT-PCR based technique in order to detect carcinoma even in a minimally invasive form. Aspirate from the 30 patients included in the study was smeared for conventional cytology (H+E and MGG staining) and the leftover material in the needle was frozen for subsequent PCR analysis. Fine-needle aspiration specimens were evaluated for the presence of galectin-3 (GAL-3), the most promising molecular marker of malignancy. As a positive control for cells of follicular origin, thyroglobulin (Tg) gene expression was performed. RT-PCR was performed on extracted RNA and with specific primers for the screened genes, based on a one-step reaction with a Biometra PCR machine. Tg expression was observed in 23 aspirates, among which 10 were positive for the expression of GAL-3 [3 cases of PTC, 1 an oxyphilic variant of FTC, 1 an oxyphilic variant of follicular adenoma (FA), 1 a foetal variant of FA, 2 of Hashimoto thyroiditis (HT) and 2 of HT with coexisting FA]. Our results are the first evidence that GAL-3 expression, previously documented in thyroid carcinoma of follicular origin, is also present in Hashimoto thyroiditis. This study reveals some limitations in nodule or multiple nodules of benign character. If the diagnosis of HT is excluded, then the usefulness of the method in the diagnosis of malignancy may still be very high.