Subclinical hypothyroidism in children and adolescents as mild dysfunction of the thyroid gland: a single-center study.

INTRODUCTION: Subclinical hypothyroidism (SH) is a biochemical diagnosis made when a serum thyroid-stimulating hormone (TSH) is ele-vated with circulating thyroid hormone levels within their reference ranges. AIM OF THE STUDY: Aim of our prospective non-randomized study was to evaluate the course of SH. MATERIAL AND METHODS: All patients with suspicion of SH referred to the Endocrinology Outpatient Clinic between 2014 and 2018 were recruited to prospective study. RESULTS: A total of 130 patients with SH were recruited for this study. Thirty-five (26.9%) patients were followed up without levothy-roxine (L-T4) (SH-T0 group) and therapy with L-T4 was randomly introduced in 95/130 (73.1%) SH children (SH-T1 group). We did not find statistical differences in hSDS and BMI Z-score between the SH-T0 and SH-T1 groups (p = 0.761 and p = 0.843, respectively). Introducing L-T4 in patients with short stature did not affect the linear growth at the end of FU ex-pressed as hSDS. OH developed in six children (6.3%) in the SH-T1 group. After conducting a multivariate logistic regres-sion, we found that the baseline TSH concentration and BMI Z-score are possible predictors of OH. CONSLUSIONS: Our study confirmed a low risk of progression of SH to overt hypothyroidism. The majority of patients remains SH or resolved for nor-mal thyroid function. The L-T4 therapy did not effect on linear growth and body weight. The main predictor of worsening to hypothyroidism were a higher TSH level and Z-score BMI.

Long-term follow up of carbohydrate metabolism and adverse events after termination of Omnitrope® treatment in children born small for gestational age.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy can affect carbohydrate metabolism and lead to impaired glucose tolerance during treatment. In addition, short children born small for gestational age (SGA) are predisposed to metabolic abnormalities. This study assessed the long-term safety of rhGH (Omnitrope®) use in short children born SGA. METHODS: This was a follow-up observational study of patients from a phase IV study. The baseline visit was the final visit of the phase IV study. Further visits were planned after 6 months (F1), 1 year (F2), 5 years (F3), and 10 years (F4). The primary objective was to evaluate the long-term effect of rhGH treatment on the development of diabetes mellitus; secondary objectives included incidence/severity of adverse events (AEs). RESULTS: In total, 130 subjects were enrolled in the follow-up study; 99 completed F1, 88 completed F2, and 13 completed F3 (no subject reached F4). The full analysis set for evaluation comprised 118 patients (64 female). Mean (standard deviation) duration of follow up was 39.6 (24.4) months. No subject was newly diagnosed with diabetes. The results for carbohydrate metabolism parameters were consistent with this finding. A total of 144 AEs were reported in 54 subjects; these were mostly of mild-to-moderate intensity (96.5%) and not suspected to be related to previous rhGH treatment (94.4%). Serious AEs (n = 18) were reported in eight patients; three (in one patient) were suspected as possibly related to previous rhGH treatment (anemia, menorrhagia, oligomenorrhoea). One fatal event occurred (sepsis), which was judged as not related to previous rhGH treatment. CONCLUSIONS: None of the participating subjects, who had all been previously treated with Omnitrope® in a phase IV study, developed diabetes during this follow-up study. In addition, no other unexpected or concerning safety signals were observed.

Subclinical Hypothyroidism as the Most Common Thyroid Dysfunction Status in Children With Down's Syndrome.

Introduction: Thyroid dysfunctions are one of the most common abnormalities coexisting in children with Down's syndrome (DS) and have been reported in up to 54% of cases. Aim of the Study: The purposes of this retrospective study were to investigate the course of subclinical hypothyroidism in children with DS, to evaluate the thyroid function of these subjects in relation to the risk of developing overt thyroid disease and autoimmunity, and to identify clinical and biochemical characteristics of patients prescribed L-T4 therapy in children and adolescents with DS and SH. Material and Methods: The records of DS patients referred to the Endocrinology Outpatient Clinic between 2010 and 2015 for screening of thyroid function were observed till the end of 2019 June and analyzed retrospectively. The children diagnosed with congenital hypothyroidism, acute lymphoblastic leukemia, and seizures and treated with drugs that may have interfered with thyroid function like lithium, antiepileptic, or iodinated drugs and glucocorticoids were excluded from the study. Results: The data of 77 DS patients were collected, evaluated, and analyzed. The study group consisted of 73 patients (32 girls and 41 boys with the mean age at baseline of 3.0 ± 4.5 years). A total of 63/73 (87%) children were diagnosed with SH. The 16/63 (25.4%) patients were followed-up without the treatment (group SH-T0), and therapy with levothyroxine (L-T4) was introduced in 47/63 (74.6%) SH children with a mean dosage of 1.8 ± 1.0 µg/kg/day (group SH-T1). Thyroxine supplementation did not improve growth expressed as ΔhSDS (0.1 ± 1.3, ranged -2.1 to 3.8 in SH-T0 vs. 0.0 ± 0.7, ranged -1.7 to 1.4 in SH-T1, p = 0.96) and ΔBMI Z-score (0.3 ± 0.9, ranged -0.9 to 2.6 in SH-T0 vs. 0.3 ± 1.1, ranged -2.1 to 2.9 in SH-T1, p = 0.65). Positive anti-TPO and anti-TG antibodies were detected in 7/63 (11.1%) DS cases. Conclusions: SH is the most frequent presentation of thyroid gland dysfunction in DS children. A small percentage of patients develop an overt hypothyroidism, particularly in females with mostly positive titer of antithyroid autoantibodies.

Growth hormone therapy in children with partial growth hormone deficiency. Are we treating the right patients?

INTRODUCTION: Diagnosis of growth hormone deficiency (GHD) in children with short stature, whose height is below -2SD for the population norm, is based on the assessment of growth hormone (GH) peaks in stimulation tests. However, cut-off values for GH secretion are arbitrary and vary in different centres. Indications for recombinant GH therapy remain disputable in children with GH concentrations between 5 and 10 ng/ml (pGHD). AIM OF THE STUDY: The aim of our study was to assess the effects of rhGH therapy in children with transient pGHD deficiency compared to untreated children with idiopathic short stature (ISS). MATERIAL AND METHODS: The study group comprised 54 patients at the mean age of 13.5 (SD 2.36) years, who were diagnosed as pGHD and treated with rhGH. The control group comprised 32 subjects with ISS matched for sex and age, untreated with rhGH. RESULTS: Mean final height was within the normal range for population norms in both groups. The average height gain was statistically significant at -1.3 SD (p < 0.001) for the study group and -1.02 SD (p ≤ 0.001) for the control group. However after exclusion of children with familial short stature (FSS) the height gains were, respectively, 1.41 SD ±0.67 for the study group and 1.22 SD ±0.77 for the control group, without statistical significance. CONCLUSIONS: The results of our study did not show beneficial effects of rhGH treatment in children with pGHD as compared to untreated ISS subjects. Therefore, it is necessary to determine criteria other than arbitrarily established GH concentration for starting rhGH treatment in children with pGHD.

Trichorhinophalangeal syndrome as a diagnostic and therapeutic challenge for paediatric endocrinologists.

Trichorhinophalangeal syndrome (TRPS) is rare genetic disorder with autosomal dominant inheritance. The TRPS1 gene is located on the long arm of the eighth chromosome (8q24.12). The phenotype is variable and presents a wide clinical spectrum. Most cases are characterised by thin, sparse scalp hair, distinctive facial dysmorphism, and various skeletal abnormalities, especially of the hands and feet. Characteristic facial features may include a "pear-shaped" nose, micrognathia, dental anomalies, prominent ears, elongated philtrum, and thin upper vermillion border. In most cases, affected individuals exhibit skeletal abnormalities including brachydactyly and clinodac-tyly, short metacarpals phalanges, short feet and metatarsals, and pectus carinatum and hip joint malformations. Additionally, patients may exhibit short stature. This report presents four cases of TRPS (three sporadic and one familial). Clinical presentation included typical facial features and vari-ous skeletal abnormalities. Some TRPS symptoms may mimic growth hormone deficiency and other endocrine disturbances. The aim of this article is to deliver TRPS symptomatology. The treatment of TRPS is symptomatic and supportive and requires the coordination of several specialists, including paediatricians, endocrinologists, orthopaedic surgeons, dermatologists, and medical rehabilitation and den-tal specialists. In some cases, recombinant growth hormone therapy may be necessary. Genetic counselling may be of benefit for affect-ed individuals and their families.

Clinical and Biochemical Phenotype of Adolescent Males with Gynecomastia

Objective: Gynecomastia is defined as a benign proliferation of male breast glandular tissue. Its prevalence during puberty varies between 50-60% and is also common in neonatal and elderly males. It develops mainly due to the disequilibrium between estrogen and androgen activity in breast tissue, where estradiol (E2) binds to estrogen receptors and stimulates ductal and glandular cells. The aim of this work was to investigate the relationship between sex hormone alterations and the natural history of gynecomastia. Methods: Participants in this study were young males referred to an outpatient clinic, between January 2011 and February 2016, with breast enlargement. Thyroid function, liver function, hormone concentrations and tumor markers were measured and anthropometric assessment was conducted. Results: Subjects comprised 93 males, aged 9 to 18 (mean±standard deviation age 13.8±2.6) years. In 63 of 93 (67.7%) the gynecomastia was confirmed and 28 were followed-up for a median period of three months. None of the boys showed any reduction in breast size during follow-up. There was no correlation between body mass index Z-score and breast size. Breast enlargement progressed in nine boys (32.1%). A positive correlation between estrogen to testosterone (E2/TTE) ratio and Tanner B stage (r=0.47; p=0.034) was observed. Conclusion: The E2/TTE ratio may be a helpful tool in diagnosing gynecomastia. Altered E2/TTE ratio might be responsible for a proportion of cases described previously as idiopathic. Additionally, weight loss does not imply reduction of breast size in boys. Nonetheless it should be the first step in the management of prolonged gynecomastia.

Resistance to thyroid hormone with a mutation of the thyroid ß receptor gene in an eight-month-old infant - a case report.

INTRODUCTION: Resistance to thyroid hormone (RTHß) is a rare syndrome of impaired tissue responsiveness to thyroid hormones (THs). The disorder has an autosomal dominant or recessive pattern of inheritance. Most of the reported mutations have been detected in the thyroid hormone receptorß gene (THRß). CASE REPORT: Authors present an eight-month-old infant with poor linear growth, decreased body weight, tachycardia, positive family history, and neonatal features suggestive of RTHß. Both our patient and his mother had elevated free thyroxine, free triiodothyronine, and non-suppressed thyrotropin (TSH) concentration. The fluorescent sequencing analysis showed a heterozygous mutation c.728G>A in TRß gene. This pathogenic variant is known to be associated with THR. CONCLUSIONS: The clinical presentation of RTHb is variable, ranging from isolated biochemical abnormalities to symptoms of thyrotoxicosis or hypothyroidism. The syndrome should be suspected in patients with increased serum TH level, accompanied by a normal or elevated TSH concentration. The affected patients require individualised management.

[Myasthenia gravis, Graves-Basedow disease and other autoimmune diseases in patient with diabetes type 1 - APS-3 case report, therapeutic complications]. / Miastenia, ch. Gravesa-Basedowa i inne zaburzenia autoimmunizacyjneu pacjentki z cukrzyca typu 1 ­ prezentacja przypadku APS-3, trudnosciterapeutyczne.

Diabetes type 1(T1D) is the most frequent form of diabetes in children and young people, which essence is autoimmune destruction of pancreatic B cells islet. Co-occurrence of other autoimmune diseases is observed in children with T1D, the most often are: Hashimoto disease or coeliac disease. We report the case of the patient, who presents coincidence of T1D with other rare autoimmune diseases such as: Graves - Basedow disease, myasthenia gravis, vitiligo and IgA deficiency. All mentioned diseases significantly complicated both endocrine and diabetic treatment of our patient and they negatively contributed her quality of life. The clinical picture of the case allows to recognize one of the autoimmune polyendocrine syndromes: APS-3 and is associated with still high risk of developing another autoimmune disease.

Auxologic parameters and response to 2-year therapy with recombinant human growth hormone in growth hormone deficient children with an ectopic posterior pituitary.

BACKGROUND: Structural defects of the hypothalamic-pituitary area in MRI are suggested as being a more accurate marker of growth hormone deficiency (GHD) than laboratory assays. OBJECTIVE: To compare auxological characteristics in GHD children with normal pituitary (NP) function and with ectopic posterior pituitary (EPP), prior to therapy with recombinant human growth hormone (rhGH), extending the follow-up to two years following treatment. DESIGN: Eighty-six (86) GHD patients were divided into two groups depending on the pituitary MRI: the EPP (23 children, 3.2-16.8 years old) and the NP group (63 children, 3.3-14.8 years old). Height deficits in the population (hSD) and parents (hSD-mpSD) and the change of hSD and bone/chronological age ratio were assessed before and after 12 and 24 months of rhGH therapy. RESULTS: Height deficits before treatment were significantly greater in EPP compared to NP [median -4.07 (-7.06, -2.75) vs -3.15 (-4.9, -2.35) for hSD, and -3.65 (-7.06, -1.21) vs -1.83 (-4.31, -0.28) for hSD-mpSD; p<0.05]. Bone age was significantly delayed in the EPP group [0.62 (0.27, 0.92) vs 0.75 (0.21, 0.71); p<0.05]; differences remained significant during follow-up. After 12 months of rhGH therapy, EPP showed significantly greater catch-up growth compared to NP [ΔhSD=1.2 (0.42, 2.69) vs 0.74 (0.05, 1.48); p<0.05]. In the 2nd year, height velocity slowed down and was comparable in the two groups. At the conclusion of the study, hSD was similar in both groups, but hSD-mpSD was more deviated in EPP [-1.79 (-3.71, -1.21) vs -1.1 (0.98, -0.07); p<0.05]. CONCLUSIONS: The study showed relevant auxologic differences between EPP and NP children, as well as beneficial effects of rhGH therapy in both groups.

How does autoimmune thyroiditis in children with type 1 diabetes mellitus influence glycemic control, lipid profile and thyroid volume?

AIM: To investigate whether autoimmune thyroiditis (AIT) in children with type 1 diabetes mellitus (DM1) has any influence on glycemic control, lipid profile or thyroid volume. METHODS: A total of 330 patients with DM1 and AIT (DM1+AIT group) were compared with 309 children with DM1 without AIT (control group). Patients were treated in four Polish academic pediatric diabetes centers from 2008 to 2012: Warsaw, Lodz, Katowice and Gdansk. All patients underwent measurements of thyroid-stimulating hormone (TSH), free thyroxine, anti-thyroid peroxidase (anti-TPO) antibody, anti-thyroglobulin (anti-TG) antibody and HbA1c levels, and thyroid ultrasound examination. RESULTS: Among AIT+DM1 patients, 62% (n=205) were female, whereas in the control group 60.8% (n=188) were male (p<0.0001). Children with AIT+DM1 had lower a BMI-SDS (mean difference of -0.5, 95% CI -0.68 to -0.33; p<0.0001), had a higher SDS thyroid volume (0.27, 95% CI 0.03-0.51; p=0.014) and needed less insulin (-0.15, 95% CI -0.20 to -0.11 U/kg body weight per day; p<0.0001) in comparison with the control group. AIT patients had higher HbA1c levels (0.66, 95% CI 0.36%-0.96%, p<0.0001), lower HDL-cholesterol levels (-3.68, 95% CI -1.41 to -5.94 mg/dL, p=0.002) and higher triglyceride levels (7.16, 95% CI 1.22-13.10 mg/dL, p=0.02). Patients with positive anti-TPO and anti-TG antibodies were older (by 1.95 years, 95% CI 0.98-2.92 years, p=0.006) and had longer DM1 duration (by 1.64 years, 95% CI 0.76-2.52 years, p=0.006). Presence of anti-TPO antibodies was associated with higher TSH levels (odds ratio 2.34, 95% CI 1.36-4.04; p=0.007). CONCLUSION: AIT accompanying DM1 is associated with worse glycemic control and lipid profile as well as a lower daily insulin requirement. The female gender is more likely to develop AIT and hypothyroidism.

Carbohydrate-lipid profile and use of metformin with micronized fenofibrate in reducing metabolic consequences of craniopharyngioma treatment in children: single institution experience.

AIM: To evaluate auxology and metabolic disturbances in children with craniopharyngioma, and to present observational results of treatment of metabolic sequels with metformin and micronized fenofibrate. METHODS: The studied group comprised 22 children [median age at diagnosis 10.5 (0.17-16.75) years; median follow-up 5.1 years]. Assessment included height standard deviations (SDS), body mass index (BMI) SDS, concentrations of lipids, glucose and insulin (fasting or oral glucose tolerance test) and homeostatic model assessment of insulin resistance (HOMA-IR) index. Ten adolescents with hyperinsulinemia and dyslipidemia received therapy with metformin (500-1500 mg/daily) and micronized fenofibrate (160 mg/daily). RESULTS: At diagnosis, median hSDS was -1.66 (range: -4.08; +0.1). Nine (40.9%) children were growth hormone-treated. There was gradual increase of BMI SDS, 18 (81.8%) patients being overweight at the final assessment. Dyslipidaemia was found in 19 patients (86.4%), hyperinsulinaemia in 11 patients (50%) and elevated HOMA-IR in 15 patients (68.2%). Decrease of triglycerides [median 263.5 (171-362) mg/dL vs. 154 (102-183) mg/dL] and HOMA-IR [8.64 (5.08-12.65) vs. 4.68 (0.7-7.9)] was significant in the group treated with metformin and fenofibrate for 6 months. CONCLUSIONS: Significant auxologic changes and metabolic abnormalities were found in children treated for craniopharyngioma. The use of metformin and fenofibrate seemed to attenuate these disturbances in a short-term observation.

L-thyroxine stabilizes autoimmune inflammatory process in euthyroid nongoitrous children with Hashimoto's thyroiditis and type 1 diabetes mellitus.

OBJECTIVE: To investigate if L-thyroxine (T4) treatment may influence the clinical course of autoimmune thyroiditis (AIT) or prevent progression to subclinical or overt hypothyroidism in euthyroid nongoitrous pediatric patients with type 1 diabetes mellitus (T1DM) and AIT. METHODS: The study was performed in four Polish pediatric diabetes centers. Of 330 children with T1DM and AIT followed between 2008 and 2012, 101 received L-T4 and 160 underwent clinical observation for 24 months. Thyroid stimulating hormone (TSH), free T4 (fT4), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG), glycosylated hemoglobin (HbA1c) levels, and lipid profile were assessed in all patients. Ultrasonographic evaluation was also performed in all children at each examination. RESULTS: Patients treated with thyroid hormones had higher TSH levels (3.99; interquantile 3.5 to 4.52 vs. 2.09 mIU/L; interquantile 1.55 to 3.06; pp<0.0001). A fall in TSH level (0.87 mIU/L 95% CI 0.43-1.30; pp<0.0001) was documented after the first year of treatment. FT4 level did not differ between the groups at baseline (p=0.7434), but rose in the treatment group and fell in the control group [mean difference 0.78 95% CI-0.22-1.53 pmol/L (p=0.02) after 12 months and 0.98 95% CI 0.04-1.76 (p=0.005) after 24 months]. Higher levels of anti-TPO were initially found in the treated patients (pp<0.0001) and significantly decreased over the 24-month period (pp<0.0001). Children in the treatment group had higher anti-TG levels (pp<0.0001), which showed a borderline decrease (p=0.08) in time. In the control group, anti-TG levels rose marginally (p=0.06) during the study. CONCLUSIONS: The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.

Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study.

PURPOSE: The purpose of this study is to assess the relationship between magnetic resonance images (MRI) of the hypothalamic-pituitary (H-P) region and response to recombinant human growth hormone (rhGH) treatment in short children with growth hormone deficiency, basing on changes of auxologic parameters, as well as to answer the question if MRI may serve for selecting and monitoring the rhGH responders. PATIENTS AND METHODS: The study group comprised 85 children treated with rhGH, aged 7.3-18.7 years, followed for the mean period of 3.2 years (range, 2.1-9.5 years). Auxologic parameters (height deficit hSDS, deviation from the mid-parental height hSDS-mpSDS, bone delay index bone age/chronological age ratio (BA/CA)) were assessed before, during and at the end of rhGH treatment; growth velocity was calculated before and during rhGH therapy. Parameters were correlated with the MRI of the H-P region. RESULTS: Structural anomalies of the H-P region were found in 22 (25.9%) children: empty sella syndrome (ESS) in 12 (14.1%) patients, ectopic posterior pituitary (EPP) in ten (11.8%). Patients' height deficit and their deviation from parental height before rhGH therapy was significantly greater in the EPP group (median hSDS = -3.8; hSDS-mpSDS = -2.5), bone age delay was the greatest in the ESS group (median BA/CA = 0.69), after therapy - in the EPP group (median BA/CA = 0.82). Growth velocity improved in the first year of the rhGH therapy in all groups; however, the most significant acceleration was observed in the EPP group (median delta hSDS = 0.9), then stabilised and was comparable in all groups. CONCLUSIONS: MRI may be helpful in predicting response to the rhGH treatment, providing midline abnormalities are taken into account.

Practical approach to childhood craniopharyngioma: a role of an endocrinologist and a general paediatrician.

OBJECTIVES: The objectives of this study are to evaluate co-morbidities in patients with craniopharyngioma and to elaborate an interdisciplinary protocol of the follow-up. PATIENTS AND METHODS: The group comprised 15 children (median age at the diagnosis, 10.1; mean follow-up period, 4 years). All patients had surgical resection of the tumour: gross total in seven, subtotal or partial removal in eight cases. Surgery was followed by radiotherapy in ten cases for tumour residue or progression. Sexual development and auxology were evaluated at diagnosis and during follow-up. Hormones were determined by chemiluminescent immunometric assays. Antidiuretic hormone dysfunction was diagnosed on the grounds of clinical symptoms, water-electrolyte balance, urine specific gravity, and serum osmolality. Metabolic control was monitored by levels of glucose, insulin, lipids, and transaminases; insulin resistance was expressed by homeostatic model assessment (HOMA) index. RESULTS: At diagnosis, median height standard deviation score (hSDS) was -1.6 (five children being short-statured). Median change hSDS for the whole follow-up was 1.2 (four children decelerating growth). Diabetes insipidus was diagnosed in eight (within 0-1.8 years of the follow-up), hypocorticolism in eight, and hypothyroidism in 12 subjects (within 0-3.75 years for both endocrinopathies). Four patients required sex hormone replacement therapy. At diagnosis, five children were overweight; during follow-up, only four children sustained normal body mass index. Hypertransaminasaemia was found in three, dyslipidaemia in 11, and hyperinsulinaemia in seven patients (with elevated HOMA in four cases). CONCLUSIONS: On the grounds of these observations, the management of craniopharyngioma in our institution includes repeated hormonal and metabolic assays in chosen time intervals. Early detection of co-morbidities and their management involves interdisciplinary team.

[Coexistance of autoimmunological diseases with type 1 diabetes mellitus in young patients based on literature and own experience]. / Wspólwystepowania chorób autoimmunologicznych z cukrzyca typu 1 u mlodocianych chorych w oparciu o dane pismiennictwa i obserwacje wlasne.

Patients with autoimmune type 1 diabetes mellitus have often, besides immune diabetic markers, also other organ-specific antibodies. In many diabetic patients autoimmune thyroid diseases, i.e. Hashimoto thyroiditis and Grave's disease, with silent clinical course can be diagnosed. Because 50% of children with diabetes and significant titres of thyroid autoantibodies (ATA) develop thyroid problems within 3-4 years, examinations of thyroid antibodies should be performed yearly. In cases of significant antibody titres, thyroid function tests and ultrasound assessment are recommended in order to minimize the risk of undiagnosed hypothyroidism in these patients. Coeliac is an other disease commonly coexisting with type 1 diabetes mellitus and autoimmune thyroid diseases. It is recommended that screening for coeliac disease should be part of the routine investigation for all patients. Potential benefits of treatment coeliac disease is more prevalent in individuals with type 1 diabetes mellitus, and when untreated is associated with a number of medical complications, including poor glycaemic control. Identification of patients with coeliac has been facilitated in recent years by serological screening. Initial normal screening does not exclude coeliac and repeated screening is indicated, a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.

[Causes of precocious puberty in children referred for evaluation in hospital conditions]. / Przyczyny przedwczesnego dojrzewania dzieci kierowanych do dianostyki w warunkach szpitalnych.

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.

Angelman syndrome and hypothyroidism - coincidence or unique correlation?

Angelman Syndrome (AS, MIM 105830), classified among neurogenetic disorders, occurs with estimated frequency of 1:10 000 to 1:40 000. The characteristics features apart from neurodevelopmental impairment and seizures include peculiar face traits, absent speech, outburst of laughter, ataxia, stereotyped jerky (puppet-like) movements. The authors report three children with Angelman syndrome who were also diagnosed with hypothyroidism.

Growth hormone deficiency associated with moyamoya disease in a 16 year-old boy.

Moyamoya disease is a rare cerebrovascular disorder which, according to a few literature reports, can coexist with hypothalamic-pituitary dysfunction. We report a 16 year-old boy referred to our Department because of short stature and headaches. He additionally, at admission, presented discrete facial dysmorphy, bruxism, luxation of temporomandibular joint and cryptorchidism. The height was 146 cm (-4.3 SDS); the sexual development was P2G2A1 and the bone age 11.5 years. The intellectual development was normal. No focal neurological deficits were observed. Based on baseline and stimulated hormonal values, isolated growth hormone deficiency was diagnosed. Malformation of the cerebral vessel was suspected on magnetic resonance imaging and upon angiocomputed tomography and panangiography, a picture suggesting moyamoya disease was obtained. Growth hormone has been administered with daily injections at the dose of 0.025 mg/kg/24h, and the first year height velocity was 12 cm/yr. No adverse events resulting from the treatment have been noted so far. This case indicates that GH deficiency may be associated with moyamoya disease, possibly resulting from chronic cerebrovascular insufficiency.

[Assessment of thyrotropin concentrations in children with somatotropin deficiency treated with growth hormone]. / Ocena stezen tyreotropiny u dzieci z somatotropinowa niedoczynnoscia przysadki, leczonych hormonem wzrostu.

BACKGROUND: There are contradictory literature opinions on the influence of GH therapy on the hypothalamus-hypophysis-thyroid gland axis concerning TSH secretion. Some researchers describe the possibility of complete inhibition of TSH secretion followed by overt hypothyroidism, the others do not confirm it. OBJECTIVE: The aim of the study was to assess influence of the rGH therapy on TSH concentrations in GH-deficient children, who were euthyroid prior to the treatment. MATERIAL AND METHODS: The study was carried out in a group of 32 children with isolated GH-deficiency in the 1st stage of sexual development according to the Tanner scale, in whom disorders of thyroid gland were excluded (T4, T3, fT4, fT3, TRH test). Recombinant GH (Genotropin a 16U-Pharmacia) was used for the treatment in the dose of 0.7 U/kg/week. Before the treatment, as well as in the 6th and 12th month of GH administration, the TRH test was performed and TSH levels were assessed in 0', 20', 30', 60' and 120 minute. The results were statistically analysed [p(alpha)<0.05]. RESULTS: Basal TSH levels prior to rGH administration were within normal range and the TSH response on TRH was normal with the maximal increase in the 20th minute. A statistically significant decrease of TSH concentrations was noted after 6 and 12 months of treatment in respective minutes of the test in all children. However, decreased TSH concentrations during the therapy were within normal range. CONCLUSIONS: During rGH therapy there is a decrease of basal and simulated TSH concentrations, however within the normal range. This phenomenon is probably connected with a direct effect of administered rGH on the release of somatostatin, a natural TSH inhibitor.

[Ultrasound examination of the scrotum in boys]. / Badanie sonograficzne worka mosznowego u chlopców.

BACKGROUND: Ultrasound examination is applied in the objective evaluation of size of scrotal structures as well as in diagnosing focal and inflammatory lesions in testes and epididymis. AIM: The aim of our study is to point out the necessity and significance of the ultrasound in diagnostics of abnormalities within the scrotum in boys. MATERIAL AND METHODS: The examination included 180 boys, aged 2-17 years, referred because of gynecomastia (70), cryptorchism (45), precocious puberty (11), palpable thickenings of the spermatic cord (30) and asymmetry of testicular size (24). Ultrasound examination was carried out with Acuson 128 XP, linear transducer 7.5 MHz, along with color flow Doppler (and/or Sequoia, linear transducer 8-15 MHz). RESULTS: Testes in the inguinal canals at different levels were visualised in all boys with unilateral or bilateral cryptorchism. Varicocele were seen in 19 boys with gynecomastia, epididymal cysts in 10, microlithiasis in 3 cases. Testicular volume in boys with precocious puberty exceeded 2 SD, additionally there was microlithiasis in one patient, in 2 patients varicocele and in one boy tumor was found (Leydig's cell tumor). Varices were left-sided in 95% boys with varicocele, in 5% they were bilateral at different stage. Additionally in one patient hygroma of the spermatic cord was found. Asymmetry of testicular size was caused by hydrocele in 16 patients and varicocele in 8 cases. CONCLUSIONS: Ultrasound is supplementary to the physical examination of testes, and in many cases it enables to reveal lesions inaccessible in the clinical examination. Considering its non-invasive character and high-resolution, ultrasound is a useful imaging method of the scrotal structure in children.