Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland.

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.

Syndrome of Congenital Insulin Resistance Caused by a Novel INSR Gene Mutation

Mutations in the INSR gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin resistance type A. Leprechaunism is an autosomal recessive disorder associated with extreme insulin resistance that leads to hyperinsulinemia, impaired glucose homeostasis, fasting hypoglycemia and postprandial hyperglycemia. Impaired insulin action causes prenatal and postnatal growth retardation. Lipoatrophy, dysmorphic facies, hypertrichosis, macrogenitosomia and hypertrophy of internal organs are also present. A male infant with congenital insulin resistance was born at term after a normal pregnancy with a weight of 1905 g (<3 c), a length of 48 cm (<3 c), and an Apgar score of 10. Intrauterine growth retardation, transient hypoglycemia, pneumonia, urinary tract infection and heart defects [patent foramen ovale (PFO); patent ductus arteriosus (PDA)] were diagnosed after birth. At 5 weeks of age, he was admitted to the regional hospital with severe fever, diarrhea and dehydration. Hyperglycemia was observed (672 mg/dL), and insulin was administered. He was referred to a hospital at 7 weeks of age for suspected neonatal diabetes and hypertrophic cardiomyopathy. The physical examination revealed a loud systolic heart murmur, tachycardia, tachypnea, dysmorphic facies, hypertrichosis, acanthosis nigricans, hypotonia, swollen nipples and enlarged testicles. Glycemic fluctuations (50-250 mg/dL) were observed. The serum insulin concentration was high (maximum 1200 IU/mL) at normoglycemia. Ultrasound of the heart confirmed progressive hypertrophic cardiomyopathy. Leprechaunism was confirmed by genetic analysis of INSR, in which a novel c.320C>G; p. Thr107Arg homozygous missense mutation was found in exon 2.

Weight gain in type 1 diabetes during the SARS-CoV-2 pandemic. Does lockdown affect the metabolic control of pediatric patients?

Background and aims: Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population. Methods: Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed. Results: A total of 185 patients with T1D were included in the study (96 boys), aged 2-18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m2 vs. 20.9 ± 4.1 kg/m2, p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period. Conclusions: The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.

Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland.

Short stature resulting from SGA is an obligatory indication for treatment with rhGH. The aim of the study was to assess the response to rhGH treatment in patients treated in the years 2016−2020 in six clinical centers in Poland. During the analysis, auxological data were collected, and anthropometrical parameters (Ht, SDS Ht, HV and ΔHV) were reassessed. Subgroups of patients with dysmorphic features (DYSM), fetal alcohol syndrome (FAS) and Silver-Russel syndrome (SRS) were selected. The study group consisted of 235 children (137 boys). The medium initial age was 9.08 years, and 190 patients were in the prepubertal stage. The poor response to treatment was defined as ΔHt SDS < 0.3 and/or ΔHV < 3 cm/year. Seventeen per cent of all patients after the first year and 44% after the second year met the ΔHt SDS < 0.3 criterion, and 56% during the first and 73% during the second year met the ΔHV < 3 cm/year criterion. Our data suggest that patients with SRS may show the best response to treatment, which was sustained throughout the follow-up period. The best response in all subgroups was observed during the first 12 months of therapy. Although the proportion of patients meeting the poor response criteria was high, only a few patients exceeded the 97th percentile for IGF-1 concentration during the first year of treatment. This might suggest that increasing the dose of rhGH in the second treatment year in order to sustain accelerated HV would be safe in these patients.

Silver-Russell syndrome and Turner syndrome in a girl with short stature treated with growth hormone - case report.

INTRODUCTION: Silver-Russell syndrome (SRS) is a rare condition, affects one in 100,000 births. Turner syndrome (TS) is a chromosomal disorder, with an incidence of one in 2,500 females. Patient with SRS and mosaic 45, X/46,X,del(X) karyotypes can have a wide range of phenotypic manifestations. The aim of this article is to present a case report of a patient with an extremely rare and not reported so far genetically confirmed diagnose of Silver-Russell syndrome and Turner syndrome. CASE REPORT: The patient is a 9-years old girl who had a karyotype of 45,X on prenatal amniocytes. After delivery she was small for gestational age and her phenotype was quite consistent with Russell-Silver syndrome: characteristic dimorphic facial skeleton with a triangular face with prominent forehead, thin nose, hypotonia and hemihyperthrophy. The girl was admitted to hospital due to short stature and deep body weight deficiency. Skin fibroblast and DNA analysis showed mosaic karyotype 45,X[14]/46,X,del(X)(p21.2) and hypomethylation of a gene H19 located on chromosome 11p15. At present the patient is treated with growth hormone in our clinic with good therapeutic results. CONCLUSIONS: The diagnosis of one genetic disorder does not rule out the possibility of a second genetic disease. Early diagnosis of coexistence of two different genetic syndromes, although very difficult, may help with quickly, appropriate therapy for patients and prevent them from developing serious complications.

Complex glycerol kinase deficiency - long-term follow-up of two patients.

Complex glycerol kinase deficiency (CGKD) is a rare genetic syndrome which belongs to the group of contiguous gene syndromes and is caused by microdeletion of genes located in Xp21. Patients with CGKD present with features characteristic for adrenal hypoplasia, glycerol kinase deficiency, Duchenne muscular dystrophy and sometimes intellectual disability. We present a long-term follow-up of two unrelated boys with molecular diagnosis of complex glycerol kinase deficiency. Genetic examinations in both patients revealed a deletion on Xp21 chromosome including complete deletion of NR0B1 and GK genes. Additionally in patient 2 IL1RAPL1 genes were deleted. In separate MLPA test DMD gene deletion was diagnosed in both patients as follow: in patient 1 whole gene while in patient 2 the C-terminal region of DMD was deleted. Although the first symptom in both was salt loss syndrome, the course of the disease was different for them. We share our experience resulting from the opportunity of caring for patients with this rare disease from the beginning of their life to the end of pediatric care.

Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control.

Klotho concentration may be considered as a prognostic factor in the development of chronic complications of diabetes. Moreover, decrease in sKlotho concentration may contribute to beta cell apoptosis and type 1 diabetes development. The aim of this study was to evaluate if sKlotho protein concentration in children with type 1 diabetes (T1D) and its correlation with classical risk factors of chronic complications of diabetes: dysglycemia and endothelial dysfunction. Material and methods: In a cross-section single center study the levels of soluble Klotho protein in 80 T1D (37 boys) and 34 healthy children (controls, 15 boys). Micro- and macroangiopathy were excluded and renal function was normal in all participants. Serum sKlotho, sICAM-1, sVCAM-1 and E-selectin levels were measured. Results: The concentration of sKlotho was lower in T1D than in the controls (2041.9 ± 1017.6 pg/mL vs. 2790.3 ± 1423.9 pg/mL, p=0.0113). sICAM-1, sVCAM-1 and E-selectin concentrations were comparable in patients and controls. In T1D, sKlotho was not correlated with the duration of diabetes. Klotho and E-selectin were correlated with HbA1c (r=-0.31, P=0.0066 and r=0.25, P=0.0351, respectively), but not with AVBG and blood glucose SD. Correlations of sKlotho with total cholesterol (r=0.31, P=0.0129), HDL-cholesterol (r=0.43, P=0.0011) and LDL-cholesterol (r=0.28, P=0.0412), but not with triglycerides, were found. Likewise, Klotho was not correlated with sICAM-1, sVCAM-1, and E-selectin concentrations. Conclusions: This study reports the significantly lower level of s-Klotho in children with type 1 diabetes, correlated with HbA1c and HDL cholesterol, but not with the adhesion molecules concentrations nor the duration of the disease. Negative correlation between the levels of HbA1c and soluble Klotho may suggest its possible involvement in the development of chronic diabetes complications.

Treatment of severe primary IGF-1 deficiency using rhIGF-1 preparation - first three years of Polish experience.

INTRODUCTION: The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. MATERIAL AND METHODS: Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below -3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 µg/kg bw twice a day and was subsequently increased to an average of 100 µg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. RESULTS: Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. CONCLUSIONS: Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.

The assessment of skeletal status in young patients with Turner syndrome by 2 densitometric techniques: Phalangeal quantitative ultrasound and dual energy X-ray absorptiometry.

BACKGROUND: Studies using dual energy X-ray absorptiometry (DXA) demonstrate a reduction in bone mineral density (BMD) in children and adolescents with Turner syndrome (TS). However, these studies do not take into account changes in bone size, which influence BMD in the case of short-statured patients. Phalangeal quantitative ultrasound (phQUS) measurements have shown an ability to reveal changes due to skeletal growth, aging, and bone and mineral disorders. There is limited data on bone mineral status in girls with TS assessed by 2 different techniques, i.e., DXA and phQUS. OBJECTIVES: The aim of this study was to investigate the potential negative impact of TS on bone status and to assess whether densitometric values were related to former fractures. MATERIAL AND METHODS: In 43 TS girls aged 5-18 years, we evaluated bone status by 2 different densitometric techniques, DXA and phQUS. RESULTS: The mean lumbar spine areal bone mineral density (LS aBMD) Z-score was significantly lower than 0 (the hypothetical mean) compared to the reference population (p < 0.001). The mean LS aBMD height-adjusted Z-score did not differ significantly from 0. The amplitude-dependent speed of sound (Ad-SoS) Z-score was significantly lower than 0 compared with a Polish reference population. There were no significant differences between fractured and fracture-free patients as regards Ad-SoS Z-score and LS aBMD height-adjusted Z-score. CONCLUSIONS: Girls with TS have normal bone density adjusted for height, but significantly decreased phQUS values. Neither DXA nor phalangeal Ad-SoS can identify young TS patients with former fractures.

Metabolic disorders in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex disease. Depending on the used criteria the prevalence of PCOS ranges from 6 to 20%. It is necessary to exclude diseases leading to androgen excess. The participation of genetic and environmental factors is considered in the etiology of PCOS development. The highest rate of incidence of PCOS is assessed in girls who were born SGA and developed premature adrenarche later in life.The free androgen index (FAI) is concerned as the most sensitive marker of hyperandrogenaemia in PCOS although insulin resistance, anti-Müllerian hormone (AMH),and deficiency of vitamin D may intensify metabolic disturbances. The ultrasound criteria used in adolescent patients prefer the estimation of the ovarian volume or the ratio of ovarian stroma to total ovary, rather than the number of ovarian follicles. PCOS is connected with different metabolic disorders. Post-binding defect in signal transduction is responsible for insulin resistance. This defect results from an impaired activity of the kinase receptor. Moreover, the adipose tissue of PCOS women differs substantially from the tissue of the others according to morphology and function. The adipocytes produce lower amounts of adiponectin, which is an insulin-sensitizing agent. Dyspidemia with high triglycerides and low high density lipoprotein cholesterol concentrations is frequently noticed. Cardio-metabolic risk factors, insulin resistance, and endothelial dysfunction accompany PCOS from the very beginning. Oxidative stress plays a role as a link among systemic inflammation and dysfunction of endothelial cells and abnormal thecal cell action. The treatment efforts in PCOS depend on the patient's main problems. Modification of diet and lifestyle is the most important recommended advice to each woman independent of age and weight.

The Influence of GnRH Analog Therapy on Growth in Central Precocious Puberty.

BACKGROUND: Children with central precocious puberty (CPP) present various somatic and psychological abnormalities. OBJECTIVES: The aim of the study was to evaluate growth changes in girls with central precocious puberty treated with GnRH analog therapy and to analyze the factors affecting the auxological response to this treatment. MATERIAL AND METHODS: The study group consisted of 40 girls with puberty onset aged 6.0 ± 1.9 years (mean, ± SD), treated with 3.75 mg decapeptyl depot intramuscularly every 28 days. The treatment was initiated at the age of 7.5 ± 2.2 years and continued for 3.3 ± 2.3 years, until the age of 11.4 ± 0.9 years. Height (Ht), height standard deviation score (HtSDS), statural age, bone age and Ht prediction. RESULTS: During the treatment a decline in HtSDS from 2.0 ± 1.36 to 1.24 ± 1.0 was observed (p = 0.0002); and a deceleration in the maturation of bones of 1.0 ± 0.29 year in the first year and 0.66 ± 0.33 year in the following years (p = 0.0008). The HtSDS at the end of the treatment was significantly higher than was predicted in pretreatment (1.33 ± 1.04 vs. 0.07 ± 1.39, p = 0.0005). Ht and HtSDS after treatment were positively correlated with the predicted Ht (PAH) before treatment and negatively correlated with the bone age/statural age ratio before treatment (p < 0.05). The PAH before and after treatment correlated inversely with the bone age/statural age ratio (p < 0.05). Two subgroups were analyzed according to the patients' age when therapy was introduced: group 1 included girls who were under the age of 7 when therapy was introduced, and group 2 included girls aged 7 or older. There was a statistically significant difference in the PAH SDS before treatment between these two subgroups: Group I (-) 1.3 ± 1.8 vs. Group II (-) 0.14 ± 1.2 and there was no difference in the PAH SDS after treatment: Group I (-) 0.7 ± 1.1 vs. Group II 0.31 ± 1.2. CONCLUSIONS: The child's age at the beginning of GnRHa therapy was an important predictor of height prognosis; the therapy introduced under the age of 7 improves the PAH during treatment. Height prediction during the entire treatment period is worse in children with more advanced bone age for their statural age at the onset of treatment.

LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

INTRODUCTION: Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. AIM: A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. CASE REPORT: A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. CONCLUSION: In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed.

The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype.

OBJECTIVE: Published data on eye disorders in patients with Turner syndrome (TS) are limited. We aimed to evaluate the prevalence of eye disorders in patients with TS and assess the association with patient karyotype. DESIGN: Cross-sectional, observational study. PATIENTS: Eighty-two patients with TS. MEASUREMENTS: We evaluated visual acuity (distance and proximity), intraocular pressure, optic system refraction, orthoposition, frontal eye segment, the eye fundus and colour vision. For eye fundus abnormalities, we conducted ultrasound examinations, visual field evaluations and fluorescein angiography. We statistically tested the association between the prevalence of eye disorders and karyotype. RESULTS: 50 (61%) patients had monosomy X; 9 (11%) had mosaicism with a normal 46,XX line; 21 (26%) had structural aberrations; and 2 patients (2%) had other chromosomal abnormalities. Eye disorders were diagnosed in 43 (52%) patients, with 29 (35%) patients having multiple eye defects. Defects related to impaired vision were the most common (44%), followed by strabismus (21%), changes in the posterior eye segment (6%), red-green colour deficiency (5%), changes in the anterior eye segment (5%) and nystagmus (4%). Amblyopia was diagnosed in 13 patients (16%). The most common combinations of ophthalmological defects were hypermetropia and astigmatism with or without other eye problems (12 patients). We found no association between the presence of eye defects and karyotype. CONCLUSIONS: Detection of eye abnormalities is necessary in all patients directly after being diagnosed with TS to prevent irreversible deterioration of eye function and permanent poor vision. All girls with TS, irrespective of their karyotype, should be referred to an ophthalmologist.

Analysis of chosen polymorphisms in FoxP3 gene in children and adolescents with autoimmune thyroid diseases.

INTRODUCTION: Forkhead box P3 (Foxp3) is an important regulatory factor for the development and function of T regulatory (Treg) cells. Moreover, it has been established that deficiency of the Foxp3 gene in Treg cells suppresses their regulatory function leading to the development of autoimmune diseases especially autoimmune thyroid diseases. The aim of our study was to estimate the association of three polymorphism of FOXP3 gene with the predisposition to Graves' disease (GD) and Hashimoto's thyroiditis (HT) in children and adolescents. MATERIALS AND METHODS: The study was performed in the group consisting of 145 patients with GD (mean age, 16.5 ± 2 years), 87 patients with HT (mean age, 15.2 ± 2.2 years) sequentially recruited from the endocrinology outpatient clinic and 161 healthy volunteers (mean age, 16.3 ± 3 years). DNA was extracted from the peripheral blood leukocytes using a classical salting-out method. The three single nucleotide polymorphisms (SNPs) rs3761549 (-2383C/T), rs3761548 (-3279G/T) and rs3761547 (-3499T/C) in the FOXP3 gene were genotyped by TaqMan SNP genotyping assay using the real-time PCR method. The levels of thyroid hormones, TSH and anti-thyroid autoantibody were determined using chemiluminescence method. RESULTS: In our study, rs3761549G/A genotype was more frequent in female patients with GD in comparison to healthy female (15% vs. 7%, p = 0.033) with OR = 2.15 and 95% confidence interval for OR: 1.07-4.63. We have also observed rs3761547T/C to be more frequent in females with GD in comparison to control females, and this difference was close to statistically important (13% vs. 7%, p = 0.066) with OR = 1.99 and 95% confidence interval for OR: 0.96-4.48. There were no significant differences in males in analyzed SNPs and in females with rs3761548 SNP. CONCLUSION: In conclusion, these results may suggest that rs3761549G/A polymorphism in Foxp3 gene could contribute to GD development in females.

Thyroidectomy in children: changing trends and surgical strategies.

BACKGROUND: Surgical thyroid pathology is an uncommon problem in children and due to environmental factors may be locally-specific. Until the mid-90's, Lower Silesia had been regarded as a region of endemic goiter but since then a better system of iodine prophylaxis has been introduced. OBJECTIVES: To assess changing trends in the epidemiology of surgical thyroid diseases in children and to examine whether they have influenced potential alterations of operative strategies during the study period. MATERIAL AND METHODS: The medical records of all children operated on for thyroid disease between 1993 and 2010 in the university pediatric surgical center were retrospectively reviewed. The data regarding the indications for thyroidectomy, details of surgical management and outcome were collected and analyzed in three periods of time 1993-1998, 1999-2004 and 2005-2010. RESULTS: There were 46, 63 and 41 children operated on in the analyzed periods of time, respectively, with no significant differences regarding their age and gender. Preoperative thyroid ultrasound scan showed nodular lesions within the thyroid gland in 145 children (94.7%). The frequency of unilateral and bilateral nodular lesions was basically similar throughout the whole study. There has been a significant decrease of subtotal resections from around 63% in the first period to less than 16% in the other two periods of the study. The reverse trend can be clearly seen with regard to unilateral total lobectomy. Since 1999, total lobectomy or total thyroidectomy has been performed in more than 80% of the children. Nodular goiter was the most common indication for surgical operation followed by follicular adenoma. Malignant disease was recorded in 7 children (4.6%). CONCLUSIONS: The gradual decrease of the number of children with surgical pathology of the thyroid gland seems to reflect an effective iodine prophylaxis. Depending on the extent of thyroid disease, unilateral lobectomy, either alone or coupled with partial or total resection of the contralateral lobe should be a standard surgical procedure in children.

Multihormonal hypopituitarism, hypothyroidism and hypoparathyroidism in a 17-years-old girl with Diamond-Blackfan anemia and secondary hemochromatosis.

Congenital hypoplastic anemia (Diamond-Blakcfan syndrom) is a genetically determined disorder which is manifested in early childhood with selective deficiency of erythrocyte line in bone marrow. Severe anemia usually appears in the first six months of life. Survival depends on blood transfusions, which in consequence lead to hemochromatosis. The most common complications of transfusional hemochromatosis are hepatic cirrhosis, hypopituitarism, hypogonadism, diabetes mellitus, other endocrinopathies, and cardiomyopathy. We present the case of 17 years old girl with congenital hypoplastic anemia and multihormonal insufficiency due to secondary hemochromatosis.

Ganglioneuroma in a patient with Turner syndrome.

INTRODUCTION: Ganglioneuroma is a benign neuroblastal tumor that derives from immature cells of the sympathetic nerve system. It is a very rare disease and affects newborns and infants more often than adolescents and adults. The benign tumors are relatively difficult to diagnose since they usually are asymptomatic. We present a case of unusual coincidence of an ganglioneuroma and Turner syndrome (TS). CASE REPORT: An 11.5-year-old TS patient was admitted into the hospital with good general condition. She was 7 months into growth hormone (GH) therapy. The reason for the admission was to carry out control tests. The patient had not complains or abnormalities on physical examination. On the ultrasound examination of the abdomen in the right adrenal area an adrenal tumor was identified. The ultrasound examination of the abdomen performed 13 months earlier did not show any abnormalities. Computed tomography of adrenal glands confirmed right adrenal tumor. The hormonal function of the adrenal gland was normal. The treatment with GH was terminated and the patient was urgently referred to surgical management. The right adrenal gland tumor together with a part of diaphragm was removed. On histopathological examination ganglioneuroma maturum was diagnosed. On the control MIBG examination physiological gaining of tracer in the left adrenal and in the rest tissue in the area of the right adrenal was found. Trepanobiopsy did not confirm neoplastic changes. CONCLUSIONS: There is a necessity of careful monitoring of TS patients also in face of the possibility of disclosure previously not stated neoplasm after starting GH therapy. It is impossible to rule out that GH therapy promote growth of existing neoplasm.

[Klinefelter syndrome in a boy with symptoms of precocious puberty]. / Zespól Klinefeltera u chlopca z objawami przedwczesnego pokwitania.

Klinefelter syndrome is one of the most frequent sex chromosomal aberration. It is usually not recognized before puberty and many patients remain never diagnosed. Delayed puberty and hypergonadotropic hypogonadism are typical in this syndrome. Early diagnosis and therapy with androgens is important for patients. We present case of 8-year old boy with Klinefelter syndrome who was admitted to our department because of precocious puberty.

Complex glycerol kinase deficiency - X-linked contiguous gene syndrome involving congenital adrenal hypoplasia, glycerol kinase deficiency, muscular Duchenne dystrophy and intellectual disability (IL1RAPL gene deletion).

Contiguous gene syndromes are disorders caused by deletions of genes that are adjacent to one another. One of them is complex glycerol kinase deficiency. It is caused by partial deletion of Xp21, which includes the genes responsible for glycerol kinase deficiency, congenital adrenal hypoplasia, Duchenne muscular dystrophy and intellectual disability. There are no definite dysmorphic features for this syndrome. The diagnosis is based on clinical and laboratory findings. Symptoms depend on the size of deletion and appear almost exclusively in the male gender. Usually the first and most severe are the signs of adrenal hypoplasia, which, if not cured, may lead to death in a short time. The symptoms of glycerol kinase deficiency occur also early in life, but they may be masked by the deficiency of mineralocorticoids. Duchenne muscular dystrophy appears in childhood and is always accompanied by certain symptoms. Developmental retardation and intellectual disability occur often with complex glycerol kinase deficiency. The reasons for it are heterogeneous, but usually, there is a connection with the deletion of DMD or I L1R A P L genes. Due to the fact that loci of all genes responsible for complex glycerol kinase deficiency were determined, it is possible to carry out molecular examination, confirm clinical diagnosis and determine female carriers of the disorder.

[Thyroid ectopy - the presentation of four patients]. / Ektopia tarczycy - prezentacja czterech pacjentów.

Ectopy of the thyroid gland means its incorrect location most often along the midline of the body from the foramen cecum to the mediastinum, usually in the dorsum of the tongue. In 75% of patients, the lingual thyroid is the only active thyroid tissue. ectopic thyroid is frequently incidentally diagnosed in patients without symptoms of hypothyroidism. The authors present four patients with lingual location of the thyroid treated due to congenital hypothyroidism. in two of them, an ultrasound examination revealed thyroid tissue in a proper location in front of the trachea, however, the tissue did not show jodine-131 uptake on scintigraphy performed after four week-cessation of thyroxin treatment. The ectopic tissue can undergo the same pathological alterations as in the properly located gland (single or multiple nodules, inflammation, neoplasms), therefore, the monitoring by imaging techniques seems crucial.