GH-secreting pituitary adenoma in the course of McCune­Albright syndrome in a 21-year-old patient complicated by hepatocellular carcinoma.

Not required for Clinical Vignette.

The Variability of Vitamin D Concentrations in Short Children with Short Stature from Central Poland-The Effects of Insolation, Supplementation, and COVID-19 Pandemic Isolation.

The aim of the study was to investigate the effects of seasonal variability of insolation, the implementation of new recommendations for vitamin D supplementation (2018), and the SARS-CoV-2 pandemic lockdown (2020) on 25(OH)D concentrations in children from central Poland. The retrospective analysis of variability of 25(OH)D concentrations during the last 8 years was performed in a group of 1440 children with short stature, aged 3.0-18.0 years. Significant differences in 25(OH)D concentrations were found between the periods from mid-2014 to mid-2018, from mid-2018 to mid-2020, and from mid-2020 to mid-2022 (medians: 22.9, 26.0, and 29.9 ng/mL, respectively). Time series models created on the grounds of data from 6 years of the pre-pandemic period and used for prediction for the pandemic period explained over 80% of the seasonal variability of 25(OH)D concentrations, with overprediction for the first year of the pandemic and underprediction for the second year. A significant increase in 25(OH)D concentrations was observed both after the introduction of new vitamin D supplementation guidelines and during the SARS-CoV-2 pandemic; however, the scale of vitamin D deficiency and insufficiency was still too high. Time series models are useful in analyzing the impact of health policy interventions and pandemic restrictions on the seasonal variability of vitamin D concentrations.

Delayed Diagnosis of Congenital Combined Pituitary Hormone Deficiency including Severe Growth Hormone Deficiency in Children with Persistent Neonatal Hypoglycemia-Case Reports and Review.

Apart from stimulation of human growth and cell proliferation, growth hormone (GH) has pleiotropic metabolic effects in all periods of life. Severe GH deficiency is a common component of combined pituitary hormone deficiency (CPHD). CPHD may be caused by mutations in the genes encoding transcription factors and signaling molecules involved in normal pituitary development; however, often its genetic cause remains unknown. Symptoms depend on which hormone is deficient. The first symptom of GH or adrenocorticotropic hormone (ACTH) deficiency may be persistent hypoglycemia in apparently healthy newborns, which is often neglected. Diagnosing CPHD is based on decreased concentrations of hormones secreted by the anterior pituitary and peripheral endocrine glands. Findings in magnetic resonance imaging vary widely, including anterior pituitary hypoplasia/aplasia or pituitary stalk interruption syndrome (PSIS). Delayed diagnosis and treatment can be life-threatening. GH therapy is necessary to recover hypoglycemia and to improve auxological and psychomotor development. We present two girls, diagnosed and treated in our departments, in whom the diagnosis of CPHD was delayed, despite persistent neonatal hypoglycemia; and a review of similar cases, with attention paid to progress in the genetic assessments of such patients, since the introduction of whole exome sequencing that is especially important for PSIS.

The prevalence of hypothyroxinemia in premature newborns.

Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases.

Frequency of oligosymptomatic gastrointestinal tract diseases and its relation to insulin-like growth factor I in idiopathic (non-GH-deficient) short stature children.

INTRODUCTION: There is a discussion about growth hormone therapy in idiopathic short stature (ISS) children. To diagnose ISS, it is necessary to exclude other diseases; gastrointestinal tract diseases (GIDs) are among them. However, GID symptoms may be scarce. The aim of the study was to evaluate the frequency of unexpected oligosymptomatic GIDs in ISS and assess their influence on auxological parameters and insulin-like growth factor I (IGF-I) concentration. MATERIAL AND METHODS: The analysis included 101 children with ISS and 95 controls. All patients were tested for celiac disease (CD), inflammatory bowel disease (IBD), lactose malabsorption (LM), cystic fibrosis (CF), Helicobacter pylori (HP) and Ascaris sp. (Asc) infections, as well as Candida albicans (Calb) colonization, by applying simple blood and stool tests and gastrofiberoscopy. RESULTS: In 75.2% of short children, one or more than one GIDs listed above were diagnosed, with the highest frequency of: Calb (46.5%), LM (33.7%), HP (24.7%) and/or Asc (21.8%). The incidence of GIDs was significantly higher than in the control group. The GID frequency increases with the age of children. In most ISS children, the IGF-I SDS was below -1.0 and it was the lowest in children with HP (p < 0.05). CONCLUSIONS: High frequency of unexpected oligosymptomatic GIDs in children diagnosed with ISS indicates the need to search for gastrointestinal (GI) causes in each case of short stature in children. The pathomechanisms responsible for short stature in these cases may vary, although it seems that reduced production of IGF-I plays an important role.

Karyotype Abnormalities in the X Chromosome Predict Response to the Growth Hormone Therapy in Turner Syndrome.

Short stature is characteristic for Turner syndrome (TS) patients, and particular karyotype abnormalities of the X chromosome may be associated with different responsiveness to recombinant human GH (rhGH) therapy. The aim of the study was to analyze the effect of different types of TS karyotype abnormalities on the response to rhGH therapy. A total of 57 prepubertal patients with TS treated with rhGH with a 3 year follow-up were enrolled in the study and categorized according to their karyotype as X monosomy (n = 35), isochromosome (n = 11), marker chromosome (n = 5), or X-mosaicism (n = 6). Height and height velocity (HV) were evaluated annually. In the first year, all groups responded well to the therapy. In the second year, HV deteriorated significantly in X-monosomy and isochromosome in comparison to the remaining two groups (p = 0.0007). After 3 years of therapy, all patients improved the score in comparison to their target height, but better outcomes were achieved in patients with marker chromosome and X-mosaicism (p = 0.0072). X-monosomy or isochromosome determined a poorer response during the second and third year of rhGH therapy. The results of the study indicate that the effects of rhGH therapy in patients with TS may depend on the type of TS karyotype causing the syndrome.

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader-Willi Syndrome.

Genotype-phenotype correlation in patients with Prader-Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age-group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Effectiveness, economical and safety aspects of growth hormone (GH) therapy in growth promoting doses in patients with isolated GH deficiency after the attainment of near-final height. Is there a need to modify the criteria of therapy withdrawal?

INTRODUCTION: Apart from growth promotion, growth hormone (GH) has important metabolic effects. Patients with severe GH deficiency (GHD) should be treated with GH throughout life. Current criteria for growth promoting therapy withdrawal in Poland differ from the latest recommendations. Aim of the study To assess cost-effectiveness and safety of continuation of GH therapy in growth promoting doses in patients with isolated GHD after the attainment of near-final height (near-FH) and the incidence of persistent GHD after the therapy withdrawal. MATERIAL AND METHODS: 160 children with isolated GHD (height < 3 centile, GH peak < 10.0 µg/l), who continued GH therapy for growth promotion after the attainment of near-FH (height velocity   2.0) at near-FH and incidence of severe GHD in retesting (performed in 62 patients). RESULTS: Height gain after near-FH was 1.1 ±0.8 cm in boys and 1.0 ±0.8 in girls. Increase of height by 1.0 cm required on average 487 mg of GH (264 injections). IGF-1 concentrations at near-FH were increased in 39 patients, with no clinical side effects. None of the patients retested had GH peak   10.0 µg/l. CONCLUSIONS: There is no rationale to continue GH therapy in growth promoting doses in the patients with isolated GHD after fulfilling the criteria of near-FH.

Comparison of nocturnal and morning ghrelin concentration in children with growth hormone deficiency and with idiopathic short stature.

Ghrelin - a growth hormone (GH) secretagogue - presents a circadian rhythm with higher nocturnal than diurnal concentration (similar to GH). However, daily ghrelin production depends on food intake and nutritional state; it is increased in the fasting state and decreased after a meal. Since most past research concerning short stature children has relied on the morning ghrelin concentration for analyses, we decided to assess ghrelin concentration at the 60th and 90th minute after falling asleep and in the morning at 06:00 h, shortly after waking up from nighttime sleep (after 12 h of fasting). We compared these ghrelin concentrations to determine differences between nocturnal and morning ghrelin release in short children, both with idiopathic short stature (ISS) and growth hormone deficiency (GHD). We also analyzed the correlation between the nocturnal and morning ghrelin concentrations with nocturnal GH concentrations, measured at the same time points, as well as with maximal GH concentration, achieved by stimulation tests, and with the insulin-like growth factor I (IGF-I). The ghrelin and GH concentration 60th and 90th minute after falling asleep, as well as fasting morning ghrelin and IGF-I concentrations, were measured in 19 (n = 10 ISS and n = 9 GHD) prepubertal short children (7 girls and 12 boys), aged 10.36 ± 3.06 y. Differences between the nocturnal and morning ghrelin concentrations were analyzed by the Wilcoxon matched-pairs signed-rank test. Typical regression and correlation analyses were used to assess relationships among parametric data for other analyses. The Wilcoxon test showed ghrelin concentration is significantly higher in the morning than both at the 60th and 90th minute after falling asleep time points (in ISS and GHD). A significant correlation was observed: a) positive - between nocturnal ghrelin (both at the 60th and 90th minute) and morning ghrelin concentrations; b) positive - between ghrelin at the 60th minute and nocturnal GH concentrations (both at the 60th and 90th minute); c) negative - between ghrelin at the 60th minute and IGF-I concentrations; and d) negative - between body mass index and ghrelin concentrations at the 60th and 90th minute. We conclude: 1) in short children, both with GHD and with ISS, morning ghrelin level reflects its nocturnal concentration; however, it is significantly higher than the nocturnal ones. There is no significant difference between the measurement of ghrelin concentration at night at the 60th or 90th minute after falling asleep; 2) morning ghrelin concentration is affected by the hunger and satiety; therefore, it appears that nocturnal measurements better reflect the pool of hormone responsible for stimulation of GH and IGF-I secretion, especially since positive correlation between nocturnal ghrelin and nocturnal GH secretion was noted; 3) it seems that a higher body mass index is an additional independent factor, associated mainly with lower nocturnal (but not morning) ghrelin secretion.

Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency.

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <-3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGFGT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

Seasonality of vitamin D concentrations and the incidence of vitamin D deficiency in children and adolescents from central Poland.

INTRODUCTION: Vitamin D3 [25(OH)D] deficiency is a significant problem in Polish children. In many regions of the world, 25(OH)D concentrations show seasonal variation and differences between boys and girls, due to seasonal differences in insolation, as well as different sociological and cultural factors. THE AIM OF THE STUDY: The aim of the study was to assess the seasonal variations of 25(OH)D concentrations and the incidence of vitamin D deficiency in children from central Poland. MATERIAL AND METHODS: The analysis comprised 1275 children, age 3-18 (11.2 ±4.0) years, with disorders of growing and/or puberty, obesity, and other complaints that could be related to endocrine diseases, except for ones with calcium-phosphorus imbalance, impaired parathyroid hormone secretion, and diseases that may influence vitamin D supply. RESULTS: Seasonal variability of 25(OH)D concentrations was observed with maximal levels in August and minimal in January and close relationship between 25(OH)D levels and insolation in the previous two months. In all the quarters, 25(OH)D concentrations were lower in girls than in boys and in older vs. younger children. The median value of 25(OH)D concentrations was below the lower limit of optimal range during the whole year. High incidence of 25(OH)D deficiency was observed (from 10.7% in August to 80.4% in January) together with low proportion of normal 25(OH)D levels (from 3.6% in January to 42.1% in August). CONCLUSIONS: Our results are consistent with previous reports on inadequate vitamin D supplementation in Polish children and adolescents, pointing out the necessity to implement current recommendations concerning vitamin D supplementation and the need for further studies on the consequences vitamin D deficiency for health of children and adolescents, with special attention to the pleiotropic effects of vitamin D.

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.

Management of Prader-Willi Syndrome (PWS) in adults - what an endocrinologist needs to know. Recommendations of the Polish Society of Endocrinology and the Polish Society of Paediatric Endocrinology and Diabetology.

Prader-Willi syndrome (PWS) is a complex genetic disorder characterised by a set of phenotypic traits, which include infantile hypotonia, short stature, and morbid obesity. Over the last 12 years, visible progress has been made in medical care management of PWS patients in Poland. Increasing awareness of the disorder in neonatal and paediatric care has led to early identification of the condition in neonates, followed by the institution of an appropriate dietary regime, introduction of physiotherapy, and early-onset recombinant human growth hormone (rhGH) treatment. Growth hormone (GH) therapy in Poland is conducted within the nationwide framework of the Therapeutic Programme: "Treatment of Prader-Willi Syndrome". The therapeutic interventions initiated in the paediatric centres need to be continued in multidisciplinary adult care settings. The main aim of PWS clinical management in adulthood is prevention of obesity and its comor-bidities, treatment of hormonal disorders, mental health stabilisation, nutritional guidance, as well as on-going physiotherapy. Integrated multidisciplinary therapeutic intervention is necessary if patients with such a complex genetic condition as PWS are to not only achieve an average life expectancy but also to enjoy higher quality of life.

National Program of Severe Growth Hormone Deficiency Treatment in Adults and Adolescents after Completion of Growth Promoting Therapy.

Growth hormone (GH) has been used in the treatment of short stature in children with GH deficiency (GHD) for 60 years, and for about 30 years also in the treatment of adults with GHD, in whom such treatment is carried out due to metabolic indications. In Poland, GH treatment is reimbursed only in children with GHD, while so far it has not been refunded in adults with GHD. There are two groups of adults (or adolescents after growth completion) with GHD, who require GH therapy: patients with GHD that occurred in childhood (childhood-onset GHD - CO-GHD) and patients with GHD acquired in adulthood (adulthood-onset GHD - AO-GHD). This review presents a brief outline of the history of GH treatment in humans, the latest data on the causes and symptoms of GHD in adults, and the complications of untreated GHD. Current recommendations regarding diagnosis, treatment and monitoring of GH therapy in adults are also discussed. Moreover, the review paper presents the objectives, assumptions, and plans of implementation of the "National Treatment Program for Severe Growth Hormone Deficiency in Adults and Adolescents after Completion of the Growth Promoting Therapy", as well as the expected health and economic effects of introduction of GH treatment in adults with GHD in Poland.

Pre-treatment growth and IGF-I deficiency as main predictors of response to growth hormone therapy in neural models.

Mathematical models have been applied in prediction of growth hormone treatment effectiveness in children since the end of 1990s. Usually they were multiple linear regression models; however, there are also examples derived by empirical non-linear methods. Proposed solution consists in application of machine learning technique - artificial neural networks - to analyse this problem. This new methodology, contrary to previous ones, allows detection of both linear and non-linear dependencies without assuming their character a priori The aims of this work included: development of models predicting separately growth during 1st year of treatment and final height as well as identification of important predictors and in-depth analysis of their influence on treatment's effectiveness. The models were derived on the basis of clinical data of 272 patients treated for at least 1 year, 133 of whom have already attained final height. Starting from models containing 17 and 20 potential predictors, respectively for 1st year and final height model, we were able to reduce their number to 9 and 10. Basing on the final models, IGF-I concentration and earlier growth were indicated as belonging to most important predictors of response to GH therapy, while results of GH secretion tests were automatically excluded as insignificant. Moreover, majority of the dependencies were observed to be non-linear, thus using neural networks seems to be reasonable approach despite it being more complex than previously applied methods.

Relationship between IGF-I Concentration and Metabolic Profile in Children with Growth Hormone Deficiency: The Influence of Children's Nutritional State as well as the Ghrelin, Leptin, Adiponectin, and Resistin Serum Concentrations.

BACKGROUND: Some, however not all, children with growth hormone deficiency (GHD) reveal a tendency towards metabolic disorders. Insulin-like growth factor I (IGF-I) is the main mediator of GH anabolic effects. OBJECTIVE: The aim of the study was to compare ghrelin, adiponectin, leptin, resistin, lipid, glucose, and insulin concentrations in GHD children, depending on the IGF-I bioavailability. METHODS: The analysis comprised 26 children with GHD, aged 5.7-15.3 yrs. Fasting serum concentrations of IGF-I, IGFBP-3, ghrelin, leptin, adiponectin, resistin, lipids, glucose, and insulin were measured. The GHD children were divided into two subgroups: (1) with lower IGF-I/IGFBP-3 molar ratio and (2) with higher IGF-I/IGFBP-3 molar ratio. The control group consisted of 39 healthy children, aged 5.1-16.6 yrs, of normal height and body mass. RESULTS: GHD children with lower IGF-I/IGFBP-3 molar ratio were found to have a significantly lower body mass and insulin and triglyceride concentrations, as well as significantly higher ghrelin and adiponectin concentrations than GHD children with higher IGF-I/IGFBP-3. CONCLUSIONS: A better metabolic profile characterised GHD children with low IGF-I bioavailability. This phenomenon may be the result of high adiponectin and ghrelin concentrations in those children and their influence on adipose tissue, glucose uptake, and orexigenic axis.

Nutritional Status in Short Stature Children Is Related to Both Ghrelin and Insulin-like Growth Factor I Concentrations.

OBJECTIVES: Ghrelin plays an important role in the growth processes in children. In addition, it regulates appetite. The aim of the study was to assess ghrelin and insulin-like growth factor type I (IGF-I) concentrations in children with idiopathic short stature, dependent on nutritional status. METHODS: The study group included 116 children, ages 10.6 ±â€Š3.5 years (mean ±â€Šstandard deviation), with idiopathic short stature (height <-2.0 standard deviation scores [SDS], maximal growth hormone [GH] secretion during 2 GH-stimulating tests->10 ng/mL). In each child, fasting ghrelin, IGF-I, insulin-like growth factor binding protein 3 (IGFBP-3), glucose, insulin, lipids, leptin, adiponectin, and resistin concentrations were assessed. The IGF-I/IGFBP-3 molar ratio was calculated to determine the IGF-I bioavailability. According to body mass index SDS calculated for height age, the children were divided into 3 groups: poorly nourished (thin), normal, and obese. The control group consisted of 19 healthy children, ages 11.0 ±â€Š3.5 years, with normal body weight and height. RESULTS: Ghrelin concentration was significantly higher in short, thin children than in short, obese children (1458.3 ±â€Š798.5 vs 917.2 ±â€Š303.0 pg/mL; P < 0.005). In turn, IGF-I/IGFBP-3 molar ratio was significantly lower in short, thin children than in short, obese children (0.16 ±â€Š0.06 vs 0.28 ±â€Š0.15; P < 0.005). CONCLUSIONS: In short, thin children, despite elevated ghrelin production, the low IGF-I concentration is observed, probably due to undernutrition and worse IGF-I formation. In short, normal-weight children and in short, obese ones, ghrelin and IGF-I production is normal, and it seems that mechanisms responsible for their short stature are other than low IGF-I.