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Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that lead to the dysfunction of the steroidogenesis pathway, resulting in steroid hormone deficiency of varied intensity. The cholesterol side-chain cleavage enzyme (P450scc), coded by the CYP11A1 gene, is vital to the first step in the biosynthesis of steroid hormones, which is the conversion of cholesterol to pregnenolone. Therefore, its deficiency causes a general steroid hormone shortage. Objective: We report a case of CAH caused by P450scc deficiency with complete 46, XY sex reversal, characteristic facial features (narrow middle section of the face, small ears with thick helix, fleshy upturned lobules), and dysmorphic macrocephaly along with shortened upper and lower extremities. Results: Our patient carries a compound heterozygotic pathogenic variant of the CYP11A1 gene, with two frameshift pathogenic variants NM_000781.3(CYP11A1):c.358del (p.Arg120Aspfs*18) in exon 2 and NM_000781.3(CYP11A1):c.835del (p.Ile279Tyrfs*10) in exon 5. To date, only around 50 cases with CYP11A1 pathogenic variants have been reported worldwide. We believe this is the first described case of a newborn with severe, classic P450scc deficiency in Poland. Conclusions: CYP11A1 (P450scc) deficiency is a rare and complex disorder that leads to primary adrenal insufficiency and may present with 46, XY disorders of sex development (DSD), phenotypic variations, and associated endocrinological abnormalities. This case, along with others cited, highlights the diverse presentations of DSD in individuals with pathogenic CYP11A1 variants. Optimal management necessitates a multidisciplinary approach by a specialized DSD team. Gonadectomy is a key consideration to decrease the teratogenic risk associated with intra-abdominal gonadal tissue. [ABSTRACT FROM AUTHOR]

Objective: Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes. Methods: Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center. Results: The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance. Conclusion: IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character. [ABSTRACT FROM AUTHOR]

Background. There is an increased risk for childhood type 1 diabetes (T1D) when T1D and type 2 diabetes (T2D) are reported in relatives. Objectives. Our objective was to evaluate current family risk factors for T1D development before implementing a national screening program for T1D. Materials and methods. A population of 879 Caucasian children and adolescents with T1D and 286 healthy controls were enrolled in the study. All participants completed the same questionnaire, which collected information about family history of diabetes over 3 generations. In statistical analyses, frequency tables and Χ2 tests evaluated possible multicollinearity among risk factors that were significantly associated with the outcomes. Results. Family history of diabetes was more frequent in controls (n = 75, 26.2%) than in patients with T1D (n = 146, 16.6%, odds ratio (OR) = 1.785, 95% confidence interval (95% CI): 1.299-2.452, degrees of freedom (df) = 12.976, p = 0.004), especially with a family history of T2D (n = 62, 21.7% compared to n = 79, 9.0%, respectively, OR = 2.803, 95% CI: 1.948-4.034, df = 32.669, p < 0.001). Also, there was a tendency for the nuclear family of T1D patients to be more frequently affected by T1D (n = 74, 8.4%) than the controls (n = 15, 5.2%, OR = 1.605, 95% CI: 0.937-2.751, df = 3.081, p = 0.079). The risk of T1D was associated with the closest family members being affected and accelerated over generations. Indeed, it was highest in siblings, especially brothers (OR = 12.985, 95% CI: 0.782-215.743, Fisher's test: p < 0.001). A positive family history of T2D burden among second-degree relatives was 2.728 times more frequent in the control group than in the T1D group (OR = 2.728; 95% Cl: 1.880-3.962, p < 0.001). Furthermore, a positive family history of T1D among first-degree relatives was less frequent in the controls than in the T1D group (OR = 0.124; 95% Cl: 0.030-0.516, p = 0.004). Conclusions. A family history of T1D, but not T2D, is a significant risk factor for T1D development. Indeed, the priority in screening for T1D should be given to first-degree relatives of T1D patients, starting from siblings. [ABSTRACT FROM AUTHOR]

Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study is to analyze patients who do not respond adequately to human recombinant growth hormone (rhGH) treatment. Material and methods: Four boys were analyzed: three patients diagnosed with SNP at the ages of 1) 8 years and 2 months, 2) 13 years and 2 months, 3) 16 years and 6 months, and patient 4) at the age of 6 years and 11 months - born small for gestational age (SGA). They underwent rhGH treatment. Results: The expected growth improvement was not observed in all boys. Patient 1 was diagnosed with aortic coarctation, and after each attempt to increase the rhGH dose, nocturnal vomiting occurred - epilepsy was diagnosed. Patient 2 had severe foot pain. Patient 3 had delayed puberty - hypogonadotropic hypogonadism was diagnosed. Patient 4 had dysmorphic features. Genetic tests revealed the following: 1) mixed gonadal dysgenesis - modifying treatment; 2) Fabry disease - enzyme treatment and rhGH improved growth; 3) Kallmann syndrome - discontinuing rhGH for testosterone supplementation; 4) KBG syndrome. Conclusions: 1. The presence of dysmorphic features and symptoms atypical for growth hormone deficiencies could warrant genetic diagnostics before initiating treatment. 2. Lack of significant improvement in growth is an indication for reevaluation of patients who have not completed growth. 3. Genetic studies in this patient group often elucidate the causes of slow growth rate. 4. The case authors have developed a proposal for a multicentre program aimed at establishing indications for genetic diagnosis in children diagnosed with SNP and SGA treated with rhGH. [ABSTRACT FROM AUTHOR]

Objectives Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. Methods This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). Results Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. Conclusion In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families. [ABSTRACT FROM AUTHOR]

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Aims: Study aims: (1) developing and validating a novel questionnaire for measuring fear of hyperglycaemia among parents of children with type 1 diabetes (T1D) – the Hyperglycaemia Fear Survey – Parent version (FoHyper‐P); (2) investigating correlations between parental fear of hyperglycaemia and objective measures of glycaemic control. Methods: A multi‐centre, multinational study of 152 parents of children with T1D was conducted in three large diabetes clinics from Israel, Poland, and Greece. Inclusion criteria were parents of children aged 6–16 years, at least 6 months from diagnosis, at least 3 months of CGM use and parental involvement in care. Parents filled the FoHyper‐P and the Hypoglycaemia Fear Survey – Parent Version (HFS‐P). Patient data were obtained via electronic medical records and informative questionnaires. Bonferroni correction was performed to counteract multiple comparisons. Results: Significant strong‐moderate correlations were found between FoHyper‐P and HFS‐P including total questionnaires scoring (r = 0.747, pBonf < 0.001), worries subscales (r = 0.735, pBonf <0.001), and behaviour subscales (r = 0.532, pBonf <0.001). Using linear regression models, we found a positive association between the worry subscale and HbA1C. Weak correlations (p < 0.05, not significant after Bonferroni correction) were found between time in range, time above range and parental fear of hyperglycaemia as well as between worry subscales and a higher HbA1C in the past year, percent of hyperglycaemia and lower TIR. Conclusions: The FoHyper‐P is a novel, validated tool for assessing parental fear of hyperglycaemia. Integrating it into clinical practice addresses an underestimated aspect of parental diabetes management, enabling better care for children with T1D. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to present the spectrum of thyroid dysfunction, including hormonal and ultrasound aspects, in a cohort of paediatric and adult patients diagnosed with inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders 2 and 3 (iPPSD). Methods: The medical records of 31 patients from 14 families diagnosed with iPPSD between 1980 and 2021 in a single tertiary unit were retrospectively analysed. Biochemical, hormonal, molecular, and ultrasonographic parameters were assessed. Results: In total, 28 patients from 13 families were diagnosed with iPPSD2 (previously pseudohypoparathyroidism [PHP], PHP1A, and pseudo-PHP) at a mean age of 12.2 years (ranging from infancy to 48 years), and three patients from one family were diagnosed with iPPSD3 (PHP1B). Thyroid dysfunction was diagnosed in 21 of the 28 (75%) patients with iPPSD2. Neonatal screening detected congenital hypothyroidism (CH) in 4 of the 20 (20%) newborns. The spectrum of thyroid dysfunction included: CH, 3/21 (14.2%); CH and autoimmune thyroiditis with nodular goitre, 1/21 (4.8%); subclinical hypothyroidism, 10/21 (47.6%); subclinical hypothyroidism and nodular goitre, 1/21 (4.8%); primary hypothyroidism, 4/21 (19%); and autoimmune thyroiditis (Hashimoto and Graves' disease), 2/21 (9.6%). Thyroid function was normal in 7 of the 28 (25%) patients with iPPSD2 and in all patients with iPPSD3. Ultrasound evaluation of the thyroid gland revealed markedly inhomogeneous echogenicity and structure in all patients with thyroid dysfunction. Goitre was found in three patients. Conclusion: The spectrum of thyroid dysfunction in iPPSD ranges from CH to autoimmune thyroiditis and nodular goitre. Ultrasonography of the thyroid gland may reveal an abnormal thyroid parenchyma. [ABSTRACT FROM AUTHOR]