Volume 32, Issue 7

Diabetic nephropathy (DN) is considered as one of the most popular microvascular complications of diabetes and the leading cause of death among diabetic patients. Currently, even though safflower yellow (SY) is widely adapted in the clinical treatment of DN, no meta-analysis can guarantee the safety of this treatment. This paper aims to evaluate the dominant method of SY on DN disease. The reliable source of information for randomized controlled trials (RCTs) and clinical research is listed as follows: the Chinese Biomedical Literature database, Chongqing VIP, Embase, the Cochrane Library and the China Academic Journals Full-text Database (CNKI). The CNKI search included Chinese journal articles, the full-text of important conferences and dissertations up to March 30, 2017. We picked out some particularly influential outcome variables including urinary albumin excretion rate (UAER), fasting blood sugar (FBG), blood urea nitrogen (BUN) and high-sensitivity C-reactive protein (hs-CRP) in each extracted study. In total, 1289 participants were included in this meta-analysis. The efficacy of SY alone or combined with Western medicine in the treatment of DN was better with statistically significant factors (odds ratio [OR] = 3.6, 95% confidence interval [CI] [2.37, 5.47], p < 0.00001). We found that SY lessened the UAER, heightened the proportion of blood sugar and beneficially improved other detective indicators related to DN. Therefore, SY used alone or in combination with Western medicine was significantly more efficacious with lower toxicity than Western medicine alone.

Background Obesity with developmental disability/intellectual disability (DD/ID) is the most common association in syndromic obesity. Genomic analysis studies have allowed the decipherment of disease aetiology, both in cases of syndromic obesity as well as in cases of isolated or syndromic DD/ID. However, more data are needed to further elucidate the link between the two. The aim of this pangenomic study was to use single nucleotide polymorphism (SNP) array technology to determine the copy number variant (CNV) type and frequency associated with both obesity and DD/ID. Methods Thirty-six patients were recruited from the Clinical Emergency Hospital for Children, in Cluj-Napoca, Romania during the period 2015–2017. The main inclusion criterion was a diagnosis that included both obesity and DD/ID. Genomic analysis via SNP array technology was performed. Results Out of the 36 patients, 12 (33%) presented CNVs with a higher degree of pathogenicity (A group) and 24 (66%) presented benign CNVs (B group). The SNP array results for the A group were as follows: pathogenic CNVs in 8/12 patients (67%); variants of unknown significance (VOUS) in 2/12 patients (16%); and uniparental disomy (UPD) in 2/12 patients (16%). Conclusions Some of these CNVs have already been observed in patients with both obesity and DD/ID, but the others were noticed only in DD/ID patients and have not been described until now in association with obesity.

Classical galactosemia is an autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in the GALT gene. With the benefit of early diagnosis by newborn screening, the acute presentation of galactosemia can be prevented. In this study, we describe the clinical phenotypes, time of diagnosis and GALT genotypes of 76 galactosemia patients from Turkey, where the disease is not yet included in the newborn screening program. The median age at first symptom was 10 days (range 5–20), while the median age at diagnosis was 30 days (range 17–53). Nearly half of the patients (36 patients, 47.4%) were diagnosed later than age 1 month. Fifty-eight individuals were found to have 18 different pathogenic variants in their 116 mutant alleles. In our sample, Q188R variant has the highest frequency with 53%, the other half of the allele frequency of the patients showed 17 different genotypes. Despite presenting with typical clinical manifestations, classical galactosemia patients are diagnosed late in Turkey. Due to the geographical location of our country, different pathogenic GALT variants may be seen in Turkish patients. In the present study, a clear genotype-phenotype correlation could not be established in patients.

Objective To investigate the relationship between brain masculinization and retinal thickness in children with congenital adrenal hyperplasia (CAH). Methods Forty-five patients with CAH aged between 4 and 18 years and 30 age-matched healthy controls were included in this prospective study. Macular area was examined with optical coherence tomography (OCT); central subfield thickness (CST), cube volume (CV) and macular retinal thickness (MT) were measured in each subject. A gender identity questionnaire (GIQ) was used for the evaluation of gender happiness index. Results Girls with CAH had a higher CV (p = 0.002) and MT (p = 0.003) than healthy girls. No significant difference was found between boys with CAH and healthy boys regarding the retinal thickness measurements. Mean CST, CV and MT were significantly higher in boys than in girls in the control group (p = 0.013, p < 0.001, respectively), but there was no significant difference in those parameters between girls and boys with CAH. The gender happiness index was not different between healthy boys and boys with CAH, but was significantly lower in girls with CAH than healthy girls (p = 0.01). Conclusions As retina is part of the brain, our finding appears to be a morphological evidence of the excess androgen exposure on brain structures in girls with CAH. In addition, we suggest using retinal thickness measurements as a marker of prenatal excess androgen exposure in future studies.

Background The aim of this study was to examine the cognitive functions of children with subclinical hypothyroidism (SH) and healthy children with the use of auditory event-related potentials (AERPs) and neuropsychological tests. Methods Twenty children aged between 8 and 17 years, diagnosed with SH, and 20 age-matched healthy controls were included in this study. A classical auditory oddball paradigm was applied during the electroencephalography (EEG) recordings, and event-related potentials (ERPs) were evaluated between the 0.5- and 20-Hz frequency intervals. P1, N1, P2, N2 and P3 amplitudes and latencies were measured in Fz, FCz, Cz, CPz, Pz and Oz electrodes. Additionally, a number of neuropsychological tests evaluating the reaction time and various cognitive functions were carried out. Results In children with SH, P3 amplitudes in FCz, Cz and CPz electrodes were significantly lower than those in controls (p < 0.05). In addition to this, the P1N1 and N1P2 peak-to-peak amplitude values were also found to be smaller for children with SH than controls (p < 0.05). With regard to the neuropsychological tests, no significant difference was observed between the SH and control groups on any of the cognitive test parameters, reaction time or correct response rates. Conclusions In the present study, while children with SH did not differ from controls with respect to their cognitive functions evaluated via neuropsychological tests, cognitive differences were detected via electrophysiological investigations. This result implies that implicit changes in cognition which are not yet overtly reflected on neuropsychological tests may be detected at an early stage in children with SH.

Objective Cardiovascular disease is a major complication among children with type 1 diabetes mellitus (T1DM). This prospective study aimed at examining the presence of cardiovascular risk factors in children with T1DM. Methods We evaluated several cardiovascular risk factors, including atherosclerosis, artery intima-media thickness (IMT) and metabolic responses, in 175 children with T1DM, with 150 non-diabetic children as normal controls. Results The diabetic children had significantly higher carotid IMT (cIMT) and aortic IMT (aIMT), higher values for diastolic wall stress (DWS), incremental elastic modulus (IEM), and flow-mediated dilatation (FMD) than the controls. The levels of tumor necrosis factor-α (TNF-α), interleukin-4 (IL4), high-sensitivity C-reactive protein (hs-CRP) and leptin were significantly higher in T1DM patients. In T1DM children, the cIMT and aIMT were correlated with several risk factors, including age, weight, body mass index (BMI), duration of diabetes, waist/hip ratio, as well as levels of total cholesterol, triglycerides and apolipoprotein B (apoB). In addition to common risk factors, cIMT was also associated with systolic blood pressure (BP). Other risk factors, such as height, diastolic BP, low-density lipoprotein (LDL)/high-density lipoprotein (HDL)-cholesterol ratio, apolipoprotein A1 (apoA1) and S-creatinine levels, were not all independent risk factors of cardiovascular disease in T1DM children. Conclusions T1DM is associated with early impairment of the common carotid and aortic artery structure and function, and the diabetic state may be the main risk factor for arterial wall stiffening and thickening.

Background Obesity is known to cause metabolic disturbances including insulin resistance, dyslipidemia and alters bone mineralization. The effects of obesity on fibroblast growth factor 23 (FGF-23), which is important in bone mineralization, have not yet been clarified. Our aim was to investigate the association between FGF-23 concentration and obesity-associated dysmetabolism. Methods Subjects comprised 46 obese children and adolescents. The same number of age-matched, healthy controls were recruited. Markers of bone mineralization and glucose metabolism were measured. Thyroid function and insulin resistance were investigated in both groups. In obese subjects; an oral glucose tolerance test (OGTT) was performed and hemoglobin A 1c and lipid fractions were measured. Bone mineral density and hepatic steatosis were investigated. Results Serum FGF-23, α-klotho and 1,25(OH) 2 D 3 concentrations were significantly lower while fasting insulin, fasting glucose, C-peptide and alkaline phosphatase (ALP) concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher in the obese group compared to controls. A significant negative correlation was observed between free tri-iodothyronine (fT3) and both FGF-23 and α-klotho in the obese group. Significant negative correlation was found between FGF-23 and C-peptide and a positive correlation was found between FGF-23 and high density lipoprotein-cholesterol (HDL-c) in the obese subjects with impaired glucose tolerance (IGT). Significant negative correlations were found between FGF-23 and both fasting insulin levels and C-peptide levels in the obese subjects with hepatic steatosis. Conclusions In our study, insulin resistance-associated hyperinsulinism and/or lower 1,25(OH) 2 D 3 levels, both present in obese children and adolescents, may lead to decreased serum FGF-23 concentrations in obese subjects.

Objective To estimate the prevalence of overweight and obesity among a cohort of children with type 1 diabetes mellitus (T1DM) and its metabolic consequences. Methods This was a cross-sectional study conducted in the Pediatric Diabetic Clinic at Shaare Zedek Medical Center and Clalit Health Care Services. Background information was taken from the patients’ files. Anthropometric measures, blood pressure, waist and hip circumference (WC and HC), hemoglobin A 1c (HbA 1c ) and lipid profile were recorded. The prevalence of metabolic derangements was compared between normal and overweight children. Results The study included 96 patients with type 1 diabetes, mean age 14.1 ± 3.7 years, mean diabetes duration 3.9 ± 3 and mean HbA 1c level 8.1 ± 1.4% (65 mmol/mol). Thirty-seven percent of the study population were overweight and of them 11.5% were obese. In the overweight group, the high-density lipoprotein (HDL) levels were significantly lower and systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were higher compared with normal weight participants. Multivariate analysis showed that BMI and age at study affected SBP and HDL levels, while age at study and HbA 1c levels affected DBP. Female patients were significantly overweight compared to males and had higher low-density lipoprotein (LDL) and cholesterol levels. Waist-to-hip ratio, an indicator of central obesity, was abnormally high among overweight males and females. Conclusions In our cohort of children with type 1 diabetes, there were a significant number of overweight children, with a higher prevalence in females. Components of metabolic syndrome were more prevalent among overweight and obese diabetic individuals.

Background Adrenal insufficiency (AI) is a life-threatening disease characterized by deficient production of glucocorticoids and/or mineralocorticoids. It is caused by primary or secondary/tertiary adrenal failure. Prompt diagnosis and management are essential and may even be life-saving. Methods We retrospectively collected clinical, laboratory and radiological data from AI patients observed over 34 years (1984–2017) in a pediatric endocrinology department of a tertiary care hospital. Results Seventy AI patients were identified: 59% with primary adrenal insufficiency (PAI) and 41% with central adrenal insufficiency (CAI). PAI patients were diagnosed at 1.5 ± 4.4 years and followed for 11.6 ± 6.2 years; 85% had classical congenital adrenal hyperplasia (CAH) and 7% had autoimmune PAI. At presentation, 73% had hyponatremia and more than half had mucocutaneous hyperpigmentation, asthenia, anorexia, weight loss, nausea and vomiting. All the patients were treated with hydrocortisone and 90% were also on fludrocortisone. Regarding CAI patients, they were diagnosed at 5.4 ± 5.0 years and they were followed for 9.6 ± 6.4 years; craniopharyngioma was present in 31% of the cases and 14% had pituitary hypoplasia. Besides corticotropin, thyrotropin (93%), growth hormone (63%) and antidiuretic hormone (52%) were the most common hormone insufficiencies. The most frequent manifestations were hypoglycemia (34.5%), nausea/vomiting (27.6%) and infectious diseases (27.6%); all the patients were treated with hydrocortisone. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population. Raising awareness and knowledge in medical teams and population about the disease is of crucial importance to improve clinical outcomes and to reduce disease morbidity/mortality.

Background About 90% of children grow up normally and attain a final height within their genetic target. In children with intrauterine growth restriction (IUGR), up to 10% will not catch up spontaneously. Turner syndrome is often diagnosed late, and a number of growth-stunted children go undiagnosed and untreated. Objectives Our primary aim was to evaluate the prevalence of stunted growth in preschool-aged children. Our secondary aim was to evaluate growth patterns in children belonging to four ethnic groups in Dreux district, France. Methods Body weight, height and body mass index (BMI) were collected for children aged 3–5 years during systematic community visits. Birth variables, family history of short stature, maternal smoking, ethnic origin, etc. were also recorded. Pubertal status was staged as per Tanner’s method. Parents were instructed to attend the hospital growth clinics if their child’s height was <−2.0 standard deviation score (SDS). Results Five hundred ninety-three children were screened (301 boys, 289 girls). The mean age was 4.33 ± 0.76 standard deviation (SD) years, and 48% were Caucasians, 13.7% were North Africans, 2.5% were Black Africans, 0.8% were Asians, 1.5% included others and the ethnicity was not specified in 33.5% of the cases. 91.5% of children were term-born and 8.5% were preterm. 84.2% of children were appropriate for gestational age (AGA) and 9.4% were small for gestational age (SGA). At 5 years of age, 22.2% of macrosomic North African children were overweight. Catch-up growth was complete in 98% children, 11/540 were short statured, 8/11 attended our growth clinics (seven short statured and one micropenis) and three were started on recombinant human growth hormone (rhGH). Conclusions Growth screening programs are important and useful tools for public health. There is a need for clear objectives, proper training and automated data collection tools, along with easy access to growth specialists.

Background Neonatal adrenoleukodystrophy (n-ALD) and X-linked ALD (X-ALD) patients present with demyelination, poor growth and progressive mental retardation. Growth factors are known to play a vital role in the development of children. Objective To examine the mitogenic activity of various growth factors in skin fibroblasts from n-ALD and X-ALD patients. Methods Skin fibroblast cultures from n-ALD and X-ALD patients, and controls were treated with 50 ng/mL of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) or insulin-like growth factor-1 (IGF-1) to examine DNA synthesis by 5-bromo-2′-deoxyuridine (BrdU) incorporation. Expression of receptors for PDGF, bFGF and IGF-1 was measured by western blotting. Serum levels of IGF-1 were assayed by enzyme-linked immunosorbent assay (ELISA). Results Fibroblasts from n-ALD and X-ALD patients had significantly (p < 0.01) less BrdU incorporation in response to fetal bovine serum (FBS). The mitogenic effect of PDGF, bFGF and IGF-1 was significantly lower in n-ALD as compared to control and X-ALD cells. X-ALD cells showed significant impairment in IGF-1-induced DNA synthesis. Expression of the FGF receptor (FGF-R) was significantly reduced in n-ALD cells. PDGF receptor remained unaffected, and IGF-1 receptor (IGF-1R) expression and serum IGF-1 levels were significantly (p < 0.01) reduced in n-ALD and X-ALD patients as compared to controls. Conclusions Growth factor activity differs in n-ALD and X-ALD patients, with marked impairment of IGF-1 function through receptor down-regulation.

Introduction Reduced bone mass will increase bone fragility and risk of fractures. Thus, it is better to note its determinants as early as possible. Objective This study aimed to find and determine the determinants for low bone mineral density (BMD) in pre-school children. Methods Between November 2014 and April 2015, a matched case-control study was performed to detect information on growth and development condition and consumption frequency of products of cases with low BMD and controls with normal BMD. Anthropometric data measurement and blood tests were conducted. Besides, the questionnaires concerning the mentioned information were completed to get relevant determinants. A paired t-test, the McNemar test and univariate and multiple conditional logistic regression models were used to explore the association between these factors and low BMD. Results In total, 88 (28 boys, 60 girls) incident cases (4.15 ± 0.78 years) of low BMD and 88 sex- and age-matched (±2 months) controls (4.16 ± 0.80 years) of normal BMD were enrolled. The results of multiple conditional logistic regression analysis indicated that if children had larger chest circumference (odds ratio [OR] = 0.763), longer duration of breastfeeding (OR = 0.899) and lower frequency of eating snacks (OR = 0.439), the risk of low BMD would decrease. Conclusions Our findings suggest that pre-school children with an association of larger chest circumference, longer duration of breastfeeding and lower frequency of eating snacks could have lower risk for low BMD. Intended measures to strengthen those protective factors could be effective in reducing the cases of low BMD.

Background The objective of this study was to investigate the association of polymorphisms in four genes, tumor necrosis factor-α ( TNFA ), patatin-like phospholipase domain containing 3 ( PNPLA3 ), adiponectin ( ADIPOQ ) and apolipoprotein C3 ( APOC3 ), with obesity and non-alcoholic fatty liver disease (NAFLD) in Asian Indian adolescents. Methods In this case-control study, 218 Asian Indian adolescents with overweight/obesity and 86 lean healthy adults without fatty liver were enrolled. Hepatic steatosis was assessed and graded by ultrasonography (USG). Serum insulin, lipids, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNF-α, adiponectin and apolipoprotein C3 were measured and genotyping was done. Frequencies of variant and wild genotypes in all adolescents and in the subgroups without steatosis, with grade 1 steatosis and with grade 2 or 3 steatosis were compared to those in the controls. The frequencies were also compared in the overweight adolescents with grade 2 or 3 steatosis and without steatosis. Results Variant genotypes of polymorphisms −863 C > A and −1031 T > C of the TNFA gene, 455 T > C of the APOC3 gene and the wild type of +276 G > T of the ADIPOQ gene were associated with obesity with odds ratios (OR, 95% confidence interval [CI]) of 2.5 (1.5–4.4), 2.5 (1.5–4.2), 2.0 (1.1–3.6) and 2.5 (1.4–5.0), respectively. Polymorphisms 455 T > C of APOC3 and rs738409 C > G of PNPLA3 were associated with NAFLD. Fasting insulin and triglycerides (TG) were higher in the adolescents with homozygous variant polymorphisms −1031 T > C of TNFA and 455 T > C of APOC3 genes, respectively. Conclusions Several polymorphisms were noted to have a significant association with obesity and NAFLD in Asian Indian adolescents.

Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4–15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55–4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK -MODY had lower glycated hemoglobin (HbA 1c ) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK -MODY was identified by incidental hyperglycemia without glycosuria. GCK -MODY without drug management and hepatocyte nuclear factor-1 alpha ( HNF4A ) or HNF1A -MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4 . The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

Background Persistent hypoglycemia (PH) beyond 3 days of life warrants investigation which includes a critical sample. We report our case series of five neonates who presented with PH as the first sign of congenital hypopituitarism. Design This is a case series. Methods/Results This is a case series of five neonates evaluated at our academic institution in a 3-year period (2013–2016), who presented with persistent severe hypoglycemia and were subsequently diagnosed with congenital hypopituitarism. All neonates were full term (mean gestational age 39.8 ± 1.4 weeks) born by caesarian section with a mean weight of 3.5 ± 0.16 kg and a mean length of 51.2 ± 1.2 cm at birth. All five neonates had PH beyond 3 days with an average blood glucose (BG) <35 mg/dL at presentation, requiring a mean glucose infusion rate (GIR) of 7.22 ± 1.98 mg/kg/min. The average BG during the critical sample was 42 ± 0.16 mg/dL (three patients). The mean duration of requirement of the glucose infusion was 6.2 ± 3 days during the immediate neonatal period. Diagnosis of the hypopituitarism took 2–52 days from the initial presentation of hypoglycemia. Besides growth hormone (GH) deficiency, cortisol deficiency was diagnosed in all the five neonates. Neuroimaging findings in all the neonates were consistent with pituitary stalk interruption syndrome (hypoplastic anterior pituitary, ectopic posterior pituitary [EPP] and interrupted pituitary stalk). Conclusions Hypoglycemia is a common metabolic complication affecting an infant in the immediate neonatal period. Delay in the diagnosis of hypopituitarism presenting as hypoglycemia is the result of the lack of awareness among neonatologists and/or pediatricians. We propose that providers be cognizant that PH can be the only presentation of hypopituitarism in the neonatal period. Therefore, having a high index of suspicion about this condition can avoid a delay in the evaluation, diagnosis and treatment of hypopituitarism.

Background Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by pathogenic variants in the LMNA gene, which leads to premature aging. The median life expectancy is shortened to 13 years due to cardiovascular complications. Case report We present a boy born with a pathogenic LMNA variant c.433G > A, which causes atypical progeria syndrome (APS) and was previously described in one single patient. When investigated for poor growth prior to the diagnosis of APS, his laboratory tests revealed growth hormone (GH) deficiency and magnetic resonance imaging (MRI) of the midbrain showed partial empty sella. GH treatment had only a limited and transient effect. His first ischemic complication manifested at age 4.2 years; at the age of 7 years, he had a fatal haemorrhagic stroke. Conclusion To the best of our knowledge, this is the first patient with APS showing partial empty sella and GH deficiency that might have contributed to his poor growth. GH failed to improve long-term outcome.

Background The clinical phenotypes of carnitine palmitoyltransferase type-2 deficiency (CPT2D) are classified into lethal neonatal, severe infantile and muscle forms. The rarest form is the lethal neonatal form. Case presentation The patient was hypotonic and bradycardic at admission. Blood urea nitrogen and creatinine were high. He had polycystic kidneys, patent foramen ovale and aortic valve insufficiency. Cranial magnetic resonance imaging (MRI) revealed increased signal intensities in the periventricular white matter. Tandem mass spectrometry (MS) analysis was compatible with CPT2D. We found a homozygous in-frame deletion in the CPT2 gene using next-generation sequencing. Conclusions We identified a novel mutation leading to the lethal form of CPT2D with polycystic kidney, cardiac malformation and cranial MRI findings. Our findings expand the spectrum of causative mutations and clinical findings in CPT2D.

Background Cyclic Cushing’s disease (CCD) is reported to occur in approximately 15% of patients with Cushing’s disease (CD). CCD is a rare phenomenon in children. Case presentation A Portuguese female with well-controlled type 1 diabetes (T1DM) on an insulin pump developed transient uncontrolled blood sugar every morning. Increased basal and bolus insulin dosing was ineffective in lowering blood sugar and she began to miss school because of nausea, vomiting, fatigue, but no ketoacidosis. Therefore, other causes of sporadic hyperglycemia were explored. Multiple 6-h urinary free cortisol (UFC) samples revealed a spike in cortisol coincident with severe hyperglycemia. Pituitary magnetic resonance imaging (MRI) revealed a 3.5 mm microadenoma and inferior petrosal sinus sampling of adrenocorticotropic hormone (ACTH) after corticotropin releasing hormone (CRH) stimulation confirmed ACTH-dependent CD. Endoscopic endonasal tumor resection led to resolution of early morning hyperglycemia and symptoms. Discussion Our case illustrates an atypical presentation of CCD. There are no previous case reports of a pediatric patient with T1DM and CCD. Unexplained hyperglycemia in a patient with previous well-controlled T1DM should prompt assessment of other causes. CCD can be easily be missed if timed 6-h UFC measurements are not obtained.

Breastfeeding replacement is the only treatment for galactosemia (GAL) and phenylketonuria (PKU) during infancy. We aimed to evaluate the stress degree in mothers who were obliged to replace breastfeeding with special formulas as the only treatment for the diseased newborns. Thirty-two mothers with GAL newborns, 19 on breastfeeding only and 13 on breastfeeding plus formula, participated in this study. Additionally, 54 mothers with PKU infants, 32 offered breastfeeding only and 22 breastfeeding plus formula, participated in the study. Stress degree was evaluated in both groups: GAL and PKU. Mothers on breastfeeding only experienced the highest degree of stress than those who were on breastfeeding plus formula. After 1 month of psychological support, most mothers were ameliorated: mothers on breastfeeding only felt better as compared to those on breastfeeding plus formula. Conversely, in mothers on breastfeeding plus formulas, symptoms and signs of stress almost disappeared. In conclusion, GAL or PKU mothers with breastfeeding only experienced the highest degree of stress when asked for breastfeeding replacement. Psychological support made all the studied groups to feel better or free of symptoms and signs of stress.