Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study.

OBJECTIVE: Since Cushing's disease (CD) is less common in the paediatric age group than in adults, data on this subject are relatively limited in children. Herein, we aim to share the clinical, diagnostic and therapeutic features of paediatric CD cases. DESIGN: National, multicenter and retrospective study. PATIENTS: All centres were asked to complete a form including questions regarding initial complaints, physical examination findings, diagnostic tests, treatment modalities and follow-up data of the children with CD between December 2015 and March 2017. MEASUREMENTS: Diagnostic tests of CD and tumour size. RESULTS: Thirty-four patients (M:F = 16:18) from 15 tertiary centres were enroled. The most frequent complaint and physical examination finding were rapid weight gain, and round face with plethora, respectively. Late-night serum cortisol level was the most sensitive test for the diagnosis of hypercortisolism and morning adrenocorticotropic hormone (ACTH) level to demonstrate the pituitary origin (100% and 96.8%, respectively). Adenoma was detected on magnetic resonance imaging (MRI) in 70.5% of the patients. Transsphenoidal adenomectomy (TSA) was the most preferred treatment (78.1%). At follow-up, 6 (24%) of the patients who underwent TSA were reoperated due to recurrence or surgical failure. CONCLUSIONS: Herein, national data of the clinical experience on paediatric CD have been presented. Our findings highlight that presenting complaints may be subtle in children, the sensitivities of the diagnostic tests are very variable and require a careful interpretation, and MRI fails to detect adenoma in approximately one-third of cases. Finally, clinicians should be aware of the recurrence of the disease during the follow-up after surgery.

Effect of acute exercise on 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) levels in obese male adolescents.

OBJECTIVE: 12,13-Dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a lipokine secreted from brown adipose tissue, and it has positive effects on dyslipidemia. Acute exercise has been shown to lead to an increase in its secretion. In this study, it was aimed to investigate the relationship of 12,13-diHOME with obesity, exercise and dyslipidaemia for the first time in the adolescent age group. DESIGN: Prospective study. PATIENTS: Twenty-eight male adolescents with obesity and the same number of age-matched healthy normal-weight male controls. MEASUREMENTS: Fasting serum glucose, insulin, lipid and 12,13-diHOME levels were measured. Cardiopulmonary exercise testing was performed in all subjects using a stress test treadmill. Peak oxygen consumption (peak VO2) and anaerobic threshold heart rate (ATHR) were measured. RESULTS: Adolescents with obesity had lower 12,13-diHOME levels than normal-weight adolescents both before and after acute exercise (p = .025 and p = .019, respectively), and after acute exercise, 12,13-diHOME levels significantly increased in both groups (p = .001 for both). 12,13-diHOME levels negatively correlated with triglyceride, total cholesterol, LDL-C, and positively correlated with HDL-C. Also, peak VO2 and ATHR levels showed positive correlation with 12,13-diHOME levels. CONCLUSION: 12,13-diHOME levels were found to be lower in adolescents with obesity than normal-weight adolescents and increased with acute exercise. Also, the close relationship of this molecule with dyslipidaemia in addition to that with obesity suggests that it has an important role in the pathophysiology of these disorders. Further molecular studies will further elucidate the role of 12,13-diHOME in obesity and dyslipidaemia.

Evaluating renin and aldosterone levels in children with organic acidemia-therapeutic experience with fludrocortisone.

Hyporeninemic hypoaldosteronism has been reported in only a few cases with methylmalonic acidemia (MMA) and has been attributed to the renal involvement. This study aims to investigate renin-aldosterone levels along with the renal functions of the patients with organic acidemia. This is a cross-sectional study conducted in patients with MMA, propionic acidemia (PA), and isovaleric acidemia (IVA). Serum renin, aldosterone, sodium, and potassium levels were measured, and glomerular filtration rates (GFR) were calculated. Comparisons were made between the MMA and non-MMA (PA+IVA) groups. Thirty-two patients (MMA:PA:IVA = 14:13:5) were included. The median GFR was significantly lower in the MMA group than in the non-MMA group (p < 0.001). MMA patients had the highest incidence of kidney damage (71.4%), followed by PA patients (23%), while none of the IVA patients had reduced GFR. GFR positively correlated with renin levels (p = 0.015, r = 0.433). Although renin levels were significantly lower in the MMA group than the non-MMA group (p = 0.026), no significant difference in aldosterone levels was found between the two groups. Hyporeninemic hypoaldosteronism was found in 3 patients with MMA who had different stages of kidney damage, and fludrocortisone was initiated, which normalized serum sodium and potassium levels.  Conclusions: This study, which has the largest number of patients among the studies investigating the renin-angiotensin system in organic acidemias to date, has demonstrated that hyporeninemic hypoaldosteronism is not a rare entity in the etiology of hyperkalemia in patients with MMA, and the use of fludrocortisone is an effective treatment of choice in selected cases. What is Known: • Hyperkalemia may be observed in cases of methylmalonic acidemia due to renal involvement and can be particularly prominent during metabolic decompensation. • Hyporeninemic hypoaldosteronism has been reported to be associated with hyperkalemia in only a few cases of methylmalonic acidemia. What is New: • Hyporeninemic hypoaldosteronism was found in one-fifth of cases with methylmalonic acidemia. • Fludrocortisone therapy leads to the normalization of serum sodium and potassium levels.

Diabetes-specific eating disorder and possible associated psychopathologies in adolescents with type 1 diabetes mellitus.

PURPOSE: It was aimed to investigate the frequency of the risk of diabetes-specific eating disorder (DSED) in adolescents with type 1 diabetes mellitus (T1DM) and to reveal the accompanying psychopathologies. METHODS: Adolescents with T1DM aged 12-18 who applied to the pediatric diabetes outpatient clinic between July 2021 and March 2022 were included. Diabetes Eating Problem Survey-Revised (DEPS-R) was applied to all patients to determine the risk of DSED. In order to detect accompanying psychopathologies, Eating Disorder Examination Questionnaire (EDE-Q), Child Anxiety and Depression Scale-Child version (RCADS) and Parenting Style Scale were applied. After completing the scales, semi-structured interviews were conducted with all patients by a child and adolescent psychiatrist. RESULTS: Ninety-two adolescents (45 boys, 47 girls) were included. DSED risk was found in 23.9% of the cases. A positive correlation was found between DEPS-R and EDE-Q scores (p = 0.001, rho = 0.370). RCADS mean scores were significantly higher in the group with DSED risk (p < 0.001). When the Parenting Style Scale was evaluated, psychological autonomy scores were significantly lower in the group with DSED risk (p = 0.029). As a result of the psychiatric interviews, 30 (32.6%) patients had at least 1 psychiatric disorder. Of these, 2 patients were diagnosed with eating disorder. CONCLUSION: Almost one-fourth of adolescents with T1DM were found to be at risk of DSED. Routine screening of adolescents with T1DM with the DEPS-R scale may provide early detection of DSED, and referral of those at risk to child psychiatry enables early diagnosis and intervention for both eating disorders and accompanying psychopathologies. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

The relationship between epileptic seizure and melatonin in children.

OBJECTIVE: Studies about the relationship between epileptic seizures (ESs) and melatonin are limited in children and have been performed in heterogeneous patient groups and with different methods. In this study, it was planned to investigate this relationship according to seizure and epilepsy characteristics. MATERIAL AND METHODS: In 91 children with ES, serum melatonin levels were measured within half an hour following the seizure and on a seizure-free day. Seizures were categorized according to the diagnosis, semiology, etiology, duration, electroencephalography (EEG) findings, and response to treatment. Melatonin levels were compared between each group and control group. In addition, basal melatonin levels of 21 patients with electrical status epilepticus in sleep (ESES) were compared with a control group. RESULTS: Basal melatonin levels were found to be lower in children with ESs and ESES group compared with the control group (p < 0.001, p < 0.001). Likewise, similar results were obtained in subgroups except for remote symptomatic etiology, severe EEG findings, and refractory epilepsy. No significant difference was observed between basal and postseizure levels of melatonin. CONCLUSION: This is the first study to reveal the relationship between ESs and basal melatonin levels according to all the characteristics of seizure and epilepsy in the largest patient group. It also demonstrates the need for more detailed studies on the role of melatonin in the pathogenesis of both ESs and ESES, which may provide a basis for a future treatment.

Acute Kidney Injury After Thyroid Hormone Withdrawal in an Adolescent with Papillary Thyroid Carcinoma.

Objectives: We report a patient with papillary thyroid carcinoma (PTC) who developed acute kidney injury (AKI) and elevated creatine kinase (CK) after thyroid hormone withdrawal (THW) prior to radioiodine therapy. Case presentation: A 12-year-old female patient who had undergone total thyroidectomy for PTC one year ago presented with leg pain for the past 2 days. Following THW 3 weeks ago, the case had received 70 mCI radioiodine treatment 6 days ago. Serum creatinine (1.53 mg/dL, normal range [NR]: 0.3-1.1), aspartate aminotransferase (102 IU/L, NR: 0-40) and CK (3451 IU/L, NR: 26-174) levels were elevated. Thyrotropin level was elevated (>100 µIU/ml, NR: 0.51-4.3), and free T4 level was decreased (0.05 ng/dL, NR: 0.98-1.63). Serum creatinine and CK levels decreased after intravenous hydration and levothyroxine treatment. Conclusion: In PTC cases with thyroidectomy, kidney function and CK elevation should be assessed after THW and dehydration should be prevented.

Ovarian reserve in children with juvenile idiopathic arthritis using biologic disease-modifying anti-rheumatic drugs.

BACKGROUND/OBJECTIVES: The aim of the study is to assess the effect of juvenile idiopathic arthritis (JIA) and biologic disease-modifying anti-rheumatic drugs (bDMARDs) on ovarian reserve in children. MATERIALS AND METHODS: A cross-sectional study was performed from March 2021 to March 2022 and included 81 patients with JIA and 49 healthy children. Serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels were analyzed using electrochemiluminescence methods. RESULTS: The mean of current age (13.5 ± 3.2 vs. 14.4 ± 2.4 years), height standard deviation score (SDS) (- 0.35 ± 1.18 vs. - 0.44 ± 0.94), body mass index SDS (0.12 ± 1.33 vs. 0.25 ± 1.28), and the median weight SDS (- 0.13 (- 2.27-3.23) vs. - 0.52 (- 3.4-3.3)) were similar in JIA patients and controls (p > 0.05). Patients with JIA were divided into two groups according to their treatment regimens: treated with methotrexate (MTX) (biologic naive) (n = 32) and treated with MTX plus bDMARDs (n = 49). No significant differences were detected between the 3 groups regarding menarche age, menstrual cycle length, and flow duration (for all p > 0.05). The median serum concentration of AMH was 2.94 (1.12-7.88) ng/ml in the control group, 3.02 (0.36-8.54) ng/ml in the biologic naïve group, and 3.01 (0.99-8.26) ng/ml in the MTX plus bDMARD group. There were no significant differences between 3 groups according to serum AMH, FSH, LH, and estradiol levels (p > 0.05). CONCLUSION: Biologic DMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment. Prospective studies with larger sample sizes are needed to confirm our findings and to evaluate the impact on the future fertility of patients. Key Points • Although biologic disease-modifying anti-rheumatic drugs (bDMARDs) are being game-changing treatment options in juvenile idiopathic arthritis, their effect on fertility and ovarian reserve is one of the most discussed issues. • In addition to treatment used, autoimmune diseases might also have a negative effect on fertility. • In this cross-sectional study, we found that anti-Mullerian hormone level of patients who were on bDMARDs, patients who were on methotrexate, and healthy controls were similar. • Our results suggest that bDMARDs are reassuring in terms of ovarian reserve in girls with JIA and demonstrate that AMH is unaffected by treatment.

The effect of anastrozole therapy on final height and sex hormone levels in pubertal boys receiving growth hormone therapy.

Objective: This research aimed to evaluate retrospectively the effect of anastrozole on height gain and sex hormone levels in pubertal boys receiving growth hormone (GH). Materials and methods: Pubertal boys who received both GH and anastrozole (GH+A) were one-to-one matched with boys who received only GH (GH-Only) for chronological and bone age, pubertal stage and height before the GH initiation, treatment duration and midparental height. Anthropometric measurements throughout treatment and adult heights were compared between the groups. Sex hormone levels were evaluated longitudinally in the GH+A group. Results: Forty-eight cases (24 in each group) were included. There was no statistical difference in adult height between the GH+A and GH-Only (p = 0.071). However, when the analysis was limited to those receiving anastrozole for at least 2 years, mean adult height was higher in the GH+A than in the GH-Only group (173.1 ± 6.2/169.8 ± 5.6 cm, p = 0.044). Despite similar growth rates between the two groups, bone age advancement was slower in the GH+A than in the GH-Only in a mean anastrozole treatment period of 1.59 years (1.37 ± 0.80/1.81 ± 0.98 years, p = 0.001). The greatest increase for FSH, LH, total and free testosterone and decrease for estradiol levels were observed in the third month after anastrozole was started, albeit remaining within the normal ranges according to the actual pubertal stages. Conclusion: Using anastrozole with GH for at least 2 years decelerates the bone age advancement resulting in adult height gain with no abnormality in sex hormone levels. These results suggest anastrozole can be used as an additional treatment to GH for further height gain in pubertal boys.

Effect of Continuous Glucose Monitoring Device Assistance on Glycemic Control of 2023 Kahramanmaras Doublet Earthquake Survivors with Type 1 Diabetes in Adana, Turkey.

OBJECTIVE: The aim of this study was to investigate the effects of the devastating 2023 Kahramanmaras earthquake on the glycemic control of children with type 1 diabetes (T1DM) in Adana, Turkey. Additionally, the study aimed to assess the impact of continuous glucose monitoring (CGM) device assistance on glycemic control after the earthquake. MATERIALS AND METHODS: A retrospective study was conducted involving 134 children with T1DM receiving intensive insulin treatment. Participants were divided into 2 groups: CGM (+) (n = 58), who benefited from CGM device assistance, and CGM (-) (n = 76), who did not utilize CGM device after the earthquake. Glycated hemoglobin (HbA1c) levels were recorded before and after the earthquake. RESULTS: Following the earthquake, the median HbA1c for all participants changed insignificantly from 8.9% to 8.6% (P = .491). However, in the CGM (+) group, HbA1c levels significantly improved post earthquake (P = .001). Conversely, the CGM (-) group experienced a deterioration in glycemic control (P = .027). A 2-way repeated measures ANOVA revealed a significant interaction effect between CGM device usage and the earthquake on HbA1c levels (F = 17.257, P <.001). Subgroup analysis based on age indicated that the effectiveness of CGM was more pronounced in adolescents (≥12 years) than in younger children (<12 years). CONCLUSION: This study highlights the adverse impact of the earthquake on glycemic control in children with T1DM and underscores the effectiveness of CGM in improving glycemic control, particularly among adolescents. The provision of CGM devices following the earthquake led to enhanced outcomes, mitigating the negative effects of the disaster on glycemic control.

Differentiated Thyroid Cancer in Children and Adolescents: Clinicopathological Characteristics of 32 Patients Followed up in our Pediatric Endocrinology Unit.

Objectives: This study aims to investigate the clinical and pathological features of patients with differentiated thyroid cancer (DTC) treated at our tertiary care institution. Methods: Thirty-two children and adolescents followed up with the diagnosis of DTC between 2001 and 2017 were enrolled. We classified patients with DTC into two groups as below and above 10 years of age, and compared their clinical and pathological features. Results: The mean age at presentation was 11.2±4 years. The female/male ratio was 7 (28:4). The diagnosis was papillary thyroid cancer (PTC) in 90.6% (n=29). The frequencies of lymph node and pulmonary metastases were 53.1% and 21.8%, respectively. The groups were comparable in terms of gender, initial clinical signs and tumor histopathology. The mean tumor size was greater in the younger age group (p=0.008). However, there was no difference between the two groups in terms of lymph node and pulmonary metastases. The pathological parameters associated with tumor aggressiveness were also similar between the groups, except lymphovascular invasion. Lymphovascular invasion was more frequent in the younger age group (p=0.01). Patients with lymph node and pulmonary metastases were more likely to have extrathyroidal extension and lymphovascular invasion. Conclusion: PTC was the most common type of DTC and presented with considerable rates of lymph node and pulmonary metastases. Tumor size was greater and lymphovascular invasion was more common in younger patients. Overall prognosis was favorable despite high rates of lymph node and pulmonary metastases.

Temporary Thyroid Dysfunction and Catecholamine Excess Due to Mercury Poisoning in 6 Cases.

OBJECTIVE: Mercury poisoning is a condition with multiple-organ dysfunction that has effects on the central nervous system, gastrointestinal system, cardiovascular system, skin, lungs, and kidneys. It can be fatal or may result in sequelae such as neurological disturbances, if treated late or left untreated. The endocrinological effects of mercury exposure are not well-known. We aimed to evaluate patients with mercury poisoning. MATERIALS AND METHODS: A total of 6 cases of mercury poisoning from 3 families were included in the study. Clinical, laboratory, and follow-up data were recorded. RESULTS: Thyroid dysfunction was presented as high thyroid hormones and normal thyrotropin level (unsuppressed) in 5 cases (83.3%). On the other hand, pheochromocytoma-like syndrome was detected in 5 cases (83.3%) with hypertension. The 4 cases were the first to use methimazole for mercury poisoning due to tachycardia and hypertension despite antihypertensive treatment due to catecholamine excess and thyroid dysfunction. Hyponatremia was detected in 3 cases (50%). CONCLUSION: Mercury poisoning is difficult to diagnose because it is rare and presents with nonspecific physical and laboratory findings. Early diagnosis and providing appropriate treatment are essential in order to prevent sequelae. Mercury poisoning should be considered in patients with unexplained hypertension and tachycardia suggesting the involvement of thyroid hormones and catecholamines.

Emergence of Ectopic Adrenal Tissues-What are the Probable Mechanisms?

Ectopic adrenal tissue, defined as the formation of adrenal tissue in an abnormal anatomical location, is not a rare entity and may have clinical significance. Even though the mechanism for their emergence has not been fully understood, numerous cases of ectopic adrenal tissue have been reported, mostly in the vicinity of the original location of adrenal gland, such as in kidneys and gonads. In these cases, most authors attributed their emergence to a probable migration defect. However, this mechanism does not simply explain the ectopic tissues in remote locations, such as in the hypophysis or lungs. This review summarizes these reports, describing many different locations in which ectopic adrenal tissues were encountered, together with their suggested mechanisms.

Effect of the COVID-19 quarantine on metabolic control in children and adolescents with type 1 diabetes.

INTRODUCTION: Metabolic control in type 1 diabetes (T1D) depends on many factors such as eating habits, exercise and lifestyle. The objective of this study was to investigate how these factors were affected during the coronavirus disease 2019 (COVID-19) lockdown and impacted metabolic control in children with T1D. MATERIALS AND METHOD: One hundred children with T1D were enrolled in the study. Anthropometric measurements, snack and meal frequency, carbohydrate consumption, HbA1c levels, and exercise patterns were recorded and compared before and after the lockdown. Subjects were divided into two subgroups-patients with decreased and patients with increased HbA1c levels after the lockdown-and comparisons of the same parameters were also made between these two subgroups. RESULTS: In the overall group, the mean HbA1c level was significantly higher after the lockdown compared to before (p=0.035). Meal schedules changed due to delayed sleep and waking times, and total daily carbohydrate consumption increased in the subgroup with increased HbA1c while it decreased in the subgroup with decreased HbA1c (p<0.001 for both). CONCLUSION: Our study supports the notion that blood sugar management in children with T1D worsened during the COVID-19 pandemic. Although it is not possible to explain this with any one factor, some behavioral changes observed in our study, such as inactivity, irregular meal frequency and timing, and irregular sleep and waking patterns appeared to be associated with blood sugar management.

Silent Corticotroph Tumor with Adrenocortical Choristoma in an Eleven-year-old Boy

Silent corticotroph tumors are composed of corticotroph cells, but do not manifest any biochemical or clinical evidence of hypercortisolism. A choristoma is a benign, congenital proliferation of histologically mature tissue elements normally not present at the site of occurrence. The existence of adrenocortical cells within the pituitary gland, which can be explained as a choristoma, is a very rare entity, and the co-occurrence of these two entities have only been reported in few cases. We report an 11-year-old boy with central hypothyroidism. On cranial magnetic resonance imaging a pituitary tumor was detected, and histopathological studies led to a diagnosis of an adrenal choristoma and a silent corticotroph tumor in the pituitary gland. The presence of adrenocortical cells were confirmed by positive calretinin, inhibin and Melan A staining, and the corticotroph cells by immunohistochemistry demonstrating adrenocorticotropic hormone positivity. Herein, we report the fourth and the youngest case of silent corticotroph tumor with adrenocortical choristoma in the literature. Even though the underlying mechanism is not fully understood, suggested mechanisms are discussed.

Insulin resistance in children with juvenile systemic lupus erythematosus and investigation of the possibly responsible factors.

OBJECTIVE: Insulin resistance (IR) has been described in adults with systemic lupus erythematosus (SLE), though its mechanism has not been fully clarified. In this study, it was aimed to investigate insulin sensitivity for the first time in children with juvenile SLE (jSLE) by considering the effect of the already known contributing factors of IR. METHOD: This is a cross-sectional study including 43 patients with jSLE and the same number of healthy controls matched for age, gender, pubertal stage, body mass index, and physical activity level. IR, as calculated by both homeostatic model assessment for insulin resistance (HOMA-IR) and a relatively new method, triglyceride glucose (TyG) index, was compared between the patients and their matched controls, also among the patients stratified by disease duration, corticosteroid use, and disease activity. RESULTS: Insulin resistance in the patient group was higher than the controls according to both HOMA-IR and TyG index (p < 0.001 for both). In the patient group, no significant effect of disease duration, corticosteroid use, disease activity, and levels of anti-dsDNA, anti-cardiolipin IgM, anti-cardiolipin IgG, C3, and C4 on IR was demonstrated. CONCLUSION: Children with jSLE were found to have higher IR even after neutralizing the effects of the contributing factors which are expected to aggravate IR. This elevation in IR in jSLE seems not to be associated with corticosteroid use, disease duration, disease activity, or autoantibody levels. Thus, the presence of IR in jSLE cannot be explained solely with neither the already known contributing factors nor the increased inflammation of the disease. Key Points • In this study, insulin sensitivity was investigated for the first time in children with jSLE. • Children with jSLE have higher insulin resistance than healthy ones. • Insulin resistance in children with jSLE is independent of corticosteroid use, disease duration, disease activity or autoantibody, and complement levels.

Effect of the COVID-19 quarantine on metabolic control in children and adolescents with type 1 diabetes.

INTRODUCTION: Metabolic control in type 1 diabetes (T1D) depends on many factors such as eating habits, exercise and lifestyle. The objective of this study was to investigate how these factors were affected during the coronavirus disease 2019 (COVID-19) lockdown and impacted metabolic control in children with T1D. MATERIALS AND METHOD: One hundred children with T1D were enrolled in the study. Anthropometric measurements, snack and meal frequency, carbohydrate consumption, HbA1c levels, and exercise patterns were recorded and compared before and after the lockdown. Subjects were divided into two subgroups-patients with decreased and patients with increased HbA1c levels after the lockdown-and comparisons of the same parameters were also made between these two subgroups. RESULTS: In the overall group, the mean HbA1c level was significantly higher after the lockdown compared to before (p=0.035). Meal schedules changed due to delayed sleep and waking times, and total daily carbohydrate consumption increased in the subgroup with increased HbA1c while it decreased in the subgroup with decreased HbA1c (p<0.001 for both). CONCLUSION: Our study supports the notion that blood sugar management in children with T1D worsened during the COVID-19 pandemic. Although it is not possible to explain this with any one factor, some behavioral changes observed in our study, such as inactivity, irregular meal frequency and timing, and irregular sleep and waking patterns appeared to be associated with blood sugar management.

Clinical and Genetic Characteristics of Patients with Corticosterone Methyloxidase Deficiency Type 2: Novel Mutations in CYP11B2

Corticosterone methyloxidase deficiency type 2 is an autosomal recessive disorder presenting with salt loss and failure to thrive in early childhood and is caused by inactivating mutations of the CYP11B2 gene. Herein, we describe four Turkish patients from two families who had clinical and hormonal features compatible with corticosterone methyloxidase deficiency and all had inherited novel CYP11B2 variants. All of the patients presented with vomiting, failure to thrive and severe dehydration, except one patient with only failure to thrive. Biochemical studies showed hyponatremia, hyperkalemia and acidosis. All patients had normal cortisol response to adrenocorticotropic hormone stimulation test and had elevated plasma renin activity with low aldosterone levels. Three patients from the same family were found to harbor a novel homozygous variant c.1175T>C (p.Leu392Pro) and a known homozygous variant c.788T>A (p.Ile263Asn) in the CYP11B2 gene. The fourth patient had a novel homozygous variant c.666_667delCT (p.Phe223ProfsTer35) in the CYP11B2 gene which caused a frame shift, forming a stop codon. Corticosterone methyloxidase deficiency should be considered as a differential diagnosis in patients presenting with hyponatremia, hyperkalemia and growth retardation, and it should not be forgotten that this condition is life-threatening if untreated. Genetic analyses are helpful in diagnosis of the patients and their relatives. Family screening is important for an early diagnosis and treatment. In our cases, previously unreported novel variants were identified which are likely to be associated with the disease.

Different clinical entities of the same mutation: a case report of three sisters with Wolfram syndrome and efficacy of dipeptidyl peptidase-4 inhibitor therapy.

OBJECTIVES: Wolfram syndrome (WS) is a rarely seen autosomal recessive multisystem neurodegenerative disorder caused by mutations in the WFS1 gene. CASE PRESENTATION: Three sisters with WS had diabetes mellitus (DM) at 4 years of age and optic atrophy. In addition, the first case had hearing impairment, and the second case had diabetes insipidus and urinary incontinence. Linagliptin was administered to the first case as add-on therapy to intensive insulin treatment 15 years after the onset of DM, and her insulin need showed a dramatic decrease. The third case had a remission phase one month after the onset of DM. CONCLUSIONS: Even in cases with the same mutation, symptoms and findings may widely vary in WS. Remission of diabetes has rarely been reported in WS. Also, this report describes the first trial of a dipeptidyl peptidase-4 inhibitor in a patient with WS which provided a decrease in exogenous insulin need.