Malgorzata Wojcik

A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents.

Abstract Aim: Fibroblast growth factor 19 (FGF19) is a hormone released from the small intestine; recently, it has emerged as an endocrine regulator of glucose and lipid metabolism. The aim of this study was to investigate the role of FGF19 in the development of nonalcoholic fatty liver disease (NAFLD). Patients: This study included 23 (17 boys) obese adolescents (mean age of 14.1 years) with NAFLD. The control group consisted of 34 (13 boys) obese peers with normal ultrasonographic imaging and normal liver function tests. Methods: The definition of NAFLD was based on clinical criteria: elevated alanine aminotransferase (>35 U/L) and liver steatosis features on ultrasound imaging. Serum FGF19 levels were measured in a fasting blood sample. The definition of insulin resistance was based on the homeostasis model assessment (HOMA) threshold: >2.5. Results: There was a significant difference between mean FGF19 levels in patients with NAFLD and controls (142.2 vs. 206 pg/mL, p=0.04). Mean fasting FGF19 levels were decreased in insulin-resistant patients in comparison with the non-insulin-resistant group (155.0 vs. 221.0 pg/mL, p=0.05). There was an inverse correlation between FGF19 and alanine aminotransferase levels (R=–0.3, p<0.05) and triglycerides (R=–0.27, p<0.05). Conclusion: A decrease in fasting FGF19 is associated with the development of NAFLD in obese adolescents. A decrease in fasting FGF19 levels may be a new important risk factor for NAFLD and the metabolic syndrome in adolescents. Further studies are needed to explain whether exogenous delivery of FGF19 might be therapeutically beneficial.

The association of FGF23 levels in obese adolescents with insulin sensitivity.

Abstract Background: The fibroblast growth factor 23 (FGF23) is the most important hormonal regulator of circulating phosphate levels. Apart from this essential role, it may also act as a ‘hormone-like’ factor involved in glucose and lipid metabolism. It is believed to have a potential role in the development of insulin resistance. Aim: The aim of the study was to compare FGF23 levels between two groups of obese adolescents: insulin resistant and non-insulin resistant. Patients: The study included 36 obese, insulin-resistant adolescents (21 boys and 15 girls) of pubertal age (mean age, 13.95 years; Tanner stage IV or V). The control group consisted of 21 obese peers with normal HOMA-IR values. Methods: FGF23 levels were measured in a fasting blood sample by Human Intact FGF-23 ELISA Kit (Immunotopics Inc., San Clemente, CA, USA). A standard oral glucose tolerance test was performed, which assessed fasting and 120 min postload plasma glucose and serum insulin levels; the insulin resistance index HOMA-IR was calculated. The definition of insulin resistance was based on a HOMA-IR threshold set for adolescents (≥3.16). Results: There was a significant inverse correlation between FGF23 levels and HOMA-IR (R=–0.26, p<0.05) in the study group. FGF23 levels were also significantly lower in the study group (9.8 vs. 11.9 pg/mL, p=0.026). Conclusions: In adolescents with simple obesity and insulin resistance, FGF23 levels are lower compared with obese adolescents with normal HOMA-IR.

Left Ventricular Diastolic Dysfunction in Adolescents with Type 1 Diabetes Reflects the Long- but Not Short- Term Metabolic Control

ABSTRACT Objective: The aim of this study was to compare the LV morphology and function in adolescents with DM1 and their healthy peers. Subjects and Methods: In 59 DM1 patients (30 girls, 29 boys,aged 14-17 years), and in control group (15 girls, 15 boys) LV was assessed by M-mode, 2D and Doppler echocardiography. The metabolic control was assessed in the long- (mean HbA1c value for the entire treatment period-HbA1c1), medium- (mean HbA1c for the past two pre-study years-HbA1c2), and short-term (HbA1c on the day of the study- HbA1c3). Results: Diabetic patients presented an increase of IRT (0.062 vs. 0.056 s,p<0.05 in boys, and 0.062 vs. 0.056 s,p<0.05 in girls), A wave (56.1 vs. 53.95 cm/s in boys, and 60.3 vs. 58 cm/s in girls), and deceleration time values (0.16 vs. 0.15 s in boys, and 0.17 vs. 0.15 s in girls), decrease of E wave (97.35 vs. 104.9 cm/s in boys, and 99.67 vs. 101.8 cm/s in girls), as well as the E/A ratio (1.79 vs. 2.0 in boys, and 1.7 vs. 1.78 in girls). The systolic function was normal. In girls there was a correlation between IRT and HbA1c1 and HbA1c2 (r=0.42,r=0.46,p<0.05); between the A wave and HbA1c2 (r=0.46,p<0.05); between LV posterior wall systolic dimension and HbA1c1, HbA1c2 (r=0.45,r=0.41,p<0.05), and in boys between the A wave and HbA1c1 and HbA1c2 (r=0.48,p<0.01;r=0.37, p<0.05). Conclusions: Pubertal patients with DM1 demonstrate discrete impairment of the diastolic function beside normal systolic function of the LV. Further investigations are needed to assess the value of this observation. It seems that LV diastolic dysfunction in girls depends on the degree of insulin resistance and DM1 duration, and similarly as in boys, on the long-term metabolic control.

Ovarian Hyperstimulation Syndrome in Newborns – A Case Presentation and Literature Review

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition in which immaturity of the gonadal axis is accepted as the cause. Based on our case and 8 cases from the literature, we made an attempt to specify the mechanisms underlying the syndrome and its pathognomonic signs. All POHS newborns were born between 24 and 31 weeks postconception age (WPCA) and developed vulvar, hypogastric and upper leg swelling, and ovarian follicular cyst/cysts (10–40 mm in diameter) with mildly or considerably elevated E2 concentrations (80–5,300 pmol/l) between 35 and 39 WPCA. The GnRH test, performed in 5 cases, confirmed gonadal axis activation. In our case the observed normalization of elevated gonadotropin values by 43 WPCA, accompanied by a simultaneously increasing E2 value (approximately 800 pmol/l), could correspond with the maturation of the gonadal steroid-dependent negative-feedback mechanism. The continuously increasing E2 levels after this period (maximum 1,300 pmol/l) suggest its autonomous secretion. In all the cases, including 3 neonates treated with medroxyprogesterone and surgery, the swelling resolved by 6 months. Conclusions: A pathognomonic sign of POHS is swelling which develops around 37 ± 3 WPCA, and the syndrome is only infrequently diagnosed when the swelling is profound. The direct etiologic factor here is not E2. POHS does not require therapy as long as there is no danger of cyst torsion.

High Incidence of Abnormal Circadian Blood Pressure Profiles in Patients on Steroid Replacement Therapy due to Secondary Adrenal Insufficiencyand Congenital Adrenal Hyperplasia without Overt Hypertension - InitialResults

Patients on steroid replacement therapy are at an increased risk of cardiovascular complications owing to the fact that disruptions in the cortisol diurnal rhythm may affect the blood pressure (BP) profile. Aim: To evaluate the circadian BP profiles of patients with secondary adrenal insufficiency (SAI) and congenital adrenal hyperplasia (CAH) on steroid replacement therapy and to compare BP profiles of patients receiving hydrocortisone (HC) in different dosing schedules. Methods: The study included 33 patients: 15 SAI and 18 CAH (mean age 13.2 years 95CI 11.3-15.1). There were no patients with previously diagnosed overt hypertension. Patients with SAI received a mean of 7.39 mg/m2 of HC in 3 daily doses (in the morning (M) 50%, in the afternoon (A) 25%, in the evening (E) 25%), CAH patients 17.9 mg/m2 of HC in the following dosing schedules: 5 patients in 3 equal doses, 7 patients received M: 40% A: 40% E: 20%, the remaining 6 patients had the same dosing schedule as patients with SAI. Fludrocortisone (FC) was given to 13 patients with CAH in 2 equal daily doses. The total dose of HC/FC as well as the dosing schedule of HC was adjusted individually based on clinical and biochemical outcomes. Standard 24-hour BP monitoring (ABPM) was performed using an Ambulatory BP Monitor (Space labs 90217, USA). Results: The majority of the patients (almost 70% SAI, 80% CAH) presented with an abnormal 24-hour BP profile. There were no significant differences in ABPM results between SAI and CAH patients, and no differences between CAH patients treated with and without FC. There was no correlation between HC and FC doses [mg/m2] and ABPM results except that mean night SBP values increased with greater HC doses (r=0.51, p<0.05). Among the CAH group the highest percentage of abnormal ABPM results was observed in patients who received HC in doses: M: 50% A: 25% and E: 25%, the most favorable BP profile was observed in patients with dosing schedule: M: 40%, A: 40%, E: 20%.However there were no significant differences between patients with different treatment protocols, the results suggest that observed disruptions of the BP profile could be related to the HC dosing schedule. Conclusions: The incidence of abnormal BP profiles in patients on steroid replacement therapy due to SAI and CAH without overt hypertension is high. The disruptions of the BP profiles are not associated with the dose of HC or FC. The abnormal BP profiles in patients with SAI or CAH may be related to the HC dosing schedule. 24-hour ABPM seems to be a useful, non-invasive and safe method for the monitoring of HC and FC replacement therapy in patients with adrenal insufficiency. Further investigations in the larger groups of patients are needed.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development

AbstractBackground The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3–43%.ObjectiveTo investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients.Patients179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). MethodsRetrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed.ResultsAnalysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%—diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%—diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%—micronodulations and in 3.9%—diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background.ConclusionPatients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

The potential impact of the hypovitaminosis D on metabolic complications in obese adolescents – Preliminary results

INTRODUCTION AND OBJECTIVE Vitamin D deficiency is common in obesity; however, its contribution in the development of metabolic complications remains uncertain. The aim of the study was to examine the relationships between vitamin D status and metabolic complications. MATERIAL AND METHODS The results of blood pressure measurements, biochemical tests and ultrasound of the liver were compared in both groups. The study was conducted at the Childrens University Hospital in Krakow, Poland. 30 obese adolescents (mean 13.23y.o.); 18 with 25OHD levels <20ng/mL, 12 with 25OHD>20 ng/mL. RESULTS The vitamin D deficient group presented with significantly higher values of the diastolic blood pressure (125.9vs.115mmHg), uric acid level (384.7vs.301.5umol/L) and lower phosphorus level (1.4vs.1.65mmol/L), higher prevalence of arterial hypertension (44vs.8.3%), and liver steatosis (25vs.8.3%); lower, but not significantly, levels of fibroblast growth factor 23 and fibroblast growth factor 19. CONCLUSIONS Hypovitaminosis D in obese adolescents is associated with higher prevalence of arterial hypertension, liver steatosis, elevated serum uric acid and low phosphorus levels. The potential contribution of the fibroblast growth factor 23 and fibroblast growth factor 19 in these complications development needs further investigation.

Testicular adrenal rest tumors in congenital adrenal hyperplasia: a case report and literature overview.

OBJECTIVE In this paper, the etiology, differential diagnosis, and therapy of testicular adrenal rest tumors (TARTs) is presented based on a patient presentation and an overview of the most recent literature concerning this subject. METHODS Retrospective analysis of the clinical and biochemical data of an 18-year-old male patient diagnosed at the age of 2 weeks with the classic salt-wasting form of congenital adrenal hyperplasia that has been monitored in the pediatric and adolescent outpatient department since the age of 4 years. RESULTS The results of adrenal hormone tests (17-hydroxyprogesterone, 17-ketosteroids, and pregnanes) had been unsatisfactory, particularly over the previous 5 years. Scrotal ultrasound detected TARTs bilaterally. After increasing the dose of hydrocortisone and introducing dexamethasone, considerable regression of the tumors was noted. CONCLUSION Lack of complete regression of the lesions is caused by fibrosis and is probably due to decreased sensitivity of adrenocorticotropic hormone and angiotensin II receptors in this tissue.

Generalized seizures as the first manifestation of multihormonal pituitary hormone deficiency causing normovolemic hyponatremia

Patient: Female, 14 Final Diagnosis: Multiple pituitary hormone deficiency Symptoms: Hyponatremia Medication: — Clinical Procedure: Endovascular embolectomy Specialty: Endocrinology and Metabolic Objective: Patient complains/malpractice Background: Hyponatremia is one of the most common electrolyte disorders. Depending on the patient’s hydration status, hyponatremia can be classified as hypovolemic, hypervolemic, or normovolemic. The last type is caused by the syndrome of ‘inappropriate’ secretion of antidiuretic hormone (SIADH), and more rarely by SIADH-like syndrome, in which oversecretion of ADH is caused by adrenal or thyroid insufficiency. Case Report: This report presents the case of a girl who, at the age of 14 years and 4 months, presented with severe normovolemic hyponatremia (Na 110 mmol/L) due to decompensation of previously undiagnosed secondary adrenal insufficiency due to a respiratory tract infection. Hyponatremia was worsened by concomitant hypothyroidism and valproic acid therapy. This case is a rare example in clinical practice of multiple pituitary hormone deficiency, that despite typical symptoms such as short stature, adrenal insufficiency (hypoglycemia, hyponatremia, and low blood pressure), or delayed puberty, was diagnosed only after the development of adrenal crisis (severe symptomatic hyponatremia and hypoglycemia). Conclusions: In prepubertal pediatric patients with severe hyponatremia, multiple pituitary hormone deficiency must be considered. Patients with hypothyroidism, as well as concomitant epilepsy treated with valproic acid, are at risk of severe hyponatremia, which may cause symptoms mimicking an epileptic attack.

A case of recurrent labial adhesions in a 15-month-old child with asymptomatic non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Abstract Labial adhesions (synechia vulvae) are a relatively common disorder of the external genitalia in prepubertal girls. They usually occur between 3 months and 6 years of age, with a peak between 13 and 23 months of life. In the majority of cases, labial adhesions are asymptomatic and noticed by the parents or a physician during a routine physical examination. Frequently, they cause recurrent urinary tract infections. This report presents the case of a 15-month-old girl with recurrent labial adhesions and urinary tract infections. She was followed-up by a urologist from the age of 3 months, treated topically (estriol cream 1 mg/g and emollients) and surgically. No signs of androgenization were seen apart from advanced bone age. Urinary steroid profile and molecular analysis confirmed the diagnosis of non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. In the described case, a coincidence of NCCAH and labial adhesion cannot be excluded particularly in view of the resolving of urinary tract infections at the same time as resolving of labial adhesions. However, it seems that in cases of recurrent labial adhesion/synechia that require repeated surgical interventions in view of ineffectiveness of conservative treatment – as it was observed in the presented case – one should consider searching for NCCAH. This may allow not only for the causal treatment of labial adhesions but, above all, NCCAH and, in consequence, the prevention of intensification of virilization, hirsutism, menstrual cycle, and fertility disturbances that are observed starting from puberty.