Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome : preliminary results

estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). Methods In 14 TS (mean age 13.8), LE ($17\beta$-estradiol, 62.5 $\mu$g daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting $17\beta$-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. Results There were no significant differences between LE and CE in the mean levels of any parameter before introduction of $17\beta$-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 $\mu$IU/mL, HOMAIR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. Conclusion Prepubertal LE is associated with healthier lipid profile than CE in girls with TS

High incidence of abnormal circadian Bood Pressure profiles in patients on steroid replacement therapy due to Secondary Adrenal Insufficiency and Congenital Adrenal Hyperplasia without overt hypertension : initial results

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

Human recombinant growth hormone normalizes growth and alleviates symptoms in children with severe growth deficit treated with glycocortisteroids due to Crohn&#8217;s disease - case presentation

Choroba Leśniowskiego-Crohna (CD) jest przyczyną niskiego wzrostu u 10&#8211;20% chorych w wyniku katabolicznego działania: 1) niedożywienia spowodowanego upośledzeniem wchłaniania oraz jelitową utratą białka, 2) przewlekłego procesu zapalnego, który wywołuje zależną od TNF-a oporność na hormon wzrostu (GH) oraz 3) przewlekłej kortykoterapii hamującej działanie osi somatotropowej. Autorzy niniejszej pracy przedstawią przypadek 14-letniego chłopca z CD, otyłością (+55%) o typie cushingoidalnym i nadChoroba Leśniowskiego-Crohna (CD) jest przyczyną niskiego wzrostu u 10&#8211;20% chorych w wyniku katabolicznego działania: 1) niedożywienia spowodowanego upośledzeniem wchłaniania oraz jelitową utratą białka, 2) przewlekłego procesu zapalnego, który wywołuje zależną od TNF-a oporność na hormon wzrostu (GH) oraz 3) przewlekłej kortykoterapii hamującej działanie osi somatotropowej. Autorzy niniejszej pracy przedstawią przypadek 14-letniego chłopca z CD, otyłością (+55%) o typie cushingoidalnym i nadciśnieniem tętniczym, którego leczono od 7 rż. glikokortykoidami (GCS) (prednizon 2 mg/kg/d., metylprednizolon 0,1&#8211;0,6 mg/kg/d.), od 9 rż. mesalazyną (0,02&#8211;0,2 mg/kg/d.), od 14 rż. azatiopryną (1&#8211;2 mg/kg/d.), a od 15 &#8212; 4/12 ludzkim rekombinowanym hormonem wzrostu (rhGH) (1 j./kg/tydz.) z powodu rozpoznania izolowanego niedoboru GH na podstawie niedoboru wzrostu &#8211;4 SDS, opóźnienia wieku kostnego (9 lat), zahamowania wzrastania (0,0 cm/rok) w okresie ostatnich 2 lat oraz maksymalnego wyrzutu GH poniżej 10 ng/ml w dwóch testach farmakologicznych. Pacjent otrzymywał ponadto analog GnRH (Diphereline 3,75 mg/4 tyg.) z powodu nasilonych w ciągu ostatnich 2 lat cech pokwitania (objętość jąder po 8 ml, maks. wyrzut LH = 9,1 mj./ml po dożylnej stymulacji 100 &#956;g GnRH). W czasie trwającego 3,5 roku leczenia rHGH uzyskano stężenia IGF-1 zbliżone do +2 SD oraz szybkość wzrastania (maks. 9,7 cm/rok), mimo równoczesnego stosowania GCS, wzrost końcowy (174 cm, &#8211;0,2 SDS), zgodny ze wzrostem docelowym (176,5 cm), oraz remisję choroby zasadniczej, pozwalającą na redukcję, a następnie całkowite odstawienie GCS. Nie obserwowano zaburzeń gospodarki węglowodanowej (glikemia na czczo 5,4 mmol/l, HbA1c 5,1%). Na podstawie tych obserwacji wykazano, że leczenie rhGH przy zastosowanych dawkach poprawia wzrost końcowy i przebieg choroby u pacjentów z CD.Crohn&#8217;s disease (CD) causes short stature in 10-20% of patients due to catabolic effects of: 1. malnutrition resulting from malabsorbtion and intestinal protein loss, 2. chronic inflammatory process triggered by TNF-alpha-dependent resistance to growth hormone (GH), and 3. chronic corticoid therapy inhibiting the somatotropic axis activity. The authors present a 14-year old boy with CD, cushingoid-type obesity (+55%), hypertension, treated with glucocortocoids (GCS) (prednizone 2 mg/kg/day, methylprednizolone 0.1-0.6 mg/kg/day) since 7 years of age, mesalazine (0.02-0.2 mg/kg/day) since 9 years of age, azatioprin (1-2 mg/kg/day) since 14 years of age, and human recombinant growth hormone (rhGH) (1 IU/kg/week) since 15 4/12 years of age due to isolated GH deficiency diagnosed based on growth deficit -4 SDS, delayed bone age (9 years), growth inhibition (0.0 cm/year) within the past 2 years, and maks. GH release below 10 ng/ml in two pharmacological tests. Additionally, he received a GnRH analog (Diphereline 3.75 mg/4 weeks) due to intensified puberty signs noted over the past 2 years (testicular volume - 8 ml each, max. LH surge release 9.1 mIU/ml following IV stimulation with 100 &#956;g GnRH). Within 3.5 years of rHGH treatment, he demonstrated IGF-I levels approximating IGF-I +2 SD, improved growth rate (max. 9.7 cm/year), despite concomitant GCS administration, final height of 174 cm, -0.2 SDS (in agreement with mean parental height - 176.5 cm) and underlying disease remission, allowing for reducing the dose and subsequent GCS termination. No carbohydrate metabolism disturbances were seen (fasting glycemia 5.4 mmol/l, HbA1c 5.1%). These observations indicate the employed doses of rhGH improve final height and the course of disease in CD patients

The treatment of severe growth failure in children with juvenile idiopathic arthritis and growth hormone deficiency - preliminary results

WSTĘP. Niedobór wzrostu należy do głównych niespecyficznych objawów młodzieńczego idiopatycznego zapalenia stawów (JIA) i dotyczy, w zależności od postaci i ciężkości choroby, 11&#8211;90% pacjentów. Wydaje się, że u około 70% tych chorych może być skuteczne leczenie ludzkim rekombinowanym hormonem wzrostu (rhGH). Celem pracy była ocena wstępnych wyników leczenia ciężkiego niedoboru wzrostu w przebiegu JIA z towarzyszącym niedoborem GH przy zastosowaniu rhGH. MATERIAŁ I METODY. Spośród 10 chorych (4 chłopców, 6 dziewcząt) w wieku 6-15,5 (średnia 12,2 roku) z niedoborem wzrostu [(-)7,7-(-2,4) SDS] do leczenia rhGH zakwalifikowano 5 chorych (2 chłopców, 3 dziewczynki) na podstawie wykazania u nich współistniejącego niedoboru GH. Wszyscy otrzymywali glikokortykosteroidy (GKS) w średniej dawce 0,08-1,4 mg/kg/24 h w przeliczeniu na prednizon, 3 chorych, u których zastosowano leczenie rhGH, oraz wszyscy nieleczeni rhGH otrzymywali ponadto lek blokujący czynnik martwicy nowotworu a (Etanercept). WYNIKI. W pierwszym roku leczenia rhGH w dawce 0,03-0,06, średnio 0,047 mg/kg mc./dobę, uzyskano zwiększenie szybkości wzrastania z 0-3,2; średnio 1 cm/rok do 0,3-16; średnio 3,3 cm/rok, wzrost stężenia insulinopodobnego czynnika wzrostu typu 1 z 69,1-331,1; średnio 197,5 ng/ml do 335-716,9; średnio 526 ng/ml. W trakcie 16,6 pacjentolat (5 pacjentów, indywidualny czas leczenia 1,8-4,5; średnio 3,8 roku) w czterech przypadkach leczenie rhGH spowodowało zwiększenia wysokości ciała o 0,1-2,2 SD. U chorych nieleczonych rhGH nie obserwowano przyspieszenia wzrastania. WNIOSKI. U chorych z JIA stosowanie rhGH w dawce zbliżonej do 0,047 mg/kg mc./dobę poprawia szybkość wzrastania i wzrost końcowy. Wyniki leczenia mogą się różnić u poszczególnych chorych z JIA i są tym lepsze, im mniejszy jest niedobór wzrostu w momencie rozpoczęcia leczenia oraz mniejsze nasilenie procesu zapalnego. Słowa kluczowe: młodzieńcze idiopatyczne zapalenie stawów, niedobór wzrostu, hormon wzrostu Endokrynologia, Otyłość i Zaburzenia Przemiany Materii 2010, tom 6, nr 2, 67-71INTRODUCTION. Short stature is one of the major, nonspecific features of juvenile idiopathic arthritis (JIA), that affects, in dependence on clinical presentation and severity, 11-90% of patients. The treatment with human recombinant growth hormone (rhGH) may be successful in almost 70% of such cases. the aim of the study was to analyze the initial results of the rhGH treatment in children with severe growth failure and GH deficiency secondary to JIA. MATERIAL AND METHODS. From among 10 children (4 boys, 6 girls), age 6-15.5, mean 12.2 years, with growth deficiency [(-)7.7-(-2.4) the SDS], 5 (2 boys, 3 girls) with coexisting GH deficiency received rhGH treatment. All patients were treated with glucocorticoids (GCS) with a mean dosage of 0.08-1.4 mg/kg/day (prednisone), 3 of the patients treated with rhGH, and all non-treated patients received biological treatment (Etanercept). RESULTS. After one year of rhGH treatment with a dosage of 0.03-0.06, mean 0.047 mg/kg/day) the growth velocity increased from 0&#8211;3.2, mean 1 cm/year, to 0.3-16, mean 3.3 cm/year, as well as the insulin like growth factor type 1 concentration from 69.1-331.1 (mean 197.5) ng/ml to 335-716,9 (mean 526) ng/ml. In 16.6 patient-years of treatment (5 patients, individual treatment period 1.8-4.5; mean 3.8 years) there was improvement of growth from 0.1 to 2.2 SD in 4 cases. CONCLUSIONS. In patients with JIA undergoing rhGH treatment, with a dosage of approximately 0.047 mg/kg/day, improves growth velocity, and final height. The results may be different in individual cases. They are better if the growth failure before treatment is less severe, and the inflammation process is less active. Endocrinology, Obesity and Metabolic Disorders 2010, vol. 6, No 2, 67-7

Should we routinely assess hypothalamic–pituitary–adrenal axis in pediatric patients with Prader–Willi syndrome?

BackgroundIt 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).ObjectiveTo 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.MethodsA 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 &gt;181.2 ng/mL (500 nmol/L) in LDAT and &gt;199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) &gt;90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve.ResultsThree 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 &gt;90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%).ConclusionWe 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