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Aim: To evaluate the long-term effects of nutritional improvement following percutaneous endoscopic gastrostomy (PEG) tube feeding stratified by previous feeding method and to assess the impact of underlying muscle tone on the outcomes of the nutritional intervention. Methods: Neurologically impaired children who underwent PEG tube insertion and nutritional intervention provided by a pediatric nutritional support team were enrolled. We measured anthropometric variables, laboratory parameters, and nutritional intake at baseline, 6 months after PEG insertion, and the last visit. We evaluated the percent ideal body weight (PIBW), body mass index (BMI)-for-age z-score, and percentiles and calculated the ratios of calorie intake compared to required requirement (CIR) and protein intake compared to recommended requirement (PIR). Results: The PIBW and BMI-for-age z-score improved during the first 6 months (p = 0.003 and p = 0.005, respectively). The CIR (p = 0.015) and PIR (p = 0.004) increased during the study period. The baseline BMI and PIBW of the previous nasogastric tube feeding group were better than those of the oral feeding group (p = 0.02 and p = 0.03, respectively). The BMI-for-age z-score, PIBW, CIR, and PIR improved in the hypertonic group (p = 0.03, 0.02, 0.03, and 0.01, respectively). Conclusion: PEG tube feeding and active nutritional intervention improved the nutritional status of neurologically impaired children immediately after PEG insertion. The nutritional requirements might vary by the muscle tonicity.

Aromatase inhibitor (AI), mostly combined with recombinant human growth hormone (rhGH), has been proposed as a effective treatment to improve the final adult height in short pubertal boys by delaying growth plate closure. However, safety concerns also remain, because of limited safety profile of AI usage in pediatric population. Several recent studies have revealed adverse effects of AI, including possible alterations in vertebral bone growth and vertebral anomalies, decreased HDL, increased hematocrit. Although that estrogens might have a role in the regulations of cognitive functions and AIs that block estrogen synthesis cross the blood-brain barrier, a recent trial suggested that AI did not impact the cognitive performance in peripubertal boys. In this report, we would like to introduce a rare case of showing obsessive and compulsive behavioral change in a early pubertal boy who was co-treated with AI and rhGH. A 13 years and 5 months-old boy visited our clinic and his initial examination revealed as follows; height was 160.5cm (45th percentile) and weight was 47.6kg (29th percentile); secondary sexual characteristics of Tanner stage IV. His pelvis x-ray showed risser stage 2, which is assessed to be about 16 years of bone age. He was otherwise healty with no other medical problems. His father's height was 170cm, his mother's height was 151cm, and his midparental height was calculated as 167cm. The patient and his parents wanted to improve his final adult height, and we commenced combination treatment of AI and rhGH after taking agreement. We prescribed letrozole 2.5mg once a day. After 2 months of the start of AI treatment, his parents compaint of his obsessive and compulsive behavioral change, which was not noticed before taking the drug. He complaint of obsessive thoughts and unwanted emotional pull that caused anxiety and distress. Also, he showed compulsive behavior of repeating reading one phrases of the same page. He was in intense stressful situation of preparing important test, however, we could not rule out the possibility of potential adverse effect of AI. Therefore, we discontinued AI. After discontinuing the drug, the symptom improved. During 3 months of combination treatment, he has achieved his height as 162.4cm with a gain of 1.9cm. The progression of bone age was successfully suppressed during the treatment. In conclusion, no significant influence on cognitive performance has been reported in previous studies, however, those studies focused on memory function. Potential effects on other behavioral change have not heen extensively evaluated. Therefore, clinicicans should be aware of possibility of compulsive behavioral change in AI-treated early pubertal boys, and further studies are needed to reveal the relationship.

Autonomous ovarian follicular cysts are known as the most common cause of peripheral precocious puberty(PPP) in prepubertal girls, and relapses of autonomous ovarian cysts resulting in prolonged estrogen exposure can precipitate early maturation of the hypothalamic-pituitary-gonadal axis, resulting in progression from PPP to central precocious puberty(CPP), which is called “combined precocious puberty”, an evolution which may require GnRH therapy. In present case, PPP caused by autonomous ovarian follicular cyst was developed concomitantly during the treatment course of CPP, with suppressed status of hypothalamic-hypophyseal-axis. In addition, a rare congenital Müllerian anomaly known as Herlyn-Werner-Wunderlich syndrome(HWWS), consisting of uterus didelphys, obstructed hemivagina and unilateral renal agenesis was incidentally diagnosed as an underlying condition. A 7-year-old girl was presented to our clinic with the development of breast buds which was examined as Tanner stage 2-3. Right renal agenesis was diagnosed in infancy. Her bone age was advanced as 10 years of age, and Luteinizing hormone(LH) showed pubertal response in LHRH stimulation test. The pelvic US revealed absence of right kidney and uterine enlargement. Brain MRI showed no specific abnormalities. Based on these results, We diagnosed idiopathic central precocious puberty. Thereafter, we commenced the treatment with Leuprolide acetate 3.75mg every 4 weeks. After the 11th injection of Leuprolide acetate, however, the patient complained of sudden breast engorgement and vagnal bleeding. Being considered as unsuccessful suppression of HPG axis, Leuprolide acetate was boosted. Hormonal analysis results revealed an extremely elevated level of estradiol and suppressed baseline gonadotropin levels. The pelvic US revealed double uterus, which had not been detected to that point. Abdominopelvic MRI demonstrated right renal agenesis and uterus didelphys with clearly separated uterine body, cervix and vagina. About 3cm sized cystic lesion with several internal daughter cysts is also discovered in left adnexa area. Based on all examinations, we concluded that PPP caused by autonomous ovarian cyst was superimposed on treatment course of CPP and HWWS was incidentally found as underlying disease. Maintaining GnRH agonist treatment, the progression of secondary sexual characteristics was halted and left ovarian cyst disappeared. In couclusion, clinician should be aware of possibility of autonomous ovarian follicular cyst when sudden progression of secondary sexual characteristics is shown in being treated CPP patients, and discriminate PPP from unsuccessfully treated CPP. Additionally, careful suspicion for HWWS that is tied to indications of renal agenesis in children may be the key for successful early diagnosis and immediate treatment intervention, which could prevent long-term complications.

The Gonadotropin-releasing hormone(GnRH) agonist has been the treatment of choice for central precocious puberty. These drugs suppress gonadotropin secretion through desensitization and downregulation of GnRH receptors, leading to reduced secretion of gonadal steroids to prepubertal levels. The regression of secondary sexual characteristics, delayed menarche, and maximization of linear growth can be achieved through this treatment. Due to initial agonistic action of this drug, withdrawal vaginal bleeding can occur after the first or second dose of the treatment. This phenomenon could occur after 6 months in rare cases. In this report, we would like to introduce a rare case of unexpected vaginal bleeding with rapid breast engorgement during the treatment course without any evidence of insufficient suppression of hypothalamic-hypophyseal-gonadal(HPG) axis. The condition was normalized with increased dosage of drug for 2 months, and suppression of HPG axis was maintained with same initial dosage untill completion of treatment. Therefore, we believed that idiopathic reactivation of HPG axis was likely a cause of this unusual condition. A 7 year-old girl visited our clinic with breast buds which was examined as Tanner stage 2-3, with pigmentation of areola. Her bone age was advanced as 10 years of age. LHRH stimulation test showed a pubertal response(LH>5.0 IU/L). Pelvic ultrasonography showed a pubertal uterus shape. Brain MRI showed no specific abnormalities. Leuprolide acetate 3.75mg was administered to the patient every 4 weeks, and until the 4th injection, she exhibited no progression of secondary sexual characteristics and changes in hormonal levels, indicating that the HPG axis was properly suppressed. However, after 5th injection, the patient complained of rapid breast engorgement and abrupt vaginal bleeding 2 weeks later. LH and estradiol was measured 0.3 IU/L(normal < 0.2 IU/L) and 38.7pg/ml(normal < 10pg/ml), respectively. Pelvic ultrasonography revealed enlarged uterus without any other pathologic findings. Leuprolide acetate 3.75mg was boosted and administered every 2 weeks for 2 months. After confirming the HPG axis suppression on studies, the injection interval was rescheduled to 4 weeks. The status of patient was stabilized without any other clinical or hormonal deterioration until completion of treatment. In conclusion, GnRH agonist can suppress HPG axis successfully in most cases, however, temporal reactivation of HPG axis can occur during the treatment course although HPG axis suppression has been maintained in serial check up. Therefore, clinician should be aware of possibility of unexpected vaginal bleeding and reevaluation should be performed to check up the status of the patient, including pelvic ultrasonography and hormonal assessment. Finally, careful advice should be given in an attempt to avoid unnecessary anxiety and achieve better compliance.

Leri-Weill dyschondrosteosis (LWD) is a rare genetic disorder of bony growth characterized by abnormal shortening of the forearms and lower legs, abnormal misalignment of the wrist (Madelung deformity), and associated short stature. As a result of shortened leg bones, LMD patients typically have short stature. Additional symptoms and severity can vary greatly from one person to another, even among members of the same family. LWD is caused by a heterozygous mutation in the short stature homeobox-containing (SHOX) gene or its regulatory elements (enhancers) located on the pseudoautosomal region 1 (PAR1) of the sex chromosomes. There are a number of reports about GH-treated SHOX-deficient patients such as LMD, idiopathic short stature, and Turner syndrome, however, in this report, we would like to introduce a rare case with underlying LWD and central precocious puberty, who was treated by combined therapy of gonadotropin releasing hormone (GnRH) agonist and recombinant human growth hormone (rhGH). A 8 years and 4 months old girl visited our clinic for short stature and breast development of Tanner stage 2. In physical examination, her height was 117 cm (

Aromatase inhibitor (AI) is a drug that blocks the converstion of androgens to estrogens, originally approved by FDA as a treatment of breast cancer in postmenopausal women. In several studies, it has been proposed that AI can be used as a off-label treatment to improve the final adult height in short pubertal boys by delaying growth plate closure, because that estrogen has an important role in pubertal growth spurt by promoting the closure of epiphyses, skeletal maturation in males as well as females. AI has been also introduced to be used for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts. In recent studies, AI appears effective in increasing final adult height, however, safety concerns also remain including androgenic adverse effect and vertebral deformities. Although that we experienced that there has been no major adverse effects in AI-treated pubertal boys as reported in other studies, we would like to introduce a case of pubertal boy showing hyperactive behavioral change when co-treated with AI and rhGH for short stature and early puberty. A 10 years and 2 months-old boy visited our clinic and his initial examination revealed as follows; height was 143.7cm (81th percentile) and weight was 45.3kg (89th percentile); secondary sexual characteristics of Tanner stage III. Bone age was assessed to be 13 years by TW3 method. He was diagnosed as ADHD in previous years, but not prescribed medicine because of well-controlled behavior. We diagnosed the patient as early puberty, and combination treatment of GnRH agonist and rhGH was started. After 10 months, GnRH agonist treatment was discontinued, and after-GnRHa AI treatment was started to slow down bone age progression and improve his height. We prescribed letrozole 2.5mg once a day. After 7 months, we discontinued AI because of his aggravated hyperactivity and uncontrolled aggressive behavior which was much more severe than before. We could not rule out the possibility of testosterone-mediated side effect. At that time, his height was 170.4cm with a gain of 26.7cm (chronological age of 13 years and 3 months). The progression of bone age was successfully suppressed during the treatment. After 1 years of completion, we checked his near-final height as 173.4cm. In conclusion, testosterone levels have been thought to be linked to aggression and violent behavior in adults and postpubertal adolescents in previous studies. Therefore, clinicicans should be aware of possible behavioral change in AI-treated early pubertal boys, which can be mainly induced by hypertestosteronemia, and further studies are needed to reveal other androgenic adverse effects.

In Central precocious puberty(CPP), the gonadotropin-releasing hormone(GnRH) agonist competes with LHRH in the pituitary gland to desensitize and downregulate the response of gonadotropin-releasing hormone receptors, effectively inhibiting the secretion of sex hormones in the gonad to prepubertal levels. During the treatment, the bone age progression is slowed, the progression of secondary growth is stopped, and the secretion of sex hormones is maintained as prepubertal levels. We report a case of CPP patient who was treated with GnRH agonist, but abnormally elevated in estradiol level without changes in FSH and LH levels, and slowly normalized without any other abnormal clinical symptoms or laboratory findings. A 5 year and 10 months old girl visited our clinic with breast development which was examined as Tanner stage 2-3. Anthropometric datas were as follows: Her height was 127.3 cm(100th percentile), body weight was 29kg(100th percentile), and BMI was 17.9 kg/cm2. Her bone age was asessed to be 9.7 years by TW3 method. In the abdominopelvic ultrasonography, her uterus showed a pubertal status and no other abnormal findings were noted. LHRH stimulation test showed a pubertal response (peak LH level: 12.1 IU/L after 30min). She was confirmed as central precocious puberty, but brain MRI could not be perfomed due to refusal of the patient’s parents. Suppressive treatment was initiated with leuprorelin acetate 3.75mg(Lorelin depo, Dongkuk pharm). There was no further progression of secondary sexual characteristics after the treatment, and we noticed the downregulation of gonadotropin(FSH,LH) and estradiol in initial follow up hormonal assessment. However, second follow up study which was perfomed after 6 months of the treatment showed a feature of peripheral precocious puberty (FSH:1.0 IU/L(normal