Ah Reum Kwon

Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia.

Purpose In male patients with congenital adrenal hyperplasia (CAH), the presence of testicular adrenal rest tumors (TARTs) have been reported, however their prevalence and clinical manifestations are not well known. Untreated TARTs may lead to testicular structural damage and infertility. This study was conducted to investigate the prevalence of TARTs in male patients with CAH, and characterize the manifestations to identify contributing factors to TART. Methods Among 102 CAH patients aged 0-30 years, 24 male patients have been regularly followed up in our outpatient clinic at Severance Childrens Hospital from January 2000 to December 2014. In order to reveiw the characteristics of TART patients, we calculated the mean levels of hormones during the 5 years before the time of investigation. Five patients underwent follow-up scrotal ultrasonography (US) after adjusting the dosage of glucocorticoids. Results TARTs were detected in 8 of the 13 patients (61.5%). The median age of TARTs diagnosis was 20.2 years with the youngest case being 15.5 years old. The mean serum level of adrenocorticotropic hormone (ACTH) was higher in the TARTs patient group compared to the non-TARTs group (P<0.05). The tumor size decreased in 3 cases, slightly increased in 1 case, and had no change in another case. Conclusion The serum ACTH level might be associated with the growth promoting factor for TARTs, but the exact mechanism has not been clearly identified. Screening for TARTs using US is important in male patients with CAH for early-detection and prevention of ongoing complications, such as infertility.

Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

Purpose There is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP. Methods We reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Childrens Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23). Results In the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm) was significantly higher than the initial PAH (156.6±3.96 cm) (P<0.001), and it was similar to the MPH (159.9±3.52 cm). In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm) was also higher than the initial PAH (154.6±2.55 cm) (P<0.001), which was similar to the MPH (158.1±3.31 cm). Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment. Conclusion In CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

Etiologies and characteristics of children with chief complaint of short stature

Purpose Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature. Methods We retrospectively reviewed the medical records of 3,371 patients who visited Severance Childrens Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed. Results Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%). Conclusion A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.

XYY syndrome: a 13-year-old boy with tall stature

When evaluating the underlying causes of tall stature, it is important to differentiate pathologic tall stature from familial tall stature. Various pathologic conditions leading to adult tall stature include excess growth hormone secretion, Marfan syndrome, androgen or estrogen deficiency, testicular feminization, and sex chromosome anomaly, such as Klinefelter syndrome and XYY syndrome. Men with 47,XYY syndrome can exhibit multiple phenotypes. A 13-year-old boy visited the hospital for evaluation of tall stature. The boy had no other physical abnormalities except tall stature. All biochemical and imaging studies were within the normal ranges. He was diagnosed with XYY syndrome in this chromosome study. When evaluating men with tall stature, XYY syndrome should be ruled out.

Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy

Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg). The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications.

Male patients presenting with rapidly progressive puberty associated with malignant tumors

In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.

A boy with 46,X,+mar presenting gynecomastia and short stature

A 15-year-old boy was referred due to gynecomastia and short stature. He was overweight and showed the knuckle-dimple sign on the left hand, a short fourth toe on the left foot, and male external genitalia with a small phallus. His levels of estradiol and follicle-stimulating hormone were increased, and his testosterone concentration was normal. Other hormonal tests were within the normal range. Radiographs showed short fourth and fifth metacarpals and fourth metatarsal bones. The karyotype was reported as 46,X,+mar, and the marker chromosome was shown to originate from the Y chromosome, which was identified by fluorescence in situ hybridization. Polymerase chain reaction and direct sequencing were used to clarify the deleted loci of the Y chromosome by making use of Y-specific sequence-tagged sites (STSs). The sex-determining region Y and centromere were verified, and there were microdeletions on the long arm of the Y chromosome. The azoospermia factor (AZF) b region was partially deleted, and AZFa and AZFc were completely deleted. Two STS probes of sY143 and the Y chromosome RNA recognition motif in AZFb showed positive signals corresponding to Yq11.223. The karyotype of the patient was interpreted as 46,X,der(Y)del(Y)(q11.21q11.222)del(Y)(q11.23qter). Herein, we report a rare case of a boy presenting with gynecomastia and short stature with 46, X, +mar, which originated from the Y chromosome, which was identified to have Yq microdeletions.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

Messenger ribonucleic acid expression of KiSS-1 and serum level of kisspeptin in rat at different developmental stages

Purpose KiSS-1 and its product, kisspeptin is necessary for pubertal onset and proper adult gonadal function due to its stimulatory effect on the secretion of gonadotropinreleasing hormone (GnRH). Although the pathophysiological importance of KiSS-1 and kisspeptin is well known, the developmental patterns of expression of KiSS-1 genes and serum level of kisspeptin have not been explored to date. We report herein the expression profile of KiSS-1 genes and serum level of kisspeptin in the rat at different developmental stages.

Turner syndrome with spinal hemorrhage due to vascular malformation

Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS.