Volume 25, Issue 11-12

Diagnosing growth hormone deficiency (GHD) remains a challenge, and the role of sex steroid priming in the diagnosis of GHD continues to be debated. This review examines existing data on sex steroid priming during GHD diagnosis. Primary literature was reviewed in the area of sex steroid priming and growth hormone stimulation tests. Studies supporting sex steroid priming suggest improved diagnostic efficiency with reduced false diagnosis of GHD in peripubertal children. Those that do not support sex steroid priming note the potential for underdiagnosis of GHD and the lack of standardization in sex steroid priming procedures. To date, there is no consensus on the use of sex steroid priming prior to performing growth hormone stimulation tests in the evaluation of GHD. A more targeted approach to using sex steroid priming may be reasonable; however, the decision of whether or not to use sex steroid priming should remain with the individual clinician.

No abstract available

Precocious pubarche (PP) is defined as the onset of pubic hair at 8 years of age in girls and at 9 years of age in boys. PP is idiopathic (IPP) in most children, but it is the earliest manifestation of non-classical congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency (NC21OHD) in 5%–20% of cases. 17-Hydroxyprogesterone (17OHP) levels after ACTH stimulation test are used to distinguish the two forms. We studied clinical indicators of NC21OHD in 289 PP children: 14 (4.8%) showed post-ACTH 17OHP levels >30 nmol/L and NC21OHD due to CYP21A2 gene mutations was confirmed. NC21OHD children were younger (p: 0.006) and thinner (p: 0.003) than IPP children. Height standard deviation score (SDS) was not different (p: 0.97). NC21OHD girls showed more advanced bone age than IPP girls (p<0.001). Earlier PP onset and bone age advance suggest NC21OHD, which requires confirmation by an ACTH stimulation test. Later, PP appearance in overweight children suggests IPP and could merit only clinical monitoring.

Background: The birth of a child with disorders of sex development (DSDs) is considered a medical and psychosocial emergency. Management of these cases requires facilities and a multidisciplinary team. In developing countries, this is made difficult by the lack of facilities in addition to sociocultural and religious factors that can affect management. This is the first experience to be published from Sudan. Objective: The aim of this study was to see the prevalence, etiological factors, management, and problems faced in handling these cases. Methods: This is a retrospective descriptive study reviewing the records of all cases referred to a pediatric endocrinology clinic over a 5-year period. Cases were managed by a multidisciplinary team. Results: One hundred fifty-six cases were seen, of which 122 were included in the study. A total of 79 (64.8%) were born at home, whereas 59 (52.2%) of the cases were not observed at birth by health-care providers. The average cost of investigating a case was $250–300. The investigations showed that 69 had XX DSD and 45 had XY DSD. The most common cause of XX DSD was congenital adrenal hyperplasia and that of XY DSD was androgen insensitivity syndrome. Twenty-three (19%) needed sex reassignment. There was a preference for the male sex. Conclusion: DSDs are not uncommon in Sudan. Because of lack of awareness and sociocultural reasons cases are referred late. Investigating these cases is expensive and has to be supported, and more multidisciplinary teams have to be trained to make services accessible and affordable.

The aim of this study was to determine the serum anti-Müllerian hormone (AMH levels) in a group of boys with cryptorchidism before and 1 year after surgery. Additionally, the effect of orchiopexy, based on the testicular position and morphology, was evaluated. Fifty boys who were 1–4 years old (median, 2.4 years) with unilateral cryptorchidism were evaluated before and 1 year after they underwent orchiopexy. Prior to the procedure, all of the patients had undergone karyotyping to exclude chromosomal abnormalities. Blood samples were collected while obtaining blood for standard laboratory tests routinely performed just before and 12 months after surgery. Twelve months after the orchiopexy, in most cases surgically treated testes were in the middle or lower pole of the scrotum. The descended glands were of comparable size and density in comparison with the testes on the opposite side. In the treated children, serum AMH levels measured at 12 months after orchiopexy were similar to preoperative basal levels. The authors found that AMH levels in children with unilateral undescended testes do not change significantly 1 year after surgical procedure. We still do not have trustworthy factors to predict fertility in children affected with cryptorchidism. We observed an upward trend in AMH concentration 1 year after orchiopexy, but it was statistically insignificant. Therefore, we plan further measurements of AMH in boys after orchiopexy to assess the influence of this procedure on gonadal function.

Steroid 5α-reductase type 2 deficiency (5α-RD2) is a rare autosomal recessive inherited disorder caused by mutations in the SRD5A2 gene. Its clinical features and pathogenesis in Chinese patients are poorly understood. This study aimed to characterize the clinical features and genetically analyze the SRD5A2 gene in three Chinese 5α-RD2 patients. The patients were characterized by ambiguous genitalia and spontaneous virilization without breast development at puberty. Elevated post-human chorionic gonadotropin stimulation T/DHT ratios were useful indicators of 5α-RD2 (with ratios of 20.4, 20.1, and 26.6 in the three patients, respectively). Two compound heterozygous mutations in the SRD5A2 gene were identified: p.G203S/p.R246Q in patients 1 and 2 and p.G203S/c.655delT in patient 3. The father and the mother of patients 1 and\xa02 were carriers of p.R246Q and p.G203S, respectively. p.G203S appears to be common in Chinese 5α-RD2 patients. Early genetic analysis should be performed in suspected patients to improve prognosis.

The syndrome of apparent mineralocorticoid excess (AME) is an autosomal recessive disorder characterized by hypertension, hypokalemia, low renin, and hypoaldosteronism. It is caused by deficiency of 11β-hydroxysteroid dehydrogenase, which results in a defect of the peripheral metabolism of cortisol to cortisone. As a consequence, the serum cortisol half-life (T½) is prolonged, ACTH is suppressed, and serum cortisol concentration is normal. The hormonal diagnosis of the disorder is made by the increased ratio of urine-free cortisol to cortisone. In patients with AME, this ratio is 5–18, while in normal individuals it is <0.5. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME. We report three siblings – two female and one male – with the syndrome of apparent mineralocorticoid excess who presented with hypertension, hypokalemia, low renin, and low aldosterone levels. The finding of abnormally high ratios of 24-h urine-free cortisol to cortisone in our three patients (case 1, 8.4; case 2, 25; and case 3, 7.5) confirmed the diagnosis of apparent mineralocorticoid excess syndrome in these children. They were treated with oral potassium supplements. The addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity in all three. In this study, the genetic testing of those three siblings with the typical clinical features of AME has detected missense mutation c.662C>T (p.Arg208Cys) in exon 3 of the HSD11B2 gene in the homozygous state.

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.

Background: Acanthosis nigricans (AN) is a dermatologic condition associated with hyperinsulinemia, a marker of insulin resistance that is the principal abnormality in metabolic syndrome (MetS). We examined the association of AN with the clustering of MetS components. Methods: A cross-sectional study was conducted in an urban school-based health center in New Mexico. Students without diabetes were evaluated for AN, a family history of type 2 diabetes, body mass index (BMI), and MetS components. The clustering of MetS components by BMI category and AN status was assessed by comparing the group means of summed average z-scores of fasting insulin, triglycerides, high-density lipoprotein-cholesterol, and systolic blood pressure among the students. A multivariate model with BMI category and AN status controlling for Tanner stage was performed to identify the variables associated with the clustering of MetS components. Results: Complete data were available for 90 children (age, 9.7±1.4 years; 94% Hispanic; 60% female). In multivariate modeling of MetS cluster z-score, significant differences were found between the students with BMI <85th percentile [–0.27; 95% confidence interval (95% CI)=–0.42 to –0.11] and (a) the students with BMI 85th–94.9th percentile with AN (0.74; 95% CI=0.17–1.31) and (b) the students with BMI ≥95th percentile with AN (0.86; 95% CI=0.54–1.18). No significant differences in the MetS cluster z-score were seen between the students with BMI <85th percentile and those with BMI 85th–94.9th percentile without AN (0.24; 95% CI=–0.33 to 0.81) or those with BMI ≥95th percentile without AN (0.31; 95% CI=–0.13 to 0.75). Conclusions: Overweight/obese Hispanic elementary school-aged children with AN exhibit clustering of MetS components and could benefit from early intervention.

Objective: Early treatment (growth hormone and nutritional support) improves development in infants with Prader-Willi syndrome. This study aimed to evaluate the nutritional and metabolic condition of nine patients who were diagnosed and treated in early infancy. Methods: Nine patients were hospitalized at the age of \xe2\u20ac\xa810 days to 11 months because of severe feeding difficulties, failure to thrive, or developmental delay. The diagnosis of Prader-Willi syndrome was confirmed by fluorescence in situ hybridization or other molecular genetic techniques. Nutritional and metabolic investigations including urinary organic acid analysis, blood amino acid, and acylcarnitine profiles were performed. Results: The diagnosis was made at the mean age of 6.3 months. A deletion of the paternal gene in the 15q11-13 region was detected in all patients. Eight patients had ketosis, seven had malnutrition, five had hyperammonemia, three had liver dysfunction, three had low blood cholesterol level, and two had hypoglycemia. All patients had reduction of serum multiple amino acids and free carnitine. Significant arginine deficiency was found in all patients. Six patients had mildly elevated blood long-chain and very long-chain acylcarnitine. After supplementation with l -arginine, medium-chain fatty acids, l -carnitine, and vitamins, all patients responded with improvement of motor development and nutritional conditions. Four patients were almost caught up on physical and psychomotor development. Conclusions: Patients with Prader-Willi syndrome are in bad metabolic condition in the early period. Early diagnosis and individual nutritional interventions may improve the nutritional and developmental progress and decrease death rate in infancy.

Background: Obesity in children increases the risk of atherosclerosis. Endothelial dysfunction is an important factor in the pathogenesis of atherosclerosis, and endothelial microparticles (EMPs) are considered as markers of endothelial dysfunction. In this study, we aimed to evaluate circulating EMPs in obese and overweight children and to disclose the measure of obesity with the strongest relation with circulating microparticles and carotid atherosclerosis. Methods: This prospective study included 55 obese and overweight children and 23 healthy controls. Insulin resistance was studied. Both in vivo and in vitro human umbilical vein endothelial cell evaluations were used for the study. Circulating EMPs (CD144 and CD146) were measured by flow cytometry. The carotid artery intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured using ultrasound and echocardiography, respectively. Study groups were compared for anthropometric measurement, insulin resistance, circulating EMP, cIMT, and LVMI. The relationship among overweight, obesity, and circulating EMPs were investigated. Results: Blood pressure, CD144+EMP levels, and LVMI were statistically higher in the patients group than in the control group. The multiple logistic regression analysis and the backward elimination method showed that CD144+EMP and systolic blood pressure had a linear relationship with overweight and obesity. Conclusion: Our results suggest that endothelial damage starts in the early stage of childhood obesity and that obese and overweight children have increased circulating CD144+EMPs, showing that endothelial dysfunction and increased CD144+EMPs may be related to obesity.

Objective: To study the treatment effect and safety of diazoxide on patients with congenital hyperinsulinism (CHI). Research design and methods: A total of 44 patients who have been hospitalized to our hospital and used diazoxide as a trial after diagnosis of CHI were chosen as research subjects. The clinical data of the patients were analyzed, and the treatment effects and safety of diazoxide on CHI were evaluated. Results: In the 44 patients studied, the blood glucoses of 36 cases recovered to normal level after using diazoxide, indicating that the 36 patients respond to the treatment of diazoxide. Eight cases still showed severe hypoglycemia after using diazoxide for 10 days, which indicated that the eight patients were unresponsive to diazoxide treatment. Eighteen patients suffered the side effect of fluid retention, and 12 patients suffered transient gastrointestinal reactions. Conclusion: Diazoxide is a first-line treatment of CHI with high safety. Most of the patients with CHI were responsive to diazoxide treatment. Diazoxide should be used as a trial immediately after CHI diagnosis was made.

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2±1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

Objective: To determine the oxidative stress and trace element levels in vivo in patients with nutritional rachitism associated with vitamin D deficiency. Materials and method: A total of 30 patients, 18 males and 12 females, were included in the study. Age, sex, medical history, vital, and physical examination findings of each patient documented at presentation were recorded. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels, as well as oxidant and antioxidant system parameters and trace element levels were studied. After being diagnosed with rachitism, the patients were administered a single dose of 300,000 IU vitamin D by intramuscular injection. The same analyses were repeated post-treatment. Thirty children with normal anthropometric measurements were included as the control group. The analyses described above were performed only once for the control group. Results: Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-OH vitamin D levels were different between the controls and children in the patient group (p<0.001). Analysis of trace element levels demonstrated markedly lower pretreatment zinc levels for the patient group compared to the controls, with a statistically significant difference (p=0.001). Comparison of pretreatment oxidant and antioxidant system markers between the patient and control groups demonstrated higher values for vitamin C, β-carotene, reduced glutathione, and superoxide dismutase in the control group, whereas MDA was higher in the patient group. Conclusion: The present study demonstrated increased oxidative stress, reduced antioxidant defence system in patients with nutritional rachitism, with reduced oxidative stress and a pronounced improvement in the antioxidant system with vitamin D treatment.

Objective: Osteoporosis is a common complex and polygenic disease in postmenopausal women, which is characterized by a decrease in bone mineral density (BMD). The osteoprotegerin ( OPG ) is an important candidate gene in the pathogenesis of osteoporosis. The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in the OPG gene and BMD. Methods: OPG gene polymorphisms and BMD were analyzed in 352 Chinese postmenopausal women. BMD was quantified at the lumbar spine (L 2–4 ), femoral neck, and total hip. Results: Through polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, an allelic variant corresponding to the G→A mutations at position 23276 in exon 3 of the OPG gene could be detected. The association between g.23276 G>A polymorphisms and BMD was analyzed, and a significant association was found between g.23276 G>A and spine BMD. The mean of genotype GG was significantly higher than those of genotype GA and AA. There was no significant difference in neck hip BMD and total hip BMD among different genotypes. Conclusions: These findings suggested that g.23276 G>A genotypes in the OPG gene were associated with spine BMD in Chinese postmenopausal women. The A-allele was associated with lower BMD and an increased risk for osteoporosis.

We report a case of a 14-year-old girl with primary amenorrhea and phenotypic as well as hormonal features of complete androgen insensitivity syndrome (CAIS), who tested positive for a novel missense androgen receptor gene mutation resulting in serine-to-isoleucine change at position 703 in exon 4 in the ligand-binding domain. The interesting features of this case include a persistence of Müllerian derivatives, Sertoli cell adenoma, Tanner III pubic hair, and a normal bone mineral density. These features are not typically described in CAIS. This novel mutation associated with a unique clinical presentation serves to significantly enrich the literature on this rare and fascinating disorder of androgen insensitivity syndrome.

Congenital hypothyroidism (CH) is the most commonly encountered endocrinological birth defect, with an incidence of approximately 1 in 3000–4000 live births. It could be sporadic or familial as well as goitrous or non-goitrous. Inactivating mutations of TSHR , which is one of the genes responsible for non-goitrogenic congenital hypothyroidism, are mostly inherited autosomal recessively and result in a wide clinical spectrum owing to the extent of receptor function loss. Here, we report detailed clinical features of two CH cases with TSHR mutations. The first case was diagnosed before the initiation of the national screening program and had a severe clinical phenotype associated with a homozygous inactivating TSHR mutation (P556R), whereas the second case was diagnosed after the introduction of the national screening program and showed a mild clinical presentation and carried another homozygous missense mutation (P162A) in the TSHR gene. We compared the clinical features of our cases with those of previously reported patients with TSHR mutations to enhance the genotype/phenotype correlations between these mutations and corresponding clinical phenotypes.

Berardinelli-Seip syndrome is an autosomal recessive disorder characterized by generalized lipoatrophy, extreme insulin resistance with dyslipidemia in childhood and development of diabetes in adolescence. Menstrual irregularities are commonly seen as a result of secondary polycystic ovarian syndrome. Delayed puberty as a manifestation of these abnormalities in girls has rarely been described earlier. We report one such case patient who had delayed puberty and portal hypertension as unique features amongst the characteristic phenotypes of this syndrome.

Patients with X-linked lissencephaly with ambiguous genitalia (XLAG) syndrome present with lissencephaly, agenesis of the corpus callosum, refractory epilepsy of neonatal onset, microcephaly, and male genotype with ambiguous genitalia. The basis of the ambiguous genitalia in XLAG syndrome is not well-known. We report a case of the fourth child of healthy consanguineous parents who was presented to the hospital because of non-febrile seizures at 2 months of life. On physical examination, microcephaly, some dysmorphic face features, and ambiguous genitalia were determined. The cranial magnetic resonance imaging of the patient showed lissencephaly, agenesis of the corpus callosum, and enlarged ventricles. His karyotype was 46, XY. He had undetectable testosterone levels and elevated gonadotropins. Neither testicular tissue nor any testosterone response to human chorionic gonadotropin stimulation test was observed. These findings suggest that the hypogonadism in this patient with XLAG syndrome is primary hypogonadism due to gonadal agenesis or dysgenesis.

Central precocious puberty (CPP) is fairly common in girls. In most girls, the etiology for the CPP is unknown. Among the more rare causes of CPP in girls are central nervous system tumors and hamartomas. Osteolipoma of the tuber cinereum, which is the most commonly diagnosed at autopsy, has been reported as a cause of CPP. We describe an 8-year-old girl with central precocious puberty in whom MRI demonstrated a lesion compatible with osteolipoma. Her symptom was breast development that begun at age 7 years and 9 months. Her case history, laboratory studies and imaging are presented. Her puberty was rapidly progressive. She was treated successfully with a GnRHa (Triptorelin 3.75 mg IM q 4 weeks). Her case brings to the forefront the need to perform an MRI in children with rapidly progressing puberty.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by aplasia of the uterus and the upper part of the vagina in an XX individual with normal development of secondary sexual characteristics. Individuals with this syndrome may also present with renal and skeletal abnormalities. We report a case of a 16-year-old girl presenting with thyrotoxicosis and primary amenorrhea. After being diagnosed with Graves disease, this patient was placed on antithyroid medication. Although her thyroid function normalized, she did not start to menstruate. Therefore, we assessed her primary amenorrhea and diagnosed the patient with MRKH syndrome through pelvic imaging. To our knowledge, an association between Graves disease and MRKH syndrome has not yet been reported.

Priapism is rare in children and may result in erectile dysfunction and sexual aversion behaviours. Testosterone therapy is commonly regarded as safe in children and is widely used in constitutional delay of growth and puberty, hypogonadism, hypospadias and micropenis. We report two cases of priapism in teenage boys with constitutional delay of growth and puberty after a change in the formulation of depot testosterone. One case required surgical intervention and the other was preceded by stuttering priapism. These cases illustrate the importance of patient and/or parent counselling before testosterone administration and consideration of lower doses in at-risk patients.

Aim: Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association. Observation: A boy aged 9 years and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record had been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of right visual acuity with diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient’s brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient’s vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH)=39 ng/mL, n≤5, prolactin (PRL)=470 ng/mL, n<15]. Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor. Conclusion: This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.

Introduction: Although craniopharyngiomas are congenital tumors, they are rarely diagnosed in the prenatal or early neonatal period. Sometimes they are very large, debilitating and life-threatening, as in the case discussed here. Observation: A 21-month-old girl was referred for craniopharyngioma that had been diagnosed at 5 months because of neurologic complications. The pregnancy and birth were considered to be unremarkable. The birth weight was 4 kg, length 53 cm, head circumference 38 cm (n=35±1). Brain CT revealed active hydrocephalus caused by a very large solid, cystic and calcified supra sellar mass. MRI confirmed the process measuring 5 cm in height, multidirectional, diving into pituitary sella, displacing the brainstem. After several resections and reservoir drainage, the patient was blind, hemiparetic and she convulsed frequently. The patient died when she was 2. Conclusion: The large head circumference at birth, the size of the tumor, blindness, and hemiparesis observed before the age of 5 months suggested an antenatal process unnoticed because of inadequate gestational monitoring.

Background: Aromatase deficiency is a rare autosomal recessive disorder caused by mutations in the CYP19A1 gene and characterized by lack of conversion of androgens to estrogens. It presents with virilization of pregnant mothers during the antenatal period, and virilization of female fetuses at birth. Affected subjects of either gender later manifest with features of estrogen deficiency and androgen excess. Patient and methods: We describe the clinical course of an Indian girl with aromatase deficiency from birth to 16 years of age. Estrogen replacement was begun at age 13.5 years. The child’s growth, hormonal, radiological, and metabolic parameters were monitored throughout the course of treatment. Results: The child presented with obesity, tall stature, delayed bone age, osteoporosis, hyperinsulinemia with acanthosis nigricans, and hypergonadotropic hypogonadism with cystic ovaries. Estrogen replacement resulted in a plateauing of height, improvement of bone maturation, and pubertal progression with the disappearance of ovarian cysts. However, hyperinsulinemia and acanthosis nigricans persisted despite estrogen replacement and metformin. Genetic analysis revealed a homozygous arginine to cysteine substitution at codon 435 in exon 10 of CYP19A1 . Conclusions: This is the first case of aromatase deficiency reported from India. This case highlights the role of estrogen in skeletal maturation and mineralization and the effect of estrogen deficiency and androgen excess over glucose metabolism in adolescent females.

Chylomicron retention disease (CRD), or Anderson disease, is a rare, hereditary cause of fat malabsorption. It is one of the familial hypocholesterolaemia syndromes, along with homozygous hypobetalipoproteinaemia (HBL) and abetalipoproteinaemia (ABL). We report clinical, laboratory and histological data as well as molecular DNA analysis in the case of a 4-month-old boy with failure to thrive and steatorrhea who was diagnosed with CRD. His mother’s first cousin, who was diagnosed as hypobetalipoproteinaemia 30 years ago, was also reviewed and his diagnosis was revised to CRD. Both patients were treated with a low fat diet and supplementation with fat-soluble vitamins resulting in significant improvement. In conclusion, CRD is a well-defined cause of fat malabsorption and can be distinguished from other forms of familial hypocholesterolaemia because of its specific lipid profile.

This case describes the first pediatric case of metastatic papillary thyroid carcinoma (PTC) to the cerebellum as the presenting sign of cancer in a child with CHARGE syndrome and complex congenital heart disease. Diagnostic radiation exposure as a strong risk factor for PTC is discussed.

Hepatic subcapsular steatosis is a rare pattern of fatty infiltration of the liver exclusively described in diabetic patients undergoing peritoneal dialysis who had received insulin in peritoneal dialysate. We describe a first case of severe subcapsular hepatic steatosis in a young diabetic patient on high dose insulin therapy (with striking subcapsular fatty infiltration of the liver documented by CT and MRI) without any evidence of chronic renal disease and not undergoing peritoneal dialysis.

Infantile malignant osteopetrosis (IMO; OMIM 259700) is a rare inherited bone disease characterized by reduced or dysregulated activity of osteoclasts, resulting in generalized osteosclerosis. The disease usually presents within the first few months of life with anemia, hepatosplenomegaly, frontal bossing, nystagmus, blindness, deafness, and bone fractures. Children with IMO are at risk of developing hypocalcemia, with attendant tetanic seizures. We report the case of a baby boy who presented with neonatal hypocalcemia. Skeletal radiographs demonstrated sclerotic bones and a dense base of the skull with typical “space alien” face confirming the diagnosis of IMO. Pancytopenia developed at 2 months of age. Visual evoked potential showed severe bilateral optic nerve damage. Genetic mutation study revealed a new mutation in exon 13 of the TCIRG1 gene. Neonatal hypocalcemia can occur as result of IMO, which is easily missed out by clinicians. This causes delay in establishing the diagnosis and starting necessary treatment. Therefore, osteopetrosis should be kept in mind as a rare cause of neonatal hypocalcemia.

Van Wyk-Grumbach syndrome is a rare disease characterized by precocious puberty associated with prolonged hypothyroidism and multicystic enlarged ovaries. A 9-year-old girl with Down syndrome visited our hospital for early menarche. At birth, she showed subclinical hypothyroidism [11.8 μg/dL of thyroxine (T4) and 6.05 μIU/mL of thyroid stimulating hormone (TSH)], but she had not been followed up in our clinic. On physical examination, pubertal Tanner stage was breast II and pubic hair I. Laboratory findings were as follows: 0.30 ng/dL of free T4, 81.30 μIU/mL of TSH, 0.1 IU/L of luteinizing hormone, and 6.35 IU/L of follicle-stimulating hormone. Her bone age was 6 years. Her pelvic sonogram revealed multiple cysts in both enlarged ovaries. She was diagnosed with Van Wyk-Grumbach syndrome. Levothyroxine treatment at a dose of 50 mg/m2/day was started. Regression of breast development was obtained after 2 months, and her vaginal bleeding did not recur.

Objective: To compare obese and non-obese adolescents in terms of their salivary cortisol response to the Trier Social Stress Test (TSST). Methods: This is a cross-sectional study involving 41 healthy adolescents aged 12–14 years in the city of Shenyang, China. The TSST response was determined using salivary cortisol measurements, and measurements were repeated after the test period. Repeated-measures ANOVA was performed to compare salivary cortisol levels between groups. Results: The male group comprised 16 individuals (10 obese and 6 non-obese), and the female group comprised 25 individuals (13 obese and 12 non-obese). ANOVA with repeated measures demonstrated that weight status (obese or non-obese) had a significant main effect on the measures of salivary cortisol levels during the TSST among females but not males. Conclusions: The finding suggested that weight status is associated with cortisol response to psychological stress among Chinese adolescent girls.

Long-term treatment with inhaled corticosteroids (ICS) may potentially lead to adrenal insufficiency in children with asthma. A sufficient adrenal response can be tested using protocols involving salivary cortisol measurements. In this study, we investigated in healthy volunteers whether inhalation of fluticasone propionate, a frequently prescribed ICS, interferes with salivary cortisol measurement (with tandem mass spectrometry as well as an immuno-assay). We found that inhalation of fluticasone propionate immediately before saliva collection does not interfere with the salivary cortisol measurement when measured by mass spectrometry. These results suggest that patients with asthma using ICS can be included in research protocols based on salivary cortisol mass spectrometry measurements.