Growth hormone response to GH-releasing peptide-2 in children.

The insulin tolerance test (ITT) has been considered the most reliable test in the diagnosis of growth hormone deficiency (GHD), but it is contraindicated in some patients. Recently, the use of GH-Releasing Peptide-2 (GHRP-2) has been validated and reported as a safe and reliable test for the diagnosis of adult severe GHD. We evaluated the GH response to GHRP-2 in 56 children with growth disorders to assess its efficacy. A dose of 2 microg/kg of GHRP-2 was administered intravenously and serum GH concentrations were determined. The Spearman correlation coefficient for GH peak values indicated a favorable correlation with the ITT (P<0.0001). Peak GH concentrations were significantly (p<0.0001) lower in children with (median: 3.39 microg/l (ng/ml)) than without (25.10 microg/l (ng/ml)) GHD. In the analysis of sensitivity-specificity curves, the serum concentration at the point where sensitivity crosses specificity was 15 microg/l (ng/ml). The GHRP-2 test was safe and required only one hour or less, and was capable of diagnosing GHD in children.

Serum concentrations of insulin-like growth factor-1 as a biomarker of improved circadian rhythm sleep-wake disorder in school-aged children.

STUDY OBJECTIVES: We aimed to investigate whether improvements in the symptoms of circadian rhythm sleep-wake disorder after treatment were associated with an increase in serum insulin-like growth factor-1 (IGF-1) concentration. METHODS: Eighty-seven school-aged children (32 males, 55 females), aged 14.31 ± 1.50 years (mean ± standard deviation), who were admitted to our hospital with circadian rhythm sleep-wake disorder received treatment for 6-8 weeks consisting of the following protocol: (1) lights-out for sleep occurred at 21:00, (2) phototherapy for waking started at 06:00 or 07:00, and (3) light exercise was required every day (eg, a 20- to 30-minute walk). Blood samples were collected at 08:00 am to measure the serum concentrations of IGF-1, pre- and posttreatment. RESULTS: The mean times of day of sleep onset and offset at the pre- and posttreatment timepoints were 23:32 ± 4.21 and 10:27 ± 2.98, and 21:26 ± 0.55 and 06:50 ± 0.70, respectively. The mean times of day of sleep onset and offset measured at the posttreatment timepoint were significantly earlier compared with the pretreatment baselines (P < .01). The mean serum levels of IGF-1 significantly increased from 315.59 ± 68.26 ng/mL at pretreatment to 335.09 ± 69.78 ng/mL at posttreatment (P < .01). CONCLUSIONS: Improvements in the symptoms of patients with circadian rhythm sleep-wake disorders were associated with increased serum concentrations of IGF-1, suggesting that serum IGF-1 may be a biomarker of improvements in school-aged children with circadian rhythm sleep-wake disorder.

Endocrine and radiological studies in patients with molecularly confirmed CHARGE syndrome.

CONTEXT: CHARGE syndrome is a complex of congenital malformations, and CHD7 has been reported as a major gene involved in the etiology. OBJECTIVE: We performed endocrine and radiological studies to determine whether endocrinological disorders such as hypogonadotropic hypogonadism, GH deficiency, or hypothyroidism are involved and also whether olfactory bulb hypoplasia and semicircular canal aplasia are major signs in patients with molecularly confirmed CHARGE syndrome. DESIGN: Clinical features, endocrinological assessments, and radiological abnormalities in eight children (five boys and three girls) whose molecular analyses were available were evaluated among 15 children clinically diagnosed with CHARGE syndrome at our institute. RESULTS: We identified heterozygous CHD7 mutations in all patients screened for mutations. Four boys had micropenis and/or cryptorchidism. One was diagnosed with GH deficiency, and the other was diagnosed with hypothyroidism. Computed tomography findings revealed aplasia of the semicircular canals. Magnetic resonance imaging studies of the olfactory bulb region revealed abnormal olfactory sulci and bulb development in all children. CONCLUSION: We suggest that hypogonadism, GH deficiency, and hypothyroidism could be possible endocrinological defects in patients with CHD7 mutations and that olfactory bulb hypoplasia as well as semicircular canal aplasia should be considered as a major sign for CHARGE syndrome and recommend a computed tomography scan of the temporal bone and magnetic resonance imaging study of the olfactory bulb region.

Comparison of clinical course of polymyositis and dermatomyositis: a follow-up study in Tokushima University Hospital.

Polymyositis (PM) and dermatomyositis (DM) are systemic inflammatory disorders affecting skeletal muscles and other organs, and are associated with high morbidity and mortality rates. In this study, we studied the prevalence, clinical features and its comparative outcome of PM/DM, comparing PM and DM. Twenty-three PM/DM patients (9 PM and 14 DM) were included in this study. The complication of interstitial pneumonia (IP) was found in 17 patients (74%). HRCT showed that non-specific interstitial pneumonia pattern was the most common in patterns of lung involvement. Twenty-one patients (91%) with PM/DM received high dose of prednisolone therapy. The percentage of patients who received methylprednisolone (mPSL) pulse and cyclosporin A was higher in DM patients than in PM patients. The percentage of patients who received mPSL pulse and cyclosporin A was higher in later (after Apr 2004) patients than in former (before Mar 2004) patients. Malignant diseases appeared in 3 patients with DM which consisted of breast cancer, epipharyngeal cancer and gastric cancer. We observed 2 deaths in DM patients during the course of therapy; one was due to IP, and the other due to miliary tuberculosis. This study showed that a poorer prognosis was observed in patients with DM when compared with those with PM, and immunosuppressive medications may be implicated at least partially in increased risk of infections and malignancies in PM/DM patients especially DM patients, indicating that patients with PM/DM may require careful monitoring during the clinical course.

A novel GATA3 nonsense mutation in a newly diagnosed adult patient of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

OBJECTIVE: Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by a GATA3 gene mutation. Here we report a novel mutation of GATA3 in a patient diagnosed with HDR syndrome at the age of 58 with extensive intracranial calcification. METHODS: A 58-year-old Japanese man showed severe hypocalcemia and marked calcification in the basal ganglia, cerebellum, deep white matter, and gray-white junction on computed tomography (CT). The serum intact parathyroid hormone level was relatively low against low serum calcium concentration. The patient had been diagnosed with bilateral sensorineural deafness in childhood and had a family history of hearing disorders. Imaging studies revealed no renal anomalies. The patient was diagnosed with HDR syndrome, and genetic testing was performed. RESULTS: Genetic analysis of GATA3 showed a novel nonsense mutation at codon 198 (S198X) in exon 3. The S198X mutation leads to a loss of two zinc finger deoxyribonucleic acid (DNA) binding domains and is considered to be responsible for HDR syndrome. CONCLUSION: We identified a novel nonsense mutation of GATA3 in an adult patient with HDR syndrome who showed extensive intracranial calcification.