Polyuria and polydipsia in a young child: diagnostic considerations and identification of novel mutation causing familial neurohypophyseal diabetes insipidus.

A 3-year 5-month-old boy was seen for second opinion regarding polydipsia and polyuria. Previously, a diagnosis of primary polydipsia was made after normal urine concentration after overnight water deprivation testing. The boy's father, paternal grandfather, and paternal aunt had diabetes insipidus treated with desmopressin acetate. Based on this young boy's symptoms, ability to concentrate urine after informal overnight water deprivation, and family history of diabetes insipidus, we performed AVP gene mutation testing. Analysis of the AVP gene revealed a novel mutation G54E that changes a normal glycine to glutamic acid, caused by a guanine to adenine change at nucleotide g.1537 (exon 2) of the AVP gene. Commonly, patients with familial neurohypophyseal diabetes insipidus (FNHDI) present within the first 6 years of life with progressively worsening polyuria and compensatory polydipsia. Since these patients have progressive loss of arginine vasopressin (AVP), they may initially respond normally to water deprivation testing and have normal pituitary findings on brain MRI. Genetic testing may be helpful in these patients, as well as preemptively diagnosing those with a mutation, thereby avoiding unnecessary surveillance of those unaffected.

Health-related quality of life and cognitive functioning in pediatric short stature: comparison of growth-hormone-naïve, growth-hormone-treated, and healthy samples.

The objective of this study was to evaluate the impact of short stature on generic health-related quality of life (HRQOL) and cognitive functioning in pediatric patients. Eighty-nine youth, 48 who were initially seen with short stature (SS group) and 41 with a history of short stature being treated with growth hormone (GHT group) and one of their legal guardians participated in the study. HRQOL and cognitive functioning were assessed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Cognitive Functioning Scale. Comparisons were made between the study groups and with a previously obtained matched healthy sample. For the GHT group, height Z score was found to be a positive predictor of overall HRQOL while duration of GHT was found to be a predictor of physical functioning. For the SS group, the difference between midparental height Z score and height Z score was found to be a negative predictor of overall HRQOL and cognitive functioning. Comparison with the healthy sample demonstrated significant negative impact on HRQOL for child self-report and on HRQOL and cognitive functioning for parent proxy-report in both study groups. The GHT group had a significantly higher child self-reported Physical Functioning score than the SS group (effect size (ES) = 0.52, p < 0.05). In conclusion, the GHT group had slightly better HRQOL scores than the SS group, but the difference was not statistically significant. Both groups had significantly lower HRQOL and cognitive functioning scores than healthy sample. Predictors of HRQOL and cognitive functioning found in this study lend support to the use of the PedsQL™ 4.0 Generic Score Scales and PedsQL™ Cognitive Functioning Scale in routine assessment of children with short stature in order to identify children at increased risk for impaired HRQOL and cognitive functioning.

Mutational analysis of PHEX, FGF23 and DMP1 in a cohort of patients with hypophosphatemic rickets.

BACKGROUND: X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets and autosomal recessive hypophosphatemic rickets make up a group of renal phosphate wasting disorders with common clinical and biochemical characteristics. These three types of rickets are related to mutations in PHEX, FGF23 and dentin matrix protein 1 (DMP1), respectively. OBJECTIVE: The objective of the study was to evaluate the frequency of mutations that occur in these three genes associated with hypophosphatemic rickets. PATIENTS AND METHODS: In this study, we sequenced these genes in 76 members of 46 kindreds from a large hypophosphatemic rickets cohort. RESULTS: Forty-two individuals from 27 kindreds were found to have mutations in PHEX; 16 of which were novel. One subject had an FGF23 mutation. No individuals were found to have mutations in DMP1 consistent with the presence of recessive hypophosphatemic rickets. CONCLUSIONS: Our data highlight the wide spectrum of genetic variation that can be seen in PHEX, FGF23 and DMP1 when screening a large cohort with hypophosphatemic rickets.

Polycystic ovaries and adrenal insufficiency in a young pubescent female with lipoid congenital adrenal hyperplasia due to splice mutation of the StAR gene: a case report and review of the literature.

We report a case of Lipoid Congenital Adrenal Hyperplasia (LCAH) secondary to Steroidogenic Acute Regulatory (StAR) gene mutation in an adolescent female with bilateral ovarian cysts. StAR gene defects follow an autosomal recessive mode of inheritance and typically present with severe adrenal insufficiency during infancy. Both sexes can be affected equally. XY males often present with sex reversal, while XX females may develop gonadal failure later in life due to premature loss of ovarian follicles. Recently there have been reported cases of successful fertility outcomes in women with LCAH. In our case report, we describe the clinical, biochemical and molecular analysis of a 16 year-old XX adolescent female who was suspected of having LCAH upon discovery of bilateral ovarian cysts in the context of adrenal insufficiency. Examination of the StAR gene revealed a homozygous splice site mutation. The patient is currently undergoing estradiol therapy to suppress ovarian cyst formation.

Sexual precocity in a 2-year-old boy caused by indirect exposure to testosterone cream.

OBJECTIVE: To report a rare case of sexual precocity caused by inadvertent exposure to testosterone cream. METHODS: We report the clinical, laboratory, and radiologic findings of a boy presenting with sexual precocity; review short- and long-term consequences; and discuss preventative measures. RESULTS: A 2 and 7/12-year-old boy had onset of pubic hair without testicular enlargement and a period of rapid linear growth. History revealed possible topical testosterone exposure from close contact with the child's father. On physical examination, the boy had Tanner stage II pubic hair distribution. Laboratory evaluation findings were normal for age except for the testosterone concentration, which was comparable to late-pubertal and adult male levels at 371 ng/dL (reference range, <3-10 ng/dL for prepubertal male). Brain magnetic resonance imaging and testicular ultrasonography were normal. Skeletal age was advanced at age 4 and 6/12 years. Repeated laboratory evaluation, after the child's father ceased testosterone use, revealed a normal testosterone concentration of 10 ng/dL. Thus, this boy's sexual precocity was attributed to inadvertent exogenous androgen exposure. CONCLUSIONS: When examining a child with sexual precocity, asking about possible exposure to androgens and estrogens is important. Patients being treated with these products should be educated about the possible risks of testosterone exposure to others and ways to limit exposure.

Treatment of type 2 diabetes mellitus in children and adolescents.

OBJECTIVES: To study possible treatment modalities for type 2 diabetes mellitus (T2DM) in children and adolescents. STUDY DESIGN: We reviewed the medical records of the 25 children and adolescents most recently seen for T2DM in the U.T. Houston diabetes clinics, comparing treatment regimens and results over time. The most common treatment modalities were insulin in combination with oral insulin sensitizing agent (metformin), and metformin alone. End-points evaluated included HbA1c, body weight, and insulin dose. PATIENTS: Patients ranged in age from 8 to 15 years at diagnosis. The female:male ratio was 1.3:1. Sixty percent of patients were Hispanic. All BMIs were above 85th percentile for age and sex. Acanthosis nigricans was present in 92% of the patients. RESULTS: Insulin was the only initial treatment in 18 patients (72%), with metformin added and insulin withdrawn as euglycemia developed. Only five of these 18 patients who were started on insulin were completely weaned to metformin monotherapy, and three of those patients later required reintroduction of insulin due to poor control. Metformin did permit reduction of insulin dose in the combination group. Metformin was used as monotherapy in seven patients (28%), but three of them later required another oral hypoglycemic agent. The mean change in HbA1c over the observed period was -2.9% in patients taking insulin only, -2.3% for patients treated with insulin + metformin, and -4.4% in patients who could be treated by metformin alone. HbA1c tended to rise after 2 years of therapy. Few patients sustained weight loss, regardless of treatment regimen. CONCLUSION: Metformin appears to be an effective medication for the treatment of T2DM in children, but did not seem to be a sufficient long-term monotherapy in our protocol, which required euglycemia for insulin withdrawal. Lifetime management strategies for children with T2DM will probably be as complex as those for adults.