Factitious hypoglycemia in children and adolescents with diabetes.

BACKGROUND: Factitious hypoglycemia is a condition of self-induced hypoglycemia due to surreptitious administration of insulin or oral hypoglycemic agents. In adults, it is an uncommon, but well known clinical entity observed in individuals with and without diabetes. OBJECTIVES: To report a case of factitious hypoglycemia highlighting diagnostic pitfalls, to identify common characteristics of children and adolescents with factitious hypoglycemia, and to examine whether the information on long-term outcome exists. METHODS: We present a case of an adolescent with type 1 diabetes who had self-induced hypoglycemia of several years' duration; and we conducted a systematic literature review on factitious hypoglycemia in pediatric patients with diabetes. RESULTS: We identified a total of 83 articles of which 14 met the inclusion criteria (describing 39 cases). All but 1 individual had type 1 diabetes and the majority was female (63%). Average age was 13.5 ± 2.0 years with the youngest patient presenting at the age 9.5 years. Blood glucose control was poor (hemoglobin A1c: 12.1 ± 4.0%). In 35%, psychiatric disorders were mentioned as contributing factors. Only 3 reports provided follow-up beyond 6 months. CONCLUSIONS: Factitious hypoglycemia typically occurs in adolescents with type 1 diabetes who use insulin to induce hypoglycemia. Awareness of this differential diagnosis and knowledge of potentially misleading laboratory results may facilitate earlier recognition and intervention. Little information exists on effective treatments and long-term outcome.

Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.

BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization. PROCEDURE: A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive. RESULTS: Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response. CONCLUSION: Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.

A novel frame shift mutation in the GHRH receptor gene in familial isolated GH deficiency: early occurrence of anterior pituitary hypoplasia.

BACKGROUND: Mutations in the genes encoding for GHRH receptor (GHRHR) and GH (GH1) are the most common cause of familial isolated GH deficiency (IGHD). GHRHR mutations are often associated with anterior pituitary hypoplasia (APH), but this has been reported almost exclusively in children older than 8 yr. We analyzed the GHRHR and measured pituitary size in a consanguineous family with the father and three of the five siblings with IGHD. OBJECTIVE: The aim of the study was to find the mutated gene in a family with severe IGHD. METHODS: We sequenced the whole GHRHR coding regions and the intron-exon boundaries from peripheral DNA of the index patient. After identifying the novel mutation, we sequenced the region of interest in the other members of the family. We measured the anterior pituitary volume from magnetic resonance imaging (MRI). RESULTS: The father and the three affected children were homozygous for a new frame-shift mutation in the coding sequence of exon 4 (corresponding to the extracellular domain of the receptor) (c.340delG) that places the downstream sequence out of frame [corrected]. The mother and two unaffected siblings were heterozygous for the mutation. Two of the affected children had MRI evidence of APH before reaching 6 yr of age. CONCLUSIONS: We describe a new mutation in the GHRHR in a family with IGHD. The presence of frank APH before age 6 yr shows that MRI-evident reduced pituitary size can be present in GHRHR mutations even in children younger than 8 yr of age.

Adolescent with Rhabdomyolysis due to Undiagnosed Hypothyroidism.

Exercise-induced rhabdomyolysis has been described in military recruits, trained athletes and daily runners. Statin use, quail ingestion, infection by Epstein-Barr virus (EBV), and hypothyroidism, though rare, are risk factors for the development of rhabdomyolysis. We describe the case of a 15-year-old female who presented with myalgias, weakness, and pigmenturia following marching band practice. Laboratory tests confirmed an elevated creatine kinase (CK) level as well as a profound hypothyroid state. Muscle biopsy revealed severe muscle necrosis and myositis. Treatment with levothyroxine resulted in obtaining an euthyroid state and regain of muscle strength as well as decrease in CK levels. Although rare, hypothyroidism should be considered as a potential cause of rhabdomyolysis in pediatric patients undergoing a myopathy workup.

Parathyroid hormone-like hormone (PTHLH) represses decidualization of human uterine fibroblast cells by an autocrine/paracrine mechanism.

CONTEXT: Parathyroid hormone-like hormone (PTHLH) is abundantly expressed by human endometrial stromal cells during decidualization. However, the role for PTHLH in the decidualization process is unknown. OBJECTIVE: To examine the effects of PTHLH on the induction and maintenance of decidualization of human uterine fibroblast (HUF) cells in vitro. DESIGN: HUF cells were treated with a PTHLH siRNA or a PTHLH receptor antagonist (bPTH(7-34)) before or after decidualization with medroxyprogesterone acetate (MPA), estradiol (E(2)), and prostaglandin E(2) (PGE(2)). Decidualization was monitored by immunocytochemistry and the induction of decidualization-specific marker genes, including IGFBP-1, prolactin, lefty, and transcription factor FOXO1. RESULTS: HUF cells decidualized after pretreatment with a PTHLH siRNA showed greater morphologic changes of decidualization, greater IGFBP-1 protein, and two- to threefold more IGFBP-1, prolactin, lefty, and FOXO1 mRNAs than cells pretreated with a nonsilencing RNA. The PTHLH siRNA pretreated cells also had 31% less DNA fragmentation (TUNEL assay) and 30-35% less caspase 3 levels during decidualization than cells pretreated treated with nonsilencing RNA. Treatment of HUF cells with PTHLH siRNA or bPTH(7-34) at 9 d after the induction of decidualization also resulted in 2.1- to 3.2-fold greater IGFBP-1, prolactin, lefty, and FOXO1 mRNA levels than that noted in control cells treated with nonsilencing RNA. CONCLUSIONS: These finding strongly suggest that PTHLH represses the induction of human decidualization, stimulates stromal cell apoptosis, and limits the extent of uterine stromal cell differentiation. Because PTHLH and its receptor are expressed by HUF cells and placental cells, the inhibitory effect of PTHLH on decidualization appears to be due, at least in part, to an autocrine/paracrine mechanism.

Small pituitary size in children with Fanconi anemia.

BACKGROUND: Fanconi anemia (FA) is a genetic disorder associated with multiple congenital anomalies, bone marrow failure, and pituitary hypofunction including hypogonadism, thyroid dysfunction, and growth hormone (GH) deficiency. PROCEDURE: Among 44 patients with FA referred to Cincinnati Children's Hospital Medical Center (CCHMC) between 1975 and 2005, 33 had neuroimaging studies, including 11 cranial magnetic resonance imaging (MRIs). Two separate measurements per patient from these MRIs were used to evaluate pituitary height compared to on-site control data of similar measurements of cranial MRIs on 22 age and gender-matched children without any pathology involving the hypothalamic-pituitary system. Growth pattern and endocrine studies were reviewed to assess potential correlation with pituitary size. RESULTS: When compared to the age-gender matched on-site control sample, the mean pituitary height of FA patients was significantly smaller (P < 0.0001; mean +/- SE from mixed effects model with age and gender as covariates: 3.96 +/- 0.32 vs. 5.76 +/- 0.24). Upon further adjusting for the effect of the small head size by including bi-parietal diameter (BPD) as a covariate, the difference remained statistically significant (P = 0.0013). Findings on the growth pattern and endocrinological measurements are as follows: 50% of patients with small pituitary gland were short. GH and adrenal function tests were normal in all tested patients. Thyroid, pubertal status, and glucose regulation were abnormal in 30, 50, and 75% of patients tested. CONCLUSIONS: Children with FA tend to have unsuspected small pituitary glands beyond what is expected from the effects of their stunted growth. Further studies are required to reveal the clinical implications of this finding.