Recombinant Human Growth Hormone Therapy in Children with Chromosome 15q26 Deletion.

BACKGROUND: The insulin-like growth factor 1 receptor (IGF IR) gene is located on chromosome 15q26.3. Heterozygous 15q26 deletions involving the IGFIR gene are rare, resulting in intrauterine and postnatal growth retardation, developmental delay and microcephaly. Limited evidence exists on the effect of growth hormone (GH) therapy in these cases. METHODS: We report a series of cases with 15q26 deletions, including response to GH treatment. RESULTS: Seven children (2 males) presented with short stature [median height standard deviation score (SDS) of -4.8 (range -3.0 to -5.6)]. GH was started at a median age of 5 years (range 1.8 to 12.4) for a median duration of 5.8 years (range 1.0 to 12.4). Median height SDS increased by +0.6 (range 0.1 to 1.0), +1.3 (range 0.1 to 2.4) and +1.4 (range 0.8 to 3.3) after 1 (n = 7), 5 (n = 4) and 10 years (n = 3) of GH treatment, respectively. Four patients reached final height after 5.8 to 12.4 years of GH with a median change in height SDS of +1.1 (range 0 to 3.3). CONCLUSION: This study demonstrates a moderate, though variable, response to GH therapy, suggesting that GH resistance caused by heterozygous IGFIR deletions can be partially overcome by GH therapy. The first-year response was moderate, and whilst long-term treatment improved height SDS, the final adult height remained reduced. Therefore, an individual trial of GH therapy may be appropriate in these patients. © 2015 S. Karger AG, Basel.

Evaluation of pituitary function after traumatic brain injury in childhood.

OBJECTIVES: Post-traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. DESIGN: Retrospective exploratory study. PATIENTS: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4-21·7 years) and median (range) interval since injury 4·3 years (1·4-7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. MEASUREMENTS: Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. RESULTS: No subject had short stature (mean height SD score +0·50, range -1·57 to +3·00). Suboptimal GH responses (<5 µg/l) occurred in six peri-pubertal boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH 3·2 µg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. CONCLUSIONS: No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.

Evidence for increased ovarian follicular activity in girls with premature thelarche.

OBJECTIVE: Inhibin B is produced by granulosa cells in small antral follicles, under the influence of FSH, and has a paracrine role in oestradiol synthesis. To test the hypothesis that premature thelarche is associated with increased FSH-driven follicular development, we measured inhibin B and FSH in girls with premature thelarche, girls with central precocious puberty (CPP) and controls matched either for age or breast stage. PATIENTS: Blood samples were collected from 11 girls with premature thelarche (breast stage 2, aged 0.4-5.6 years), 11 prepubertal controls age-matched to the thelarche girls (0.5-5.4 years), 13 girls with CPP (breast stage 2, 3.9-8.2 years) and nine normal pubertal controls (breast stage 2, 9.0-13.2 years). MEASUREMENTS: Dimeric inhibin B was measured in plasma by double-antibody enzyme-linked immunoassay and FSH by immunoradiometric assay. Pelvic ultrasonography was performed on all girls with CPP and 10/11 girls with premature thelarche. RESULTS: Seven of the 13 girls with CPP and three of the eight girls with premature thelarche whose ovaries could be visualized had visibly nonhomogeneous ovarian structure on ultrasonography. Girls with premature thelarche had inhibin B and FSH concentrations higher than those in their age-matched controls (P < 0.01 and P < 0.05, respectively), and similar to those observed in girls with CPP and normal pubertal controls matched for breast stage. In thelarche girls, as in precocious puberty girls and normal pubertal controls, inhibin B and FSH were positively related (rs = 0.54-0.61). CONCLUSIONS: This study provides further evidence that premature thelarche is associated with enhanced follicular development, similar to that which occurs in early puberty, probably under the influence of FSH.

Children with acute Perthes' disease have asymmetrical lower leg growth and abnormal collagen turnover.

BACKGROUND: Abnormalities in distal growth and low levels of insulin-like growth factor (IGF)-I have been reported in children with Perthes' disease. Our aim was to establish whether the acute phase of Perthes' disease is associated with abnormalities of growth, of bone or of collagen turnover. METHODS: We performed a cross-sectional study of 15 children (3-11 years of age, 13 boys) at acute presentation and a longitudinal cohort study of 9 children. We measured (1) the lengths of both lower legs (by knemometry) at weeks 1, 2, 6 and 12, (2) height and weight at presentation and at the second-year follow-up, and (3) levels of IGF-I, IGFBP-3, collagen markers and bone alkaline phosphatase at weeks 1 and 12, and in year 2. RESULTS: Height SD scores were normal at presentation but declined thereafter. Lower leg growth was not impaired at presentation but was asymmetrical, ceased during weeks 2-6, and then resumed symmetrically. Patients had persistently low IGF-I, low soft tissue collagen synthesis and enhanced collagen breakdown compared with age- and sex-related reference data. Markers of bone formation increased during follow-up. INTERPRETATION: Acute changes in lower leg growth reflected differential weight bearing, then immobilization and remobilization. Persistently low IGF-I may have contributed to low soft tissue collagen synthesis and growth. Changes in bone formation markers most likely reflected bone healing.