Wendy F. Paterson

Poor uterine development in Turner syndrome with oral oestrogen therapy.

OBJECTIVE To evaluate uterine development in Turner syndrome (TS) patients in relation to treatment with oral ethinyl oestradiol (E2) for pubertal induction.

Effect of oxandrolone and timing of pubertal induction on final height in Turner’s syndrome: randomised, double blind, placebo controlled trial

Objective To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner’s syndrome receiving a standard dose of growth hormone. Design Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. Participants Girls with Turner’s syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m2/week). Interventions Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 μg daily; year 3, 4 months each of 6, 8, and 10 μg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14. Main outcome measure Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P=0.001, n=82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P=0.05, n=48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P<0.001). No cases of virilisation were reported. Conclusion Oxandrolone had a positive effect on final height in girls with Turner’s syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner’s syndrome. Trial registration Current Controlled Trials ISRCTN50343149.

Auxological outcome and time to menarche following long‐acting goserelin therapy in girls with central precocious or early puberty

objective  Following a successful clinical trial in 1996, the long‐acting GnRH analogue goserelin (Zoladex LA 10·8 mg; Astra Zeneca) has been our preferred treatment for central early (CEP) or precocious puberty (CPP). However, some female patients have expressed concern about perceived weight gain during therapy and delay in the onset or resumption of menses on completion of therapy. The primary aim of this study was to investigate these concerns by determining the auxological parameters and timing of menarche or re‐menarche in all girls with CEP/CPP who have completed a course of Zoladex LA treatment. The secondary aim was to assess auxological outcome in girls who have attained final height.

Final height outcome and value of height prediction in boys with constitutional delay in growth and adolescence treated with intramuscular testosterone 125 mg per month for 3 months

objectives Constitutional delay in growth and adolescence (CDGA) is common in boys, some of whom request treatment to accelerate growth and attainment of secondary sexual characteristics. The aims of this study were to confirm that a 3‐month course of intramuscular testosterone oenanthate does not impair final height in boys with CDGA, and to determine the accuracy of height prediction in this condition.

Maternal age in patients with septo-optic dysplasia

AIM To determine whether patients with septooptic dysplasia (SOD) are of normal birth weight and gestation but are born to mothers who are significantly younger than average. METHODS Retrospective study of 30 patients with SOD attending the Royal Hospital for Sick Children, Glasgow. Birth data for the Scottish population were used for comparison. RESULTS Mean birth weight was 3.42 (range 2.66-4.18) kg. One patient was born preterm while the rest were born at term. Data for the Scottish population were available from 1979 onwards and 26 patients born after this year were selected for analysis. Median maternal age in this group was 21 (range 16-41) years, significantly lower than the median maternal age for Scotland of 27.12 (range 25.8-28.6) years (95% CI 4.8-8.0 years). CONCLUSION Patients with SOD are of normal birth weight and gestation but are born to mothers who are significantly younger than average.

Hashimoto’s Thyroiditis in Down’s Syndrome: Clinical Presentation and Evolution

Aim: It was the aim of this study to describe the presentation and clinical course of Hashimoto’s thyroiditis (HT) in children with Down’s syndrome (DS) in 2 Scottish health regions. Patients and Methods: We retrospectively analysed clinical, biochemical and thyroid antibody status in 38 patients with DS with HT diagnosed from 1989 to 2004. Results: The sex distribution was similar (20 males, 18 females), with a median age of 12.3 years (range 2.1–17.7). Of the 38 patients reviewed, 29 were identified by screening. A goitre was present in 6/38 patients. Thyroid antibodies were positive in 36/38 patients, negative in 1/38, and data were unavailable for 1/38. At presentation, 37/38 patients were hypothyroid: 21/37 with compensated hypothyroidism (6 treated initially) and 16/37 with decompensated hypothyroidism (all treated). Of the 15/21 compensated patients who were untreated initially, only 3 remitted while 12 showed disease progression prompting treatment. In the decompensated group, 1/16 patient pursued a fluctuating course between hypo- and hyperthyroidism. The final patient, who was hyperthyroid at presentation, also showed marked fluctuation in thyroid function over a 5-year period. Conclusion: The natural history of HT in DS is unusual, with no female predominance and infrequent goitre in our cohort. While almost all patients required treatment eventually, clinicians should be aware that the disease may pursue a fluctuating course between hypo- and hyperthyroidism.

Growth hormone therapy in the Prader-Willi syndrome

Who should receive it and when? In November 2000 the Department of Health in England granted a licence to Pharmacia Limited for the use of their recombinant growth hormone, Genotropin (somatropin rbe), in the Prader-Willi syndrome. The indications for use were given as “improvement of body composition and growth”. In this leading article we shall attempt to examine the role of growth hormone in the Prader-Willi syndrome by considering linear growth and body composition in untreated and treated individuals, the pathophysiology of the abnormal linear growth, and the scope for future research. While the growth and body composition aspects of the Prader-Willi syndrome are important, they must be seen in the context of a disabling disorder with major implications for the individual and family.1 Therefore a brief account of the condition is in order. The Prader-Willi syndrome results from loss of an imprinted gene or genes on the long arm of chromosome 15 within the q11–13 region, usually as a result of a deletion on the paternal chromosome or less commonly to inheritance of both chromosomes from the mother—maternal disomy.2 The gene(s) presumably encode(s) a protein or proteins important for brain development, loss of which leads to a generalised brain disorder which affects the hypothalamus in particular.3 Indeed, many of the characteristic traits of the syndrome, such as hyperphagia, somnolence, skin picking, and hypogonadism, are attributable to hypothalamic dysfunction. Severe hypotonia and weakness cause reduced fetal movements, poor feeding from birth, usually requiring tube feeding, weak or absent cry, and inertia during infancy, with developmental delay and failure to thrive. Tone and movement improve towards the end of the first year and developmental milestones are achieved, albeit delayed. By 2 or 3 years of age the hyperphagic phase of the condition begins, and unless diet is strictly …

Effect of high versus low initial doses of L-thyroxine for congenital hypothyroidism on thyroid function and somatic growth

Background and aims: The optimal dose of thyroxine (T4) in congenital hypothyroidism (CH) during infancy is controversial. Higher doses lead to improvement in cognitive scores, but have been linked to later behavioural difficulties. We have examined the effects of initial T4 dosage on somatic growth — a putative surrogate marker of overtreatment. Methods: 314 CH children (214 girls, 100 boys) were analysed according to initial daily dose of T4: Group 1 (25 μg, n = 152), Group 2 (30–40 μg, n = 63) and Group 3 (50 μg, n = 99). Thyroid function and weight, length and occipito-frontal head circumference (OFC) standard deviation score (SDS) were compared at 3, 6, 12, 18, 24 and 36 months of age. Linear growth SDS was compared between the three groups using a regression adjustment model at 12 and 18 months of age using birth weight and 3-month data as baselines. Thyroid function was also compared at diagnosis (T0), and 7–21 days after the start of treatment (T1). Results: At T1 median thyroid stimulating hormone (TSH) for Groups 1, 2 and 3 was 58, 29 and 4.1 mU/l, respectively (p<0.001), Group 3 values remaining significantly lower at 3 and 6 months. Median free T4 (fT4) was within or just above the reference range in all groups at T1, but 7.4% of Group 1 had values <9 pmol/l compared with 5.1% and 0% for Groups 2 and 3, respectively. At 3 months weight, length and OFC SDS values were −0.39, −0.35, 0.09; −0.30, −0.47, 0.32; and −0.03, −0.13, 0.18 for Groups 1, 2 and 3, respectively, indicating relatively large OFC in all infants. A regression adjustment model showed no significant difference in growth rate from baseline and 12 or 18 months of age, between the three groups. Conclusion: An initial T4 dose of 50 μg daily, normalises thyroid function several months earlier than lower-dose regimes, with no evidence of sustained somatic overgrowth between 3 months and 3 years.

A Novel Missense Mutation in Dax-1 with an Unusual Presentation of X-Linked Adrenal Hypoplasia Congenita

A male presented at age 2.2 years with a 6-week history of intermittent vomiting and hyperpigmentation. Investigations showed salt wasting with hyperkalaemia, a grossly impaired cortisol response to ACTH stimulation, elevated renin and ACTH. Family history revealed that two maternal uncles had died soon after birth. A third uncle failed to thrive during infancy but improved with a course of cortisone, then being untreated until further investigation revealed adrenal insufficiency. A fourth uncle died aged 10 days, with urinary salt loss and hypoplastic adrenal glands at postmortem. Molecular studies on the proband, his mother, maternal grandmother, and surviving uncle showed a novel C to G substitution at nucleotide position 794 (missense mutation T265R) in the DAX1 (NR0B1) gene. The proband has responded well to steroid replacement but has proved sensitive to 9α-fludrocortisone treatment, developing hypertension on a dose of 133 µg/m2/day. At 8.8 years he was noted to have testicular volumes of 4 ml, despite no other evidence of secondary sexual development and prepubertal gonadotrophin levels. Novel features of this family include a novel DAX1 mutation, marked variability in age of presentation, hypertension on ‘standard’ doses of 9α-fludrocortisone and mild testicular enlargement.

Measured versus reported parental height

Background: Parental height data are essential in the assessment of linear growth in children. A number of studies have documented inaccuracy in self-reported adult height. Aims: To determine whether there is a tendency for men to overestimate and women to underestimate their height. Methods: Heights of parents of children attending outpatient clinics were measured (MHt) and compared with reported heights (RHt). Results: Two hundred parents (100 males; 100 females), mean (range) age 37.8 (20.8–69.3) years, were measured. Males overestimated height, with mean (SD) RHt–MHt 1.09 (1.96) cm, while females reported height relatively accurately, with RHt–MHt −0.09 (2.37) cm. Conclusions: The hypothesis that males overestimate height is confirmed. While the hypothesis that women underestimate is not supported, we recommend accurate measurement of both parents, given the considerable degree of individual variation in RHt−MHt for both sexes.