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Biomedical subjects

M D Donaldson

Publications and source records attributed to M D Donaldson.

At least 19 recordsLinked to original sources
PubMed2001

Foot problems in Turner's syndrome.

In a randomized, prospective study, data were collected on 23 girls with Turner's syndrome (TS) and an age- and sex-matched control group of 47 girls in order to document foot problems and to establish their cause. History revealed that 6 (26%) girls with TS had problems with ingrowing toenails compared with none of the control subjects. Compared with the control subjects, girls with TS showed a significantly increased incidence of short, broad feet; hyperextension of the great toes at the interphalangeal joint; toe nail involution; inflammation of the periungual tissues; and intermittent lymphedema. These features in combination with excessive subtalar joint pronation predispose to an increased risk of ingrowing toenails. We conclude that foot care problems are common in TS because of a number of predisposing factors and that foot examination should be part of routine surveillance.

Adolescent↗
PubMed2001

Phenotype, ovarian function, and growth in patients with 45,X/47,XXX Turner mosaicism: implications for prenatal counseling and estrogen therapy at puberty.

OBJECTIVE: Our objective was to determine whether girls with the rare Tur-ner 45,X/47,XXX mosaic karyotype are less severely affected than girls with 2 commoner karyotypes. STUDY DESIGN: We evaluated growth status, phenotype, and ovarian function in 7 girls with 45,X/47,XXX mosaicism, age-matching each with 2 girls with 45,X and 1 with 45,X/46,Xi(X)(q10) karyotypes. RESULTS: For the index, 45,X, and 45,X/46,Xi(X)(q10) groups, respectively, the median/mean height SD score at the start of growth hormone therapy/comparable age was -2.0 (-1.2), -2.3 (-2.4), and -2.6 (-2.6), cardiac anomalies were identified in 0 of 7, 4 of 14, and 1 of 7, renal abnormalities in 0 of 7, 4 of 14, and 3 of 7, middle ear problems in 2 of 7, 11 of 14, and 4 of 7, and special educational needs in 0 of 7, 3 of 14, and 1 of 7. Complete spontaneous puberty with menarche was seen in all but 1 girl older than 12 years in the index group compared with only 1 girl in the comparison groups. Ovarian tissue was identified in 6 of 7, 0 of 14, and 1 of 7 girls, and the mean follicle-stimulating hormone was 6, 25, and 21 U/L, respectively. CONCLUSION: Girls with 45,X/47,XXX karyotype are mildly affected, with good preservation of ovarian function. This result has important implications for prenatal counseling and the need for estrogen therapy at puberty.

Adolescent↗
PubMed2001

Short stature in Noonan syndrome: response to growth hormone therapy.

BACKGROUND: Growth hormone (GH) has been used to promote growth in both the short and long term in a number of dysmorphic syndromes, including Turner syndrome. As this condition shares many clinical features with Noonan syndrome, it would seem logical to treat the latter group with GH. AIMS: To assess the short and long term response to GH therapy in patients with Noonan syndrome. METHODS: Analysis of patients with Noonan syndrome in the Pharmacia & Upjohn International Growth Study (this post-marketing database contains data on the majority of patients currently treated with GH in the UK). A questionnaire was also sent to participating clinicians. RESULTS: Data on 66 patients (54 males) were available for study. At the start of GH therapy children were short, compared with both normal and Noonan children. During the first year of GH therapy height velocity increased from a mean of 4.9 to 7.2 cm per year. For patients treated long term with GH, mean height SDS increased from -2.9 pretreatment to -2.6 after one year and -2.3 after five years. Of the 10 patients at near final height, only one had a height above the 3rd centile for normal adults and above the mean for untreated Noonan patients. The mean increment in final height was 3.1 cm (range -1.1 to 6.5 cm). CONCLUSIONS: GH therapy in patients with Noonan syndrome will improve height velocity in the short term. Longer-term therapy results in a waning of effect; initial indications are that final height is not improved substantially in most patients.

Adolescent↗
PubMed2001

Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity.

BACKGROUND: Overweight children become obese adults who are prone to develop the "metabolic syndrome" and premature coronary arterial disease (CAD). AIMS: To assess whether sex hormone binding globulin (SHBG) is a potential marker for hyperinsulinaemia/insulin resistance in prepubertal obese children. METHODS: Twenty five obese children (body mass index (BMI) >2SD) who warranted investigation on clinical grounds were enrolled. Their insulin response to an oral glucose tolerance test was assessed. RESULTS: Fourteen children were hyperinsulinaemic. Despite being matched for age and BMI, SHBG concentrations were below the sex related reference range in the hyperinsulinaemic group. CONCLUSION: Our results indicate that a subnormal SHBG concentration in a prepubertal child is strongly predictive of hyperinsulinaemia. By measuring the circulating SHBG concentration, it might be possible to identify those at most risk of premature CAD, targeting them for lifestyle changes.

Adolescent↗
PubMed2000

Gigantism due to growth hormone excess in a boy with optic glioma.

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

Adult↗
PubMed2000

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement.

OBJECTIVE: To determine the feasibility of annual hypothyroid screening of children with Down's syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children. DESIGN: Establishment of a register of school children with Down's syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre. SUBJECTS: All school age children with Down's syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8. RESULTS: 200 of 214 school children with Down's syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto's thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is >/= 8.9%. CONCLUSION: Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down's syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.

Adolescent↗
PubMed2000

The boom that never was: results of a 10 year audit of paediatric growth hormone prescribing in Scotland.

OBJECTIVE: To investigate trends in paediatric growth hormone (GH) prescribing in Scotland. DESIGN: Annual audit of paediatric GH patients, analysed by geographical distribution, diagnosis, age and duration of treatment, dosage, sex ratio and prescribing body. SUBJECTS AND SETTING: Paediatric patients receiving GH who attended the four tertiary referral centres in Scotland: Glasgow, Edinburgh, Dundee and Aberdeen, from 1990-1999. RESULTS: The annual total number of paediatric GH recipients ranged from 296-393. The maximum was recorded in 1994, with a progressive decline thereafter. The latest total (296, 1999) represents a 19% decrease since 1990. There is a marked disparity between these figures and projections published by the Scottish Office Clinical Research and Audit Group (CRAG) in 1990 of 500 patients in 1995 and 600 by 2000. CRAG postulated that GH would prove efficacious in a wider range of conditions, that the number of survivors of childhood cancer would increase and that GH therapy would continue following clinical trials. While there has been a relative increase in oncology survivors during the 10-year period, the overall decline in numbers is largely attributable to familial short stature patients in whom there has been a five fold decrease, following completion of clinical trials of GH. The number of children classified "idiopathic growth hormone deficient" has also decreased, as the overlap between this condition and normal variant short stature is increasingly recognised. CONCLUSION: This expensive drug is being used relatively conservatively in Scotland, in the light of research experience. While a small degree of ad hoc usage is inevitable, we strongly support participation in national trials wherever possible. The adoption of an open approach with the Scottish Office regarding GH usage has proved beneficial in alleviating fear of escalating costs and preventing prescribing problems in a country in which 98% of GH is prescribed by general practitioners.

Adolescent↗
PubMed1999

A decade of growth hormone treatment in girls with Turner syndrome in the UK. UK KIGS Executive Group.

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m2/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.

Adolescent↗
PubMed1998

Increased incidence of congenital malformations in children with transient thyroid-stimulating hormone elevation on neonatal screening.

We investigated the incidence of congenital malformation in all infants with raised thyroid-stimulating hormone (TSH) levels on neonatal screening in Scotland between August 1979 and December 1993. Of 344 infants with elevated TSH, 31 (9%) had one or more malformations: 12 cardiac 15 noncardiac, and 16 dysmorphic syndromes (including 5 with Down syndrome). Criteria were devised to distinguish between definite or probable congenital hypothyroidism and transient TSH elevation. Congenital hypothyroidism was considered definite in 224 (65.1%) infants and probable in 11 (3.2%). Eighty-eight (25.6%) infants had transient TSH elevation, whereas thyroid status was uncertain in 21 (6.1%). In the definite group 12 (5.4%) infants had one or more malformations compared with 13 (14.8%) in the transient group. Cardiac malformation, noncardiac malformation, dysmorphic syndromes, and "sickness" were much more frequent in the transient compared with the definite group: 5.7% versus 1.8%, 8.0% versus 1.8%, 6.8% versus 2.7%, and 37.5% versus 7.1%, respectively. The incidence of congenital malformation in bonafide congenital hypothyroidism is lower than has been previously reported. The high incidence of congenital malformation associated with transient TSH elevation indicates the need to reevaluate the diagnosis of hypothyroidism in all infants with TSH elevation and concurrent illness or malformation.

Case-Control Studies↗
PubMed1998

Two sisters with prenatal growth failure, disproportionate short stature, and feeding difficulties.

A familial short stature syndrome is described in two sisters. Clinical features include severe pre- and post-natal growth failure, stridor, feeding difficulties in the first 2 years requiring nasogastric feeding and facial dysmorphism reminiscent of Three M syndrome. Intellectual function is normal. Skeletal surveys show short long bones, small square iliac bones, short femoral necks and vertebral bodies which are short in the antero-posterior diameter with narrowing of the interpedicular distance inferiorly.

Bone Diseases, Developmental↗
PubMed1998

Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty.

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.

Antineoplastic Agents, Hormonal↗
PubMed1997

Variable effect of growth hormone on growth and final adult height in Scottish patients with Turner's syndrome.

The aim of this work was to assess the outcome of recombinant growth hormone (rGH) therapy in a large unselected group (72) of patients with Turner's syndrome (TS), 26 of whom have reached final height. Growth data were collected from Scottish patients with TS and outcome was assessed in three ways: response to therapy in the first year, response in subsequent years and final height. Phenotypic, auxological, genetic and biochemical factors, all of which may have affected the first-year response, were investigated. Fifty-one percent of the cohort had a clinically "good" first-year response to therapy and 49% had a "poor" response, a "good" response was defined as a change in the TS standard deviation score (SDS) of +0.5 or more and a "poor" response as a change in the TS SDS of less than +0.5. The percentage of children showing a positive change in TS SDS after 2, 3 and 4 years of therapy declined (88%, 78%, 41%). Mean (range) final height was 142.6 (133.4-153.6) cm, mean (range) pretreatment TS SDS was -0.27 (-2.1 to +1.09) and mean (range) final TS SDS was -0.05 (-1.4 to +1.59). Thirteen (50%) patients attained a final height that was greater than projected, eleven did not attain their projected final height and two achieved their exact projected final height. Short girls with TS appear to benefit more from rGH supplementation than tall girls, but otherwise there was no significant correlation between any of the parameters studied and the response to treatment. It is concluded that large-scale prospective studies are still required to assess the impact of rGH on final height in TS and to identify factors responsible for the variability in response.

Adolescent↗
PubMed1997

Audit of screening programme for congenital hypothyroidism in Scotland 1979-93.

OBJECTIVE: To evaluate the efficiency of the screening programme for congenital hypothyroidism in Scotland and to determine the outcome in the cohort of children with positive testing for thyroid stimulating hormone (TSH). DESIGN: Establishment of comprehensive database for all Scottish infants with high TSH, detected on Guthrie screening. SUBJECTS: 344 infants born between August 1979 and December 1993 with TSH greater than 40 mU/l on initial Guthrie, or 15-40 mU/l on repeat Guthrie. MAIN OUTCOME MEASURES: Ages at time of: (a) Guthrie collection, (b) notification of positive result by laboratory, and (c) start of treatment; audit of late diagnosis/missed cases; categorisation of positive cases into definite and probable congenital hypothyroidism, transient TSH elevation, and uncertain status; educational status of children with definite and probable congenital hypothyroidism. RESULTS: 344 positive cases were categorised as having definite (224) and probable (11) congenital hypothyroidism, transient TSH elevation (88), and status uncertain (21). The overall incidence of definite/probable congenital hypothyroidism was 1 in 4400 live births. For the definite/probable groups median age of Guthrie collection was consistently between 6 and 7 days from 1983 onwards but for the whole cohort was later than 10 days in 10.5%. Median age of notification fell from 14 days in 1980 to 11 days in 1993. Median age of starting treatment ranged between 11 and 15 days from 1983 onwards. Treatment was delayed in four cases, three due to failed or late Guthrie card submission. Of 149 children with definite/ probable congenital hypothyroidism who were of school age, educational status was ascertained in 139 (93%). Only two children (1.4%) were attending special school, one of whom was known to have mild hypothyroidism. Sixteen children (11.5%) were receiving extra help in mainstream education compared with 18% of control children in the Scottish very low birth weight study. CONCLUSION: The current screening programme is working well, but efficiency could be increased by earlier and more reliable Guthrie collection. A substantial proportion of children picked up on the screening programme have a transient rise in TSH rather than true congenital hypothyroidism. The incidence of special education and learning support in Scottish children with congenital hypothyroidism appears to be no different to that of the general population.

Age Factors↗
PubMed1997

Growth hormone therapy in Turner syndrome--current uncertainties and future strategies.

The effect of growth hormone (GH) on short-to-medium-term growth in girls with Turner syndrome is well-established. However, it is only relatively recently that final height data have become available. This paper reviews 10 reports from Europe (including Sweden, Austria, France, Holland, Belgium and Scotland), Canada, USA and Japan, on final height and near-final height in girls with Turner syndrome receiving GH therapy. An improvement in final height outcome versus projected adult height was found in all the studies, except for the Scottish study, in which the median final height was only 142.6 cm, and the Canadian study, in which the projected adult height was unexpectedly high at 148.2 cm. Although the mean final height was 150 cm or greater in six studies, all 10 showed considerable individual variation in final height with minimum values ranging between 131.5 and 145 cm. These results must be interpreted cautiously since the mean age of starting treatment was relatively late at 9.1-13.1 years. However, the overall modesty and interpatient variability of response to GH in Turner syndrome, and continuing uncertainty as to the role of oxandrolone and the timing of estrogen therapy, emphasizes the need for further research. National and international collaboration in both retrospective and prospective studies are necessary to achieve sufficient data to offset the large number of variables to be analysed. In the UK, the British Society for Paediatric Endocrinology and Diabetes hopes to do a retrospective meta-analysis of final/near-final height outcome, comparing this with midparental and maternal height, as well as projected height and control data. A prospective study with GH dose standardized at 30 IU/m2 per week in the form of daily injections, with randomization to receive oxandrolone or not at 9 years, and estrogen at either 12 or 14 years, is also planned.

Growth Hormone↗