ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02681.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Octreotide, a potent long‐acting synthetic somatostatin analogue, has been reported to have a beneficial effect in thyroid eye disease (TED), but the precise mechanism of action remains unexplained.111In‐DTPA‐D‐Phe1‐octreotide (Octreoscan‐111) has been used to localize a number of endocrine tumours and visualize somatostatin receptors in the retrobulbar tissue of patients with TED. Furthermore, this technique can predict the inhibitory effect of octreotide on hormone secretion by endocrine tumours, as there is a close relation between the clinically observed Inhibition and visualization of the tumour using Octreoscan‐111. The alms of the present study were to confirm the beneficial effect of octreotide in patients with TED, to investigate the presence of somatostatin receptors In the orbital area and also, if possible, to ascertain whether this technique could select those patients with TED who might benefit from treatment with octreotide.DESIGN A prospective study.SETTING An endocrine clinic of a national hospital.PATIENTS Twenty treated thyrotoxic patients with TED, 5 treated thyrotoxic patients without TED and 5 normal Individuals were studied. In 12 patients with TED, 5 without TED and 5 normal individuals, Octreoscan‐111 scintigraphy of the orbits was performed. The remaining 8 patients with ophthalmopathy served as controls. In patients with TED who were Investigated with Octreoscan‐111, 300 μg octreotide dally was given for 12 weeks.RESULTS Six patients In both eyes and one patient In one eye showed an improvement In ocular manifestations as assessed by clinical criteria and changes in the NOSPECS score, while the rest showed no Improvement. The patients who showed an Improvement had a high number of somatostatin receptors and positive orbital scans, while with one exception the patients who did not respond had a low number of receptors and negative orbital scans (P<0.02). None of the 5 patients without TED nor the normal individuals had a positive orbital scan. Seven out of 8 control patients with TED showed no change in the disease during the trial, while 1 deteriorated.CONCLUSIONS We conclude that octreotide has a beneficial effect in thyroid eye disease and that Octreoscan‐111 could predict those patients with thyroid eye disease who might benefit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02682.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Thalassaemia major Is a common and serious medical problem, worldwide. However, there are few data concerning the various endocrine disorders which occur in this condition. We have surveyed 25 Italian centres in order to establish the prevalences and times of onset of endocrine disorders In patients with β‐thalassaemia major.PROJECT AND PATIENTS A questionnaire specifically designed to investigate the prevalences of endocrinopathles was sent to 25 paediatric and haematology departments. The following data were recorded in the questionnaire: sex, age, height and weight, pubertal status according to Tanner's classification, history of secondary amenorrhoea, type of endocrinopathy and hormone levels at diagnosis, associated complications, serum ferritin level, liver enzymes (ALT) and compliance with treatment.RESULTS An analysis of data from 1861 patients showed that failure of puberty was the major clinical endocrine problem and was present in 51 % of boys and 47% of girls, all over the age of 15 years. Secondary amenorrhoea was recorded in 23% of patients (mean age 18.3 years), primary hypothyroidism in 6.2% (mean age 15.8 years), insulin dependent diabetes mellitus in 4.9% (mean age 18.1 years) and hypoparathyroidism In 3.6% of the patients (mean age 18.7 years). At present, the ma|orlty are in the second or third decades of life. The prevalences of hypothyroidism, insulin dependent diabetes mellitus and hypoparathyroidism differed in the various centres, whereas the frequency of pubertal disorders was very similar.CONCLUSIONS Our study has demonstrated several points. Endocrine evaluation in thalassaemic patients must be carried out regularly, especially in those patients over the age of 10 years with Iron overload and poor compliance with chelation therapy.The prevalences of some complications, such as insulin dependent diabetes and hypothyroidism, were lower than previously recorded. Hence, It is to be hoped endocrine complications will be less common In the future, for patients who have started chelation therapy during the first years of life.Because of the improved survival of thalassaemic patients with insulin dependent diabetes, and the high Incidence of multiple endocrine complications, ft is important to carry out careful follow‐up studies for the early detection of any other associated complications to facilitate correct treat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02683.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND and objective Growth failure In homozygous β‐thalassaemia has been recognized for many years, and has persisted despite major treatment advances. In this cross‐sectional study, sitting and standing height were measured to determine whether growth failure was disproportionate.DESIGN Patient data were analysed In three age groups, 2‐10 years, 11‐18 years and 19 and over. Sitting height and sublschlal leg length were also determined In a cohort of parents (n= 19) and normal Greek adolescents (n= 32).PATIENTS AND MEASUREMENTS Of the known 156 patients with homozygous β‐thalassaemla In the State of Victoria, 154 (98.7%) attend our Institution. Sitting and standing heights were measured, using Harpenden stadlometers, In 57 of 60 (95%) patients aged 2‐18 years and in a random selection of 51 of 89 patients aged 19 and over (57%). Measurements are expressed as mean ± SDS. Other data analysed Included serum concentrations of ferritin, zinc, copper, FSH, LH, oestradlol and testosterone, according to standard laboratory assays, together with pubertal status and bone age in patients aged less than 19 years.RESULTS Standing height standard deviation scores in the 2–10 age group were −0.687 ± 0.861 (n= 9), in the 11–18 age group were −1.838 ± 1.413 (n= 48) and In the age group 19 and over were −1.175 ± 1.126. In Individuals aged 2–10 years, sitting height standard deviation scores (SDS) were −1.56 ± 1.02, In Individuals 11–18 years were −3.76 ± 1.51 (n= 48), and In individuals 19 years and over were −2.77 ± 1.20 (n= 51), compared with sublschlal leg length SDS which were, In Individuals aged 2–10 years 0.214 ± 0.91; In 11‐18 years, −0.063 ± 1.347, and In individuals 19 and over, 0.37 ± 1.18. These data show that the reduction in standing height was the result of truncal shortening. Mean sitting height SDS was significantly lower In children with homozygous β‐thalassaemla, compared with their parents (P<0.001), and in a subgroup of Greek adolescents with homozygousβ‐thalassaemia compared with age and sex matched normal Greek adolescents (P<0.001). No correlation was found between truncal shortening and other clinical and biochemical variables measured.CONCLUSIONS Short stature In our patients with homozygous β‐thalassaemla is due to disproportionate truncal shortening. The aetiology of truncal shortening in this patient group is likely to be multifactorial, although hypo

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02684.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE With the development of new long‐acting depot preparations of bromocriptine (bromocriptine LAR), we investigated the effectiveness of intramuscular injections of long‐acting bromocriptine in patients with prolactin and GH secreting macroadenomas.STUDY DESIGN AND PATIENTS Fourteen patients with PRL secreting (8 patients) and GH secreting (6 patients) macroadenomas were treated with monthly intramuscular Injections of a long‐acting and repeatable form of bromocriptine for 3–6 months. A 50‐mg monthly dose was administered In the majority of patients with PRL secreting macroadenomas. A 100‐mg monthly dose was administered In all patients with GH secreting macroadenomas.MEASUREMENTS Plasma PRL and/or GH levels were measured 6 and 12 hours after the first injection and then on days 1, 2,14 and 28 after each Injection, up to a maximum period of 6 months. Patients were hospitalized for 48 hours after each Injection and were specifically questioned with respect to side‐effects. Pituitary imaging with MRI or CT scans was performed In all patients before commencing treatment and was subsequently repeated In 5/8 patients with macroprolactinomas and 5/6 patients with GH secreting macroadenomas after the completion of a 6‐month course of treatment.RESULTS In ail patients with macroprolactinomas, serum PRL levels decreased significantly after their first 50‐mg injection with nadir levels obtained by 24–48‐hours post Injection (12815 ± 8704vs1480 ± 1859 mU/l; mean ± SD,P<0.01). At their latest follow‐up, on a 50‐mg monthly dose, 4 patients developed normoprolactinaemia (PRL levels<360mU/l) while two patients demonstrated a significant reduction In serum PRL levels (70 and 87% of pretreatment values). In two patients, although a substantial decrement of serum PRL levels was achieved 12‐24 hours post injection, serum PRL levels Increased to pretreatment values by day 14 post injection. Both patients received a higher (100mg) monthly dose which was partially effective In one patient. In two patients with GH secreting macroadenomas, a sustained decrease of elevated GH levels was observed; in two patients, while a substantial reduction of the elevated serum GH levels was achieved 12–24 hours after the first and subsequent injections, serum GH levels increased to pretreatment values by day 14 post injection; in two patients there was no effect on the elevated serum GH levels. Significant tumour shrinkage (24–50%) was observed In 5/5 patients with PRL secreting macroadenomas assessed at completion of a 6‐month course of treatment. Significant tumour shrinkage was also documented In 2/5 acromegalics tested (29 and 46% respectively).CONCLUSION It is concluded that bromocriptine LAR Is an effective treatment in the majority of patients with macroprolactinomas; it is also partially effective in some pati

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02685.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE There has been much debate concerning the relative contribution of Insulin resistance to the development of polycystic ovaries (PCO). We therefore aimed to assess ovarian morphology and insulin/androgen status in females with the hepatic glycogen storage diseases types la (GSD‐la) and III (GSD‐III), disorders associated with abnormalities of Insulin secretion.DESIGN A cross‐sectional study of ovarian ultrasonography, oral glucose tolerance tests (oGTTs) and single measurements of gonadotrophins and androgens were performed.PATIENTS Twenty‐seven patients were evaluated: 13 with GSD‐la, median age 11.2 years (range, 3.3–26.7) and 14 with GSD‐III, aged 13.2 years (4.2–31.3). None had clinical signs of hyperandrogenlsm and only two of the 13 adults (15%) had menstrual Irregularities. They were compared to 9 normal adult female controls, aged 21–28 years.MEASUREMENTS Ovarian morphology and volume were measured. Blood glucose and plasma insulin concentrations were measured at the beginning and end of a 2‐hour oGTT. Single measures of LH, FSH, testosterone, dehydroepiandrosterone sulphate, androstenedione, IGF‐I and SHBG were made on samples taken at the beginning of the oGTT.RESULTS In both GSD‐la and III, all those older than 4.8 years of age had a polycystic ovarian appearance. Pre‐pubertal GSD‐la patients had lower basal and 2‐hour blood glucose and plasma insulin concentrations than pre‐pubertal GSD‐III patients. In adults with GSD‐la and GSD‐III, although basal and 2‐hour blood glucose concentrations did not differ, both basal and 2‐hour plasma Insulin concentrations were significantly higher than controls. Serum gonadotrophins, androgens, IGF‐I and SHBG were mostly normal.CONCLUSIONS A polycystic ovarian appearance is a common finding In patients with glycogen storage disease even before puberty. In GSD‐III and adults with GSD‐la, this ovarian appearance was associated with hyperinsulinism, suggesting an aetiological link, but this was not the case in pre‐pubertal children with GSD‐la. Inborn errors of carbohydrate metabolism may act as useful models for examining contr

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02686.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE There are few data on urinary markers of collagen breakdown In children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline In children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross‐links.DESIGN A cross‐sectional study of a group of healthy children and sequential samples from children receiving GH treatment.PATIENTS One hundred and nine healthy children aged 2–15 years, 8 healthy children aged 4–11 years and 4 children receiving GH treatment.MEASUREMENTS Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two‐site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorlmetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine.RESULTS High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen In children receiving GH treatment with no significant correlation to height velocity.CONCLUSIONS There is a high excretion of the pyrldi‐nium cross‐linking amino acids in children of all ages compared to adults. However, a high variability exists In single morning urine samples which will limit the usefulness of these markers in gro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02687.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE It Is possible that the degree of perceived well‐being may Influence the decision of an adult with GH deficiency to receive GH replacement. We have therefore sought factors which Influenced whether or not such a patient wished to enter a study of GH replacement.DESIGN Biochemical, anthropometric and demographic characteristics, and well‐being, of patients who chose to enter a 12‐month study of GH replacement at Christie Hospital NHS Trust were compared with those of patients who declined to enter the study.PATIENTS Sixty‐five adults with GH deficiency who entered a study of GH replacement and 33 adults with GH deficiency who were approached but who declined to enter the study.MEASUREMENTS The two groups of patients were compared according to sex, age, height, weight, body mass Index, peak serum GH response to provocative testing, estimated duration of GH deficiency, whether GH deficiency was of childhood or adult onset, presence or absence of additional pituitary hormone deficiencies, aetiology of GH deficiency, previous therapeutic Interventions, employment status, marital status and living arrangement (65 entered vs 33 declined to enter). Well‐being or distress was measured using the Nottingham Health Profile (NHP) (65 entered vs 20 declined to enter) and the Psychological General Well‐being Schedule (PGWBS) (33 entered vs 19 declined to enter).RESULTS Those who entered the study had significantly higher scores on the energy (P= 0.03) and emotional reaction (P= 0.02) subsections and on the total score (P= 0.04) of the NHP, indicating greater distress, and had a significantly lower score (P= 0.009) on the vitality subsection of the PGWBS, again indicating greater distress. Those who entered the study had a significantly lower prevalence of non‐functioning pituitary adenoma (P= 0.02) but there was no other difference in biochemical, anthropometric or demographic characteristics between the two groups.CONCLUSION Adults who enter a study of GH replacement exhibit greater distress on questionnaire assessment than those who decline to enter such a study. This bias must be considered when Interpreting studies of the effect of GH replacement on well‐

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02688.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE It Is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function. We have therefore Investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH (r‐hGH) treatment in children with idiopathic short stature and a normal pretreatment height velocity.STUDY DESIGN Randomized controlled study.PATIENTS Twenty‐nine short (height SDS−1.5), prepubertal children referred to two specialist growth clinics.INTERVENTIONS Children were randomly assigned to an observation group or to receive ‘standard’ (20IU/m2/ week) or ‘high’ (40 IU/m2/week) dose r‐hGH by dally subcutaneous injection. At the end of 1 year the observation group were randomly assigned to ‘standard’ or ‘high’ dose r‐hGH therapy for the second year of the study. Regular growth, biochemical and echocardiographic monitoring were performed throughout the study period.MAIN OUTCOME MEASURES Change In height velocity, HtSDS for bone age (HtSDSBA), left ventricular mass Index (LVMI) and left ventricular function (fractional shortening) during 2 years treatment.RESULTS Twenty‐seven children completed the study. Ht velocity SDS Increased with r‐hGH therapy In a dose dependent fashion. First‐year height velocity SDS was +5.7 in the high dose r‐hGH group compared with +2.7 in the standard dose r‐hGH group and −0.5 In the observation group (P<0.001). In those children treated for 2 years HtSDSBA was −0.5 In the high dose group but had not changed significantly In the standard dose group (−1.7) (P= 0.01).After one year r‐hGH treatment LVMI was 71g/m2(observation group), 73g/m2(20 IU/m2/week group) and 74g/m2(40 IU7m2/week group) (P= 0.77). LVMI Increased significantly from baseline to 76 g/m2after 2 years therapy with 40 IU/m2/week r‐hGH (P= 004) but nevertheless remained within the normal range. Fractional shortening did not change significantly over 2 years of r‐hGH therapy.CONCLUSIONS High dose (40 IU/m2/week) r‐hGH treatment of children with idiopathic short stature resulted in a greater short‐term acceleration In growth rate than ‘standard’ dose therapy without an excessive advance In skeletal maturity and probably represents the optimal growth promoting dose for short, normally growing children. Whether continued high dose r‐hGH therapy increases final height requires further study. Left ventricular morphology and function remained within the normal range during r‐hGH therapy but regular monitoring of cardiovascular status should continue In non‐GHD chi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02689.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency.DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months.PATIENTS Twenty‐two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency.MEASUREMENTS Single‐energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single‐photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual‐energy X‐ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD.RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change −0.009g/cm2,P=0.01), forearm Integral BMD (SPA: median change −0.016g/cm2,P=0.03), lumbar spine BMD (DXA: median change −0.022g/cm2;P=0.003) and femoral neck BMD (DXA: median change −0.029g/cm2,P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change −0.035 g/cm2,P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies.CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer‐term studies are required to determine whether prolonged GH replacement has a benef

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02690.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY