bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a continuous infusion of a somatostatin analogue (octreotide) for two years on growth hormone secretion and height prediction in tall children
Authors: Hindmarsh P. C. , Pringle P. J. , Stanhope R. , Brook C. G. D. 
Published: March 2008

SummaryOBJECTIVE Strategies to limit the final height of tall children have centred on the use of high doses of sex steroids to advance skeletal maturation. This limits therapy to the peripubertal years whereas the greatest gain In height is in the prepubertal years. Prepubertal growth Is largely GH dependent and previous work has documented modulation of GH secretion by once or twice daily subcutaneous Injection of the somatostatin analogue octreotide. In this study we have determined the effects of a nocturnal infusion of octreotide on height prediction, GH and TSH secretion in tall children.DESIGN A patient controlled study in which height prediction and 24‐hour GH and TSH secretion were compared prior to and during the course of a 2‐year treatment programme with a nocturnal infusion of octreotide in a dose of 1–1.5 μg/kg body weight given subcutaneously.PATIENTS Nine tall children (4M; 5F) aged 7–14 years with final height predictions of 179 cm or greater in the girls and between 183 and 202 cm in the boys were studied.MEASUREMENTS Height prediction using the Tanner‐Whltehouse system prior to and at the end of 2 years of treatment. Twenty‐four‐hour serum GH and TSH concentration profiles, thyroxine, IGF‐I and GH responses to GHRH(1–29)NH2 were studied prior to and at the end of the first year of therapy.RESULTS Treatment with octreotide led to a significant reduction in height prediction In 7 of the 8 children who completed treatment (median reduction 3.5 cm, range +2.8 to −11.5; Wilcoxon, P=0.05). Twenty‐four‐hour mean serum GH concentration decreased by 50% (MANOVA, P=0.03) during therapy and this was accompanied by an increase In the percentage of samples giving values less than 0.5mU/1 (MANOVA, P=0.02). There was no overall change in the serum GH response to GHRH(1‐29)NH2 or serum IGF‐I concentrations. Nocturnal serum TSH concentrations were reduced to levels observed during the daytime but these changes had no effect on serum thyroxine values. One patient developed gallstones during the course of therapy.CONCLUSIONS A nocturnal infusion of octreotide reduces GH secretion and height prediction in tall children. Therapy with somatostatin analogues allows a reduction In growth rate to be Instigated in the prepubertal years reducing the actual height from which will commence the pubertal growth spurt.
Lymphocytic hypophysitis: unusual features of a rare disorder
Authors: Jenkins P. J. , Chew S. L. , Lowe D. G. , Afshar F. , Charlesworth M. , Besser G. M. , Wass J. A. H. 
Published: March 2008

SummaryOBJECTIVE Lymphocytic hypophysitis is a rare disorder which usually affects women and Is often associated with pregnancy. We reviewed our experience of this disorder In order to see whether these features were universal amongst our patients.DESIGN A retrospective review of case notes.PATIENTS Four patients with histologically proven lymphocytic hypophysitis.MEASUREMENTS Each patient had undergone full radiological and biochemical assessment of anterior and posterior pituitary function.RESULTS Only one woman presented during pregnancy, one patient was a man with coexistent active acromegaly, and one progressed over 5 years to panhypopituitarism. In one further patient, histological analysis revealed normal anterior pituitary tissue adjacent to lymphocytic follicles.CONCLUSIONS Lymphocytic hypophysitis should be considered in the differential diagnosis of any patient with a pituitary mass. We suggest that the entire removal of such a mass is warranted both for accurate diagnosis and definitive treatment.
Multicentre study on prevalence of endocrine complications in thalassaemia major
Authors:   Italian Working Group on Endocrine Complications In Non‐endocrine Diseases
Published: March 2008

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 treatment.
Short stature in homozygous β‐thalassaemia is due to disproportionate truncal shortening
Authors: Rodda C. P. , Reld E. D. , Johnson S. , Doery J. , Matthews R. , Bowden D. K. 
Published: March 2008

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 hypogonadism and chelation therapy may be contributory factors.
The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism
Authors: Lee Philip J. , Patel Anita , Hindmarsh Peter C. , Mowat Alex P. , Leonard James V. 
Published: March 2008

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 control mechanisms of ovarian physiology and development.
Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency
Authors: Holmes Sarah J. , Whitehouse Richard W. , Swindell Ric , Economou Georgia , Adams Judith E. , Shalet Stephen M. 
Published: March 2008

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 beneficial effect on bone mass.
Dysfunction of the growth hormone/insulin‐like growth factor‐I axis in women with polycystic ovarian syndrome
Authors: Piaditis G. P. , Kounadi T. G. , Rangou D. B. , Trovas G. P. , Kaklas N. A. , Tzonou A. J. , Chlouverakis C. S. 
Published: March 2008

SummaryOBJECTIVE Although a defect In G H regulation has been suggested In women with polycystic ovarian syndrome (PCOS), the data are limited and mechanism obscure. We have assessed the function of the GH/IGF‐I axis In women with PCOS by measuring basal IGF‐I levels and the ability of the pituitary to secrete GH following dopamine and GHRH.DESIGN For each woman the complete study lasted 3 days. On the 1st and 2nd days, saline (0.9%, 5 ml/h for 3 h) and dopamine (4μg/kg min for 3h) Infusion tests were performed, respectively, In all PCOS and control women. Blood samples for G H measurement were obtained before and at 20‐mlnute Intervals for 3 hours. On the 3rd day a GHRH test (100μg, i.v.bolus) was performed In 9 of the women with PCOS and In 9 controls. Blood samples for G H measurements were obtained before and at 20‐minute Intervals for 3 hours. Basal IGF‐I levels were measured In the basal blood samples from the saline infusion test in all patients studied.SUBJECTS Thirteen women with PCOS and 11 normally menstruating women (control group), aged 18‐35 years, were studied. All women with PCOS had hirsutism and oligomenorrhoea since menarche, elevated serum values of at least one ovarian androgen and the typical ultrasound appearances of PCOS.RESULTS Growth hormone releasing hormone (GHRH) induced a significant increase In GH secretion In both control and PCOS groups. However, the GH response to GHRH was found to be significantly lower In women with PCOS. The 3‐hour infusion of dopamine induced a significant increase in GH levels only in the control group, while it failed to stimulate G H release in the women with PCOS. Although both dopamine and GHRH failed to induce a normal GH response in women with PCOS, their IGF‐I levels did not differ significantly from those observed In control women.CONCLUSIONS The diminished G H responses to both GHRH and dopamine In women with PCOS, in the presence of normal circulating IGF‐I levels, suggests a dysregulation in GH secretion. Although the data are suggestive of a hypothalamic defect, further studies are required to clarify the underlying mechanism and the role, if any, of GH In the pathogenesis of polycyctic ovarian syndrome.
Acute pre‐tibial myxoedema following radioiodine therapy for thyrotoxic Graves' disease
Authors: Harvey R. D. , Metcalfe R. A. , Morteo C. , Furmaniak W. , Weetman A. P. , Bevan J. S. 
Published: March 2008

SummaryA 54‐year‐old woman was treated with an oral dose of S55MBq of 131I radioiodine for thyrotoxicosis. She had no clinically detectable extrathyroidal manifestations of Graves' disease at the time, but within two months developed moderately severe ophthalmopathy and very extensive thyroid dermopathy affecting her face, arms, hands and feet, in addition to the classic pre‐tlblal area. Although she developed mild post radioiodine hypothyroidism, this was detected at an early stage and its treatment had no effect on the extrathyroldal signs. Thyrotrophin receptor antibodies (TRAb) were positive before treatment (22% Inhibition of T S H binding in neat serum), rose to very high levels following radioiodine (97.6% Inhibition), and fell progressively over the following year during treatment with prednisolone. Thyroglobulln autoantibodies became detectable following radioiodine but thyroid peroxidase antibodies were undetectable throughout. Serum and purified IgG from blood samples obtained prior to steroid therapy and over the subsequent year were tested on a dermal fibroblast cell line in vitro for the stimulation of synthesis of glycosamlnoglycans, protein and DNA, but no increase in radiolabel incorporation was apparent for any sample when compared to controls. The temporal relation between the radioiodine and the acute onset of dermopathy and ophthalmopathy, together with the abrupt rise in TRAbs, indicates a probable causal association.However, the absence of In‐vitro fibroblast stimulation would suggest that the pathogenesis of Graves' dermopathy is not dependent solely on any simple humoral factor.
Vitamin D intoxication causes hypercalcaemia by increased bone resorption which responds to pamidronate
Authors: Selby P. L. , Davies M. , Marks J. S. , Mawer E. B. 
Published: March 2008

SummaryOBJECTIVE Vitamin D intoxication is a relatively rare but treatable cause of hypercalcaemia. In the past this has been undertaken using corticosteroids. Previous observations have suggested that there is increased bone resorption in hypervitaminosis D. If this were to be the case, specific inhibitors of bone resorption might provide more effective treatment. We have therefore studied the mechanisms of hypercalcaemia and response to therapy in a group of patients with vitamin D intoxication.DESIGN Vitamin D metabolites were measured in six patients with vitamin D intoxication; in five of these the components of hypercalcaemia were calculated. These measurements were repeated following treatment with corticosteroids (two patients) or the bisphosphonate, pamidronate (three patients).RESULTS In each case the serum 25‐hydroxyvitamin D was grossly elevated and there was a more modest elevation in serum 1,25‐dihydroxyvitamin D. The components of hypercalcaemia suggest that there was a significant degree of bone resorption in all six patients and that this Is the major determinant of hypercaicaemia. Pamidronate treatment resulted in a brisk reduction in plasma calcium concentration. Following corticosteroids the return of calcium to normal was more delayed.CONCLUSION The hypercalcaemia of vitamin D intoxication is mediated by Increased bone resorption and bisphosphonates have a role in its management.
Endocrine effects of GnRH analogue with low‐dose hormone replacement therapy in women with endometriosis
Authors: Howell R. , Dowsett M. , King N. , Edmonds D. K. 
Published: March 2008

SummaryOBJECTIVE GnRH analogues are being used Increasingly for a number of oestrogen dependent conditions In women. The resultant profound hypo‐oestrogenism is a disadvantage, however, but the preservation of pituitary sensitivity to negative feedback by oestradiol is not well defined. We have determined the effect on gonadotrophins and Inhibin of GnRH analogue plus low‐dose continuous combined hormone replacement therapy In comparison with GnRH analogue therapy alone.DESIGN Randomized controlled trial.PATIENTS Fifty premenopausal women with endometriosis randomized to treatment with goserelin alone (Group 1) or goserelin plus 17βoestradiol and medroxyprogesterone acetate (Group 2).MEASUREMENTS FSH, LH, oestradiol, oestrone, Inhibin before and during treatment.RESULTS Oestradiol and oestrone were suppressed in both groups, but Group 2 had significantly higher oestradiol during the hormone replacement therapy period. LH was suppressed in both groups. In Group 1, FSH levels recovered during treatment but, in contrast, in Group 2, FSH levels remained suppressed throughout treatment. Inhibin was significantly lower in Group 2, but not In Group 1, during treatment compared to pretreatment.CONCLUSIONS Pituitary secretion of FSH appears to remain responsive to feedback control by oestradiol during GnRH analogue therapy and Is Incompletely suppressed, unlike LH which remains completely suppressed. The possible mechanisms for this are discussed.
Chronic myeloid leukaemia following 131I treatment for thyroid carcinoma: a report of two cases and review of the literature
Authors: Shimon Ilan , Kneller Abraham , Olchovsky David 
Published: March 2008

SummaryLeukaemia is an uncommon late complication of exposure to the Ionizing radiation of radioactive Iodine (131I). Most cases reported have been of acute ieukaemias developing after high doses of 131I. Only a few cases of chronic myeloid leukaemia (CML) have been reported in this setting to date.We report two new cases of CML after low dose radioactive iodine and review the literature. We present an analysis of the minimal relative risk of CML developing in thyroid cancer patients treated with 131I in Israel.Two male patients, 35 and 51 years old, developed CML following low dose 131I therapy for metastatic mixed papillary and follicular carcinoma of the thyroid. Both had undergone thyroidectomy and neck dissection and thyroid ablation with 131I (total dose: 56 and 130 mCl respectively). Four and 10 years later, respectively, a leucocytosis was noticed with typical blood smears, and CML was diagnosed either by Philadelphia translocation or bcr‐abl gene rearrangement. Thyroid cancer at that time was in remission.Estimated minimal relative risk of CML after 131I therapy where the population considered at risk comprised all thyroid cancer patients detected during the years 1981–1991 in Israel was 8.95 (95% confidence limits 2.26–35.16).Literature review disclosed five additional similar cases. The mean radioiodine dose given to the seven CML patients was 11416 MBq (range 1134–32130 MBq), considerably lower than the dose given to patients reported in the literature who subsequently developed acute leukaemias (mean 34965, range 3856–54810 MBq). We suggest that CML is a potential complication of low dose 131I therapy given for thyroid carcinoma even at the lower end of the dose range used for this indication. Leucocytosis appearing in these patients should raise the suspicion of secondary CML.