bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative tetany in patients with Graves' disease: a risk factor analysis
Authors: Yamashita Hiroyuki , Noguchi Shiro , Tahara Kazuki , Watanabe Shin , Uchino Shinya , Kawamoto Hitoshi , Toda Masakatsu , Murakami Nobuo 
Published: November 2003

OBJECTIVEThere is little information regarding the clinical risk factors for postoperative tetany in patients with Graves' disease. We analysed the risk factors responsible for postoperative tetany by univariate and multivariate analysis in thyroidectomized patients with Graves' disease, and we discuss the mechanisms of hypocalcaemia and tetany after surgery.PATIENTSThe subjects were 1742 consecutive patients with Graves' disease who underwent subtotal thyroidectomy between 1992 and 1994.RESULTSUnivariate analysis of 15 possible risk factors demonstrated that 10 were significant: sex, required operation time, blood loss, preoperative serum calcium level, estimated weight of thyroid remnant, size of goitre, amount of excised thyroid tissue, serum alkaline phosphatase concentration, age at operation and TSH‐binding inhibitory immunoglobulin (TBII). In multivariate analysis in female patients, the risk factors were: preoperative lower serum calcium level, younger age, higher serum alkaline phosphatase concentration, larger size of goitre and higher value of TBII, in order of decreasing probability of significance.CONCLUSIONThese results, combined with previous observations in which a significant decline in serum parathyroid hormone level was found in patients with Graves' disease who suffered postoperative tetany, suggest that postoperative tetany may occur during the period of bone restoration due to antithyroid drug  therapy and be due to continuation of a calcium    flux into bone concomitant with transient hypoparathyroidism induced by surgery. Calcium supplements during the preoperative period and/or after surgery may be appropriate for patients who are anticipated to develop postoperative tetany based on these risk factors.
Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome
Authors: Gilling‐Smith C. , Story H , Rogers V. , Franks S. 
Published: November 2003

OBJECTIVEPolycystic ovary syndrome (PCOS) is a common endocrinopathy of unknown aetiology. The aims of this study were to identify whether ovarian thecal cell steroidogenesis is abnormally regulated in PCOS by measuring steroid responses to a single dose of hCG before, and during, suppression of endogenous LH levels by a GnRH analogue (GnRHa).DESIGNSerum levels of LH, FSH, 17αhydroxyprogesterone (17OHP), androstenedione, testosterone and dehydroepiandrosterone sulphate were measured before, and 48 hours after, a single intramuscular injection of 10 000 IU hCG. The test was repeated 4 weeks after suppression of endogenous LH levels by GnRHa.PATIENTSThe ovarian responses to hCG were compared in three groups of women. Eleven women had normal ovaries and regular cycles, eight had polycystic ovaries but no clinical features of the syndrome (PCO group) and eight had polycystic ovaries, anovulation and either severe hirsutism or alopecia (PCOS group).RESULTSBefore GnRHa treatment, LH levels were significantly higher in the PCOS group but hCG stimulated a similar rise in 17OHP in all three groups. Following analogue, LH levels were suppressed in all three groups but the 17OHP responses to hCG were significantly higher in both the PCO and PCOS groups compared with normal controls.CONCLUSIONSThese findings provide further evidence in favour of an intrinsic abnormality of thecal cell steroidogenesis in the polycystic ovary.
Increased thyrotrophin levels and loss of the nocturnal thyrotrophin surge in Sheehan's syndrome
Authors: Abucham Julio , Castro Vania , Maccagnan Paulo , Vieira Jose G. H. 
Published: November 2003

OBJECTIVESince panhypopituitarism in patients with Sheehan's syndrome is due to massive pituitary necrosis with only minor hypothalamic involvement, we hypothesized that serum TSH levels would be low but its circadian rhythm preserved in these patients.DESIGN AND PATIENTSBasal and TRH‐stimulated mean afternoon (1500–1700 h) and nocturnal (0100–0300 h) TSH levels were determined in 10 patients with Sheehan's syndrome before and during T4/glucocorticoid replacement and in seven controls.MEASUREMENTSSerum concentrations of T3, T4, free T4 (fT4) and cortisol were measured by radioimmunoassay; TSH, GH, PRL and LH were determined by immunofluorimetric assay.RESULTSAfternoon TSH levels were markedly increased in Sheehan's syndrome patients compared with controls (3.3 ± 1.0 vs 0.5 ± 0.15 mU/l, respectively, P = 0.002). At night, TSH levels remained unchanged in Sheehan's syndrome patients (3.3 ± 1.1 mU/l) but rose significantly in controls (1.1 ± 0.34 mU/l, P = 0.016). The nocturnal TSH increment was significantly higher in controls than in patients (143 vs−4.9%, respectively, P = 0.0001). In eight patients with normal serum fT4 levels during treatment, basal TSH levels decreased to 0.16 ± 0.05 mU/l (P≤ 0.008), being barely detectable or undetectable in four patients. In the six patients with detectable TSH during treatment, nocturnal TSH increments were normal in four and blunted in two. There was a strong correlation between pre‐ and post‐treatment basal TSH (r = 0.82, P = 0.012) and between pre‐ and post‐treatment peak TSH after TRH (r = 0.91, P = 0.0017), but no significant correlation between TSH and thyroid hormone levels. The per cent ratio of peak TSH after TRH between treated patients and controls, an estimate of the relative size of the functional thyrotroph pool in Sheehan's syndrome patients, was 7%.CONCLUSIONSLoss of TSH rhythm in Sheehan's syndrome is usually secondary to hormonal deficiency and results from maximally increased secretory activity of a decreased pool of thyrotrophs. The paradox of increased TSH levels and decreased thyroid function in Sheehan's syndrome could result from decreased TSH bioactivity and/or from a critically reduced thyrotroph population that fails to sustain sufficient TSH secretion in the face of rising serum thyroid hormone levels.
Cabergoline treatment of acromegaly: a preliminary dose finding study
Authors: Jackson Stephen N. J. , Fowler Jane , Howlett Trevor A. 
Published: November 2003

OBJECTIVES:Studies of the dopamine agonist cabergoline in the treatment of hyperprolactinaemia have shown it to be a potent, long‐acting and well‐tolerated. The older dopamine agonist, bromocriptine, has traditionally had a place in the medical management of acromegaly, but poor patient tolerance of the high doses required, the need for multiple daily administration and incomplete biochemical responses have limited its role. We therefore sought to investigate the effect of cabergoline on growth hormone (GH) secretion in acromegaly and to define the most appropriate dose for suppression of GHDESIGN AND MEASUREMENTS:Patients with active acromegaly (defined as most recent random GH > 5mU/l) were identified from the departmental clinical information system. After informed consent was obtained, basal GH levels were estimated during a 5 point day curve at least 2 months after withdrawal of any existing medical therapy for acromegaly. The cabergoline dose was escalated on a monthly basis for 4 months with a repeat 5 point GH day curve at the highest dose, and 0900 and 0930 GH estimations at the intermediate dose increment stages. Serum IGF‐1 and prolactin were estimated on each occasion. Biochemical remission was defined as serum GH < 5mU/l.PATIENTS:Eleven acromegalics were investigated. Previous treatment included surgery (7), radiotherapy (5) and bromocriptine (5). Three patients had not received any previous treatment. All had random GH persistently > 5mU/l prior to the study.RESULTS:Ten patients completed the study. Of these, 7 showed a fall in the GH to ≤33% and IGF‐1 to ≤67% of the basal value but only 2 achieved biochemical remission. All subjects showed maximum GH response at a dose of 0.5 mg daily of cabergoline. Four patients were unable to tolerate the maximum dose of 1 mg daily (nausea in one and non‐specific symptoms in three). The patient excluded from the analysis discontinued cabergoline and underwent surgery after 1 month because of worsening visual field defects.CONCLUSIONS:Cabergoline may be a useful adjunct to the currently available treatment for acromegaly, but rarely achieves the goal of mean GH < 5mU/l. The maximum suppression of GH is achieved within the dose range 1 mg twice weekly to 0.5 mg daily.
Influence of residual C‐peptide secretion on nocturnal serum TSH peak in well‐controlled diabetic patients
Authors: Coiro V. , Volpi R. , Marchesi C. , Capretti L. , Speroni G. , Caffarri G. , Chiodera P. 
Published: November 2003

OBJECTIVESeveral alterations in hypothalamo–pituitary–thyroid (HPT) function have been described in diabetes mellitus and have been attributed to metabolic decompensation. The present study was performed in order to establish whether residual endogenous insulin secretion in patients with insulin‐dependent diabetes mellitus (IDDM) may play a role in the control of HPT function.DESIGNThe nocturnal (2230 h–0200 h) serum TSH surge, the TSH response to TRH (200 μg as an i.v. bolus) and serum free thyroid hormone levels were evaluated in C‐peptide positive (CpP) (subjects with residual detectable endogenous pancreatic beta‐cell activity) and C‐peptide negative (CpN) patients both before and after optimization of metabolic status by 3 days of treatment with continuous subcutaneous insulin infusion, and in normal controls. TSH response to TRH and serum free thyroid hormone levels were assessed in the morning.SUBJECTSTwenty male diabetic patients hospitalized to achieve a better control of hyperglycaemia were subdivided into 10 CpP (age: 33 ± 1.5 years (mean  ± SE); body mass index (BMI): 22.6 ± 0.3) and 10 CpN (age: 32 ± 1.7 years; BMI: 22.5 ± 0.4) patients. Nine normal men (age: 34.0 ± 1.2 years; BMI: 23.1 ± 0.4) served as controls.MEASUREMENTSThe nocturnal serum TSH peak was measured by dividing the highest night‐time TSH value by the next morning TSH value and then multiplying by 100. Serum TSH levels were measured in samples taken just before (time 0) and 30 minutes after TRH administration. Serum free thyroid hormone levels were measured in samples taken at time 0 of the TRH test.RESULTSBefore improvement of hyperglycaemia, CpP and CpN patients showed similar alterations in HPT function; i.e. serum free T3 levels and TSH responses to TRH were lower than normal; the nocturnal TSH surge was absent. Correction of hyperglycaemia normalized all examined HPT parameters in CpP diabetics, whereas normalization in serum free T3 levels and pituitary TSH responsiveness to TRH in CpN patients was not accompanied by restoration of the nocturnal TSH peak.CONCLUSIONSThese data indicate that the absence of residual pancreatic beta‐cell function in patients with insulin‐dependent diabetes mellitus is associated with neuroendocrine dysfunction in the regulation of circadian TSH secretion, which is not reversible after restoration of good glycaemic control.
An analysis of testosterone implants for androgen replacement therapy
Authors: Handelsman David J. , Mackey Mary‐Anne , Howe Chris , Turner Leo , Conway Ann J. 
Published: November 2003

OBJECTIVETo review 13 years of experience using fused crystalline testosterone implants for androgen replacement therapy in order to identify pattern of usage (including continuation rates) and adverse events emerging during therapy and factors associated with adverse events including implant extrusions.DESIGNRetrospective review of prospectively collected data on characteristics of patients and implant procedures performed as well as adverse events reported during routine follow‐up.PATIENTSOver 13 years 973 implant procedures using fused crystalline testosterone implants were performed in 221 men.MEASUREMENTSContinuation rates and adverse events such as extrusions, bleeding, infection or others were recorded and analysed in relationship to characteristics of the patient and the implant procedure performed.RESULTSOverall rate of adverse events (108/973, 11.1%) was significantly related to increased numbers of implants (4.2 ± 0.1 vs 4.0 ± 0.03, P = 0.031) and higher levels of physical activity at work (P = 0.030). The most common adverse effect was extrusion (83/973, 8.5%) which was related to occupational classification (P = 0.033) and increasing work activity (P = 0.044) and occurred more frequently than by chance in multiple (16 vs 3.3 expected) rather than single (65 vs 76.1 expected) episodes. Bleeding (22/973, 2.3%) was significantly associated with an increased number of implants (4.5 ± 0.2 vs 4.0 ± 0.03, P = 0.020) but even in the worst cases (3/22) it was of minor clinical importance. Infection was rare (6/973, 0.6%) but occurred more among thinner men. The overall continuation rate was 92.7% increasing from 86% after the first implantation to >99% after the tenth implant.CONCLUSIONSThis study demonstrates the very satisfactory clinical acceptability of testosterone pellet implants for androgen replacement therapy within a single unit with experienced operators. The only regular adverse effect is extrusion, which may be related to mechanical factors such as habitual work activity but also possibly procedural factors. Other adverse effects such as bleeding, infection and fibrosis were rare. An improved method of implant delivery would enhance this old but durable technology.
Serum LH concentrations in hypogonadal men during transdermal testosterone replacement through scrotal skin: further evidence that ageing enhances testosterone negative feedback
Authors: Winters Stephen J. , Atkinson Linda 
Published: November 2003

OBJECTIVEThe present study was designed to explore further the mechanism for the decline in androgen production as men age by studying the influence of ageing on testosterone negative feedback control of gonadotrophin secretion.DESIGNCirculating testosterone, dihydrotestosterone, oestradiol, SHBG and LH concentrations were measured during long‐term treatment of men with primary hypogonadism using transdermal testosterone via scrotal skin.PATIENTSResults were compared in 12 hypogonadal men below age 40 years (34 ± 1.1 years; mean ± SEM), 13 middle‐aged men, aged 51 ± 2.2 years, and 10 men age 64 years or older (68 ± 1.4 years).RESULTSDuring the course of therapy, circulating LH levels were suppressed 48% (F = 2.42, P = 0.018) from 19.8 ± 6.0 IU/l at baseline to 10 ± 7.7 IU/l during month 15 in elderly men. By contrast, LH levels were unchanged (F = 0.31; P = 0.97) in young men (20.3 ± 7.4 IU/l at baseline and 17.7 ± 14.9 IU/l during treatment month 15). Intermediate results were observed in middle‐aged men in whom LH levels declined slightly (F = 1.34; P = 0.24). Transdermal testosterone treatment produced similar circulating testosterone levels (F = 1.49; P = 0.24) and oestradiol levels (F = 0.60; P = 0.42) in elderly and young men. Mean plasma DHT levels were approximately 20% higher (F = 9.91; P = 0.01) during treatment in elderly men (overall mean values of 8.03 ± 0.37 nmol/l) than in young men (6.68 ± 0.08 nmol/l). When total DHT was adjusted for higher plasma SHBG levels in elderly men, the free DHT index during treatment was similar (F = 0.23; P = 0.64) in both groups.CONCLUSIONSThese data provide further evidence that the set point for androgen negative feedback control of gonadotrophin secretion in men is altered by ageing. Taken together with previous findings, these results provide a potential explanation for the unchanged or slightly increased plasma LH levels and reduced testosterone production characteristic of elderly men. Accordingly, ageing‐associated Leydig cell insufficiency leads to a decline in testosterone production, but circulating LH levels do not rise appropriately because the set‐point for negative feedback is decreased.
Mortality and morbidity in transsexual subjects treated with cross‐sex hormones
Authors: Van Kesteren Paul J. M. , Asscheman Henk , Megens Jos A. J. , Gooren Louis J. G. 
Published: November 2003

OBJECTIVEThe optimum steroid hormone treatment regimes for transsexual subjects has not yet been established. We have investigated the mortality and morbidity figures in a large group of transsexual subjects receiving cross‐sex hormone treatment.DESIGNA retrospective, descriptive study in a university teaching hospital.SUBJECTSEight hundred and sixteen male‐to‐female (M  →  F) and 293 female‐to‐male (F  →  M) transsexuals.INTERVENTIONSSubjects had been treated with cross‐sex hormones for a total of 10 152 patient‐years.OUTCOME MEASURESStandardized mortality and incidence ratios were calculated from the general Dutch population (age‐ and gender‐adjusted) and were also compared to side effects of cross‐sex hormones in transsexuals reported in the literature.RESULTSIn both the M  →  F and F  →  M transsexuals, total mortality was not higher than in the general population and, largely, the observed mortality could not be related to hormone treatment. Venous thromboembolism was the major complication in M  →  F transsexuals treated with oral oestrogens and anti‐androgens, but fewer cases were observed since the introduction of transdermal oestradiol in the treatment of transsexuals over 40 years of age. No cases of breast carcinoma but one case of prostatic carcinoma were encountered in our population. No serious morbidity was observed which could be related to androgen treatment in the F  →  M transsexuals.CONCLUSIONMortality in male‐to‐female and female‐to‐male transsexuals is not increased during cross‐sex hormone treatment. Transdermal oestradiol administration is recommended in male‐to‐female transsexuals, particularly in the population over 40 years in whom a high incidence of venous thromboembolism was observed with oral oestrogens. It seems that in view of the deep psychological needs of transsexuals to undergo sex reassignment, our treatment schedule of cross‐sex hormone administration is acceptably safe.
Final height in non‐growth hormone deficient children treated with growth hormone
Authors: Bernasconi S. , Street M. E. , Volta C. , Mazzardo G. , The Italian Multicentre Study Group  
Published: November 2003

OBJECTIVETo evaluate the final height of non‐growth hormone deficient (N‐GHD) children treated with growth hormone (GH).DESIGNMulticentre retrospective study.PATIENTS71 (54M/17F) N‐GHD children (peak GH after pharmacological stimulation >14–24 mU/l) who had been treated for 4.19 ± 0.14 years with GH (0.69 ± 0.02 IU/kg/week).MEASUREMENTSHeight (H) and height velocity (HV) expressed as standard deviation score (SDS) for chronological age (CA) and bone age (BA), BA/CA ratio, and predicted adult height (PAHSDS) were evaluated before and during treatment, and at each pubertal stage. Target height (TH), and final height (FH) were also calculated, and expressed as SDS.RESULTSIn the whole group, HSDS for CA increased significantly after the first year on GH, and remained significantly increased for 4 years. This did not occur to HSDS for BA, owing to a significant increase in BA/CA after the first year of therapy. In addition, this increase coincided with stages 4 and 5 of puberty. HVSDS for CA and BA also increased significantly after the first year of treatment, and remained significantly elevated for 4 years. PAHSDS did not change significantly during treatment. FHSDS (−1.69 ± 0.07) was similar to PAHSDS (−1.6 ± 0.12) and target height (THSDS) (−1.46 ± 0.08). FHSDS was ≥THSDS in 36.6% of the patients, and ≥initial PAHSDS in 34.5%. Male patients were subdivided into 2 groups (A and B). Patients in Group A (n = 26) started treatment at puberty, while group B (n = 28) consisted of subjects who started therapy during prepubertal years. Height, height velocity and predicted adult height showed the same pattern as in the whole group, in each subgroup. BA/CA advanced significantly in group A after the second year on GH and in group B, after at least 3 years of therapy. FHSDS, THSDS, and PAHSDS were similar in both groups (−1.7 ± 0.13, −1.29 ± 0.2 and −1.39 ± 0.15 in group A and −1.48 ± 0.11, −1.85 ± 0.15 and −1.36 ± 0.12 in group B, respectively). However, in group B (prepubertal), FHSDS was ≥initial PAHSDS in 60% of the patients and ≥THSDS in 40.7%, while in group A (pubertal), FHSDS was ≥initial PAHSDS only in 22.7% of the patients and ≥THSDS in 34.6%. FHSDS was found to be correlated with THSDS, PAHSDS at the onset of treatment, and after 1 year of treatment. The age at the beginning of puberty, and the duration of puberty were appropriate in all groups.CONCLUSIONSGH treatment was effective in increasing height velocity of short non‐GH‐deficient children, but final height was not definitely improved with respect to initial predicted adult height.
Pituitary dysfunction in recently post‐menopausal women
Authors: Lyons Anthony , Ng Connie , Fielding Katherine , Hosking David , Selby Colin , Lawson Nigel ,   on behalf of the Nottingham EPIC Study Group
Published: November 2003

OBJECTIVESome recently post‐menopausal women have lower than expected FSH concentrations, raising the possibility of subclinical hypothalamo–pituitary impairment. We have therefore performed pituitary stimulation tests in a group of recently post‐menopausal women recruited to a bone loss prevention study.DESIGNProspective study of health volunteers.SETTINGOutpatient, teaching hospital in Nottingham UK.SUBJECTSForty‐seven women selected from a cohort of 428 healthy volunteers to an osteoporosis prevention study all within 10 years of the menopause.MAIN OUTCOME MEASURESResponse of the pituitary to formal stimulation tests and its relationship to bone mineral density.RESULTSA significantly attenuated response to pituitary stimulation was found in a group of otherwise healthy women with an FSH considered to be inappropriately low for the level of circulating oestradiol. The impaired responses were significant not only for FSH as expected but also to LH and prolactin at 1 hour after injection of GnRH and TRH (area under the curve, FSH P = 0.01, LH P = 0.001, prolactin P < 0.0001). TSH secretion was not significantly impaired. Baseline cortisol, growth hormone and thyroxine (T4) were normal in both control and test subjects. The test group was both heavier and taller, with a higher lean body mass, a higher body mass index and a greater total body fat than the controls. Bone mineral density showed no significant differences between the groups. Test subjects also had a higher free oestradiol index (P < 0.001) which correlated strongly (r = 0.534, P = 0.00026) with baseline FSH levels and possibly reflects a greater tissue exposure to biologically active hormone. Oestrone concentrations were, however, no different between the groups.CONCLUSIONSSerum FSH concentrations are not invariably elevated in recently post‐menopausal women and use of FSH as a determinant for post‐menopausal status in clinical trials should be used with caution. Notwithstanding their higher free oestradiol index, women found to have an abnormally low basal FSH had evidence of poor prolactin, FSH and LH but not TSH responses to pituitary stimulation. This may represent either a degree of subclinical pituitary failure or a variant of normal. The low levels of gonadotrophin activity did not affect bone mineral density.