bluuebunny/crossref_metadata_2025 huggingface dataset:
Which adults develop side‐effects of growth hormone replacement?
Authors: Holmes Sarah J. , Shalet Stephen M.
Published: March 2008

OBJECTIVE Although the nature of the side‐effects of G H replacement In adults are well described, the factors Influencing their development are III understood. The aim of this study was to determine whether there were any characteristics of adults with G H deficiency that predicted whether or not they developed side‐effects of G H replacement

DESIGN A 12‐month study (double blind placebo controlled for the first 6 months and open for the second 6 months) of G H replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) In adults

PATIENTS Sixty‐three adults (27 men, 36 women, aged 34.9 ±1.4 (mean ± SE, range 20.1‐59.5 years)) with G H deficiency (peak serum G H response to provocative testing of less than 10mU/l) who took part In a 12‐month study of G H replacement. Twenty‐five patients (40%) did not develop side‐effects, 19 patients (30%) developed side‐effects which did not necessitate a reduction In dose of G H, and 19 patients (30%) required a reduction In dose of G H because of side‐effects

MEASUREMENTS The three groups of patients were compared according to age, height, weight and body mass index (BMI) at entry Into the study and to pretreatment peak serum G H response to provocative testing. They were also compared according to serum concentration of Insulin‐like growth factor (I G F)‐I and IGF binding proteln‐3, and age‐adjusted serum IGF‐I standard deviation score (SDS), at entry Into the study and by change In these measurements after 6 months of GH replacement. The patient's sex, whether GH deficiency was of childhood or adult onset, estimated duration of G H deficiency, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder and previous therapeutic Interventions were also compared In the three groups of patients

RESULTS Those patients who required a reduction In dose of G H because of side‐effects were more likely to have a peak serum G H response of greater than 1 mU/l (P=0.005) and to have adult onset G H deficiency (P = 0‐04) than those who did not develop side‐effects or who did not require a reduction In dose of G H because of side‐effects. In addition, those who needed a reduction In G H dose were older (P = 0‐002), heavier (P = 0‐04) and had a greater BMI (P = 0‐003) than those who did not develop side‐effects. Those who developed side‐effects but did not require a reduction In dose of GH had a greater increment in I G F‐I S D S after 6 months of G H replacement than those who did not develop side‐effects (P‐0‐03). CONCLUSION Side‐effects of G H replacement are more likely to occur In older patients, In those with a peak serum G H response to provocative testing of greater then 1 mU/l, In those with a greater increment In serum I G F‐I S D S whilst receiving G H replacement, In those with greater weight and BMI, and those with adult onset G H deficiency
Factors influencing the desire for long‐term growth hormone replacement in adults
Authors: Holmes Sarah J. , Shalet Stephen M.
Published: March 2008

OBJECTIVE Growth hormone replacement In adults may be considered beneficial by clinicians, but patients may not perceive any benefits. The purpose of this study was to determine whether there were any factors which Influenced whether an adult wished to continue on long‐term GH replacement after taking part In a study of GH replacement.

DESIGN A 12‐month study (double‐blind placebo controlled for the first 6 months and open for the second 6 months) of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) In adults.

PATIENTS Sixty‐three adults (27 men, 36 women, aged 34.9 ±1.4 (mean ± SE, range 20.1‐59.5) years) with GH deficiency (peak serum GH response to provocative testing less than 10mU/I) who entered a 12‐month study of GH replacement. Thirty patients (48%) wished to continue on GH replacement and 33 patients (52%) did not wish to continue on GH replacement after the study.

MEASUREMENTS Biochemical, anthropometric and demographic characteristics, and well‐being, were compared In those patients who wished to continue on long‐term GH replacement and in those who did not. In the two groups of patients the age, height, weight, body mass Index, serum insulin‐like growth factor (IGF)‐I, IGF binding protein (IGFBP)‐3 and IGF‐I age matched standard deviation score (SDS) were compared at entry Into the study, and changes In IGF‐I, IGFBP‐3 and IGF‐I SDS were compared after 6 months of GH replacement. The patients were compared according to pretreatment peak serum GH response to provocative testing, sex, estimated duration of GH deficiency, whether GH deficiency was of childhood or adult onset, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder, previous therapeutic Interventions, employment status, marital status and living arrangement, and according to development of side‐effects of GH replacement and the requirement for reduction In dose of GH because of side‐effects during the study. Scores on two questionnaire measures of well‐being or distress, the Nottingham Health Profile (NHP) and the Psychological General Weil‐Being Schedule (PGWBS), were compared at entry Into the study In the two groups, as were change in scores on these questionnaires after 6 months of GH replacement.

RESULTS Those who continued on GH replacement tended to have a greater severity of GH deficiency (median peak serum GH concentration 0.7 vs 2.3mU/I, P = 0.06), tended to have greater distress in terms of energy (NHP, P= 0.06) and vitality (PGWBS, P= 0.06) at entry Into the study and showed an improvement In energy during the study compared with no change In those who did not wish to continue on GH replacement (NHP, P= 0 06).

CONCLUSION Those adults who wished to continue on GH replacement tended to have a greater severity of GH deficiency, to experience more distress in terms of energy and vitality at entry into the study and to experience an improvement in energy after 6 months treatment with GH.
Effect of haemoglobin and endogenous erythropoietin on hypothalamic‐pituitary thyroidal and gonadal secretion: an analysis of anaemic (high EPO) and polycythaemic (low EPO) patients
Authors: Ramirez German , Bittle Polly A. , Rabb Hamid A. , Ballester Oscar , Bercu Barry B.
Published: March 2008

OBJECTIVE Correction of anaemia with recombinant human erythropoietin (rHu‐EPO) Improves the responsiveness of thyroidal and gonadal axes to exogenous TRH and GnRH In chronic haemodialysis patients, but the mechanisms remain to be fully elucidated. In order to assess the Influences of endogenous erythropoietin on the hypothalamo‐hypophyseal thyroidal and gonadal axes, we studied the response of polycythaemic and anaemic patients, In comparison to normal controls, after the administration of exogenous TRH and GnRH.

DESIGN Exogenous hypothalamic factors, 500μg TRH and 100μg GnRH, were administered as a bolus and blood samples were obtained over a 3‐hour period at 30, 60, 90, 120 and 180 minutes.

PATIENTS Five male polycythaemic patients (low EPO), three male anaemic patients (high EPO) and six normal age and sex matched controls were studied.

MEASUREMENTS Blood samples were centrifuged Immediately and the serum was stored at −20°C until assayed for total T4, free T4, free T3, TSH, prolactin, growth hormone (TRH test), and FSH, LH, testosterone (GnRH test). Haematological parameters and biochemical profiles were also measured.

RESULTS After TRH administration, both patient groups showed a normal TSH response; however, their free T4 and free T3 secretion was blunted compared to controls. Normal basal PRL levels Increased in an exaggerated fashion, whereas, when compared to chronic renal failure patients on chronic haemodialysls, we did not see a paradoxical GH response or a basal GH Increase in these 5 patients. GnRH administration In the study groups elicited a normalization In the LH response without an increase in testosterone levels; however, an exaggerated FSH response was found in the polycythaemic patients (low EPO)

CONCLUSIONS Thus by Investigating the role of low endogenous EPO levels In non‐anaemic and anaemic patients with high EPO levels, our study suggests that the underlying chronic disease state may be the major contributing factor in the regulation of the hypothalamo‐hypophyseal thyroid and gonadal axes, rather than the EPO levels.
Impaired social status of growth hormone deficient adults as compared to controls with short or normal stature
Authors: Rikken Berthon , van Busschbach Jan , le Cessle Saskla , Mantenf Wendy , Spermon Tamara , Grobbee Rick , Wit Jan‐Maarten ,   the Dutch Growth Hormone Working Group
Published: March 2008

OBJECTIVES In adults with growth hormone deficiency (GHD) social problems have been reported, but so far the relative contributions of GHD, additional pituitary deficiencies and short stature have not been distinguished.

We therefore compared social data from GHD patients with social data from controls with short or normal stature. Furthermore we Investigated whether social problems are caused solely by the deficiency of GH or also by the associated absence of other pituitary hormones.

DESIGN A questionnaire was sent to patients and controls with Items on education, profession, Income, partner and living situation.

PATIENTS Two hundred and ten GHD patients treated In childhood but not In adulthood with GH (93 Isolated GHD (IGHD), 111 patients with multiple pituitary deficiency (MPD)) were compared with 53 short controls (height In childhood < third percentile for population) and 39 normal stature controls.

RESULTS There were no differences between short and normal controls. There were also no differences between IGHD and MPD patients In any of the Investigated Items. GHD patients did not differ from controls on education level, but scored lower on the profession scale, had a lower Income and had a partner less often; If they had a partner they less often had children; also, more of them lived with their parents.

CONCLUSION Since patients with multiple pituitary deficiency did not differ from patients with Isolated growth hormone deficiency, this suggests that the lower scores on the social parameters are the result of the growth hormone deficiency Itself. Since short stature controls had higher scores than patients with growth hormone deficiency and did not differ from normal stature controls in any of the aspects Investigated, It seems unlikely that the problems of the patients with growth hormone deficiency can be attributed to short stature.
Glycosylated and non‐glycosylated prolactin forms are increased after opioid administration as part of surgical anaesthesia
Authors: Priou A. , Bruder N. , Bégou D. , Morange I. , Grazianl N. , Grisoll F. , Brue T.
Published: March 2008

OBJECTIVE Previous studies have shown that non‐glycosylated prolactin (NG‐PRL) Increased more markedly than glycosylated hormone (G‐PRL) after TRH or metoclopramlde stimulation. The aim of the present study was to determine whether such results could be extended to oplold‐lnduced PRL stimulation.

DESIGN Open and prospective study. Using a newly developed IRMA specific for NG‐PRL, we determined G‐PRL and NG‐PRL immunoreactivities after administration of 0.8‐1.2 mg of the opioid drug phenoperidlne as part of an anaesthesia.

PATIENTS Ten male patients anaesthetized for surgical treatment of a prolapsed lumbar intervertebral disc.

MEASUREMENTS Samples were obtained hourly pre and post‐operatively, and every 15 minutes during operation for determination of plasma PRL, NG‐PRL and G‐PRL. Plasma Cortisol, ACTH and GH levels were measured in an attempt to differentiate the respective roles of stress and opiate agonists In the variations of PRL levels during surgery.

RESULTS A dramatic Increase in PRL levels was observed In all patients from an average of 300 ± 90 to 1200 ± 330 μ/l (mean + SEM) 30 minutes after drug administration. The proportion of G‐PRL immunoreactivity was not significantly different when basal (25‐2%) and stimulated (27%) values were compared (P> 0.05), and when mean increments of NG‐PRL and G‐PRL were compared (345 and 348%, respectively). The opioid drug induced a significant decrease In Cortisol levels after injection and during operation (from 585 ± 63 to 99 ±51nmol/l) with a concomitant decrease In ACTH levels. GH levels were not significantly altered during anaesthesia but were significantly greater (P < 0–05) after than before surgery (5–0 ±1.3 vs 0.98 ± 0.54 mU/l, respectively).

CONCLUSIONS We conclude from the present and from previous data that opioid induced anaesthesia is accompanied by an increase In both glycosylated and non‐glycosylated PRL and that different PRL secreta‐gogues may Induce distinct responses In terms of PRL molecular forms.
Familial hyperparathyroidism associated with jaw fibroma: case report and literature review
Authors: Inoue Hiroyuki , Miki Hitoshi , Oshimo Kazushi , Tanaka Katuhiro , Monden Yasumasa , Yamamoto Akihiro , Kagawa Susumu , Sano Nobuya , Hayashi Eijl , Nagayama Masaru , Hayashi Yoshio
Published: March 2008

A 53‐year‐old female suliering from renal stones and hypercalcaemia was diagnosed as having primary hyperparathyroidism caused by hyperplasia of the parathyroid glands. She underwent total parathyroidectomy and implantation of parathyroid tissue. After one year, she underwent surgery for a jaw tumour. The pathological findings indicated it to be a cementifying fibroma. Jackson et al. (1990) reported the familial association of hyperparathyroidism with Jaw tumours, and they suggested that this condition represents a new clinical syndrome. We believe that our case belongs to this syndrome.
Response to methimazole in Graves' disease
Authors: Benker Georg , Vitti Paolo , Kahaly George , Raue Friedhelm , Tegler Lennart , Hirche Herbert , Reinwein Dankwart ,   European Multicenter Study Group
Published: March 2008

OBJECTIVE A variety of regimens continue to be used In the treatment of Graves' disease with antithyrold drugs. We have lnvestigated the factors which determine the initial response to methimazole (time until euthyroidism Is achieved) In Graves' disease.

PATIENTS Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months.

MEASUREMENTS Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary Iodide excretion were measured centrally. Twenty‐minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, Index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase.

RESULTS Within 3 weeks, 40.2% of patients responded to 10mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroldism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), Index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed In patients with large goitres, iodine excretion of ≧ 100μg/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10‐mg group, 46% of patients were euthyrold within 3 weeks when urinary Iodide was <50μg/g of creatinine, and only 27% when iodide was above 100μg/g. By stepwise logistic regression, the main factors for the response to methimazole were dally dose, pretreatment T3 levels, and goitre size. CONCLUSION Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole In Graves' disease, at least In areas comprising low, subnormal and normal iodine supply.
Altered endogenous growth hormone secretory kinetics and diurnal GH‐binding protein profiles in adults with chronic liver disease
Authors: Cuneo Ross C. , Hickman Peter E. , Wallace Jennifer D. , Teh Bin Tean , Ward Greg , Veldhuis Johannes D. , Waters Michael J.
Published: March 2008

OBJECTIVE Increased serum GH concentrations and GH responses to a variety of stimuli have been reported in patients with chronic liver disease (CLD). We Investigated the pulsatile pattern of endogenous GH release and GH‐binding protein (GHBP) and insulin‐like growth factor‐I (IGF‐I) diurnal profiles in adults with cirrhosis, in comparison with healthy, matched control subjects.

DESIGN Case‐control, cross‐sectional.

PATIENTS Seven patients with biopsy proven cirrhosis, and sex, age, height, weight and oestrogen status matched controls.

MEASUREMENTS Serum immunoreactive GH concentrations in samples collected at 20‐minute Intervals for 24 hours were analysed using a multi‐parameter deconvolution method to simultaneously resolve endogenous GH secretory and disappearance rates. Diurnal patterns of GHBP (specific immunoprecipitation method) and serum IGF‐I (RIA after acid‐ethanol extraction) were assessed.

RESULTS The mean dally GH secretion rate in patients with CLD was Increased (210±93 vs 100±55mU/1/day; P= 0.025), and GH disappearance half‐time was prolonged (43±10 vs 24±9 min; P= 0.006) compared to controls. Detectable GH secretory bursts were more frequent In patients with CLD (10±1 vs 6±3/day; P= 0.038), but of similar mean mass (21±10 vs 17±8mU/l) compared to controls. In patients with CLD, mean serum GHBP was slightly lower (63±36 vs 71±14% pooled control; P > 0.1). Fasting serum IGF‐I concentrations (after size‐exclusion HPLC) were lower in the patients with CLD (13±5 vs 21±2 nmol/I; P < 0.0001). Multiple regression analysis showed that GH secretion rate was increased In patients with CLD with higher Child's classifications (R2= 0.86; P= 0.002) and with lower serum IGF‐I concentrations measured after HPLC (R2= 0.11; P= 0.044).

CONCLUSIONS Adults with chronic liver disease have (1) Increased total daily GH secretion rates, which appear to be influenced by disease severity and diminished serum IGF‐I‐mediated negative feedback; (2) markedly impaired endogenous GH clearance, possibly reflecting changes In hepatic GH‐receptor status; and (3) GHBP levels which do not correlate with GH kinetics or serum IGF‐I concentrations.
Raised serum 11‐deoxycortisol in men with persistent acne vulgaris
Authors: Ramsay B. , Alaghband‐Zadeh J. , Carter G. , Wheeler M. J. , Cream J. J.
Published: March 2008

OBJECTIVE Acne vulgaris is androgen dependent but the hormonal mechanisms are unclear. Although there have been many studies of serum hormones in women with acne there are few studies in men and the results are conflicting. We have therefore carried out a further study in men.

DESIGN AND PATIENTS Fifty men with acne vulgaris were age‐matched against 50 normal men.

MEASUREMENTS Serum levels Of dehydroepiandrosterone sulphate (DHEAS), 17α‐hydroxyprogesterone, 11‐deoxycortisol, androstenedione and testosterone were measured by radioimmunoassay, sex hormone binding globulin (SHBG) by immunoradiometric assay and LH, FSH and oestradiol by automated ELISA.

RESULTS The acne patients had higher levels of androstenedione, median 7.35nmol/l, (Interquartile range 2.7) vs 6.05 (2.3), P=0.004; testosterone, 21.7nmol/l (7.5) vs 17.55 (7.7), P=0.04; and free androgen index (FAI) 78.26 (40) vs 65.06 (20), P=0.007, but also had higher levels of 11‐deoxycortisol, 13.65 nmol/l (4.3) vs 12.0 (4.3), P= 0.022. The LH, FSH, 17α‐hydroxyprogesterone, DHEAS, oestradiol and SHBG levels were not significantly different. Examination of the Spearman rank correlation coefficient matrices for the serum levels of 17α‐hydroxyprogesterone, androstenedione and 11‐deoxycortisol showed that the strongest correiation was between androstenedione and 11‐deoxycortisol.

CONCLUSION Although there was overlap between the results of the acne patients and controls the acne patients tended to have higher levels of androstenedione, testosterone, free androgen Index and 11‐deoxycortisol. The higher levels of 11‐deoxycortisol are suggestive of 11β‐hydroxlase dysfunction which could be due to a primary adrenal defect or a consequence of raised androgens. Also, a pathway between androstenedione and 11‐deoxycortisol has been described in sheep and, although unsubstantiated in man, requires consideration.
Hypothalamic‐pituitary‐testicular function in end‐stage non‐alcoholic liver disease before and after liver transplantation
Authors: Handelsman David J. , Strasser Simone , McDonald Jennifer A. , Conway Ann J. , McCaughan Geoffrey W.
Published: March 2008

OBJECTIVE Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol‐Induced liver disease. We have evaluated hypothalamic‐pituitary‐testicular function In patients with end‐stage non‐alcoholic liver disease before and at 6 and 12 months after hepatic transplantation.

DESIGN A prospective study of hypothalamic‐pituitary‐testicular endocrine function before and after cadaveric hepatic transplantation.

PATIENTS Fifty four consecutive patients with end‐stage, non‐alcohollic liver disease were evaluated before and after liver transplanatation.

MEASUREMENTS Hypothalamic‐pitultary‐testicular(HPT) axis function was evalutated under basal conditions by single morning measurements of plasma total and free testosterone, sex hormone‐binding globulin and by plasma LH and FSH responses to 100 μg i.v. GnRH.

RESULTS Men with chronic non‐alcoholic liver disease had reduced levels of total and free teststerone and increased levels of SHBG compared with controls with normal liver function. Total and free testosterone were positively correlated with basal and stimulated LH (but not FSH) concentrations. Gonadotrophin responses to GnRH were preserved but delayed compared with healthy controls consistent with a predominantly hypothalamic defect in regulation of pitultary‐testicular function. Increasing severity of underlying liver disease was associated with declining total and free testosterone as well as peak GnRH‐stimulated LH concentrations. Splronolactone treatment was associated with decreased circulating testosterone levels only in men with liver disease of lntermedlate severity (Child‐Pugh class B). Following hepatic transplantatlon, total and free testosterone and SHBG concentrations returned progressively towards eugonadal control levels over the first 12 months but total and free testosterone levels remained subnormal.

CONCLUSIONS Hypothalamic‐pitultary regulation of testicular function Is Impaired in end‐stage non‐alcoholic liver disease In proportion to the severlty of underlying liver disease. Splronolactone reduces circulating testosterone but only among men with Chlld‐Pugh B liver cirrhosis. Gonadal function Improves, but is not normalized, over the first year following successful liver transplantation.
GH responses to intravenous bolus infusions of GH releasing hormone and GH releasing peptide 2 separately and in combination in adult volunteers
Authors: Tiulpakov A. N. , Brook C. G. D. , Pringie P. J. , Peterkova V. A. , Volevodz N. N. , Bowers C. Y.
Published: March 2008

OBJECTIVE Synthetic growth hormone releasing peptides (GHRP) have potent GH‐releasing activity in vivo and in vitro. The nature of the Interaction of GHRP and naturally occurring GH releasing hormone (GHRH) is still far from clear. We investigated GH release in response to individual peptide doses or combined doses of GHRH1–29NH2 and GHRP‐2, a novel GH‐releasing peptide, in normal adults.

DESIGN Subjects underwent three tests in a randomized order: (1) i.v. bolus of GHRH1‐29NH2 (1 μg/kg BW), (2) i.v. bolus of GHRP‐2 (1 μg/kg BW), (3) i.v. bolus of GHRH1‐29NH 2 combined with GHRP‐2 (same dosages).

SUBJECTS Eight healthy non‐obese male volunteers, aged 25–34 years.

MEASUREMENTS Serum GH concentrations were measured by IRMA at −15,0, + 10, 20,30,45,60,75,90 and120 minutes after the boluses.

RESULTS Peak GH levels in response to GHRH1‐29NH 2, GHRP‐2 and the combined GHRH1‐29NH 2 and GHRP‐2 administrations were observed between 20 and 45 minutes. Peak GH levels at30 minutes were 32.8 ± 27.3 (mean ± SD), 109.7 ± 56.1 and 140.9 ± 80.6mU/l, respectively. The area under the curve for GH levels (GH AUC) calculated for the first 90 minutes after the GHRH1‐29NH 2 test (2061.2 ± 1601.9mU/1 min) was significantly lower than those after GHRP‐2 (6205.1 ± 3216.9mU/l min) and the combined GHRH1‐29NH 2 and GHRP‐2 challenge (9788.3 ± 5530.4mU/l min) (P = 0.0003 and P = 0.00005, respectively; palred Student's t‐test for log transformed data). Although the GH AUC of the GHRP‐2 test and the combined GHRHl‐29NH 2 and GHRP‐2 test differed significantly (P = 0.016, t‐test), the latter was not signlflcantly dlfferent from the sum of the GH AUCs of each subject after the separate tests.

CONCLUSION Although the GH releasing potency of GHRP‐2 significantly exceeded that of GHRH1‐29NH 2, we were not able to demonstrate synergy between the two substances. It is possible that GHRP‐2 given in our study in higher molar quantities than GHRH1‐29NH 2 masked the effect of the latter.
Relations between sex hormones, sex hormone binding globulin, insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐I in post‐menopausal breast cancer patients
Authors: Lønning Per E. , Helle Svein‐Inge , Johannessen Dag C. , Adlercreutz Herman , Lien Ernst A. , Tally Michael , Ekse Dagfinn , Fotsis Theodore , Anker Gun B. , Hall Kerstin
Published: March 2008

OBJECTIVE Oestrogens, androgens and anti‐endocrine drugs such as tamoxifen and aminoglutethimide influence plasma Insulin‐like growth factor‐I (IGF‐I). IGF‐I, in turn, has been found to stimulate the peripheral aromatase in vitro. The aim of this study was to examine relations between sex hormones, IGF‐I and insulin‐like growth factor binding protein‐1 (IGFBP‐1) In post‐menopausal women with breast cancer.

DESIGN To measure plasma sex steroids, sex hormone binding globulin (SHBG), IGF‐I, IGFBP‐1, Insulin and urinary oestrogen metabolites In post‐menopausal women with breast cancer not receiving any endocrine therapy.

PATIENTS Thirty‐two patients had fasting blood samples obtained between 0800 and 1000h. A sub‐group of 10 patients had 24‐hour urine oestrogen metabolites determined.

MEASUREMENTS Plasma steroids and proteins were measured by radioImmunoassays. Urinary oestrogens were measured by GC‐MS.

RESULTS SHBG correlated negatively with plasma androstenedione (P < 0·001), insulin (P < 0·001), IGF‐I, height and plasma oestrone sulphate (P < 0·025 for all), but positively with plasma IGFBP‐1 (P < 0·025). IGFBP‐1 correlated negatively with IGF‐I (P < 0·001) and the testosterone/SHBG ratio (P < 0·05). Neither IGF‐I nor IGFBP‐1 correlated with any of the plasma or urinary sex hormones or with the oestrone/androstenedione and oestradiol/testosterone ratios.

Multivariate analysis revealed plasma SHBG to correlate positively with IGFBP‐1 (P= 0·029) and negatively with Insulin (P= 0·031). Plasma IGFBP‐1 correlated negatively with IGF‐I (P < 0·0001) but not with insulin.

CONCLUSION Our results do not suggest any influence of plasma sex steroids in physiological concentrations on IGF‐I or IGFBP‐1 in post‐menopausal breast cancer patients, nor do they indicate IGF‐I at physiological concentrations Influences the ratios between plasma oestrogens and their androgen precursors.
Measurement of TSH receptor blocking immunoglobulins using 3H‐adenine incorporation into FRTL‐5 and JPO9 cells: use in a child with neonatal hypothyroidism
Authors: Michelangell Vaido P. , Poon Cathy W. , Arnus Emllia E. , Frauman Albert G. , Connelly John , Colman Peter G.
Published: March 2008

OBJECTIVE The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H‐cAMP production following incubation of FRTL‐5 or JPOS cells with 3H‐adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism.

DESIGN The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding Inhibitory antibodies), and the thyroid antibodies anti‐thyroid peroxidase and thymoglobulin antibodies were measured in both mother and child over a 6‐month post‐natal period.

PATIENT The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Haehimoto's thyrolditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid.

RESULTS Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum.

CONCLUSIONS This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism.
Effect of chronic daily oral administration of 17βoestradiol and norethisterone on the isoforms of serum gonadotrophins in post‐menopausal women
Authors: Wide Leif , Naessén Tord , Phillips David J.
Published: March 2008

OBJECTIVE Chronic treatment with 17βoestradlol (E2Implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post‐menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post‐menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum.

DESIGN Serum samples were obtained from 20 post‐menopausal women, mean age 60 years (range 50–72 years), treated with continuous dally oral medication of 2 mg E2 combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2 in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0·1% agarose suspension. Sera from 20 post‐menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post‐menopausal women treated with E2 Implants and on women with normal menstrual cycles.

RESULTS The E2 level in the oral‐E2+ NETA treated women was 198‐610 pmol/l, within the range expected during the mid‐luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2 Implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0·001), the E2 Implant group (P < 0·001) and at the follicular phase of the cycle (P < 0·01). The mean FSH level was slmllar to that of the folllcular phase and the E2 implant group but lower than that of the controls (P < 0·001) and higher than at the luteal phase of the cycle (P < 0·01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0·001) but more acidic than those for the E2 Implant group (P < 0·01; P < 0·001) and for different phases of the menstrual cycle (P < 0·05; P < 0·001). The mean degree of charge heterogeneity of FSH was larger (P < 0·01), while that of LH was smaller (P < 0·01), than for the controls. The mean concentrations of SHBG in the oral E2+ NETA group, the E2 implant group and the controls were similar.

CONCLUSION Chronic oral therapy with 2mg 17β oestradiol combined with 1 mg norethisterone in post‐menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2 Implant and the oral E2+ NETA treated groups may be due to the differences in route of administration of E1 or to the effect of norethisterone or both.
The acute effects of oral ethanol on the hypothalamic‐pituitary‐adrenal axis in normal human subjects
Authors: Inder W. J. , Joyce P. R. , Wells J. E. , Evans M. J. , Ellis M. J. , Mattioll L. , Donald R. A.
Published: March 2008

OBJECTIVE To evaluate the acute effects of oral ethanol on the hypothalamic‐pituitary‐adrenal axis in normal human subjects and, in particular, to examine the effect of background alcohol intake and gastrointestinal side‐effects on this response.

DESIGN Plasma ethanol, cortisol, ACTH, corticotrophin‐releasing hormone (CRH) and AVP were measured half‐hourly for 4 hours following 1·1 ml/kg of 95% ethanol or placebo in a cross‐over study. At least one week elapsed between each procedure.

SUBJECTS Twelve healthy non‐alcoholic volunteers with a wide range of background alcohol Intakes.

MEASUREMENTS Peptide hormones were measured by radioimmunoassay, cortisol by ELSA and blood ethanol by headspace gas chromatography. Results are expressed as mean ± SEM.

RESULTS Blood ethanol levels peaked at one hour post ethanol ingestion. Three subjects developed significant gastrointestinal (GI) side‐effects, with two vomiting and one experiencing moderate to severe nausea. There was no difference between peak blood ethanol levels in the groups with and without GI side‐effects (34·5 ± 2·4 mmol/l vs 34·3 ± 1·7 mmol/l respectively). ACTH and cortisol rose in those subjects who experienced GI side‐effects (P < 0·0001 for each). The remaining subjects had a tendency for ACTH and cortisol to be higher on the placebo day. The group with GI side‐effects following ethanol administration had a significant rise in AVP (P < 0·02) that was synchronous with ACTH and cortisol. No consistent alcohol related changes were seen in peripheral CRH levels, although there was a significant increase over time on both active and placebo days (P < 0·0001). In the group with no GI side‐effects, AVP did not significantly fail in the first half hour following ethanol, while a significant fall did occur following placebo (P < 0·05). Plasma renin activity was, however, increased by ethanol (P < 0·05). The background alcohol intake of the group with GI side‐effects was significantly lower than the group without (18 ± 7 vs 235 ± 51 g/week, P < 0·05), but no hormonal response was seen in two subjects with a relatively low alcohol intake (< 100g/week) who did not experience GI side‐effects.

CONCLUSION intoxicating levels of ethanol per se do not result in activation of the hypothalamic‐pituitary‐adrenal axis in humans. However, gastrointestinal side‐effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side‐effects occur appears to be background alcohol Intake.
Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults
Authors: Al‐Shoumer Kamal A. S. , Beshyah Salem A. , Niththyananthan Ratnam , Johnston Desmond G.
Published: March 2008

BACKGROUND AND OBJECTIVES Excess Impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy Including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults.

DESIGN A 3‐hour 75‐g oral glucose tolerance test (OGTT) was performed on two study days, at least one week apart. On one study day, the glucocorticoid replacement morning dose was taken 60 minutes before the OGTT, and on the other it was left until after the OGTT. All other pituitary replacement therapies were kept unchanged on the two study days.

PATIENTS Eight hypopituitary adults (3 males and 5 females; aged 46–76 years) on conventional replacement therapy were studied. Their duration of hypopituitarism was mean (range) 15 (5–31) years. Their mean body mass index (BMI) was 28·4 (24·1–35·1) kg/m2. Their total daily cortisol dose was 26 (15–30) mg.

MEASUREMENTS Plasma glucose, insulin, non‐esterified fatty acids (NEFA), glycerol and 3‐hydroxybutyrate were measured at 30‐minute intervals and plasma cortisol levels were measured hourly. RESULTS Fasting glucose and insulin concentrations were similar on the glucocorticoid day (GD) and the non‐glucocorticoid day (NGD) (glucose (mean ± SD) 4·9 ± 0·9 vs 4·4 ± 0·5 mmol/l, insulin (median (range) 5 (1‐17) vs 2 (1‐15) mU/l, respectively). Post‐glucose glycaemia was higher on the GD than on the NGD with a significantly higher glucose area under the curve (AUC) (45·0 ± 82 vs 38·9 ± 11·7 mmol/l h, P < 0·05). Post‐glucose insulinaemia was also higher on the GD than on the NGD with significantly higher insulin AUC (270 (47‐909) vs 207 (46‐687)mU/l h, P < 0·02). Impaired glucose tolerance was found in three patients on the GD, one of whom continued to have impaired glucose tolerance on the NGD. The areas under the curves of NEFA, glycerol and 3‐hydroxybutyrate were not significantly different on the two days. On the NGD, plasma cortisol levels were undetectable (<50nmol/l) in all patients and on the GD the median (range) peak was 500 (330–740) nmol/l dropping to 125 (60‐330) nmol/l at 180 minutes. The difference in glucose AUC between the two days correlated with the maximal plasma cortisol levels (Spearman's p= 0·83, P < 0·01).

CONCLUSIONS Glucocorticoid replacement therapy taken pre‐prandially In hypopituitary adults induces mild elevations In circulating glucose and insulin levels even with acceptable plasma cortisol concentrations. Optimal regimens for glucocorticoid replacement require more study.
Effects of gonadal androgens and oestrogens on adrenal androgen levels
Authors: Polderman Kees H. , Gooren Louis J. G. , van der Veen Eduard A.
Published: March 2008

OBJECTIVE The physiological role of adrenal androgens In humans remains unclear. Furthermore, there are few data on the relation between sex steroids and adrenal androgen production. We have assessed the effects of sex steroid hormone administration on adrenal androgen levels, by studying a large group of transsexual patients. DESIGN A non‐randomized intervention.

SETTING A university teaching hospital.

PATIENTS Thirty‐one male‐to‐female and 22 female‐to‐male transsexual patients.

MEASUREMENTS Plasma levels of adrenal androgens were measured in a group of male‐to‐female and female‐to‐male transsexual patients both before and during cross‐gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethlnyloestradiol and cyproterone acetate to men. RESULTS High dose sex steroid administration had marked effects on adrenal androgens levels, which decreased by 27–48% in males treated with ethinyloestradiol and increased by 23–70% in females treated with testosterone.

CONCLUSION We conclude that administration of high doses of testosterone and oestradiol exert opposing effects on adrenal androgen production.
A comparison of the naloxone test with ovine CRH and insulin hypoglycaemia in the evaluation of the hypothalamic‐pituitary‐adrenal axis in normal man
Authors: Inder W. J. , Ellis M. J. , Evans M. J. , Donald R. A.
Published: March 2008

OBJECTIVE It has been suggested that naloxone might be useful in clinical testing of the hypothaiamic‐pituitary‐adrenal (HPA) axis. We have therefore evaluated this non‐selective oploid receptor antagonist, as a test of HPA axis function, and compared the results to ovine cortlcotro‐phin‐releasing hormone (oCRH) and the Insulin tolerance test (ITT).

DESIGN Following i.v. administration at the zero of naloxone 20mg (n= 12) on day 1, and either oCRH 1 μg/kg (n= 6) or soluble insulin 0.15 U/kg (n= 6) on day 2, venous blood was sampled at times ‐20, 0, 15, 30, 45,60,90 and 120 minutes for cortisol, ACTH and AVP. Peripheral CRH was also measured following naloxone and insulin hypoglycaemia.

SUBJECTS Twelve normal males (age 20–57 years) with no history of hypothalamic‐pituitary‐adrenal axis disease.

MEASUREMENTS Peptide hormones in plasma samples were measured by radioimmunoassay and cortisol by ELISA. Results are expressed as mean ± SEM.

RESULTS Following naloxone, there was a highly significant overall rise in ACTH (P < 0.0005) and cortisol (P < 0.0001), but 1 out of the 12 subjects failed to respond. This subject had a normal ACTH and cortisol response to oCRH, indicating normal pituitary‐adrenal function. Peripheral levels of CRH also increased significantly following naloxone (P < 0.002), while AVP did not alter significantly (P= 0.38). Maximal levels of CRH were seen following the ACTH peak however, at a time when ACTH was returning to baseline.

All six subjects who received oCRH had an increase in ACTH and cortisol, and the ACTH response to oCRH was greater than that to naloxone (P < 0–05). One subject who developed nausea and hypotension following oCRH had a large rise In AVP and very high levels of ACTH and cortisol.

Following Insulin each subject had symptomatic hypoglycaemla and significant rises in cortisol (P < 0.0001), ACTH (P < 0.0001), AVP (P < 0.0005) and CRH (P < 0.01) were seen. Both cortisol and ACTH responses to ITT were significantly greater than those to naloxone (P < 0.05 for each).

CONCLUSION The HPA axis response to naloxone Is smaller In magnitude overall compared to oCRH or insulin hypoglycaemia and Is variable in normal subjects. This variability probably reflects changes In central opiold tone rather than alterations in pituitary responsiveness to CRH. It Is unlikely that the naloxone test will replace currently used clinical tests of HPA axis function, particularly in the setting of possible ACTH deficiency, because some subjects with a normal HPA axis appear not to respond to naloxone. As the mechanism involved in the ACTH response to naloxone has not yet been defined with certainty, the naloxone test should not be regarded simply as a test of endogenous CRH release.
Dehydroepiandrosterone sulphate in critical illness: effect of dopamine
Authors: Van den Berghe Greet , de Zegher Francis , Wouters Pieter , Schetz Miet , Verwaest Charles , Ferdinande Patrick , Lauwers Peter
Published: March 2008

OBJECTIVE As part of a study on the effect of dopamine therapy on pituitary dependent hormone secretion in critical illness, we documented the impact of this inotropic and vasoactive catecholamine on the serum concentrations of dehydroepiandrosterone sulphate (DHEAS). Concomitantly, serum levels of PRL and cortisol were determined.

PATIENTS AND DESIGN In a prospective, randomized, controlled, open‐labelled clinical study, 20 critically ill, adult polytrauma patients receiving dopamine treatment (5 μg/kg/ml i.v. for a median 109 hours (range 21–296 hours), were studied to evaluate the effect of dopamine withdrawal on serum concentrations of DHEAS, PRL and cortisol. The median age of the studied patients was 37 years (range 18–83 years)

MEASUREMENTS Serum DHEAS and cortisol concentrations were measured by RIA and PRL by IRMA. The assessed serum samples were obtained at 0300h on each of two consecutive study nights.

RESULTS Withdrawal of dopamine infusion was found to elicit a median 25% Increase of serum DHEAS concentrations within 24 hours whereas no significant change in DHEAS levels was observed when dopamine infusion was continued throughout both study nights (P= 0.01 continued vs interrupted dopamine). Prolactin levels were undetectable as long as dopamine was infused, and increased to a median of 317 IU/I after 24 hours of dopamine withdrawal (P = 0.0007). Elevated serum cortisol levels remained comparable with continued and interrupted dopamine infusion.

CONCLUSIONS Dopamine infusion appears to suppress serum DHEAS concentrations in critically ill patients without affecting their elevated serum cortisol levels, suggesting a differential regulation of DHEAS and cortisol metabolism in critical illness. The lowering effect of dopamine on DHEAS levels could be linked to the concomitant suppression of circulating PRL. The simultaneous suppression of circulating PRL and DHEAS by dopamine infusion may be an iatrogenic factor maintaining or aggravating the anergic state of prolonged severe illness.
High prevalence and little change in TSH receptor blocking antibody titres with thyroxine and antithyroid drug therapy in patients with non‐goitrous autoimmune thyroiditis
Authors: Cho Bo Youn , Kim Won Bae , Chung Jae Hoon , Yi Ka‐Hee , Shong Young Kee , Lee Hong Kyu , Koh Chang‐Soon
Published: March 2008

OBJECTIVE We have reevaluated the prevalence and pathogenetic importance of TSH receptor blocking antibodies (TRBAb) in autoimmune hypothyroidism, and investigated the changes in TRBAb activities during thyroxine and antithyroid drug treatment.

DESIGN Serum TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulation blocking antibody (TSBAb) were measured serially in all patients with non‐goitrous autoimmune thyroiditis (AT) and measured monthly during methimazole treatment in 6 patients.

PATIENTS Ninety patients with non‐goitrous AT and 95 patients with goitrous AT were entered consecutively into this study. All patients with non‐goitrous AT were treated with thyroxine and followed at intervals of 6 months for 2 years initially and then yearly intervals. The duration of follow‐up was 1–8 years. Six patients from the TRBAb‐positive non‐goitrous AT group who were treated with thyroxine were randomly selected and given additional treatments with methimazole (40 mg per day) for 6 months.

MEASUREMENTS Serum TBII was measured by 8 radioreceptor assay, TSBAb by using FRTL‐5 cells, and antithyroid peroxidase and antithyroglobulin antibodies by radioimmunoassay.

RESULTS The prevalences of TBII and TSBAb in non‐goitrous AT were 47–8 and 58.9%, respectively, which were significantly higher than those in goitrous AT (6.3% for TBII, 10.5% for TSBAb). All but one patient showed persistent TBII and TSBAb activities during the thyroxine treatment for up to 8 years. A high dose of methimazole (40 mg per day) did not affect the titres of TBII and TSBAb in 5 out of 6 patients with non‐goitrous AT tested. However, antithyroid peroxidase and antithyroglobulin antibodies activities were significantly decreased during the methimazole treatment.

CONCLUSION The high prevalence of TSH receptor blocking antibodies (TRBAb) suggests that TRBAb may play a major role in the development of hypothyroidism and thyroid atrophy in the vast majority of patients with non‐goitrous autoimmune thyroiditis. Most TRBAb activities are stable for at least 8 years and are not affected by thyroxine and antithyroid drug treatment.