bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐Endorphin and adrenocortical function in obesity
Authors: Zelissen P. M. J. , Koppeschaar H. P. F. , Erkelens D. W. , Thijssen J. H. H.
Published: March 2008

Summary. objective To test the hypothesis that the hyperendorphinaemia In obesity originates from outside the pituitary.

design Intravenous administration of corticotrophin‐releasing hormone (CRH) after overnight suppression with 2 mg of dexamethasone in normal‐weight controls and in obese subjects before and after weight reduction.

patients Eleven obese females, age (mean±SEM) 30.21 years, body mass index (BMI) 41.2±1.9 kg/m2. Eight normal‐weight females served as controls, age 26.2.1 years, BMI 21.4±0.5 kg/m2. Five obese subjects were also studied after weight loss of 18.4±1.0% of original weight.

measurements Plasma β‐endorphin, ACTH and cortlsol. Cortisol production rate In 24‐hour urine. Basal (without dexamethasone suppression) plasma β‐endorphin levels.

results Basal (without dexamethasone suppression) β‐endorphin levels were 7.7±0.8 pmol/1 In the obese and 3.8±0.5 pmol/1 in the control subjects (p<0.005). The degree of suppression of β‐endorphin after dexamethasone was similar in the obese (23.2±3.7%) and In the control subjects (28.2 ±012%). Administration of CRH following dexamethasone suppression resulted in a small but significant increase of plasma β‐endorphin In both obese (from 1.55.0.12 to 2.32±0.28 pmol/1) and control subjects (from 0.98 ± 0.24 to 1.69± 0.33 pmol/1). The groups did not differ regarding this response, nor regarding the release of ACTH and cortisol after CRH. Cortisol production rate was higher (p<0.001) In the obese (68.7±3.3 μmol/24 h) than In the controls (40.0± 3.0 μmol/ 24 h). No correlation between cortisol production rate and basal β‐endorphin levels was found. Weight loss appeared to have no influence on cortisol production rate, basal β‐endorphin levels, or on the responses to dexamethasone or CRH.

conclusions Plasma β‐endorphin in obese subjects can be affected by manipulations of the hypothalamicpituitary‐adrenocorticai axis; the hypothesis that the hyperendorphinaemia of obesity originates from outside the pituitary cannot be confirmed.
The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh
Authors: Beshyah Salem A. , Anyaoku Victor , Niththyananthan Rathnam , Sharp Patrick , Johnston Desmond G.
Published: March 2008

objectives

To investigate whether growth hormone (GH) absorption is site dependent.

design and measurements

Human growth hormone (hGH, Norditropin) 4 IU, was injected subcutaneously on two separate occasions: into the thigh on one occasion and into the abdomen on a second occasion. Blood was sampled for GH, insulin, glucose, non‐esterified fatty acids and glycerol at baseline and hourly for 12 hours. Serum insulin‐like growth factor I was measured at baseline, and after 12 and 24 hours.

subjects

Eleven healthy young adults (8 M, 3 F).

resultsFollowing the injection serum GH had risen by 1 hour and peaked by 3–6 hours. The peak GH and growth hormone area under the curve were significantly higher after injection in the abdomen compared with the thigh (GH peak (mean±SEM) 103.20 vs 41 .8 mU/l,P= 0.002 and GH area 528.88 vs 239.34 mU/l h,P= 0.003 respectively). Serum insulin‐like growth factor I at 12 and at 24 hours showed a significant rise from the baseline level, but no significant difference was observed between the two injection sites. No significant difference in plasma insulin, glucose, non‐esterified fatty acids or glycerol was observed between the two methods of injection.

conclusion

Subcutaneously injected GH is better absorbed from the abdominal site than from the thigh.
Rapid preoperative preparation in hyperthyroidism
Authors: Baeza A. , Aguayo J. , Barria M. , Pineda G.
Published: March 2008

Summary. objective We have evaluated an alternative method of preparation of hyperthyroid patients for surgery, using betamethasone, lopanoic acid and propranolol.

design Betamethasone (0.5 mg every 6 hours), lopanoic acid (500 mg every 6 hours) and propranolol (40 mg every 8 hours) were given orally for 5 days; thyroidectomy was performed on the 6th day. We analysed patient acceptability, clinical and hormonal effects, ease of surgery and final outcome.

patients Thirteen females and 1 male, aged 16–59 years, ten with diffuse goitre and four with nodular goitre were submitted to subtotal thyroidectomy because antithyrold drugs had failed to control thyrotoxicosis or because hyperthyroidism coexisted with other conditions (pregnancy, hypertensive disease).

measurements

Daily clinical assessments were made together with T3, T4 and rT3 serum concentrations before and while on drug treatment, during the surgical procedure and post‐operatively.

results Daily assessment showed progressive clinical improvement so that on day 5 the patients were considered clinically euthyroid. Serum levels of T3 (mean ± SD) showed significant decrease (by 38.2±24.9%, P < 0.01) as early as 24 hours after medication was started, reaching almost euthyroid levels on day 3; on the day of operation T3 had diminished by 64.5±16.6% (P < 0.0001). Serum T4 concentration showed a slight but significant decrement only from day 4 on and never reached euthyrold levels. Serum rT3 values exhibited a brisk Increment at 24 hours (+ 333.194%, P < 0.0001) and remained elevated between 8 and 10 nmol/l until medication was stopped. Drug tolerance was considered as excellent since no serious side‐effects were noted, even in pregnant patients. There were no anaesthetic incidents or post‐operative complications and patients were discharged 48–72 hours after operation. The final outcome has been satisfactory and pregnant patients continued their pregnancies without Incident, bearing normal children.

conclusions Pharmacological combination of betamethasone, lopanoic acid and propranolol has proved to be safe and effective and is of low cost. Provided there Is adequate supervision of the patients, it may be used in patients requiring urgent thyroidectomy or In those who for reasons of non‐compliance need a short preoperative regime.
The relation between pharmacokinetics and endocrine effects of buserelin implants in patients with mastalgia
Authors: Klijn Jan G. M. , van Geel Bert , de Jong Frank H. , Sandow Jurgen , Krauss Birgit
Published: March 2008

Six patients with mastalgia were treated with polylactide/ glycolide SO: 50 implants containing 6 6 mg buserelin once every 4 weeks, to study the relationship between buserelin pharmacokinetics and suppression of pituitary‐ovarian function. On the first treatment day there was an initial rise in plasma and urinary buserelin levels followed by a rapid fall during the next 2 days. After a plateau phase (60–80 μg/g creatinine) urinary buserelin/creatinine ratios decreased slowly to a mean value of 25 μg/g creatinine 4 weeks after Implantation. Plasma oestradiol concentrations dropped to castrate values within 2 weeks of treatment reaching a mean concentration of 17 pmol/l compared to 27 pmol/l (P<0.01) determined In 680 postmenopausal control women. After the last implant injection urinary buserelin/creatinine ratios remained relatively high (> 5 μg/g creatinine) during more than 8 weeks followed by an exponential decrease (half‐life of buserelin release: 15 days) to undetectable buserelin levels at 16–22 weeks after the last implantation. A rise of suppressed plasma oestradiol concentrations to above castrate levels was found 15–20 weeks after the last buserelin Implantation, at a time when urinary buserelin excretion had decreased below 0.2 μg/g creatinine. It Is concluded that after initial suppression of pituitary‐ovarian function only very low concentrations of buserelin are needed to maintain suppression of ovarian activity by using slow release preparations.
A cluster of male pseudohermaphrodites with 5α‐reductase deficiency in Papua New Guinea
Authors: Imperato‐McGinley J. , Miller M. , Wilson J. D. , Peterson R. E. , Shackleton C. , Gajdusek D. C.
Published: March 2008

We report a cluster of male pseudohermaphrodites from the Simbari Anga linguistic group in the Eastern Highlands of Papua New Guinea. These subjects are born with a rudimentary clitoral‐like penis and pseudovaginal perineoscrotal hypospadias. At puberty, the penis enlarges with concurrent growth of pubic and axillary hair and significant muscular development. There is significant facial hair, but it is less than that of their normal male siblings or other male relatives. Plasma collected from four adult subjects revealed elevated plasma testosterone levels, low to low normal dihydrotestosterone levels, and elevated testosterone/dihydrotestosterone ratios. All subjects had high urinary aetiocholanolone/androsterone ratios, and C12 and C21 5β/5α metabolite ratios. Decreased 5ot‐reductase activity was demonstrated in fibroblasts cultured from genital skin. The data indicate a phenotypic and biochemical profile similar to patients studied in the Dominican Republic, except tor a greater abundance of facial and body hair. The phenotypic variability, as pertains to facial and body hair, may be related to differences in familial expression, as well as the degree of enzyme deficiency. Infants, thought to be females at birth, were reared as girls until puberty in a society practising one of the strictest gender segregations known. At puberty, these ‘girls’ were discovered to be boys, and a switch of gender roles was instituted. Recently, however, some Muniri, Dunkwi and northern Simbari hamlets recognize these individuals as male in infancy and rear them as boys, calling them ‘kwalatmala’ to distinguish them from normal males, accepting them as an intersex destined to occupy male adult roles.
The effects on anterior pituitary hormone secretion of salmon calcitonin in healthy volunteers
Authors: Trainer P. J. , Kirk J. M. W. , McLoughlln L. , Touzel R. J. , Perry L. , Rees L. H. , Besser G. M.
Published: March 2008

The reports of the effect of calcitonin on pituitary function are confusing and often refer to uncontrolled studies. We have now carried out a double‐blind placebo‐controlled trial of Intravenous and subcutaneous salmon calcitonin on anterior pituitary function in 17 healthy volunteers. Visual analogue scores for the nausea and vomiting seen after salmon calcitonin correlated with the rise in ACTH and, secondarily, Cortisol. Calcitonin had no effect on growth hormone, prolactin, thyrotrophin, luteinizing hormone or follicle stimulating hormone. It is concluded that the stimulation of ACTH secretion following a single dose of salmon calcitonin Is probably the result of the stress of nausea rather than a direct effect on the pituitary.
Glucose metabolism in patients with Cushing's syndrome
Authors: Bowes S. B. , Benn J. J. , Scobie I. N. , Umpleby A. M. , Lowy C. , Sonksen P. H.
Published: March 2008

Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a Irequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over‐production or under‐utiliza‐tion, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3‐3H glucose in 14 normoglycaemlc patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post‐operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 ± 0.06 ml/min/kg) and glucose turnover rate (9.09 ± 0.36 μmol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 ± 0.1; P< 0.001; 10.90±0.50; P<0.01) and rose post‐operatively to normal values (2.35 ± 0.14 ml/ min/kg; 11.07 ± 0.48 μmol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production.
Role for cyclic adenosine monophosphate in the synergistic interaction between oxytocin and corticotrophin‐releasing factor in isolated human gestational myometrium
Authors: Quartero Hendrlk W. P. , Srivatsa Geeta , Glllham Brian
Published: March 2008

objective We wished to investigate the role of cAMP In the synergistic effect of corticotrophin‐releasing factor and oxytocin on human myometrial contractility

design Isolated human gestational myometrium obtained from Caesarean sections at term was studied in vitro. Static incubation techniques as well as tension recordings were applied to the tissue obtained.

patients The subjects were healthy pregnant women undergoing lower segment Caesarean section at term, prior to labour

measurements Specimens obtained were immediately dissected into small strips and either incubated In multiwell trays (strip weight 2·75 mg) or superfused and used for tension recordings (strip weight 2·00 mg). cAMP accumulation was measured after incubation with oxytocin (0·1–10 nm), corticotrophin‐releasing factor (1 nm) or a combination of both peptides

Tension generated by the muscie strips was recorded isometrically and response to oxytocin (0·01–10 nm), corticotrophin‐releasing factor (1 nm) and forskolin (10 nm) expressed in force per gram wet tissue (N/g)

results Oxytocin (0·1 nm) causes a statistically significant dose‐related decrease in cAMP when combined with 1 nm corticotrophin‐releasing factor (P > 0·001), as compared with cAMP stimulation by corticotrophin‐releasing factor alone. Time course studies suggest a maximal effect at 1 minute. The hypothesis that an intracellular reduction of cAMP is a prerequisite for the synergistic response In contraction force was tested with tension recordings. Prevention of a decrease in cAMP in the tissue by addition of 10 nM forskolin to the superfusate abolished the potentlation between oxytocin and corticotrophin‐releasing factor.

conclusions These results indicate that a fall in cAMP concentration plays a vital mediating role in the synergistic interaction between oxytocin and corticotrophin‐releasing factor
Pituitary–ovarian function in women with minimal or mild endometriosis and otherwise unexplained infertility
Authors: Bancroft K. , Vaughan Williams C. A. , Elstein M.
Published: March 2008

objective To determine whether abnormalities of pltuitary–ovarian function are associated with minor degrees of endometriosls in women with Otherwise unexplained infertility

design Comparison of pituitary–ovarian function in a group of 22 patients with that in a control group of 10 healthy fertile women

patients Twenty‐two women with minimal or miid endometrlosls and otherwise Unexplained infertility

measurements Ovarian ultrasound and radloimmunoassay of pituitary and ovarian hormones

results Abnormalities, including lutelnizatlon of unruptured follicles, broad LH surges and low concentrations of progesterone during the luteal phase, were demonstrated in 82% of study cycles

conclusion Pituitary‐ovarian dysfunction appears to be associated with minimal or mild endometriosis in women with otherwise unexplained infertility but the diversity of endocrine abnormalities demonstrated suggests that endometriosis is unlikely to be an aetlologlcal factor in their development
Results of long‐term continuous subcutaneous octreotide administration in 14 patients with medullary thyroid carcinoma
Authors: Modlgliani E. , Cohen R. , Joannldis S. , Slame‐Mourot C. , Guliana J. M. , Charpentier G. , Cassuto D. , Bentala Pessayre M. , Tabarin A. , Roger P. , Caron P. , Gulllausseau P. J. , Lalau J. D. , Tournlafre J. , Bayard F. , Aulévre P. , James‐Deldier A. , Catmettest C.
Published: March 2008

objective Treatment by octreotide has been suggested In medullary thyroid carcinoma patients with post‐surgery metastases. The purpose of this study was to evaluate If the tumoral regression could be Improved by a high dose and by prolonged octreotide treatment

design Fourteen thyrofdectomized patients were studled. All patients had persistently elevated plasma calcltonin levels with normal or elevated carclno‐embryonlc antigen levels. Five hundred μ g/day of octreotide were administered by continuous subcutaneous Infusion for 90 days.

measurements Plasma calcltonin and carcino‐embryo‐nic antigen levels were determined at days –30, –20, –2, –1, 0, +30, +60, +90, +120; morphological extension was evaluated every month

results Continuous infusion of octreotide did not Induce any significant decrease of calcitonln levels, or any morphological improvement, and had no major undesirable effect. However, in 4/14 patients calcitonln levels fell during treatment (–43, –50, –15, –20%), and in 9 patients calcitonln increased (+ 22 to +130%) after cessation of therapy

conclusion Biological or morphological parameters of medullary thyroid carcinoma are not significantly improved in a large series of patients treated by octreotide
Changes in stimulating and blocking TSH receptor antibodies in a patient undergoing three cycles of transition from hypo to hyper‐thyroidism and back to hypothyroidism
Authors: Kralem Z. , Baron E. , Kahana L. , Sadeh O. , Shelnfeld M.
Published: March 2008

We report a patient who underwent, over a mere 3‐year period, three successive cycles of oscillation from hypo to hyper‐thyroidism and back to hypothyroidism. This unusual sequence of events originated In a rare passage of primary hypothyroidism to hyper‐thyroidism. The hy‐perthyroldlsm seemed typical of the autolmune subgroup of toxic multlnodular goitre. Stimulating and blocking TSH receptor antibody activities were measured (by cAMP functional bioassays using cultured human thyrocytes) during the course of the fluctuating phases of hypo and hyper‐thyroidism. Measurement of such antibody activities revealed the coexistence of both stimulatory and blocking types of antibody In several serum samples from the patient. Throughout the whole course of alterations In thyroid function, thyroid stimulating antibodies were present. This was not the case with thyrotrophln receptor antibodies exhibiting TSH antagonist activity which seemed to appear and disappear. Monitoring such activity Indicated that the emergence of blocking antibody seems to herald the onset of hypothyroidism
Growth hormone treatment in Turner's syndrome: short and long‐term effects on metabolic parameters
Authors: Haeusler Gabriele , Frisch H.
Published: March 2008

objective The effect of GH administration on various metabolic parameters and on growth and bone age development was studied in patients with Turner's syndrome

design Patients were treated with daily s.c. GH (20 IU/m2/ week) and ethinyloestradiol p.o. (100 ng/kg/day) during the first year and with additional oxandrolone (0·125 mg/ kg/day) during the second year. The responses of free fatty acids (FFA), urinary excretion of hydroxyproline (HP) and IGF‐I were evaluated after short‐term GH application. Glucose tolerance was investigated before any therapy, during treatment with GH and oestradiol and after adding oxandrolone, respectively. The course of growth, bone age and IGF‐I levels was followed throughout the study.

patients Eleven patients with Turner's syndrome aged 12·6±1·9 years (mean ± SD) were included

results Free fatty acids increased significantly 4 hours after one s.c. injection of GH (0·7±0·2–1·1±0·3 mmol/l; mean ± SD). Mean urinary hydroxyproline excretion remained unchanged after 6 weeks of GH therapy (337 ± 206–299 ± 145 μ mol/m2/24 h), but there was a significant negative correlation between individual hydroxyproline values and the peak serum GH followed stimulation. IGF‐I was in the prepubertal range and increased significantly after 3 days of GH injection (30·0±10·0–42·5±10·0 nmol/l). Growth velocity (in Turner's syndrome related SD) increased from 0·0±0·3 SD before treatment to 0·9±0·8 SD after the first year and to 3·4±1·3 SD during the second year of treatment. There was no undue acceleration of bone age. During long‐term treatment, IGF‐I increased significantly only when oxandrolone was added. Two patients had impaired glucose tolerance prior to GH therapy and three additional children developed impaired or abnormal glucose tolerance after GH therapy. Insulin concentrations increased significantly only after introduction of oxandrolone.

conclusions Patients with Turner's syndrome who had lower basal IGF‐I levels had signlflcantly higher responses of IGF‐I, free fatty acids and hydroxyproline (P > 0·01 for all parameters) after short‐term GH appllcation. The data Indicate adequate endocrine and metabolic responses in patients with Turner's syndrome which are the basis for growth promoting action. A considerable number of patients had impaired glucose tolerance during GH treatment.
A prospective examination of octreotide‐induced gall‐bladder changes in acromegaly
Authors: Eastman Richard C. , Arakaki Richard F. , Shawker Thomas , Schock Roxanne , Roach Paris , Coml Richard J. , Gorden Phillip
Published: March 2008

objective We wished to determine the effects of octreetide acetate, a somatostatin analogue, on gall‐bladder function during treatment of acromegaly

desiqn We used a prospective, open label trial of somatostatin analogue

patients Seventeen patients with acromegaly took part

measurements Ultrasonographic evaluation of gallbladder contents were performed pretreatment, after 1 month, and subsequently at intervals of 3–6 months

results Non‐shadowing floating echogenic particles were observed in the gall‐bladder in 12 of 17 patients after (mean ± SEM) 24·5±0·46 months of treatment. During longterm treatment (mean 20·8±4·3, median 13, range 1–59 months), ultrasound evidence for cholelithiasis was observed In four patients after 20·4 months (range 4·2±43) months of octreotide therapy. No symptoms of biliary tract disease have been observed. Duration of acromegaly, average GH, average IGF‐I, gender, age at entry, dose of analogue, and concurrent use of non‐steroldal anti‐inflammatory drugs did not affect the occurrence of sludge or gallstones

conclusions Formation of non‐shadowing, floating echogenic particles occurs commonly during the first 6 months of treatment with octreotide acetate. Cholelithiasis is a risk of long‐term treatment
Impact of octreotide, a long‐acting somatostatin analogue, on glucose tolerance and insulin sensitivity in acromegaly
Authors: Ho Ken K.Y. , Jenkins Authur B. , Furler Stuart M. , Borkman Mark , Chisholm Donald J.
Published: March 2008

objective We aimed to investigate the impact of a longacting somatostatin analogue, octreotide, on glucose tolerance and on insulin sensitivity in acromegaly

design We performed a non‐randomized controlled trial

patients Seven patients with active acromegaly were assessed before and during octreotide therapy given in a dose of 500 μ g three times daily subcutaneously.

measurements The effects of octreotide on carbohydrate metabolism were assessed by performing a glucose tolerance test and a euglycaemlc hyperinsulinaemic clamp. These latter tests were undertaken 8 hours after the last dose, allowing GH and glucagon to return to pretreatment levels during the study

results Octreotide significantly reduced (P > 0·05) mean ± SEM 12‐h GH (from 42·13 to 10·3 mIU/l) and IGF‐I (from 4·2±0·5 to 2·1±0·5 U/ml) concentrations. Glucose tolerance was normalized in four of five patients with impaired glucose tolerance without a significant change In mean insulin concentrations. The improvement In fasting and mean blood glucose during glucose tolerance testing was dependent on the pretherapy blood glucose concentrations (r=–0·95, P= 0·002). The glucose infusion rate during the hyperinsulinaemic (5 U/h) clamp was significantly increased (P > 0·05, 15·3±1·8 vs 24·2±5·4 μ mol/kg min) following octreotide treatment. Insulin infusion during the glucose clamp completely suppressed hepatic glucose production during but not before octreotide treatment (79·2±4 vs 0·7±2·2 μ mol/kg min, P= 0·02). Insulin‐mediated stimulation of peripheral glucose uptake was unaffected by treatment. Mean GH and glucagon levels during both clamp studies were no: significantly different.

conclusions Octreotide improves whole body insulln sensitivity by an increased ability of Insulln to suppress hepatic glucose production without affecting the substantial Impairment of perpheral insutin action. Octrectide has beneficial attects on carbohydrate metabollsm in acromegallc patients with glucose intoferance
Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin
Authors: Tellez Marlsol , Cooper Jackie , Edmonds Charles
Published: March 2008

objective We aimed to study the effect of cigarette smoking on the prevalence and severity of Graves’ ophthalmopathy (GO)

patients One hundred and fifty‐five newly diagnosed patients with Graves’ disease (GD) were diagnosed clinically and by routine biochemical methods. Twenty‐five per cent (39) were of Asian origin

methods Eye signs were classified according to the American Thyroid Association Classification. A detailed smoking questionnaire and data from hospital notes were used to calculate an index of cigarette consumption

results Thirty‐four per cent of all patients had Graves’ ophthalmopathy, and the prevalence in males (26%) and females (36%) did not differ significantly. There was a prevalence of 42% among Europeans compared to 7·7% in Asians (P= 0·0002). The overall risk for Europeans for developing Graves’ ophthalmopathy was 6·4 (1·78–22·7 confidence interval) times higher than for Asians. Corrected for the ethnic factor the increased risk from smoking for Europeans was 2·4 (1·12–5·18, 95% confidence interval) times higher. There was a significant dose effect (P= 0·008).

conclusions The present findings confirm an effect of cigarette smoking on Graves’ ophthalmopathy and in addition show that Europeans have a substantially greater risk of developing Graves’ ophthalmopathy than have Asians
Hypothyroidism and chemodectoma in father and daughter: a new syndrome of a coincidence?
Authors: Hart W. , Maartense E.
Published: March 2008

A family is described, in which the father and one daughter were found to suffer from primary hypothyroidism and chemodectoma. We could not find any previous description of this combination. The possibility of a new syndrome is considered
Galanin reinstates the growth hormone response to repeated growth hormone‐releasing hormone administration in man
Authors: Arvat E. , Ghigo E. , Nicoiosi M. , Boffan G. M. , Bellone J. , Yin‐Zhang W. , Mazza E. , Camanni F.
Published: March 2008

objective To clarify the mechanism by which galanin, a 29‐amino‐acid peptide, increases GH secretion in man

design We studied the GH‐releasing effect of this neuro‐hormone (galanln, 15 μ/kg) Infused over 60 minutes after 120 minutes of saline, following a previous GHRH bolus (GHRH 1 μ/kg i.v. at 0 minutes, galanin infused from 120 to 180 minutes) and coadministered with the second of two consecutive GHRH boluses (GHRH every 120 minute galanin infused from 120 to 180 minutes).

patients Fourteen healthy male subjects, aged 20–34 years, in two groups (group A, 20–31 years (n= 8); group B, 25–34 years (n= 6)) were studied.

measurements Blood samples were drawn every 15 minutes for 255 minutes. Serum GH was measured In duplicate by IRMA. Statistical analysis of the data was carried out by non‐parametric ANOVA test

results The GH response to galanin infused 120 minutes after saline overlapped with that Induced by the neuropeptide infused following previous GHRH bolus (AUC, mean ± SEM: 317·3±73·2 vs 326·8±54·2 μ/l/h). The GH‐releasing effect of the second GHRH bolus (126·9±32·3 μ/l/h) was lower than that of the first one (503·4±41·3 μ/l/h; P= 0·0002). Galanln markedly enhanced the GH responses to the second GHRH bolus (1118·0±212·7 μg/l/h; P= 0·0002 vs second GHRH bolus alone) so that it did not significantly differ from the first one (710·9±107·8 μg/l/h).

conclusions Our results show that the GH‐releasing effect of galanin is not modified by GHRH pretreatment and that the neuropeptide reinstates the GH response to the repeated GHRH stimulation in man. They suggest that these effects are due to the inhibition of hypothalamic somatostatin release
Efficacy of a new long‐acting injectable form of bromocriptine in hyperprolactinaemic patients
Authors: Paganl M. D. , Tengattini F. , Montini M. , Pagani G. , Pedroncelli A. , Gianola D. , Gherardi F. , Mazzocchi N. , Cortesi L. , Lancranjan I.
Published: March 2008

objective The objective of this study was to assess the relationship of different doses of a long‐acting bromocriptine preparation (Pariodel LAR) to the degree and duration of PRL suppression. We also measured circulating bromocriptine levels and altered tolerability of the drug

design A double‐blind randomized study of three different doses 25, 50 and 100 mg of Pariodel LAR

patients Twenty‐one female patients (seven patients/dose) with both tumoral and non‐tumoral hyperproiactinaemia

measurements After a single injection of Parlodel LAR 25, 50 or 100 mg, serum PRL and plasma bromocrlptlne levels were assessed during a follow‐up of 60 days together with changes in clinical symptoms and signs of hyperproiactinaemia

results Serum PRL levels normailzed In 19 of 21 patients. The suppression of PRL secretion lasted 28 days in four of seven patients treated with either 25 or 50 mg Parlodei LAR and in five of seven patients who received Parlodel LAR 100 mg. In five of seven patients treated with the 100 mg dose, serum PRL levels were still within the normal range on day 60. Plasma bromocriptine levels remained therapeutically active for 28 days in all three groups. On day 60 they were within the therapeutic range only in the 100 mg group. Clinical data show a rapid disappearance of symptoms and signs of hyperprolactlnaemla. Adverse events were mostly mild and transient

conclusions These data support the excellent efficacy and good tolerability of Pariodel LAR in patients with hyperproiactinaemia
Age‐related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of bone metabolism in Chinese women
Authors: Chan E. L. P. , Lau E. , Shek C. C. , MacDonald D. , Woo J. , Leung P. C. , Swamlnathan R.
Published: March 2008

objective To study the age‐related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of calcium metabolism in Chinese women who habitually have a low calcium intake

design Cross‐sectional study

subjects One hundred and fifty‐six healthy Chinese women aged 20–83 years. None were on any medication or vitamin supplements. Subjects over the age of 60 years were all living in a hostel; younger subjects were nurses or subjects attending a family clinic for minor illnesses

measurements Fasting blood and urine samples were collected for biochemical measurements and calcium absorption was measured using Ca by the method of Marshall and Nordin. Bone density was measured by dual energy X‐ray densitometry (Norland X R20 X‐ray bone densitometer) at the left hip and lumbar spine. Serum parathyroid hormone was measured by a chemiluminometric assay

results Plasma Ionized calcium concentration, alkaline phosphatase, bicarbonate, plasma creatinine and serum B2 microgiobulin were significantly higher in the elderly than in the young, whereas plasma phosphate and the anion gap were higher in the young. Urinary excretion of calcium, phosphate and hydroxyproiine were all higher in older women. Plasma parathyroid hormone concentration was positively correlated with age even after taking into account the decline in renal function (as indicated by the rise in B2 microglobulin (r= 0·506, P > 0·001). Serum concentrations of 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D were not lower In the older women. Fractional calcium absorption from an oral load of radlolabelled calcium was slgnificantly lower in the older women and 37% of the older women were below the 2.5 percentile found in the younger women. Bone density measured by dual energy X‐ray densitometry was also significantly lower in the elderly.

conclusion In Chinese women there is an Increase in PTH and a decrease in calcium absorption with age in spite of the presence of normal vitamin D metabolites
Social, educational and vocational status of 48 young adult females with gonadal dysgenesis
Authors: Aran O. , Galatzer A. , Kaull R. , Nagelberg N. , Roblcsek Y. , Laron Z.
Published: March 2008

objective The purpose of this study was to evaluate the educational, vocational and social function of young adults with gonadal dysgenesis

design Forty‐eight female patients with gonadal dysgenesis (17, 45XO; 26, 45XO/46XX or other mosaics; and five pure gonadal dysgenesis) followed by our multidisciplinary team from childhood, were re‐evaluated in adult age

results Mean age ±SD at diagnosis was 11·4±5·0 years and mean age at the time of survey was 29·6±6·3 years. The mean final height for the patients was 145·5±8·3 cm (range 134–170 cm). Mean verbal IQ (WISC‐R) for the 39 subjects tested was 101·4±20·7 and mean performance IQ was 86·8±17·7. No difference in verbal IQ levels was found between the various karyotype groups. Twenty‐five had an academic education. All were employed except for one housewife; 37 work in white collar professions. A significant corelatlon was found between verbal IQ and education (P= 0·005) and between verbal IQ and profession (P= 0·005). Twenty‐three served in the army. Fourteen are married: three have an adopted child and two a child born after in vitro fertilization (IVF); others are waiting for IVF or adoption. Five patients had some form of psychiatric problem that required psychiatric or psychological treatment in the past (two had transitory anorexia nervosa and three behavioural problems). Sixty‐three per cent reported having wide and satisfactory social relations but limited to female friends.

conclusion Positive adjustment in the professional area and fair adjustment in the social area were not related to physical stigmata or to any other independent variable tested, but rather to intellectual ability and a high degree of achievement motivation
Changes in growth hormone concentrations during puberty in adolescents with insulin dependent diabetes
Authors: Batch Jennifer A. , Werther George A.
Published: March 2008

objective To document the changes in pulsatile growth hormone secretion in diabetic adolescents during puberty, and to investigate their relationship to both metabolic control and stature

design Auxological parameters, overnight growth hormone secretion, fasting IGF‐I, hourly glucose and metabolic control were assessed in a group of adolescents with diabetes

patients Fifty‐two diabetic adolescents (28 males and 24 females) at different pubertal stages and with varying degrees of metabolic control were studied. Ten of those with poor diabetic control were studied on two occasions

measurements Height and weight measurements, pubertal staging, growth velocity data and bone age estimation were obtained on all the patients. Overnight growth hormone profiles (Pulsar program analysis), glycosylated haemoglobin and fasting IGF‐I were performed on all the subjects. Hourly overnight glucose measurements were also obtained on the ten subjects who had two overnight growth hormone studies

results For the whole diabetic growth, GH area under curve (AUC) was maximal in late puberty (pubertal stage 4), and was paralleled by maximal GH peak amplitude. No relationship between GH‐AUC and metabolic control was demonstrated. No difference in GH parameters was demonstrated between the male and female subgroups. The relationship between growth hormone secretory parameters and stature was not significant. However, GH‐AUC was significantly correlated with growth velocity in the males but not the females

conclusions The pattern of GH secretion in adolescents with diabetes parallels that seen in normal adolescents during puberty, with increases in GH concentration associated with increased GH pulse amplitude. The degree of metabolic control had no effect on this pattern and there was no relationship between GH secretory parameters and stature
Mineralocorticoid excess and inhibition of 11 β‐hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome
Authors: Walker Brian R. , Campbell Jill C. , Fraser R. , Stewart Paul M. , Edwards Christopher R. W.
Published: March 2008

OBJECTIVE 11 β‐Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from Cortisol by converting Cortisol to inactive cortisone. We hypothesize that 11 β‐dehydrogenase is inhibited by ACTH, providing a mechanism whereby Cortisol induces hypokalemic alkalosis in ectopic ACTH syndrome.

DESIGN/MEASUREMENTS The principal sources of plasma cortisone were assessed by selective venous catheterization with measurement of Cortisol and cortisone by radioimmunoassays. The effect of ACTH on peripheral plasma cortisol/cortisone ratio was assessed in healthy volunteers during circadian rhythm, insulin induced hypoglycaemia, and infusions with exogenous ACTH or Cortisol. In patients with Cushing's syndrome plasma cortisol/cortisone ratios were related to plasma potassium, corticosterone, and 11‐deoxycorticosterone concentrations.

PATIENTS Catheterization was performed in 24 patients with valvular or ischaemic heart disease. Cushing's syndrome patients included: 15 with pituitary adenoma; two with adrenal adenoma; and nine with ectopic ACTH secretion.

RESULTS Plasma cortisol/cortisone ratios were low in renal vein and high in hepatic vein. In healthy volunteers plasma cortisone increased during Cortisol infusion but did not change with increases in endogenous or exogenous ACTH. Plasma cortisol/cortisone ratios were higher in ectopic ACTH syndrome than in other forms of Cushing's syndrome. However, the cortisol/cortisone ratio was no better a predictor of hypokalaemia than the levels of 11‐deoxycorticosterone or corticosterone.

CONCLUSIONS Peripheral conversion of Cortisol to cortisone occurs mainly in the kidney and is inhibited by ACTH. In ectopic ACTH syndrome the characteristic mineralocorticoid excess can be accounted for by a combination of increased secretion of Cortisol, corticosterone and of 11‐deoxycorticosterone and decreased inactivation of Cortisol and corticosterone by 11 β‐dehydrogenase.
Administration of human recombinant insulin‐like growth factor‐I to patients following major gastrointestinal surgery
Authors: Miell John P. , Taylor Alastair M. , Jones Jennifer , Buchanan Charles R. , Rennie John , Sherwood Roy , Leicester Roger , Ross Richard J. M.
Published: March 2008

OBJECTIVE The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF‐I (rhIGF‐I) administered to patients following major gastrointestinal surgery.

DESIGN A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery.

MEASUREMENTS After a baseline blood sampling day, IGF‐I (40 μg/kg by single subcutaneous dose, n= 20) or placebo (n= 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF‐I, IGF‐II, IGF binding proteins (IGFBP‐1, IGFBP‐3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology.

RESULTS Serum immunoreactive IGF‐I levels peaked at 4hours following injection of IGF‐I (1– 0.9 ± 0.12 U/ml mean ± SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF‐I injection. Mean levels of IGFBP‐1 and IGFBP‐3, IGF‐II and GH were unaffected by IGF‐I administration. Insulin levels were suppressed at 30 minutes following injection of IGF‐I compared with the placebo group (16.9 ± 3.0 mU/l vs 32.3 ± 7.1, P=0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF‐I (‐6.3 ± 3.0 mmol/l) was significantly different from that in the control group (± 7.2 ± 6.2, P= 0.03). Creatinine clearance rose from a mean of 71.6 ± 7.5 ml/ min to 83.2 ± 7.6 ml/min after IGF‐I treatment (P= 0.02). In the IGF treated patients, cholesterol levels consistently fell (‐0.20 ± 0.05 mmol/l); this was not observed in the placebo group (+ 0.20 ± 0.14, P=0.006). Basal serum potassium levels in the IGF treatment group (4.1 ± 0.1 mmol/l) fell to 3.8 ± 0.1 at 4 hours (P= 0.002) and 3.6 ± 0.1 at 10 hours (P= 0.001) returning to a level of 4.0 ± 0.1 (P= 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF‐I measurements revealed a slow absorption of the administered dose with a Tmax of 5.0 ± 0.43 hours and an elimination half‐life of 10.8 ± 1.2 hours. The computed volume of distribution was 0.33 ± 0.05 l/kg and the clearance on average 25 ml/min.

CONCLUSIONS A single subcutaneous dose of IGF‐I normalized circulating IGF‐I levels in post‐operative patients, was well tolerated and without side‐effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long‐term studies are now required to assess the anabolic effects of rhIGF‐I in this type of patient group.
Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic‐pituitary and parasellar pathology
Authors: Webb S. M. , Ruscalleda J. , Schwarzstein D. , Calaf‐Alsina J. , Rovira A. , Matos G. , Pulg‐Domingo M. , de Leiva A.
Published: March 2008

OBJECTIVE We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions.

DESIGN We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. PATIENTS We studied 40 patients submitted for hypothalamic‐pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated post‐operatively.

MEASUREMENTS Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis.

RESULTS Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67±5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH‐secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery.

CONCLUSIONS In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.
Reactivity to stress and psychological adjustment in adults with pituitary insufficiency
Authors: Stabler Brian , Turner J. Rick , Girdler Susan S. , Light Kathleen C. , Underwood Louis E.
Published: March 2008

OBJECTIVE Hypopituitary adults who were affected during childhood have a below‐average rate of marriage, a rate of unemployment that exceeds national norms, and often indicate dissatisfaction with their life circumstances. We undertook the present study to determine the effects of short stature versus those of pituitary hormone deficiency.

DESIGN AND PATIENTS We compared hypopituitary adults (n= 25) with normal short adults (n= 25) who were matched for height, sex, age and socioeconomic status.

MEASUREMENTS In these two groups of subjects, we compared the physiological responses to a simulated social stressor, a public speaking task, and we measured the psychometric attributes that are indicators of social assertiveness and extraversion.

RESULTS Before, during and after the stress of public speaking, patients with multiple pituitary hormone deficiencies (n= 20) had lower mean systolic and diastolic blood pressures than controls, while patients with isolated growth hormone deficiency (n= 5) were equivalent to controls. The reactivity to stress, assessed using delta scores based on changes in blood pressure and heart rate, was also decreased in multiple hormone deficient patients. Psychometric test results indicated that patients with multiple hormone deficiencies showed lower openness, lower assertiveness, greater neuroticism and a tendency towards less extraversion than did controls. The responses of patients with isolated GH deficiency on the psychometric tests were not statistically different from controls, but the number of subjects in this group (n= 5) was too small to draw conclusions.

CONCLUSIONS The impaired cardiovascular responses to stress in patients with multiple hormone deficiencies, compared to short control subjects and to patients with GH deficiency leads us to conclude that factors other than stature and GH are responsible for these observations. The differences might be related to insufficiency of cate‐cholamines or cortisol in the patients with multiple hormone deficiencies. These hormonal deficiencies might also account for the socially inhibited behaviour of these patients. Our results suggest that more attention needs to be directed at preparing hypopituitary patients for the challenges of adulthood. Also, these patients may be helped by more intensive efforts at hormonal replacement in adulthood.