bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction of growth hormone releasing hormone and somatostatin in the generation of a GH pulse in man
Authors: Hindmarsh P. C. , Brain C. E. , Robinson I. C. A. F. , Matthews D. R. , Brook C. G. D.
Published: March 2008

Summary. objective To study the regulation of the growth hormone (GH) response to growth hormone releasing hormone (GHRH) in the presence or absence of somatostatin pretreatment.

design Seven healthy adult male volunteers of normal height and weight and aged between 19 and 29 years underwent four separate studies (each containing three cycles In one day) In random order. The studies were separated from each other by at least a week. On day 1, three consecutive cycles (between 0800 and 2000 hours) consisted each of a saline infusion for 3 hours which was stopped prior to a bolus Injection of saline and followed by 60 minutes of more intensive blood sampling.

On day 2, the bolus Injections were of GHRH given after saline infusion. On days 3 and 4 somatostatin Infusions were administered instead of saline over the 3‐hour periods followed by bolus injections of saline or GHRH respectively.

In all studies, samples were collected for the measurement of serum GH concentration at 15‐minute Intervals from time 0 to 180 minutes and then at 5‐minute Intervals for a further 60 minutes, this cycle being repeated three times.

measurements Serum GH concentrations were analysed by serial array averaging.

results Prompt release of GH was observed In response to GHRH given against a saline background (day 2, cycle 1) (mean at 60 minutes 49.2±14.7 mU/1) but the responses observed during the second and third cycles were attenuated (mean at 60 minutes 17.2±4.0 mU/1; p=0025). GH release between somatostatin infusions (somatostatin withdrawal; day 3) occurred twice as often as that observed during saline Infusions (62% day 3: 29% day 1). The response, although qualitatively similar to that Induced by GHRH, was reduced in amplitude and the time of onset variable (5–45 minutes).

On day 4, the administration of GHRH as a bolus injection combined with somatostatin withdrawal led to consistent and repeatable GH responses (mean at 60 minutes, cycle 1, 39.7±10.8 mU/1; cycles 2 and 3, 37.4±9.4 mU/1) which were similar to those observed with GHRH alone (day 2, cycle 1) (mean 39.7±10.8 mU/1) (p=NS).

conclusions These data suggest that endogenous somatostatin secretion is important In determining the ability of the somatotroph to respond to repeated growth hormone releasing hormone stimulation and that for regular GH pulse generation a close Interplay between growth hormone releasing hormone and somatostatin is required.
The effect of a highly specific serotonin agonist on osmoregulated vasopressin secretion in healthy man
Authors: Faull C. M. , Rooke P. , Baylis P. H.
Published: March 2008

Summary. objective To explore a possible Interaction of the serotonin neurotransmitter system and posterior pituitary function, we have looked at the effect of fluoxetine treatment on osmoregulated vasopressin secretion in normal men in two placebo controlled studies.

design in each study subjects took in random order for 7 days one capsule daily of placebo or 40 mg fluoxetine. On the 8th day subjects underwent assessment. Study 1 A hypo‐osmotic stimulus of an oral water load of 20 ml/kg. Study 2 A hyperosmotic stimulus of intravenous infusion of 5% (855 mmol/l) saline at 0.06 ml/kg/min for 120 minutes.

patients Normal, healthy male volunteers. Study 1, 9; Study 2, 10.

measurements in both studies regular measures of plasma osmolality, sodium and vasopressin were made. In Study 1 urine osmolality was measured together with urine volume at set time points and an accumulative measure of percentage of water load excreted. Free water clearance was calculated. In Study 2 the relationship of plasma vasopressin to change in plasma osmolality was calculated for each subject by linear regression analysis. RESULTS Serotonin agonism had no effect on baseline measurements in either study. Study 1 After 4 hours subjects excreted 95 and 99% of the water load after placebo and fluoxetine respectively (P= 0.407). There was no effect of fluoxetine compared to placebo on the pattern or extent of change of plasma osmolality (nadir 285.9±1.4 mosm/kg placebo, 283.1±1.1 mosm/kg fluoxetine, P= 0.145) or on free water clearance or maximum urine dilution after oral water loading. Plasma vasopressin suppressed to a minimum concentration after both treatments in response to hypo‐osmolality 0.510±1 pmol/l (placebo), 0.3±0.01 pmol/l (fluoxetine), P= 0.195. Study 2 Fluoxetine had no significant effect on the sensitivity of vasopressin release to change in plasma osmolality (0.33±0.06 pmol/l per mosm/kg placebo, 0.36±0.06 pmol/l per mosm/kg fluoxetine, P= 0.347). Nor was there a significant effect on the theoretical osmotic threshold for release of vasopressin (287.011.21 mosm/kg placebo, 286.9±1.09 mosm/kg fluoxetine, P= 0.700).

conclusion

We have found no evidence of a physiologically relevant effect of serotonin agonism on osmoregulated vasopressin release, or on the ability of normal man to excrete a water load. The possible reasons for this contrast to animal work are discussed.
Correlations between mean LH levels and LH pulse characteristics: differences between normal and anovulatory women
Authors: Bennet A. , Lacaze J. CI. , Caron Ph. , Berrada R. , Barbe P. , Louvet J. P.
Published: March 2008

Summary. objective Since LH secretion occurs as a series of pulses, relationships between mean LH levels and LH pulse characteristics are to be expected. The aim of this study was to determine whether such relationships are similar in normal women and anovulatory patients.

design We studied the correlations between mean LH levels and the products amplitude X frequency and area X frequency of LH pulses in normal women and In patients with disorders of ovulation. Blood samples were taken from each subject every 10 minutes during 6 hours on the 8th day after the last menses.

patients The patients were divided into three groups: patients with polycystic ovary syndrome (n= 11), patients with idiopathic anovulatlon (n= 14) and patients with short luteal phase (n=13). Their results were compared to those of 12 normal women.

measurements

LH was evaluated with an Immunoradlometric assay. LH data were analysed with a 3 standard deviation threshold criterion for significant peaks, and with cluster analysis algorithm using 1, 2.5 and 5% false positive error rates and ‘optimal parameters’ (which give less than 5% false positive and false negative error rates in LH male data).

results Highly significant correlations between amplitude x frequency, area x frequency and mean LH were found In normals and patients with short luteal phase; no significant correlation was found in patients with polycystic ovary syndrome, while significant correlations were found in patients with idiopathic anovulatlon only with some of our criteria for peak detection.

conclusion The differences that we found between the groups suggest that when commonly used methods are employed to determine LH pulse characteristics, most of the significant LH pulses are taken Into account in normals and patients with short luteal phase, but not in anovulatory patients, especially in patients with poiycystic ovary syndrome. This method using two correlations appears to be a simple and useful way to show the differences In the mechanisms by which mean LH levels are achieved In normal subjects and patients.
The effect of thyroxine on small intestinal motility in the elderly
Authors: Rahman Q. , Haboubi N. Y. , Hudson P. R. , Lee G. S. , Shah I. U.
Published: March 2008

Summary.objectiveTo study the effects of thyroxine on orocaecal transit time In a group of elderly hypothyroid patients on long‐term thyroxine replacement therapy.

designMeasurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time.

patientsFifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60–94 years (median 78 years) receiving initially 50–200μg of oral thyroxine daily (median 100μg).

measurements

Serum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy.

resultsOn withdrawal of therapy, the median transit time Increased from 75.0 to 135 minutes (P< 0.01), the median TSH Increased from 1.8 to 2.3 mU/l (P= NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P< 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P= NS), the median TSH decreased to 1.1 mU/I (P= NS) and the median FT4 increased to 14.1 pmol/l (P< 0.01).

conclusions

These findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.
Effects of growth hormone administration on dehydroepiandrosterone sulphate, androstenedione, testosterone and Cortisol metabolism during nutritional repletion
Authors: Ziegler Thomas R. , Barbieri Robert L. , Young Lorraine S. , Ferrari‐Baliviera Elizabetta , Wilmore Douglas W.
Published: March 2008

This study evaluated whether pharmacological doses of recombinant human growth hormone (hGH) influences androgen or Cortisol metabolism during nutritional repletion following prolonged illness. Stable hospitalized adults (three male, seven female) receiving constant calorie and protein intake were studied. An initial control week was followed by a treatment period during which hGH (10 mg/day s.c.) was administered daily. Prior to hGH treatment, serum and 24‐h urinary concentrations of dehydroepiandrosterone sulphate (DS) were below the normal range; serum androstenedione and testosterone concentrations were within the lower limit of normal. In contrast, serum Cortisol (F) and 24‐h urinary F excretion were normal. During hGH treatment, nitrogen balance became positive and plasma insulin‐like growth factor I (IGF‐I) concentrations rose five to seven‐fold. However, serum DS, androstenedione, testosterone and F, and urinary F excretion did not change, while 24‐h urinary DS excretion fell significantly. Growth hormone administration markedly stimulated protein anabolism but did not increase the low concentrations of circulating androgens or alter the disassociation between adrenal androgen and F release in stable hospitalized males and females. Thus, hGH does not appear to function as a cortical adrenal androgen stimulating hormone (CASH) or regulate adrenal Cortisol or gonadal androgen release in this clinical setting.
A retrospective audit of the combined pituitary function test, using the insulin stress test, TRH and GnRH in a district laboratory
Authors: Pavord Sue R. , Girach Anlz , Price David E. , Absalom Steve R. , Falconer‐Smith James , Hewlett Trevor A.
Published: March 2008

objective To assess the value of the combined insulin stress test (IST), thyrotrophin‐releaslng hormone (TRH) and gonadotrophin hormone‐releasing hormone (GnRH) tests

design A retrospective audit of 232 such tests performed between 1980 and 1989 inclusive

patients One hundred and ninety‐seven patients with known or suspected pituitary disease

measurements IST, TRH and GnRH responses were retrieved from laboratory records. Case notes were surveyed for clinical data and additional results

results A basal serum cortisol level of > 100 nmol/l (or > 200 nmol/l in patients who had recently received glucocorticoid replacement therapy) accurately predicted a subnormal response to hypoglycaemla. All patients with a basal cortisol level of >400 nmol/l, except those who had recently received steroids, showed a normal cortisol response. In retrospect, by consideration of such basal values, 55% of ISTs could have been avoided if the only aim was to assess cortisol reserve. A deficient growth hormone (GH) response to hypoglycaemia was, however, common In patients with a normal cortisol response. Two‐thirds of patients with GH deficiency would have been missed If an IST had been avoided on the basis either of basal cortisol levels alone, or of cortisol responses to an alternative test which did not test GH reserve. There was poor agreement between the pituitary response to TRH and GnRH and basal levels of thyroxlne and gonadotrophins respectively, suggesting that these releasing hormone tests are misleading.

conclusions The IST provides information regarding pituitary function not provided by other tests of the hypothalamlc‐pltuitary‐adrenal axis, so that the choice between the IST and alternative tests must depend on a critical assessment of what Information is required. Routine TRH and GnRH testing appears to yield little Information of practical clinical value
Pituitary imaging using a labelled somatostatin analogue in acromegaly
Authors: Ur E. , Mather S. J. , Bomanji J. , Ellison D. , Britton K. E. , Grossman A. B. , Wass J. A. H. , Besser G. M.
Published: March 2008

objective A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I‐labelled Tyr3‐octreotlde analogue of somatostatin In the visualization and functional characterization of growth hormone‐secreting pituitary adenomas.

patients Fifteen patients with biochemically‐proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics

measures Planar and single‐photon‐emlsslon computerized tomographic (SPECT) images of the head were obtained using a gamma‐camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 μ g octreotide.

results Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients In whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning

conclusions Uptake of 123I‐labelled Tyr3‐octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.
Growth hormone and lean tissue catabolism during long‐term glucocorticoid treatment
Authors: Bennet William M. , Haymond Morey W.
Published: March 2008

objectives The aim of the study was to determine whether growth hormone (GH) treatment decreased net protein catabolism of lean tissues in patients receiving chronic glucocorticoid treatment

design Whole body leuclne kinetics were measured In post‐absorptive conditions using a 1‐14C‐leucine infusion before and during GH administration (0·0125 mg/kg/day; 0·033 U/kg/day) for 7 days.

patients We studied four patients (age range 31–71 years) who had taken prednisone (mean ± SEM 0·21·0±03 mg/kg/day, total dose 10–27·5 mg/day) for longer than 5 months for various lung diseases

results During GH treatment leucine oxidation decreased (baseline 0·44·0±07 vs GH 0·37·0±05 μ mol/kg lean body mass/min, P= 0·01) and non‐oxidative leuclne disposal increased (1·95·0±10 vs 2·05·0±09 μ mol/kg lean body mass/min, P= 0·02) but leuclne appearance was unaltered.

conclusions We conclude that GH decreased amino acid catabolism and improved protein synthesis without altering protein breakdown in patients receiving chronic glucocorticoid treatment. There may be a role for GH in mitigating the protein catabolic side‐effects of prolonged glucocorticoid treatment
Rate of change (modulation) of serum growth hormone concentrations is a more important factor in determining growth rate than duration of exposure
Authors: Hlndmarsh P. C. , Matthews D. R. , Stratton I. , Prfngle P. J. , Brook C. G. D.
Published: March 2008

objective To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are Important factors In determining the growth rate of short children

design An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study Investigating the relationship between growth and GH In childhood

patients Sixty‐four short prepubertal children (48 male, 16 female) aged between 4·7 and 11·9 years were studied. Thirty‐one children were growing with a height velocity standard deviation score between 0 and – 0·8 and were defined as short normal. Thirty‐three children were growing with a height velocity standard deviation score less than – 0·8 and were defined as short slowly growing

measurements Twenty‐four hour serum GH concentration profiles were constructed by withdrawing samples at 20‐minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear problts against log serum GH concentration. Estimates of peak (OC45), Intermediate (OC50) and trough (OC5) occupancies were calculated. A first‐order derivative of the concentration‐time data array was determined for each profile as a measure of rate changes.

results First‐order derivative values were significantly greater In the short normal group than In the short slowly growing children (short normal median 1·41 mU/l/min; short slowly growing median 0·72 mU/l/min; P > 0·001). OC56 values were significantly higher in the short normal group (median 19·31 mU/l) than the short slowly growing group (median 7·69 mU/l) (P > 0·001). There was no difference In OC50 values. OC5 values were lower In short normal children (median 0·20 mU/l) than in the short slowly growing children (0·55 mU/l) (P > 0·003).

The most Important factor In determining growth rate was the rate of change In serum GH concentration (FOD). Occupancy percentage played no part In the relationship. The regression equation was

Height velocity SDS =

1·16 (In FOD) – 1·03; r= 0·75; P > 0·001

conclusions These data suggest that the pattern of presentation of GH In the circulation Is an Important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it Is the rate of change of the hormone in the circulation which appears to be the more Important ‘signal’ In terms of modulating growth
Long‐term treatment with the dopamine agonist CV 205–502 of patients with a clinically non‐functioning, gonadotroph, or α‐subunit secreting pituitary adenoma
Authors: Kwekkeboom D. J. , Lamberts S. W. J.
Published: March 2008

objective We aimed to assess the effects of prolonged treatment with the dopamine agonist CV 205–502 on tumour volume, visual field defects, and serum gonadotrophin and α‐subunit concentrations in patients with gonadotroph, α‐subunit secreting, or clinically non‐functioning pituitary adenomas.

design The patients were treated with CV 205–502 in a final daily dose of 300 μ g for at least 1 year. The patients were seen at 2 or 3‐week intervals during the first 3 months of treatment, and thereafter every 1 or 2 months. Computerized tomography and Goldmann perimetry were performed before treatment and during follow‐up. Blood samples were drawn before treatment and at each out‐patient visit.

patients One patient with gonadotroph, two with α‐subunit secreting, and two with clinically non‐functioning pituitary adenomas were studied.

results Computerized tomography showed tumour shrinkage in one patient. In two other patients an improvement of visual field defects was observed. In four patients, a significant decrease in serum FSH and/or α‐subunit concentrations occurred within the first 3 months of treatment. In the remaining patient, a significant decrease of serum FSH and α‐subunit concentrations was found after more than 3 months of treatment.

conclusions In patients with clinically non‐functioning, gonadotroph, or α‐subunit secreting pituitary tumours, long‐term treatment with the dopamine agonist CV 205–502 decreases serum FSH and/or α‐subunit concentrations. This decreased secretory activity from the pituitary tumour may be accompanied by an improvement of visual field defects, or tumour shrinkage on computerized tomography. Therefore, treatment with CV 205–502 may be useful in patients with clinically non‐functioning, gonadotroph, or α‐subunit secreting pituitary tumours, who cannot be operated upon.
The tubular maximum for calcium reabsorption: a normal range in children
Authors: Shaw N. J. , Wheeldon J. , Brocklebank J. T.
Published: March 2008

objective We aimed to establish a normal range for the tubular maximum rate of reabsorption of calcium corrected for glomerular filtration rate

design A prospective survey was used

patients One hundred and ten normal children aged 2–14 years were studied

measurements Total plasma calcium, ultrafiltrable calcium and parathyroid hormone. Urinary calcium, sodium and creatlnlne excretion

results The normal range was found to be 1·87–3·39 mmol/l of glomerular filtrate with a geometric mean value of 2·40 mmol/l. There was a significant Inverse relationship between the tubular maximum for calcium and the urinary sodium excretion. No significant relationship was found between the tubular maximum for calcium and the level of parathyroid hormone In this group of normal children

conclusions The normal range seen In children is higher than that seen in adults with a higher mean value. This normal range should be useful in the assessment of renal calcium handling In children with disorders of calcium homeostasls
Lack of linear relationship between hyperinsulinaemia and hyperandrogenism
Authors: Toscano V. , Bianchi P. , Balducci R. , Guglielmi R. , Mangiantlnl A. , Lubrano C. , Sclarra F.
Published: March 2008

objective Because of continued debate about the role of Insulin in the development of hirsutism and in the induction of the polycystic ovary syndrome, we have evaluated the hormonal pattern in a group of hirsute patients

patients Fifty‐four hirsute patients (age range 18–39 years) of whom 26 patients were obese (O) (BMI 28–53 kg/m2 and W/H < 0·85), 12 with ultrasonographic evidence of polycystic ovaries (O PCO) and 14 with normal ovaries. Twenty‐eight patients were within normal weight range, and, of these, 14 presented ultrasonographic evidence of polycystic ovaries and 14 had normal ovaries. Two groups of age‐matched subjects (obese and normal weight), normally menstruating, without hirsutism or history of endocrinopathies or ultrasonographic evidence of polycystic ovaries, served as controls.

measurements Androstenedione and testosterone were evaluated in all patients by RIA, following ether extraction, DHEAS, LH, FSH and insulin were evaluated directly by RIA. SHBG was evaluated by the concanavalin method. Free testosterone (FT%) was calculated according to the formula FT = 4·038–1·607 log SHBG. integrated areas under the response curve were calculated for LH and insulin respectively following i.v. administration of GnRH (100 μ g) or oral administration of glucose (75 g).

results Results (mean ± standard deviation) showed comparable values of androstenedione in all groups of obese patients and in obese controls (7·3 ± 2·6 in patients with polycystic ovaries, 7·1 ± 2·9 in non‐polycystic ovary patients and 7·4 ± 2·6 nmol/l in obese controls, respectively), regardless of baseline and area insulin, the presence or absence of polycystic ovaries, or hirsutlsm. SHBG levels showed a similar pattern (24 ± 10, 23·8 ± 7·9 and 36 ± 19 nmol/l) as did the percentage of free testosterone, regardless of the presence or absence of hirsutism. Regression analysis of the insulin and LH values (baseline and area) against the androgens and SHBG plasma levels showed that only LH area correlated positively with testosterone (r= 0·36, P > 0·03), androstenedione (r= 0·44, P > 0·02), % free testosterone (r= 0·53, P > 0·001), testosterone/SHBG ratio (r= 0·39, P > 0·03) and inversely with SHBG (r=– 0·57, P > 0·001).

conclusions These results showed (1) no linear relationship between high levels of insulin, ovarian androgen production or free hormone availability, and (2) make it very doubtful that insulin plays a primary role in polycystic ovarian syndrome or hirsutlsm
Normal bone mineral density following cure of Cushing's syndrome
Authors: Manning Patrick J. , Evans Margaret C. , Reid Ian R.
Published: March 2008

objective Both endogenous and exogenous glucocorti‐cold excess are well established as causes of osteoporosis. However, there are few data describing bone mineral density in these subjects following the restoration of normal steroid levels. The present study addresses this issue

design A cross‐sectional assessment of bone mineral density in patients cured of Cushing's syndrome, and comparison of each with four normal subjects matched by age, sex, weight, menopausal status and race, was used

patients Seventeen adults cured of Cushing's syndrome 8·6±1·6 years (mean ± SEM) took part

measurements The bone mineral density of the lumbar spine and proximal femur was measured by dual energy X‐ray absorptiometry

results Bone mineral densities, relative to control, were 100·16, 98·14, 97·19 and 98·16% (mean ± SD), in the lumbar spine, femoral neck, Ward's triangle and trochanteric regions, respectively. There was a positive relationship between bone density and time since cure (r= 0·24–0·59, in the four regions). In contrast, bone density was significantly reduced in five subjects with active Cushing's disease when similarly matched (BMD = 87·4, 83·4, 75·6 and 82·6%, in the respective regions; 0·01 > P > 0·05).

conclusions Bone density is reduced in subjects with Cushing's syndrome but not in those having undergone cure some years previously. This Implies that steroid‐induced osteoporosis is substantially reversible, though long‐term prospective studies will be necessary to estab‐lish this definitively
The effects of the specific serotonin antagonist ICI 169, 369 on the pituitary hormone response to insulin‐induced hypoglycaemia in humans
Authors: Thompson C. J. , Jones I. R. , Walker M. , Baylis P. H. , Kendall‐Taylor P.
Published: March 2008

objective To examine the role of serotonin in pitultary hormone release by studying the effect of a specific 5HT2 receptor antagonist, ICI 169,369, on the ACTH, prolactin, growth hormone and AVP response to insulin‐Induced hypoglycaemia in healthy humans.

design A double‐blind, within‐subject trial using a cross‐over design to compare the effect of placebo with two doses of ICI 169,369 on pituitary hormone responses to insulin‐induced hypoglycaemia

patients Ten healthy subjects were studied In the low‐dose (30 mg × 2) limb and 11 healthy volunteers in the high‐dose (80 mg × 2) limb

measurements Plasma concentrations of prolactin, growth hormone, ACTH, cortisol and AVP, and blood glucose

results In the low‐dose study, pretreatment with 30 mg ICI 169,369, 10 and 2 hours before the study, had no effect on the fall in blood glucose or the rise in plasma ACTH, prolactin, growth hormone, AVP or plasma cortisol following insulin injection, when compared with placebo. In the high‐dose study the effect of a higher dose (80 mg) of ICI 169,369 on the pituitary hormone response to hypoglycaemia was compared with that of placebo. Although the fall in blood glucose was similar following drug (4·3±0·1 to 1·5±0·5 mmol/l, mean ± SEM, P > 0·001) and placebo (4·3±0·1 to 1·4±0·4 mmol/l, P > 0·001), the rise in plasma AVP was lower (P > 0·05) following pretreatment with drug (0·5±0·2 to 2·1±0·6 pmol/l, P > 0·05) than with placebo (0·7±0·2 to 3·4±0·9 pmol/l, P > 0·01).

conclusions The ACTH, prolactin, growth hormone and cortisol responses were unaffected by ICI 169,369. The data are compatible with an Inhibitory effect of the serotonin antagonist ICI 169,369 on the AVP, but not the ACTH, proiactin or growth hormons to insulln‐induced hypoglycasmia in humans
Half‐life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin‐dependent) diabetes mellitus
Authors: Mullis Primus E. , Rani Pal B. , Matthews David R. , Hindmarsh Peter C. , Phillips Paula E. , Dunger David B.
Published: March 2008

objective To estimate the half‐life of growth hormone In young adult patients with type I (insulin‐dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates

design In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous Infusion of somatostatin under three different glucose clamp conditions: normoglycae‐mla (5 mmol/l) with normoinsulinaemla (65 pmol/l); hyperglycaemia (12 mmol/l) with normofnsulinaemia; and normoglycaemia with hyperlnsullnaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half‐life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS Six young adult patients with type I (insulin‐dependent) diabetes mellitus were studied in both the bolus and the infusion study

results Mean GH half‐lives by mono‐exponential analysis were not significantly different remaining unaltered by the short‐term metabolic changes of hyperglycaemia and hyperinsullnaemla. Data were therefore pooled yielding an overall mean GH half‐life of 13·6 minutes (range 11·9–19·4). Applying a bl‐exponentlal model mean GH half‐lives were 3·1 minutes (range 2·5–5·9) for the rapid phase of distribution of the hormone and 13·4 minutes (range 9·6–16·9) for the decay of GH from the circulation

The GH half‐life during the infusions studies did not vary with repeated exposure but was Significantly longer (mean half‐life of 25·7 minutes; range 19·4–37·1) than during the bolus studies (P > 0·001).

conclusions The half‐life of exogenous r‐hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (Insulin‐dependent) diabetes mellitus
Cyclical Cushing's syndrome first diagnosed after pituitary surgery: a trap for the unwary
Authors: Atkinson A. B. , McCance O. R. , Kennedy L. , Sheridan B.
Published: March 2008

Three patients were studied after transsphenoldal microsurgery for Cushing's disease because their symptoms and signs were slow to settle and/or because they had variable endocrine results. All were established as having cyclical Cushing's syndrome, first diagnosed post‐operatively. This may be a much more common finding than previously realized and emphasizes the need for detailed and ongoing endocrlnologlcal Investigation after transsphenoldal surgery for Cushing's disease
IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF‐I
Authors: Laron Z. , Klinger B. , Blum W. F. , Silbergeld A. , Ranke M. B.
Published: March 2008

objective The aim of the study was to investigate the serum levels of IGFBP‐3, the major IGF‐I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF‐I treatment

design and patients Eight Laron type dwarfism patients (four children and four adults) were treated for 7 days by one daily s.c. injection of blosynthetic IGF‐I In doses of 120 or 150 μ g/kg/day.

measurements Blood was sampled in the fasting state before and 1 and 7 days after the last Injection

results It was found that IGF‐I administration significantly reduced plasma hGH levels with recovery after one week of no treatment. Serum IGFBP‐3 was abnormally low (0·70·0±37 mg/l) and decreased significantly further during IGF‐I treatment (to 0·48·0±28 mg/l) (P > 0·065).

conclusions The finding that serum IGFBP‐3 is low in Laron type dwarfism, a disease due to molecular defects in the GH receptor, is compatible with the hypothesis that this IGF binding protein is GH‐dependent. On the other hand the decrease during IGF‐I administration and concomitant suppression of GH secretion may denote either that GH activity is not completely blocked in this syndrome or that there are additional mechanisms regulating IGFBP‐3 synthesis
The evaluation of patients with a suspected pituitary microadenoma: computer tomography compared to magnetic resonance imaging
Authors: Johnson Mark R. , Hoare Richard D. , Cox Tim , Dawson John M. , Maccabe Jeffery J. , Huw Llewelyn D. E. , McGregor Alan M.
Published: March 2008

objectives To perform a prospective study to compare the ability of magnetic resonance Imaging (MRI) and computer assisted tomography (CT) to predict the position of a tumour within the pituitary fossa and to assess the clarity of the image generated by the two modalities in patients with suspected pituitary microadenomas

design Nineteen patients were investigated with CT and MRI scans and underwent trans‐sphenoldal exploration of the pituitary fossa. Both scans were assessed blind and independently by three neuroradiologists, A, B, and C; A and B examined the CT scans and B and C the MRI scans. The predicted site was then compared to the size and position of the tumour at surgery

patients Twenty‐five patients were recruited and had both CT and MRI scans, 19 subsequently underwent trans‐sphenoldal exploratiom of the pituitary fossa and formed the study population

results The Joint opinions of A and B of the CT scans were correct in 10/19, and those of B and C of the MRI scans were correct in 17/19 cases, P= 0·008. Observer agreement was used to assess the clarity of the image. A and B agreed about the site of the tumour on the CT scan in 14 of 19 cases (Kappa statistic 0·556); B and C agreed on the MRI scans in 19/19 cases (Kappa statistic 1), P= 0·025. After the exclusion of five cases found to be macroadenomas at surgery, the joint opinions of A and B of the CT scans were correct in 8/14, and those of B and C of the MRI scans were correct in 12/14 cases, P= 0·133. A and B agreed about the site of the tumour on the CT scan in 12/14 cases (Kappa statistic 0·653), B and C agreed on the MRI scans in 14/14 cases (Kappa statistic 1, no significant difference).

conclusions In the assessment of suspected pituitary mlcroadenomas MRI is the imaging technique of choice in view both of its greater diagnostic accuracy and the avoidance of radiation exposure
Growth hormone binding protein in Werner's syndrome
Authors: Hattori Naokl , Hino Megumu , Ikekubo Katsuji , Ishihara Takashi , Moridera Kunisaburo , Kurahachi Hiroyuki
Published: March 2008

objective GH and growth hormone binding protein in Werner's syndrome were investigated to elucidate their relation to the short stature

design The levels of GH binding protein and GH response to insulin‐induced hypoglycaemla were determined. GH binding protein levels and its Scatchard analysis in Werner's syndrome were compared with those in normal subjects

patients Three patients with Werner's syndrome (one man aged 45 years and two women aged 39 and 38 years) and 41 normal subjects (18 men and 23 women aged 39·3±5·5 years, mean±SD) were studied

measurements GH binding protein levels were determined using an Ultrogel AcA44 minicolumn and GH levels were measured by a highly sensitive enzyme immunoassay

results Two out of three patients with Werner's syndrome had GH binding protein levels above the mean + 2SD value in normal subjects. GH secretion was impaired in Werner's syndrome as judged by the low GH response to insulin‐induced hypoglycaemia

conclusions Elevated GH binding protein levels may lead to an increase in the bound form of GH, which is probably less bloactive, resulting in growth failure In association with the impaired GH secretion in Werner's syndrome
Failure of somatostatin analogue to control Cushing's syndrome in two cases of ACTH‐producing carcinoid tumours
Authors: Cheung N. W. , Boyages S. C.
Published: March 2008

objective To determine the effectiveness of somatostatin analogue (octreotide) in controlling hypercortisolism in two patients with ectopic ACTH‐producing carcinoid tumours, and to review the literature

design The two patients were treated with octreotide administered by subcutaneous injection, for 5 days with 150 μ g three times daily and for 7 days with 100 μ g three times daily respectively. They were subsequently treated with oral metyrapone 250 mg three times daily.

patients Patient 1 had a metastatic carcfnoid tumour but the primary was not identified. Patient 2 had a pulmonary carcinoid. Cushing's syndrome due to ectopic ACTH syndrome was established by demonstration of failure of cortisol suppression by dexamethasone, elevated ACTH levels, and immunoperoxidase staining for ACTH within the tumours

measurements Urinary free cortisol (UFC) was measured on consecutive days during treatment with octreotide. Serum cortisol and ACTH levels were taken daily in patient 2, and on days 0 and 3 in patient 1

results Patient 1 had a baseline 24‐hour urinary free cortisol of 5340 nmol/24 h, serum cortisol of 915 nmol/l, and serum ACTH of 163 ng/l (ACTH ng/l X 0·23 = pmol/l). After 3 days of octreotide, serum cortisol was 782 nmol/l and ACTH 164 ng/l. Twenty‐four hour urinary free cortisol was 4136 nmol/24 h after 7 days of treatment. Metyrapone, however, resulted in a rapid fall in urinary free cortisol to 290 nmol/24 h, with marked clinical improvement

Patient 2 had a baseline 24‐hour urinary free cortisol of 2520 nmol/24 h, serum cortisol of 747 nmol/l, and ACTH of 103 ng/l. Urinary free cortisol rose to 2970 nmol/24 h on day 6 of treatment with octreotide. Serum cortisol and ACTH levels fell slightly to 611 nmol/l and 70 ng/l respectively. On changing to metyrapone, the urinary free cortisol fell to 821 nmol/24 h in 4 days

conclusions Octreotide failed to significantly reduce 24‐hour urinary free cortisol, serum cortisol and ACTH in the two patients reported. We conclude that it should probably not be regarded as primary treatment for control of hypercolisolism in patients with ACTH‐producing carcinolds, but reserved as adjunctive therapy
Circulating immunoreactive inhibin and testosterone levels in men with critical illness
Authors: Dong Qlhan , Hawker Felicity , McWilliam David , Bangah Mohan , Burger Henry , Handelsman David J.
Published: March 2008

objective We aimed to concurrently characterize serial changes in circulating immunoreactive inhibin (IrlNH) and testosterone (T) as reflections of Sertoli and Leydig cell responses to acute critical illness in man

design Blood samples were drawn within 24 hours of admission to an intensive Care Unit and at weekly intervals thereafter for up to 4 weeks while the patient remained in intensive Care Unit or after discharge to a general ward

patients We studied 13 male subjects with critical illness requiring intensive therapy

measurements Plasma levels of IrlNH, T, LH, FSH and sex hormone binding globulin (SHBG) were analysed in relation to (i) the severity of Illness as indicated by a sepsis score, acute physiology and chronic health evaluation score, and reverse triiodothyronine (rT3) levels and (ii) the outcome of illness as determined by discharge from intensive Care Unit and the two‐month mortality

results Overall IrlNH levels remained normal and correlated negatively with rT3 (r=–0·63, P= 0·001) but not with sepsis, acute physiology and chronic health evaluation score, or gonadotrophin levels. Neither admission nor serial IrlNH levels significantly distinguished between the different clinical outcomes. In contrast, T levels were depressed and inversely correlated with both sepsis and acute physiology and chronic health evaluation scores (P > 0·02), and positively with gonadotrophips (P > 0·01), but not rT3 levels. Men eventually discharged from the intensive Care Unit showed a rise, while those remaining showed a fall, in T levels (P= 0·02, time–course interaction). Similarly, T levels were lower in patients who died than in survivors, despite the comparable T levels on admission (P= 0·02, time–course interaction). Despite the fall in T levels, gonadotrophin levels remained inappropriately in the eugonadal range but higher in men who were discharged from intensive Care Unit (P= 0·02, time–course interaction). FSH but not LH levels were correlated with sepsis score (P= 0·402) but not acute physiology and chronic health evaluation score or rT3.

conclusions Sertoli cell function as judged by circulating IrlNH levels is much less affected by acute critical Illness than is Leydig cell function as judged by circulating T levels. The suppressive effect of acute critical Illness on Leydig cell function is consistent with a hypothalamicpitultary lesion
Abnormalities of intermediary metabolism following a gestational diabetic pregnancy
Authors: Chan S. P. , Gelding S. V. , McManus R. J. , Nlcholls J. S. D. , Anyaoku V. , Nlththyapanthan R. , Johnston D. G. , Dornhorst A.
Published: March 2008

objective The aim of this study was to compare intermediary metabolism in glucose tolerant women with previous gestational diabetes and control women without a history of gestational diabetes

subjects Fifteen women with previous gestational diabetes and 15 controls individually matched for race age and body mass index were included. Only subjects with normal glucose tolerance were included in this study

methods Plasma glycerol, 3‐OH butyrate, non‐esterlfled fatty acids (NEFA), glucose and insulin were measured fasting and following a 75 g oral glucose load

results The women with previous gestational diabetes and their matched controls were of similar racial origin, age and body mass index. There was no difference between those with previous gestational diabetes and controls in fasting glycerol, 3‐OH butyrate, NEFA, glucose or insulin concentrations. Following the oral glucose load, glycerol, 3‐OH butyrate and NEFA concentrations fell in both groups. However, compared with controls at 120 minutes, those with previous gestational diabetes had significantly higher concentrations of glycerol (median 57, range 24–216 vs 27, range 8–89 μmol/l, P > 0·005) and 3‐OH butyrate (9, range 1–18 vs 5, range 2–11 μmol/l, P > 0·01). NEFA concentrations were similar in the two groups. Despite similar glucose concentrations during the oral glucose tolerance test the insulin response during the first 60 minutes following oral glucose was significantly reduced in the subjects with previous gestational diabetes when compared with controls (Insulin area, 0–60 minutes; 2172, range 788–4767 vs 2830, range 996–4784 pmol mln/l, P > 0·05).

conclusions Women with a previous history of gestatlonal diabetes, despite having normal glucose tolerance, have defective insulin release with resultant abnormalities of intermediary metabolism
The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen‐dependent alopecia in women
Authors: Hugh Rushton D. , Ramsay Ian D.
Published: March 2008

object To evaluate the treatment with cyproterone acetate and ethinyl oestradlol of diffuse androgen‐dependent alopecia in women

design Twenty women were treated for a period of 12 months in a reverse sequential regimen employing cyproterone acetate (CPA, 50 mg once dally from Day 5 to Day 15) and ethinyl oestradlol (EE2, 30 μg once dally from Day 5 to Day 24 of the menstrual cycle), and 20 were left untreated and acted as controls. Half of each group had serum ferritin concentrations above or below 40 μg/I

patients Forty Caucasian premenopausal women aged between 18 and 47 years, presenting with diffuse and rogen‐dependent alopecia, were enrolled into this study

measurements Hair variables were assessed initially by the unit area trlchogram and again in the same sites 12 months later. Biochemical investigations were performed before treatment and after 3, 6, and 12 months

results In the treated group, a significant (P > 0·01) mean increase in total hair density (hair/cm2) and meaningful hair density (non‐vellus hair/cm2) was found in patients in whom the serum ferritin was above, but not below 40 μ g/l. However, in the control group a significant (P > 0·05) mean decrease in total hair density and meaningful hair density was observed after 12 months. No correlation between serum ferritin levels and the degree of hair loss within this group could be established.

conclusion Patients treated with the anti‐apdrogen cyproterone acetate and ethinyl oestradlol respond best when serum ferritin is above 40 μg/I
Hormonal management of prostate cancer
Authors: Wasan Harpreet S. , Waxman Jonathan
Published: March 2008

In advanced disease, androgen deprivation remains the usual treatment. The completion of current trials is awaited to confirm whether total androgen blockade will prolong survival. To make further advances in treatment the fundamental biology of the prostate cell, benign or malignant, and its relationship to endocrine manipulation, must be understood. This may then lead to an understanding of clonal escape mechanisms in transformed cells and the clinical correlate of escape, relapse.
Circadian changes in pulsatile TSH release in primary hypothyroidism
Authors: Adriaanse Ria , Brabant Georg , Prank Klaus , Endert Erik , Wiersinga Wilmar M.
Published: March 2008

OBJECTIVE We evaluated pulsatile and circadian TSH secretion in primary hypothyroidism.

DESIGN In a prospective study, blood was sampled every 10 minutes during 24 hours for assay of TSH (IRMA). Thyroid hormones and TSH responsiveness to TRH were then measured.

SUBJECTS Nine patients with overt primary hypothyroidism, seven patients with subclinical hypothyroidism and 16 healthy controls.

MEASUREMENTS Computer‐assisted analysis by the Desade and Cluster programs.

RESULTS Both computer‐assisted programs revealed an increased TSH pulse amplitude in both overt and subclinical hypothyroidism versus controls (Desade: 36 9 ± 31 4 (mean ± SD)(P<0 001)and2 8 ± 1 9(P<0 001) vs0 4 ± 0 2 mU/l; Cluster: 25 6 ± 25 1 (P<0 001) and 24 ± 14 (P< 0 001) vs 0 4 ± 0 2 mU/l). TSH pulse frequency remained unchanged with approximately 10 pulses/24 hours. A highly significant correlation was found between the mean 24‐hour TSH concentration and the TSH pulse amplitude in all controls and patients but not to TSH pulse frequency. The nocturnal TSH surge was absent in six out of nine patients with overt primary hypothyroidism. The deficient nocturnal rise of TSH in primary hypothyroidism vs controls (22 ± 51 vs 82 ± 41%, P< 0 001), was associated with a loss of the usual nocturnal increase In TSH pulse amplitude and frequency.

CONCLUSIONS Mean 24‐hour TSH pulse amplitude is increased in primary hypothyroidism, but TSH pulse frequency remains unchanged. The decrease of the nocturnal TSH increase in primary hypothyroidism is associated with a loss of the usual nocturnal increase in TSH pulse amplitude and frequency.