bluuebunny/crossref_metadata_2025 huggingface dataset:
HORMONAL STUDIES ON WOMEN WITH POLYCYSTIC OVARIES DIAGNOSED BY ULTRASOUND
Authors: OBHRAI M. , LYNCH S. S. , HOLDER G. , JACKSON R. , TANG L. , BUTT W. R.
Published: March 2008

Eighty‐six patients were diagnosed by ultrasound to have polycystic ovaries. Twelve have fairly regular but anovular cycles (P1), 56 had oligomenorrhoea (P2) and eight had primary or secondary amenorrhoea (P3). The remaining 10 patients had raised progesterone concentrations and were excluded from the hormonal studies. Gonadotrophins, steroid hormones and sex hormone binding globulin (SHBG) were measured in all patients and the results were compared with those of 29 normal women who acted as controls. A high LH: FSH ratio was the most frequently found abnormality (raised in 68.4% of patients) followed by LH (65.8%), free testosterone (FT, calculated from total testosterone (T) and SHBG) (59.2%) and 17‐OHP (48.7%). Each of these four estimations was above the normal ranges in 25% of patients: proportionally most of the results outside the normal range occurred in group P3 followed by P2 and P1 respectively. To obtain a quantitative measure of the abnormalities, results were expressed as percentages of the mean control value for each hormone and these percentages were then summated. The four measurements, LH: FSH ratio, LH, FT and 17‐0HP gave abnormality scores ranging from a mean of 667 in P1 to 1189 in P3 compared with 405 in controls. Twenty‐one of the 76 patients were hirsute with significantly higher androgens than the non‐hirsute patients. Their mean abnormality score was 1141 compared with 855 in the non‐hirsute group and they all had at least one hormonal abnormality. The study demonstrates that there is a relationship between the degree of hormonal abnormality and the menstrual irregularities and hirsutism in women with PCOS suggesting that there may be a progressive nature to the syndrome.
MELATONIN IN INFANTS AND MOTHERS AT DELIVERY AND IN INFANTS DURING THE FIRST WEEK OF LIFE
Authors: KIVELÄ AARRE , KAUPPILA ANTTI , LEPPÄLUOTO JUHANI , VAKKURI OLLI
Published: March 2008

To evaluate the possible effect of the extreme and permanent changes in the hormonal milieu and in the lighting conditions at birth on the pineal hormone, melatonin (MT), we measured maternal vein and umbilical artery concentrations of MT in 19 parturients, post‐partum urinary concentrations of MT in 14 mothers and their infants, and daytime (0800‐2000 h) and night‐time (2000‐0800 h) urinary concentrations of MT and 6‐sulphatoxymelatonin in 22 infants during the first 8 days of life. The mean MT concentrations in maternal venous blood and umbilical arterial blood did not differ significantly from each other and there was a positive correlation between them. The same was true for postpartum urinary MT of the mothers and their infants. There was no diurnal rhythm of MT during the first week of life. MT excretion in neonates was 2‐5 pmol/12 h (only 1‐5% in comparison with adults) and that of 6‐sulphatoxymelatonin 150‐300 pmol/12 h. In reverse phase high pressure liquid chromatography (HPLC) studies, 84‐100% of total MT immunoreactivity was eluted at the same position as synthetic MT, and a small amount of hydrophobic MT‐like immunoreactive material was also detected in five of the 10 urine extracts studied. This material (perhaps a novel neonatal metabolite of MT) may be indicative of immaturity of neonatal metabolism of MT although 6‐hydroxylation is also functional in neonates. Although infant MT immediately after delivery at least partly reflects maternal MT secretion, our results show that the pineal gland is capable of producing MT at this time. However, the diurnal rhythm of MT is not yet developed, possibly because of the inability of the pineal gland to react to external stimuli at this stage, or because increased secretion of gonadotrophins after delivery suppresses the pineal gland.
GROWTH OF MALES WITH IDIOPATHIC HYPOPITUITARISM WITHOUT GROWTH HORMONE TREATMENT
Authors: VAN DER WERFF TEN BOSCH J. J. , BOT A.
Published: March 2008

We report auxologic data on 23 males with idiopathic hypopituitarism who grew up at a time when human growth hormone (GH) was not yet available, while receiving other appropriate hormonal substitution. We had reported previously that their adult heights were not significantly less than those of similar patients who had received GH. In the absence of GH the pubertal growth period was remarkably protracted, averaging 8.7 years for 19 patients during androgen substitution. Pubertal increment in height averaged 20.4 cm during induced puberty, a figure which compares favourably with those reported for GH‐treated patients. This implies that GH does not increase the height gained during pubertal growth; the increase in the rate of growth appears to be off‐set by a rise in the rate of skeletal maturation. During pubertal growth acceleration of growth of the skeleton seems unavoidably associated with acceleration of its maturation. Adult heights were significantly correlated with the heights at the time of onset of pubertal growth. This is evidence in favour of attempts to stimulate prepubertal growth much more than hitherto by earlier, higher, and more frequent doses of GH. It remains to be proved, however, that before puberty the processes of growth and maturation of the skeleton can be dissociated.
A long‐term dose‐response study of somatostatin analogue (SMS 201–995, octreotide) in resistant acromegaly*
Authors: McKnight John A. , McCance David R. , Sheridan Brian , Mcllrath Edward , Hadden David R. , Kennedy Laurence , Atkinson A. Brew
Published: March 2008

Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201–995 (octreotide) In active acromegaly. Twenty‐four‐hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 μg three times a day throughout the first month. The dose was increased by 300 μg/day at monthly intervals to a maximum of 1500 μg/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24‐h GH fell from a basal level of 34·3 ± SEM 7·6 mU/I to 8·0 ± 1·3 mU/I (P > 0·05) after 6 months. At 1 month (300 μg/day) mean GH was 13·6 ± 2·2 mU/I and at 2 months (600 μg/day) 10·8 ± 2·2 mU/I (P > 0·05 vs 300 μg/day dose), and at 5 months (1500 μg/day) 11·3 ± 2·0 mU/i (all P > 0·05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 μg/day. After 1 year the mean GH of the group (n= 8) was 7·5 ± 1·3 mU/I (P > 0·05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1‐year period. We found no evidence that routinely increasing the dose beyond 600 μg/day was helpful.
Effect of low dose iodide supplementation on thyroid function in potentially susceptible subjects: are dietary iodide levels in Britain acceptable?†
Authors: Chow C. C. , Phillips D. I. W. , Lazarus J. H. , Parkes A. B.
Published: March 2008

objective The aim of the study was to evaluate the risk of exposure to an Increase in dietary Iodide Intake amongst potentially susceptible population groups in Britain.

design A randomized controlled trial was performed in healthy women and In women with underlying thyroid abnormalities due to subcllnical Hashimoto's thyroiditis (diagnosed on the basis of antithyroid antibodies) or previous Iodide deficiency of supplementation with 500 μg/day iodide (giving a total Intake of approximately 750 μg/day) for 28 days versus placebo.

patients Two hundred and twenty‐five women aged 25–54, randomly selected from a general practice In Cardiff, were screened for thyroid microsomal antibody. Antibody positive women (n=20), and antibody negative controls (n=30) were recruited Into the trial comparing Iodide and placebo. In addition, groups of patients aged 60–75 randomly selected from the Cardiff practice (n=29), an Iodide sufficient area, and a practice in Dowlals (n= 35), a previously iodide deficient area, were also enrolled Into the trial.

measurements Changes In free thyroxine and thyro‐trophin levels were measured after 14 and 28 days of Iodide supplementation.

results All the iodide supplemented groups responded in the same way with a small fall in free thyroxine and rise In thyrotrophin levels (combined fall In free thyroxine 14 days after the start of supplementation –1.22 (95% confidence interval – 0.59 to −1.84) pmoUl and at 28 days – 0.86 (– 0.30 to –1.43) pmol/I and rise in thyrotro‐phin at 14 days 0.55 (0.19 to 0.92) mU/I and at 28 days 0.59 (0.12 to 1.07) mU/I). In two of the iodide supplemented subjects thyrotrophin levels rose above the laboratory reference range and In a further three subjects initially elevated thyrotrophin values Increased further. In contrast, no changes In thyroid function were observed in the placebo treated controls and none developed biochemical hypothyroidism.

conclusions Dietary Iodide Intakes of 750 μg/day or more may adversely affect thyroid function, especially in individuals with borderline hypothroidism
Defects in monocyte polarization and dendritic cell clustering in patients with Graves’ disease. A putative role for a non‐specific immunoregulatory factor related to retroviral p15E
Authors: Tas M. , de Haan‐Meulman M. , Kabel P. J. , Drexhage H. A.
Published: March 2008

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent Infections of the respiratory tract and In various types of malignancies. These Impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; > 25 kDa) circulating In the serum of the patients. The factor, which seems to be a non‐specific Immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenlc retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendrltic cells of Graves’ patients, monocytes were Isolated from the peripheral blood and dendritlc cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogenelc lymphocytes. A defective fMLP‐Induced monocyte polarization was found (16 vs 37% In healthy controls), whereas the dendrltic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of > 25kDa prepared from the serum of Graves’ patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E‐like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendrltlc cell clustering. A mixture of two monoclonal antibodies directed against p15E was able to neutralize these suppressive effects. The relationship of this p15E‐like factor occurring In the serum of Graves’ patients to the recently reported genomic expression of retroviral sequences in thyrocytes/leucocytes of Obese Strain chickens and Graves’ patients (ev 22, HIV gag) needs further clarification.
Effect of the new dopaminergic agonist CV 205–502 on plasma prolactin levels and tumour size in bromocriptine‐resistant prolactinomas
Authors: Duranteau L. , Chanson P. , Lavoinne A. , Horlait S. , Lubetzki J. , Kuhn J. M.
Published: March 2008

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10|X% and to reduce tumour size in one‐third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long‐term effects of bromocriptine and CV 205–502 (a non‐ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine‐resistant prolactinomas. Bromocriptine reduced significantly (P > 0.001) plasma prolactln levels (from 2307 |Mp 518 to 568 |Mp 279 μg/I) (conversion to SI units: 1 μg/I = 20 mU/I). Visual field defects observed in five patients Improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side‐effects at the beginning of the treatment, CV 205–502 was well tolerated In five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205–502 and it was necessary to reduce the daily dose. CV 205–502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205–502 was more potent than bromocriptine as demonstrated by the further 90|X% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205–502 treatment. However, no further change in visual disturbance or in tumour size was observed during the treatment with CV 205–502. These results show that CV 205–502 appears to be more potent than bromocriptine in reducing plasma prolactin levels in some bromocriptine‐resistant prolactinomas and suggest that different mechanisms may be Involved In such a resistance.
TRIAC (3,5,3′‐triiodothyroacetic acid) has parallel effects at the pituitary and peripheral tissue levels in thyroid cancer patients treated with l‐thyroxine
Authors: Mechelany C. , Schlumberger M. , Challeton C. , Comoy E. , Parmentier C.
Published: March 2008

Summary. objective To investigate whether the addition of 3,5,3′‐ triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery.

design Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5±0.3 μg/kg/day) and after reduction to a physiologic dose (1.8±0.3 μg/kg/day); then with the addition of TRIAC 500 or 1000 μg/day to the physiologic T4 treatment dose. PATIENTS Twenty‐two patients who had total thyroid ablation for differentiated thyroid carcinoma.

measurements

Clinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone‐oestradiol binding globulin, procollagen III and osteocalcin levels.

results

The addition of TRIAC induced a significant and dose‐dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater Inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression.

conclusions

Even at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients.
Isolated ACTH deficiency
Authors: Orme S. M. , Belchetz P. E.
Published: March 2008

Summary. Isolated ACTH deficiency is a rare disorder. We report four cases of this disease which presented to the Department of Endocrinology at Leeds General Infirmary over a one‐year period. The diagnostic clinical and biochemical features of each case are discussed and the pertinent literature is reviewed. The clinical investigations vary somewhat between cases as the four patients presented in markedly different ways. Well validated dynamic endocrine investigations were employed including glucagon stimulation test (GST) and the corticotrophin releasing hormone (CRH) test (using 100 μg of human CRH with samples for ACTH and cortisol). Two patients probably had CRH deficiency and two had ACTH deficiency. All the cases are instructive, illustrating different features of this heterogeneous condition.

We conclude that the diagnosis of this condition may be difficult due to the varied clinical presentation. We suggest that it is commoner than previously thought and that the precision of diagnosis can be improved using the CRH test.
The assay of urinary growth hormone in normal and acromegalic adults
Authors: Evans A. J. , Willis D. S. , Wood P. J.
Published: March 2008

objectives

To establish a normal range for urinary growth hormone in adults and to investigate the urinary growth hormone levels in patients with acromegaly, comparing these with the serum growth hormone results of a glucose tolerance test. We also studied the molecular Identity of the growth hormone recognized by our assay method.

design Overnight urine samples and, in some cases, timed urine samples taken during the day were obtained from healthy volunteers and acromegalic patients. A standard glucose tolerance test with serum growth hormone measurements was performed on the acromegalic patients.

patients One hundred and thirty‐five normal adults and 33 acromegalic patients were studied.

measurements

Urinary growth hormone was measured using a sensitive and precise assay developed previously. RESULTS in healthy volunteers overnight urinary growth hormone values fell gradually with increasing age, but there was no significant difference between men and women in any decade or between smokers and non‐smokers. Sexual intercourse had no detectable effect on the values, but there was a large increase following strenuous exercise. Studies of the diurnal patterns in normal and abnormal adults suggested that it might be possible to diagnose acromegaly on a random urine sample. Gel filtration studies on a urine sample from an acromegalic patient showed a single peak of molecular weight 22000. Using overnight collections there was clear discrimination between the values given by the normal adults and the acromegalic patients and an excellent correlation between urinary growth hormone levels in acromegatlc patients and the mean serum growth hormone in a glucose tolerance test.

conclusions in contrast to some other groups we conclude that urinary growth hormone provides a useful, non‐invasive screening test for acromegaly, but this conclusion depends crucially on the assay being sensitive and precise at low values.
Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin‐like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients
Authors: Mullis P. E. , Patel M. S. , Brlckell P. M. , Hindmarsh P. C. , Brook C. G. D.
Published: March 2008

Hypochondroplasia, a heterogeneous and usually mild form of chondrodystrophy, is a common cause of short stature. It often goes unrecognized in childhood and is diagnosed in adult life when disproportionate short stature becomes obvious.

We performed restriction enzyme analysis of the Insulinlike growth factor I (IGF‐I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r‐hGH) treatment, in 60 children with Isolated growth hormone deficiency and in SO normal Individuals. The frequency of the heterozygous pattern (Hind III: 8.2, 5.2, 4.8, 3.2 kb fragments, Pvu: 8.4, 5.1, 4.7, 2.5 kb fragments) in children with hypochondroplasia was significantly higher (X2:P<0.05) than in the control groups. The hypochondro‐plastic children whose response to r‐hGH treatment was characterized by a proportionate Increase in both spinal and sublschial leg length were all heterozygous for two co‐inherited IGF‐I gene restriction fragment length polymorphism (RFLP) alleles (Hind III: 5 2,4 8 kb; Pvu II: 5 1,47 kb). Children whose response was characterized by accentuation of the body disproportion by r‐hGH treatment were all homozygous for these alleles (Hind III: 4 8,4 8 kb; Pvu II: 4.7, 4.7 kb). Their response to r‐hGH treatment is significantly different (P<0.01). Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3 311 at zero recombination) of the IGF‐I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia. The 5 2 kb Hind III and 51 kb Pvu II alleles are in strong linkage disequilibrium with this trait. These data indicate that IGF‐I gene may be a candidate gene for involvement in the aetiology of short stature presenting with hypochondroplastic features and a proportionate response to r‐hGH treatment; they also provide support for the concept of genetic heterogeneity in chondrodystrophy.
Inter‐relations between growth hormone, insulin, insulin‐like growth factor‐l (IGF‐I), IGF‐binding protein‐1 (IGFBP‐1) and sex hormone‐binding globulin in acromegaly
Authors: Holly J. M. P. , Cotterlll A. M. , Jemmott R. C. , Shears D. , Al‐Othman S. , Chard T. , Wasa J. A. H.
Published: March 2008

Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF‐I, an important mediator of its actions. IGF‐I itself is intimately related to insulin both in structure and function. IGF‐I circulates associated with specific binding proteins which appear to have Important effects on its activity. We have examined the inter‐relations between GH, prolactin, insulin, IGF‐I and one of the binding proteins, IGFBP‐1, in 62 patients with acromegaly of varying activity. Serum IGF‐I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P < 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF‐I. IGF‐I concentrations were independent of prolactin. Fasting Insulin levels were high and unrelated to mean GH levels but correlated with those of IGF‐I (r = 0.542; n = 57; P<0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP‐1 (r = 0.684; n = 57; P< 0.001). Even In subjects whose acromegaly was well controlled or cured, as indicated by GH levels of <1 mU/l or IGF‐I levels of <2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP‐1 levels were low and unrelated to mean GH but were Inversely related to fasting insulin levels (r=−0.593; n = 57; P<0.001). We propose that a cascade of events occurs In acromegaly. GH hypersecretion causes chronic elevation of IGF‐I levels which In turn could lead to increased pancreatic insulin production. This raised insulin could then have additional effects, raising IGF‐I levels further and lowering IGFBP‐1; the latter could then result in accentuated IGF‐activity.
Effect of growth hormone on human sleep energy
Authors: Aström Christina , Trojaborg Werner
Published: March 2008

objective We wished, by means of power spectrum EEC analysis, to examine REM and delta sleep energy in adults with high and normal plasma growth hormone (GH) concentration

design After a 3‐day regular sleep/wake schedule, all‐night polysomnographic recordings were performed on two consecutive nights before as well as one year after treatment for acromegaly by adenomectomy. The sleep energy was calculated by power spectrum analysis

patients We studied nine patients aged 24–45 years with untreated active acromegaly. The same patients were reexamined one year after adenomectomy when plasma GH concentrations were normal

measurements The acromegaly was verified biochemically by measuring basal plasma GH concentration and plasma GH during hyperglycaemia as well as Insulin‐like growth factor. Cerebral computer tomography (CT) and magnetic resonance (MR) scans revealed an intrasellar adenoma in all patients. The resulting sleep records obtained before and after adenomectomy were subjected to power spectrum analysis and a manually blinded sleep scoring

results The power spectrum analysis showed that when circulating GH was elevated the energy In the REM sleep per minute was significantly higher compared to the REM energy/mm after surgery when GH concentration had normalized. A similar relation was found for delta sleep (stage 3 + 4, deep sleep) where the energy per minute was higher before treatment than after

conclusions The study demonstrates that plasma GH concentration was correlated to sleep energy. During high GH concentration the REM and delta sleep energy were high and normalization of plasma GH was followed by normalization of REM and delta sleep energy per time unlt
Human chorionic gonadotrophin contributes to the bioactivity of Pergonal
Authors: Rodgers M. , Mitchell R. , Lambert A. , Peers N. , Robertson W. R.
Published: March 2008

OBJECTIVE We examined batch variation in the LH‐like bioactive content of Pergonal and determined whether hCG contributes to this.

DESIGN Random selection of three batches of Pergonal, consisting of three ampoules in each batch.

MEASUREMENTS The LH content in each ampoule was determined by radioimmunoassay (R‐LH), immunoradio‐metric assay (l‐LH) andin vitroLeydig cell bioassay (B‐LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I‐hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5– 7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance.

RESULTS THE GONADOTROPHIN CONTENT OF EACH BATCH (IU/AMPOULE, MEAN ± SEM,N=3 AMPOULES) WAS R‐LH (40.9 ± 0.5, 40.8 ± 0.2, 39.3 ± 0 7,P<0.15), I‐LH (39.0 ± 1.5, 28.3 ± 0.8, 36.9 ± 3.3,P< 0.001), B‐LH (27.3 ± 0.3,12.0 ± 0.9, 19.3 ± 0.9,P< 0001) AND I‐HCG (16.4 ± 0.7, 11.7 ± 0.2, 10.5 ± 0.5,P< 0.001). THE CHROMATOFOCUSSING RECOVERIES BELOW PH 5.5 EXPRESSED AS A PERCENTAGE OF THE TOTAL AMOUNT OF ANALYTE ELUTED FROM THE COLUMN AND COLLATED FOR ALL THREE BATCHES OF PERGONAL WERE (MEAN %± SD,N= 3 BATCHES) R‐LH (58.4 ± 4.0), I‐LH (41.3 ± 7.5), B‐LH (81.4 ± 2.8) AND I‐HCG (87.8 ± 3.7).

CONCLUSIONS There was significant batch variation in the I‐LH, B‐LH and I‐hCG (P< 0.001) but not the R‐LH (P> 0.15) content of Pergonal. More than 80% of the total B‐LHrecoverychromatofocussed below pH 5.5 and corresponded to the region of highest I‐hCG (>87%) and lowest I‐LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH‐like bioactivity of Pergonal.
Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion
Authors: Koppeschaar H. P. F. , ten Horn C. D. , Thljssen J. H. H. , Page M. D. , Dieguez C. , Scanion M. F.
Published: March 2008

OBJECTIVE We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion.

DESIGN Six healthy, non‐obese volunteers underwent seven separate studes in random order. They received (1) insulin alone at 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0–30 minutes; (4) arginine at 0–30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0–30 minutes; (6) Insulin at 0 minutes, GHRH at 15 minutes and arginine at 0–30 minutes; (7) Insulin at 0 minutes and GHRH at 15 minutes.

MEASUREMENTS GH and PRL were measured from —30 to 150 minutes at Intervals of 15 minutes.

RESULTS Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH.

CONCLUSIONS The findings suggest that arglnine‐Induced GH release is mainly mediated by a decrease In somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and Inhlbition of somatostatin.
Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross‐links: a longitudinal and cross‐sectional study
Authors: Hassager C. , Colwell A. , Assiri A. M. A. , Eastell R. , Russell R. G. G. , Christiansen C.
Published: March 2008

OBJECTIVE To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline.

DESIGN AND PATIENTS Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2–3 years in 15 healthy women aged 45–54 years. Nine remained premenopausal and six became post‐menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 postmenopausal women, aged 45–54 years, who were participating in a double‐blind study.

MEASUREMENTS Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion.

RESULTS Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post‐menopausal values were 30–50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean ± SEM: urinary pyridinoline (premenopausal) = 29 ± 2 vs urinary pyridinoline (post‐menopausal) = 38 ± 6, P <0.05; urinary deoxypyridinoline (premenopausal) = 8 ± 1 vs urinary deoxypyridinoline (post‐menopausal) = 12 ± 1, P <0.05). Three months of post‐menopausal hormone replacement therapy decreased (P <0.001) both to premenopausal levels.

CONCLUSION Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.
Interleukin‐6, a growth promoting cytokine, is present in human pituitary adenomas: an immunocytochemical study
Authors: Tsagarakis S. , Kontogeorgos G. , Glannou P. , Thalassinos N. , Woolley J. , Besser G. M. , Grossman A.
Published: March 2008

OBJECTIVE The aim of this study was to investigate the presence of interleukin‐6 (IL‐6) in human pituitary adenomas.

DESIGN Immunocytochemistry was performed in 15 cases of pituitary adenomas obtained at transsphenoldal surgery.

PATIENTS Fifteen cases of pituitary adenomas were examined; these included five GH‐secreting adenomas, four prolactinomas, four ACTH‐secreting adenomas and two null‐cell (‘functionless’) adenomas.

MEASUREMENTS Each tumour was stained for the presence of IL‐6 by means of the avidin‐blotin‐peroxidase complex (ABC) technique, and was also stained for GH, prolactin, ACTH and α‐subunit by conventional immunocytochemistry.

RESULTS Fourteen of the 15 tumours examined, excepting one GH‐secreting tumour, demonstrated clusters of IL‐6 positively stained cells; the specificity of the staining was established by a significant decrease in staining in parallel sections of all tumours studied when the anti IL‐6 antibody was preabsorbed with recombinant human IL‐6. CONCLUSIONS It is concluded that IL‐6 immunoreactivity is present in human pituitary tumours, and is independent of the specific secretory cell product. The role of this cytokine in the pathogenesis of such tumours requires further investigation.
Analysis of trough serum growth hormone concentrations: comparison of an immunoradiometric assay and a sensitive ELISA for growth hormone
Authors: Pringle P. J. , Silvio L. Di , Hindmarsh P. C. , Matthews D. R. , Kurtz A. B. , Brook C. G. D.
Published: March 2008

OBJECTIVES We compared a sensitive assay for GH (ELISA) with a conventional immunoradiometric (IRMA) assay with particular reference to the oscillatory activity detected by Fourier transformation and the estimation of trough concentrations using occupancy analysis.

DESIGN Eight healthy adult male volunteers underwent 24‐hour profiles during which samples were drawn at 20‐minute intervals. Samples were analysed by an ELISA and an IRMA system.

MEASUREMENTS The 24‐hour serum GH concentration profiles were subjected to Fourier transformation and to occupancy analysis.

RESULTS No additional GH periodicities could be determined in the ELISA data other than the well documented 180–200‐minute periodicity. Median observed concentrations (OC) at 5% occupancy were 0.035 mU/l (range 0.004–0.22) for the ELISA and 0.035 mU/l (range 0.001–0.50) for the IRMA. For all OC parameters, 5,50 and 95%, there was a good correlation between the ELISA and IRMA systems. The mean difference (bias) between the ELISA and IRMA were ‐ 0.05, ‐ 0.28 and ‐1.40 mU/l at OC values of 5, 50 and 95% respectively and the standard deviations of the difference at the same OC values were 0.10, 0.50 and 1.61 mU/l.

CONCLUSION Although there is a qualitative improvement on visual inspection of individual 24‐hour serum GH profiles obtained using the ELISA system, there is little additional information gained in terms of pulse periodicity or occupancy analysis.
A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF‐oma, hypercalcitoninaemia and intractable peptic ulceration
Authors: Price David E. , Absalom Stephen R. , Davidson Katharine , Bolia Amman , Bell Peter R. F. , Howlett Trevor A.
Published: March 2008

A 42‐year‐old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF‐oma, hyperprolacti‐naemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immuno‐staining was positive for insulin, calcitonin, somatostatin and glucagon. Post‐operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2‐blockers, and died of gastro‐intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma.

This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require peri‐operative omeprazole treatment even if serum gastrin levels are normal.
Determination of urinary testosterone and epitestosterone during pubertal development: a cross‐sectional study in 141 normal male subjects
Authors: Raynaud E. , Audran M. , Pagès J. Ch. , Fédou C. , Brun J. F. , Chanal J. L. , Orsetti A.
Published: March 2008

OBJECTIVES Exogenous testosterone administration is classically detected by measuring the ratio of testosterone to epitestosterone in urine. Athletes are considered to be positive for drug abuse if the urinary testosterone to epitestosterone ratio is greater than 6. We aimed at investigating the urinary excretion of testosterone and epitestosterone during pubertal development.

DESIGN We performed a cross‐sectional study of 141 normal male subjects between ages 8 and 26 years.

PATIENTS We studied 141 subjects: 32 at stage 1 of Tanner, 27 at stage 2,30 at stage 3,25 at stage 4 and 27 at stage 5.

MEASUREMENTS Subjects performed a 24‐hour urine collection. Urinary testosterone and epitestosterone were measured by gas chromatography‐mass spectrometry with selected ion monitoring.

RESULTS Urinary testosterone was 20.5 ± 1.7 nmol/24h (mean ± SEM) at stage 1, 49±2.9 at stage 2, 98.8 ± 3.4 at stage 3,371.8 ± 21.8 at stage 4 and 403.4 ± 16.1 nmol/24h at stage 5. Urinary epitestosterone was 13.1 ± 1.5 nmol/24h at stage 1, 291 ± 3.3 at stage 2, 48.3 ± 3.7 at stage 3, 156.3 ± 14.8 at stage 4 and 221.1 ± 18.6 nmol/24h at stage 5. The urinary excretions of both steroids increased significantly during puberty and were highly correlated with chronological age (P<0.001). Comparison of the correlation slopes (P<0.001) showed that the urinary profiles of testosterone and epitestosterone are not parallel during pubertal development.

Two subjects presented a testosterone to epitestosterone ratio above 6, corresponding to a low urinary concentration of epitestosterone, without pathological explanation.

CONCLUSION Testosterone and epitestosterone do not present the same urinary profiles throughout puberty. Marked increases of the testosterone to epitestosterone ratio can be observed at this period and may interfere with doping tests.
Malignant prolactinoma with extracranial metastases: a report of three cases
Authors: Walker J. D. , Grossman A. , Anderson J. V. , Ur E. , Trainer P. J. , Benn J. , Lowy C. , Sönksen P. H. , Plowman P. N. , Lowe D. G. , Doniach I. , Wass J. A. H. , Besser G. M.
Published: March 2008

OBJECTIVE Prolactin‐secreting tumours of the pituitary almost never metastasize extracranially. However, we have recently seen three such patients, whose presentation, clinical course and response to treatment are reviewed in order to determine whether they possess unique clinical features, and to assess optimum therapy.

DESIGN AND PATIENTS Three patients with extracranial metastases from prolactinomas have been retrospectively reviewed.

MEASUREMENTS Clinical courses, biochemical parameters and imaging modalities (CT, MR and radiolabeled somatostatin analogue scanning) and histopathology were assessed before and during different therapeutic regimens.

RESULTS All three patients’presentations were initially unremarkable, but later each had persistent and relentlessly increasing serum prolactin concentrations and evidence of distant spread of their tumours. The first patient presented aged 32 and was treated with repeated transsphenoidal resections of the tumour, pituitary radiotherapy, high dose bromocriptine therapy, the somatostatin analogue octreotide and chemotherapy. Nine years after the original diagnosis a liver biopsy revealed carcinoma cells positively immunostaining for prolactin. At autopsy further microscopically similar metastases were seen in both lungs and the left hilar lymph nodes. The second patient presented aged 48 and was treated with external beam pituitary radiotherapy, bromocriptine, transsphenoidal hypophysectomy and chemotherapy. Fifteen years after the original diagnosis bone biopsy revealed carcinoma cells positively immunostaining for prolactin; the patient developed interstitial nephritis and died in renal failure. The third patient presented aged 48 with hypogonadism and bitemporal hemianopia due to a macroadenoma. This was removed transfrontally and followed by external beam radiotherapy. After recurrence, further surgery and radiotherapy were undertaken, but the tumour continued to grow and the patient died suddenly of a pulmonary embolus. At autopsy, tumour was found in thoracic lymph nodes and lung capillaries.

CONCLUSIONS These three patients may be added to the previous two reported cases of malignant prolactinoma with extracranial spread. Several different therapies were tried but were of limited value in controlling the progression of the disease, although chemotherapy is an important modality to be considered. No particular factor or combination of factors at presentation differentiated these patients from more typical patients whose disease is much less aggressive.
Effect of growth hormone administration frequency on 24‐hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome*
Authors: van Teunenbroek A. , de Muinck Keizer‐Schrama S. M. P. F. , Stijnen T. , Mouton J. W. , Blum W. F. , Mercado M. , Baumannl G. , Drop S. L. S. ,   the Dutch Working Group on Growth Hormone
Published: March 2008

OBJECTIVE The optimal dose and frequency of GH administration in Turner's syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single dally dose. We therefore wished to study the influence of the frequency of GH administration on 24‐hour GH profiles and levels of other growth‐related factors in Turner's syndrome.

DESIGN Four weeks after initiation of 005 μg/kg/day ethinyl oestradiol, we compared twice daily (b.I.d.‐fractionated dose) with once daily (o.d.) s.c. injections of 6 IU GH/m2/day in a 2‐week cross‐over design with a 2‐week washout Interval. Each treatment period was concluded with 24‐hour GH profile tests. Pretreatment plasma/serum levels of GH, IGF‐I, binding proteins for GH (GHBP) and IGF‐I (IGFBP‐3) were used as a basis for comparison of the levels found after each regimen. A one‐compartment open model was used for estimation of pharmacokinetic parameters.

SUBJECTS Ten previously untreated girls with Turner's syndrome aged 11 years.

MEASUREMENTS Plasma levels of GHBP by standardized binding assay; GH, IGF‐I, and IGFBP‐3 serum/plasma levels by radioimmunoassay.

RESULTS There were significantly higher maximum GH levels and a greater area under the curve with o.d. than with b.I.d. GH, while GH clearance was greater with b.I.d. The pharmacokinetic values with o.d. injections were in conformity with values for healthy and GH‐deficient children. Pretreatment GHBP levels tended to be high compared with values in healthy prepubertal children. These levels decreased with GH therapy, significantly so with b.I.d. GH only. There was a significant increase in levels of IGF‐I and IGFBP‐3, irrespective of regimen. The IGF‐I to IGFBP‐3 ratio, a possible indicator of the growth response, rose significantly and comparably with both regimens. There was no consistent diurnal variation with either regimen in GHBP, IGF‐I or IGFBP‐3 levels. Four‐hourly levels of GH, GHBP, IGF‐I and IGFBP‐3 were not correlated.

CONCLUSIONS Although the 24‐hour profiles differed during once or twice daily administration of the same total growth hormone dose, the diurnal pattern and mean levels of factors involved in the biological effects of GH are comparable for both regimens.
Interindividual differences in the pituitary‐thyroid axis influence the interpretation of thyroid function tests
Authors: Meier C. A. , Maisey M. N. , Lowry A. , Müller J. , Smith M. A.
Published: March 2008

OBJECTIVE We investigated interindividual differences in the shape, slope and setpoint of the pituitary‐thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the PTA than the currently used univariate approach.

DESIGN In two separate trials (A and B), healthy volunteers were given small, increasing doses of T3 (7 5.45 μg/day orally) over 5 days. The regulation characteristics of the individual PTAs and the effects of age and gender were assessed by general linear regression models. In addition, serum samples were collected from normal persons to establish the proposed bivariate approach for the interpretation of thyroid function tests.

SUBJECTS The regulatory characteristics of the PTA were determined in a total of 21 normal volunteers (eight females, 13 males; age 24‐49 years). Single blood samples were collected from 257 normal volunteers. The participants had no history of pituitary or thyroid disease.

MEASUREMENTS Free and total thyroid hormone and TSH concentrations were determined in the serum. All samples from one person were analysed in the same assay in duplicate.

RESULTS A log‐linear relationship between T3 and TSH was found to describe best the individual PTA (multiple r= 0.96). However, significant differences in the setpoint (P < 0.001) and to a lesser degree in the slope (P± 0.05) of the PTA were detected; this variability was not dependent on age or gender. Since these findings invalidate the assumptions on which the current univariate interpretation of thyroid function tests is based, we propose a novel model for the evaluation of thyroid function tests derived from the experimentally determined shape and average slope of the PTA.

CONCLUSIONS The presence of significant age and gender‐independent interindividual variations in the set‐point of the pituitary‐thyroid axis raises conceptual problems with the current approach for interpreting thyroid function tests. An easy to use graphical bivariate representation of the normal ranges for thyroid function tests is presented and exemplified by the thyroid hormone and TSH measurements in a large reference population. This concept should improve the diagnostic accuracy in the borderline‐normal, and particularly subclinical hypothyroid region of these hormone measurements.
Ovarian electrocauterization causes LH‐regulated but not insulin‐regulated endocrine changes
Authors: Tiitinen Aila , Tenhunen Anssi , Seppälä Markku
Published: March 2008

OBJECTIVE We studied the effects of ovarian electrocauterization on the serum levels of luteinizing hormone (LH), testosterone, insulin, sex hormone‐binding globulin (SHBG) and insulin‐like growth factor binding globulin‐1 (IGFBP‐1) in women with polycystic ovarian disease (PCOD).

DESIGN Prospective.

PATIENTS Ten women with PCOD admitted to a University Infertility Clinic.

MEASUREMENTS Fasting blood samples for determination of hormone levels were taken during the follicular phase before and one month after laparoscopic ovarian electrocauterization.

RESULTS One month after electrocauterization the serum mean ± SE LH levels had decreased from 14 4 ± 1 9 to 10 9 ± 1 1 U/l (P<0 05), while the serum insulin levels showed no significant change (10 3 ± 2 0 and 8 1 ±1 3 μ/l). The levels of IGFBP‐1 (33 9 ± 8 2 and 38 4 ± 13 7 μg/l) and SHBG (48 ± 10 4 and 43 ± 5 7 nmol/l) showed no significant changes. Testosterone decreased from 3 9 ± 2 6 to 2 9 ± 0 3 nmol/l (P<0 001) and androstenedione from 15 0 ± 1 2 to 12 0 ± 1 5 nmol/l (P= 0 05). After electrocautery seven out of ten PCOD patients ovulated either spontaneously (n= 3) or with clomiphene citrate (n= 4), and two of them conceived.

CONCLUSIONS Ovarian electrocautery leads to resumption of ovulatory cycles in some but not all PCOD patients. This effect seems to be mediated by reduction of serum LH and androgen levels, while the insulin‐driven pathway via SHBG and IGFBP‐1 remains unaffected.
The relationship between cortisol production rate and serial serum Cortisol estimation in patients on medical therapy for Cushing's syndrome
Authors: Trainer P. J. , Eastment C. , Grossman A. B. , Wheeler M. J. , Perry L. , Besser G. M.
Published: March 2008

OBJECTIVE The aim was to determine the target range into which mean daily serum Cortisol should be lowered in patients on medical therapy for Cushing's syndrome, using isotopically estimated Cortisol production rates as'gold standard.

DESIGN Patients with Cushing's syndrome on medical treatment were given 12 ng of tritiated Cortisol intravenously and a 24‐hour urine collection was made in a single day. On the same day, serum Cortisol was measured at 0900,1200,1500,1800, 2100, and at 2400 h in in‐patients. In addition, serum Cortisol was measured at the same times as above in a group of healthy volunteers.

SUBJECTS Twenty‐two patients on medical therapy for Cushing's syndrome were studied on a total of 29 occasions. In addition, serum Cortisol profiles were obtained in 12 healthy volunteers.

RESULTS The median serum Cortisol in patients with Cushing's syndrome was 400 (range 66–839) nmol/l, and in the healthy volunteers 178 (range 137–299) nmol/l. The median isotopic Cortisol production rate in the patients with Cushing's syndrome was 84 μmol/24 h, range 10–343 (normal range 22–83) μmol/24 h. In the patients with Cushing's syndrome, the correlation of mean serum Cortisol to Cortisol production rate was +0.77 (P<0.001). Normal rates were found when mean serum Cortisol levels were between 150 and 300 nmol/l.

CONCLUSIONS The aim of drug therapy for Cushing's syndrome should be to lower the mean serum Cortisol through the day into the range 150–300 nmol/l.