bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian sensitization to gonadotrophins by human growth hormone. Persistence of the effect beyond the treated cycle
Authors: Burger Henry G. , Kovacs Gabor T. , Polson David M. , McDonald Jillian , McCloud Phillip I. , Harrop Malread , Colman Peter , Healy David L.
Published: March 2008

Summary. objective To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses. DESIGN We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5–7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy.

patients

We studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea.

measurements

We measured body mass Index, FSH, LH, prolactin, growth hormone, insulin‐like growth factor I (IGF‐I), oestradiol and Inhibin at baseline and growth hormone, IGF‐I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75IU) and the last pre‐hCG dose of gonadotrophin used before, during and after growth hormone therapy.

results Baseline growth hormone levels were low but IGF‐I levels were normal. IGF‐I Increased by 20% in the subject given 4 IU growth hormone, and by 50–100% in the other two. Pretreatment dally gonadotrophin dosage of 8–11 ampoules pre‐hCG was reduced to 3–6 ampoules during growth hormone and 3–4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject.

conclusion Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs
GH response to growth hormone releasing hormone and hypoglycaemia is unaltered by high endogenous plasma calcitonin levels in patients with medullary thyroid carcinoma
Authors: Popovic V. , Micic D. , Damjanovic S. , Durbaba M. , Pelakov M. , Zorlc S. , Djurovic M. , Manojiovlc D. , Micic J.
Published: March 2008

Summary. objective As it has previously been reported that calcitonin suppresses stimulated growth hormone release, we have studied the serum growth hormone response to growth hormone releasing hormone and insulin‐Induced hypoglycaemia In patients with high calcitonin levels due to medullary carcinoma of the thyroid. DESIGN Growth hormone releasing hormone (100 μg i.v.,) and insulin (0.15 units/kg i.v.) were given and the growth hormone responses in the patients with medullary carcinoma of the thyroid and normal healthy controls were compared.

patients

Eight with hlstologically confirmed medullary thyroid carcinoma, two females and six males, aged 21–77 years, were studied and compared with seven healthy age and sex matched controls.

measurements

Growth hormone and calcitonin were measured.

results

No significant difference was found between the growth hormone responses observed in patients with medullary carcinoma when compared with normal controls either after GHRH or during Insulin‐Induced hypogiycaemia.

conclusion

We conclude that calcitonin does not alter the pituitary response to GHRH in medullary thyroid carcinoma and Is unlikely to play an important role in regulating growth hormone secretion because calcitonin did not modify the release of growth hormone after Insulin‐induced hypoglycaemia.
Biochemical and hormonal changes induced by one week of administration of rIGF‐I to patients with Laron type dwarfism
Authors: Laron Z. , Klinger B. , Jensen L. T. , Erster B.
Published: March 2008

Summary. objective The purpose of this investigation was to evaluate the effectiveness of short‐term administration of recombipant bfosynthetfc IGF‐I on patients with an hereditary inability to generate this hormone.

design and patients Ten patients with Laron type dwarfism (LTD) (4 males, six females) aged 3° to 37° years were submitted to seven daily s.c. Injections of recombinant IGF‐I in doses of 120 or 150 μg/kg/day.

measurements

Blood samples were drawn before, after three and seven Injections, and one week after stopping the trial.

results The main biochemical and hormonal changes registered were (mean ± SD): a marked rise in serum type III procollagen (PIHNP) from 4.2±0.9 to 7.3.2 μg/l (P < 0.0003) and decrease in the following blood components: plasma hGH from 32.51±43.77 to 4.02±2.48 mU/I (P < 0.001), serum cholesterol from 5.9±1 to 5.7±0.8 mmol/l (P < 0.04), serum SGOT from 28.9±11.6 to 15.5±7.6 U/I (P < 0.01) and serum LDH from 286.88 to 222.37 U/I (P 0.0005). The response of plasma insulin was variable, decreasing in seven of ten and Increasing in three. Some of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIIINP).

conclusions

IGF‐I mlmics the biochemical and hormonal changes described after administration of hGH. The administration of IGF‐I In patients with Laron type dwarfism is devoid of side‐effects and warrants assessment in long‐term studies.
Effects of hypo or hyper‐thyroidism on growth hormone‐binding protein
Authors: Amit Tamar , Hertz Pnina , Ish‐Shalom Sophia , Lotan Rachel , Luboshitzki Raphael , Youdim Mousse B. , Hochberg Zeev
Published: March 2008

Summary. objective Growth hormone (GH) receptors are Influenced by the thyroidal state of experimental animals. It has been suggested that GH‐binding protein (BP) might serve as an Indirect measure of the GH receptors. The present study was undertaken to investigate the growth hormone binding protein in patients with hypo or hyperthyroidism.

patients Patients Included 42 adults with untreated hyperthyroidism (FT4 > 25 pmol/l; TSH < 0.15 mU/I) and 29 adults and three children with untreated hypothyroidism (FT4<10 pmol/I; TSH>15 mU/I).

measurements Growth hormone binding protein was measured by a binding assay with dextran‐coated charcoal separation. The specific binding of 125I‐human GH (1 ng) obtained with 50 μl serum was expressed as a percentage of the total c.p.m.

results Growth hormone binding protein specific binding In hypothyroid adults and children was significantly lower than In their respective controls in both adults and children (P < 0.001). In patients with FT4 levels > 40 pmol/I, the mean (.SEM) growth hormone specific binding (12.89±0.59%) was higher than in controls (P < 0.05). However, In 15 hyperthyroid patients with levels of FT4 of 25–40 pmol/l, the mean growth hormone binding protein specific binding (11.22 ± 0.76%) was not different from that In normal human subjects. The affinity constants (Ka) obtained by Scatchard analysis for the hypothyroid and hyperthyroid patients' sera were not significantly different from that for normal human sera. Binding capacity for the hypothyroid sera was significantly lower (P < 0.02), while that of hyperthyroid sera was Increased (P < 0.001).

conclusions

Growth hormone binding protein correlates positively with the thyroid status. It can be indirectly deduced that this reflects a similar relationship with the human GH receptor.
The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices
Authors: Engelhardt D. , Weber M. M. , Miksch T. , Abedinpour F. , Jaspers C.
Published: March 2008

Summary. objective The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro.

measurements After Incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0–2000 μM), radioactive metabolites were separated by thin‐layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium‐labelled precursors to products.

results In vitro, ketoconazole showed a significant Inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20‐desmolase (IC50 2 μM), 16α‐hydroxylase (IC50 9 μM), 17α‐hydroxylase (IC50 18 μM), 18‐hydroxylase (IC50 28 μM), and 11 β‐hydroxylase (IC50 35 μM). In the tested concentrations ketoconazole had no Inhibitory effect on the 21‐hydroxylase, the 3β‐hydroxysteroid dehydrogenase and the 20‐hydroxysteroid dehydrogenase component of the C17,20‐desmolase enzyme system.

conclusions

The data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17,20‐desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states.
Short and long‐term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome
Authors: Verhelst J. A. , Trainer P. J. , Howlett T. A. , Perry L. , Rees Lesley H. , Grossman A. B. , Wass J. A. H. , Sesser G. M.
Published: March 2008

Summary. objective To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome.

design An evaluation of the standard clinical practice at one institution.

patients Ninety‐one patients with Cushing's syndrome: 57 pituitary‐dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.

measurements

The acute response to metyrapone was assessed by measuring cortisol, 11‐desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer‐term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean.

results A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours In all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11‐desoxycortisol levels Increased in all patients, while plasma ACTH Increased In patients with pituitary Cushing's disease and the ectopic ACTH‐syndrome. Fifty‐three patients with Cushing's disease were followed on short‐term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408–2240) dropped to the target range of < 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750–6000). Metyrapone was given long term In 24 patients with Cushing's disease who had been given pituitary Irradiation, for a median of 27 months (range 3–140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750–6000) reduced their mean cortisol levels (median 847 nmol/l, range 408–2000) to < 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH‐syndrome the ‘mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823–6354) were reduced to < 400 nmol/l In 13 patients (70%), on a median dose of 4000 mg/day (range 1000–6000). Reduction of cortisol levels was clearly associated with clinical and biochemical Improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side‐effects.

conclusions In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.
The effect of drinking on atrial natriuretic peptide, vasopressin and thirst appreciation in hyperosmolar man
Authors: Burrell Louise M. , Lambert Heather J. , Baylis P. H.
Published: March 2008

objectiyes

To assess whether drinking and oropharyngeal stimuli mediate the release of plasma atrial natrluretic peptide (ANP) in man.

design Hypertonic saline was infused into male volunteers to stimulate thirst. In order to avoid any effect of volume change on ANP release, the studies were performed with the subject in the seated position.

subjects Seated normal male volunteers (n= 6) were Infused with hypertonic saline at a rate of 0.06 ml/kg/min for 90 min on two separate occasions. After a 15‐min equilibrium period, subjects were allowed to drink for the following 45‐min period on one occasion, but no drinking was permitted on the other occasion.

measurements

Aliquots of blood were withdrawn at 30‐min intervals for 90 min during hypertonic saline Infusion, and +3, 6, 9, 12, 15, 30 and 45 min during the drinking/control period for the measurement of plasma ANP, plasma vasopressin, plasma osmolality, serum sodium and haematocr< thirst was assessed at the same time points using a visual analogue scale. Blood pressure was measured at 15‐min Intervals.

results Hypertonic saline infusion induces increases in plasma vasopressin, plasma osmolality, serum sodium and thirst appreciation (P < 0.005), and blood volume (P < 0.05) on both study days; there was no increase in plasma ANP during hypertonic saline infusion. During the drinking period there was the expected decrease in plasma vasopressin (P < 0.01), plasma osmolality (P < 0.05), serum sodium (P < 0.05) and thirst appreciation (P < 0.01); no significant changes occurred In plasma atrial natriuretic peptide, mean arterial blood pressure or haematocrlt during either the drinking or the control period.

conclusions

The drinking‐mediated inhibition of thirst appreciation and plasma vasopressin is not associated with any change in plasma ANP concentrations; it does not appear that oropharyngeal stimuli contribute to the release of ANP in man.
A distribution method for analysing the baseline of pulsatile endocrine signals as exemplified by 24‐hour growth hormone profiles
Authors: Matthews D. R. , Hindmarsh P. C. , Pringle P. J. , Brook C. G. D.
Published: March 2008

Summary. objective To develop a method for quantifying the distribution of concentrations present in hormone profiles, which would allow an observer‐unbiased estimate of the time concentration attribute and to make an assessment of the baseline.

design The log‐transformed concentrations (regardless of their temporal attribute) are sorted and allocated to class intervals. The number of observations in each Interval are then determined and expressed as a percent‐age of the total number of samples drawn In the study period. The data may be displayed as a frequency distribution or as a cumulative distribution. Cumulative distributions may be plotted as sigmoidal ogives or can be transformed into discrete probabilities (linear probits), which are then linear, and amenable to regression analysis. Probability analysis gives estimates of the mean (the value below which 50% of the observed concentrations lie, which we term ‘OC50’). ‘Baseline’ can be defined in terms of percentage occupancy—the ‘Observed Concentration for 5%’ (which we term ‘OCs’) which is the threshold at or below which the hormone concentrations are measured 5% of the time.

patients

We report the use of applying this method to 24–hour growth hormone (GH) profiles from 63 children, 26 adults and one giant.

results We demonstrate that GH effects (growth or gigantism) In these groups are more related to the baseline OCs concentration than peak concentration (0C5± 95% confidence limits: adults 0.05 ± 0.04, peakheight‐velocity pubertal 0.39 ± 0.22, giant 8.9 mU/I).

conclusions

Pulsatile hormone profiles can be analysed using this method in order to assess baseline and other concentration domains.
Long‐term follow‐up of hypothalamic‐pituitary function in patients with transsphenoidal pituitary herniation and midfacial anomalies*
Authors: Ellyin Fredrick M. , Potchynok Alan , Song Chung
Published: March 2008

Summary. objective We wished to determine whether patients with transsphenoidal pituitary herniation were at risk of developing pituitary failure.

design We followed up hypothalamic‐pituitary function annually In patients with midfacial anomalies and pituitary herniation.

patients Two patients who had transsphenoldal pituitary herniation and midfacial anomalies were Included and the literature was reviewed.

results Both patients became gonadotrophin, TSH and growth hormone‐deficient despite neurosurgical repair.

conclusion We conclude that the early diagnosis and neurosurgical repair of transsphenoidal pituitary herniation may prevent central nervous system Infection and rhinorrhoea. Surgical repair may not prevent pituitary failure as was evident in both of our cases. Periodic evaluation of the hypothalamic‐pituitary axis is essential to determine whether early hormonal replacement therapy is necessary.
Effects of sex and age on serum GH binding protein levels in normal adults
Authors: Hattori Naoki , Kurahachi Hiroyuki , Ikekubot Katsuji , Ishlhara Takashi , Morldera Kunisaburo , Hino Megumu , Saikit Yasuhiko , Imura Hiroo
Published: March 2008

Summary. objective The effects of sex and age on serum growth hormone binding protein (GHBP) levels during adulthood were investigated.

design The levels of GHBP, insulin‐like growth factor‐I (IGF‐1), and growth hormone (GH) were determined and analysed as a function of sex and age.

patients We studied 101 normal adults (45 men, aged 20–77 years; 56 women, aged 20–80 years).

measurements GHBP levels were determined using an Ultrogel AcA 44 minicoiumn.

results During the second and third decade, GHBP levels were not different between men (22.8±1.1%) (mean ± SE) and women (23.2±0.8%). After the age of 40 years, however, GHBP levels in men were significantly decreased (19.1 ± 0.7%), and were lower than those in women (22.7±0.9%). IGF‐I levels correlated positively with GHBP levels in men (r= 0.51, P < 0.01) but not in women (r= 0.16, NS).

conclusions These results indicate that both sex and age may have some effects on the GH‐GH receptor‐IGF‐I axis.
Serum and follicular fluid insulin like growth factors I and II during growth hormone co‐treatment for in‐vitro fertilization and embryo transfer
Authors: Owen E. J. , Torresani T. , West C. , Mason B. A. , Jacobs H. S.
Published: March 2008

Summary. objective We wished to assess the changes in serum IGF‐I and IGF‐ll concentrations during gonadotrophin treatment alone or with additional GH treatment and to compare follicular fluid IGF‐I and IGF‐II concentrations in the two treatment groups.

design We performed an open study of co‐treatment with GH and subsequently a randomized double blind comparison of addition of placebo or GH to clomiphene citrate and gonadotrophins.

patients We studied previously poor responders to superovulation regimens for in‐vitro fertilization and embryo transfer, six women in an open study, four of whom had ultrasound diagnosed polycystic ovaries, and 17 women in a double blind study, 12 of whom had polycystic ovaries.

measurements

We measured serum IGF‐I and IGF‐II concentrations throughout treatment cycles. Follicular fluid concentrations were measured at the time of oocyte recovery.

results

Neither serum IGF‐I nor IGF‐ll concentrations were altered by gonadotrophin treatment alone. However, co‐treatment with GH led to a significant rise In serum IGFI concentrations In women with ultrasound diagnosed polycystic ovaries. Concentrations of IGF‐I and IGF‐ll In follicular fluid were lower than in serum, although follicular fluid IGF‐I concentrations were higher in women receiving GH than in those receiving placebo.

conclusions

Poor responders to superovulation regimens may have an abnormality of growth factor response. GH co‐treatment leads to an increase in circulating IGF‐I concentrations in women with polycystic ovaries but our results do not support the hypothesis that GH stimulates IGF‐I production in the human ovary.
Treatment with biosynthetic growth hormone of short thalassaemic patients with impaired growth hormone secretion
Authors: Scacchi M. , Danes' L. , Martin M. De , Dubin' A. , Fornl L. , Masalat A. , Gallisait D. , Burrai C. , Terzoll S. , Boffa C. , Marzano C. , Cavagninl F.
Published: March 2008

Summary. objective Impairment of linear growth is a common clinical feature In patients with β‐thalassaemia major. Although growth hormone secretion appears to be normal in many short thalassaemic patients, it proves to be deficient in some of them. In these cases, administration of biosynthetic growth hormone seems justified. The aim of this study was to evaluate the effect of such treatment in a group of patients with β‐thalassaemla major presenting with growth failure and impairment of growth hormone secretion.

design Recombinant human growth hormone, 0.6 U/kg body weight per week, given subcutaneously In three divided doses, was administered for 12 months

patients Eight prepubertal patients with β‐thalassaemia‐major, presenting with severe growth retardation and Impaired growth hormone secretion In response to provocative stimuli (insulin‐induced hypoglycaemia, L‐dopa and growth hormone‐releasing hormone), were Investigated.

measurements

Height and pubertal stage of the patients, as well as plasma levels of Insulin‐like growth factor I, were determined before, during and after biosynthetic growth hormone treatment.

results During the first 6 months of therapy, a significant Increase of growth velocity was observed, from a mean pretreatment value of 20.1 ± 0.45 cm/year to a value of 4.8 ± 0.66 cm/year (P < 0.002). Mean growth rate at 12 months (4.1 ± 0.50 cm/year), though slightly decreased in comparison to that recorded at 6 months, was still significantly higher than basal (P < 0.001). A significant Increase In plasma levels of Insulin‐like growth factor I was recorded during treatment (2.82 ± 0.47 vs 0.96 ± 0.22 U/ml, P < 0.005). No side‐effects, adverse reactions or alterations in routine laboratory examinations ensued during or after therapy.

conclusions It appears from these data that biosynthetic growth hormone administration Is worth serious consideration In patients with β‐thalassaemia major presenting growth retardation and Impaired growth hormone secretion.
Follicle stimulating hormone stimulates the production of gonadotrophin surge attenuating factor (GnSAF) in vivo
Authors: Messinis I. E. , Hirsch P. , Templeton A. A.
Published: March 2008

Summary. objective To study the time‐course production of gonadotrophin surge attenuating factor (GnSAF) after the onset of FSH treatment in women.

design Normally cycling women were treated with FSH injections (225 IU per day) starting on cycle day 2 (0800 h). The response of LH to an i.v. Injection of 10 μg GnRH (GnSAF bioactivity) was investigated 12, 24, 36 and 48 hours after the first FSH Injection, as well as during the early follicular phase of an untreated spontaneous cycle. PATIENTS Six normally ovulating women with long‐standing unexplained infertility were studied. The women were used as their own controls during the spontaneous cycles. MEASUREMENTS Pituitary response to GnRH was calculated as the net Increase in LH at 30 min (ALH30) above the basal value.

results

δLH30 was significantly attenuated 12, 24, 36 and 48 hours after the first FSH injection as compared to the spontaneous cycles. In the latter cycles, ALH30 decreased significantly from day 2 (12 hours) to day 4 (48 hours). Serum oestradiol levels at 12 and 24 hours did not differ significantly between the FSH and the spontaneous cycles.

conclusions

These results demonstrate that in superovulated women, a marked attenuation in the pituitary response to GnRH occurs as early as 12 hours from a single injection of FSH before any significant Increase In serum oestradiol levels. It is suggested that FSH is a potent stimulus of GnSAF production in women.
Meningitis as a late complication of surgically and medically treated pituitary adenoma
Authors: Flad T. M. , McKenna T. Joseph
Published: March 2008

Summary. objective To report meningitis occurring as a late complication of both medical and surgical treatment of pituitary tumour.

design Two case reports.

patients One patient developed meningitis 9 years after she underwent transsphenoidal hypophysectomy for Nelson's syndrome. The second patient developed rhinorrhoea while on treatment with bromocriptine for a prolactin‐secreting pituitary adenoma and subsequently developed meningitis.

measurements

In Patient 1, CT scanning identified a small defect in the floor of the sells turcica. In Patient 2, CT scan examinations performed with a 3‐year interval demonstrated marked shrinkage of a pituitary tumour which had invaded the sphenoid sinus so that the tumour no longer plugged the erosion.

results

Both patients experienced rhinorrhoea for over a year prior to the onset of meningitis. Both patients dismissed the occurrence of rhinorrhoea as insignificant and did not bring it to medical attention. In Patient 1, rhinorrhoea and presumably the entry site for pneumococaal infection was through a defect in the floor of the sella turcica consistent with transsphenoidal hypophysectomy performed 9 years previously. In Patient 2, rhinorrhoea and presumably entry of infection was facilitated by unplugging of a defect in the wall of the sphenoid sinus by bromocriptine‐induced shrinkage of the pituitary adenoma.

conclusions

Meningitis can occur as a late complication of surgical or medical treatment of pituitary tumours. This may be preceded by rhinorrhoea which should be regularly enquired for as the symptom may not prompt patients to disclose its presence spontaneously. These reports document only the third occurrence of meningitis as a late complication of transsphenoidal hypophysectomy and the first occurrence of meningitis as a consequence of treatment of a pituitary tumour with bromocriptine.
Changes in concentrations of cortisol, dehydroepiandrosterone sulphate and progesterone in fetal and maternal serum during pregnancy
Authors: Donaldson Amanda , Nicolini Umberto , Symes Elizabeth K. , Rodeck Charles H. , Tannirandorn Yuen
Published: March 2008

Summary. objective In fetuses, adrenal steroids have been Implicated In organ maturation and in some species in initiation of labour. The fetal adrenal gland differs from the adult in its complement of steroid metabolizing enzymes. This study sought to examine the changes in peripheral cortisol, progesterone and dehydroepiandrosterone sulphate (DHEAS) in unstressed fetuses during pregnancy. DESIGN Paired maternal and fetal samples were collected from 47 patients. Fetal blood samples were collected by transabdominal needling. All fetuses were appropriately grown for age which ranged from 18 to 41 weeks.

measurements

Hormones were measured using specific, validated Immunoassays.

results Fetal progesterone (mean, 822 nmol/l; 95% data Intervals 196–1449 nmol/l) varied considerably between Individuals but there was no significant change In serum concentration with gestational age, nor was there any difference between male and female fetuses. There was a small, but significant (y= 0.339x2–13.5x+ 231; r= 0.72, P= 0.0001) rise in cortisol in the fetal circulation from 32 to 41 weeks gestational age, whereas the mean fetal DHEAS concentration decreased linearly with gestational age from 4.1 μmol/l at 18 weeks to 2.6 μmol/l at 41 weeks (r=–0.41; P= 0.007). Mean progesterone concentration in the maternal serum Increased linearly from 98 nmol/l at 18 weeks to 783 nmolll at 41 weeks. In the fetus there was a significant correlation between progesterone and cortisol concentrations.

conclusions

These results are compatible with the proposed role of cortisol in fetal lung maturation, confirm high levels of progesterone in the fetus from an early stage of gestation, and provide further evidence for placental progesterone being the precursor of fetal cortisol.
Attenuation of gonadotrophin release and reserve in superovulated women by gonadotrophin surge attenuating factor (GnSAF)
Authors: Messinis Loannis E. , Templeton Allan
Published: March 2008

In‐vivo and in‐vitro studies have provided evidence that a non‐steroidal ovarian factor, called gonadotrophin surge attenuating factor (GnSAF), attenuates the endogenous LH surge in superovulated women. To study the mechanism of action of GnSAF, the LH response to two i.v. pulses of GnRH (10 μg each, 2 h apart) was investigated in eight normally ovulating women during the late follicular phase of a spontaneous and an FSH superovulated cycle. The maximal LH increase in response to the first pulse (initial release) was considered as representing the acutely releasable pool and the δLH area under the whole curve (integrated response) the reserve pool of LH. Both the initial release and the integrated response to GnRH were markedly attenuated in the FSH as compared to the spontaneous cycles. The response to the second pulse was significantly greater than the response to the first pulse (self‐priming effect of GnRH) in both the spontaneous and the FSH cycles. However, in the FSH cycles the self‐priming effect of GnRH was markedly reduced as compared to the spontaneous cycles. We conclude that during superovulation induction in women the two pools of pituitary LH are markedly attenuated. It is suggested that GnSAF attenuates both the GnRH‐induced initial release of LH and the self‐priming effect of GnRH on the pituitary.
d‐Fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen‐induced alteration
Authors: O'Keane V. , O'Hanlon M. , Webb M. , Dinan T.
Published: March 2008

The prolactin (PRL) response to fenfluramine (FEN), a serotonin (S‐HT) releasing agent, is used as an index of 5‐HT sensitivity in studying disorders associated with central S‐HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid‐cycle and late luteal phase with either d‐FEN, a more specific 5‐HT agent than the racemic mixture, or placebo. Responses to d‐FEN were maximal at mid‐cycle, lowest during the early follicular phase, with responses premen‐strually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated In parallel with neuroendocrine responses to d‐FEN. The possible mechanisms are discussed, Including an effect that oestradiol may exert at central serotonin sites.
Serum androgens in intensive‐care patients: correlations with clinical findings
Authors: Luppa P. , Munker R. , Nagel D. , Weber M. , Engelhardt D.
Published: March 2008

Serum androgen levels were studied In 100 patients (50 male) with varying degrees ot severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes:

Basal dehydroeplandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P< 0.001) as well as in the III males (two groups, P<0.01; P<0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P< 0.001), but not in females.

The low testosterone concentrations in the severely ill male patients correlated Inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated In men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not In III females.

17α‐OH‐progesterone and 17α‐OH‐pregnenolone levels in subgroups of the patients suggested a probable enzymatic block In the A5‐pathway of androgen biosynthesis in severe illness. The ratio of 17α‐OH‐pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17α‐OH‐progesterone to androstenedione showed no difference between healthy and ill subjects.
Serum levels of free and bound testosterone in hyperthyroidism
Authors: Ford H. C. , Cooke R. R. , Kelghtley E. A. , Feek C. M.
Published: March 2008

objective The aim of this study was to improve knowledge about the relationships between free and bound forms of testosterone in serum and the major testosterone‐binding proteins during hyperthyroidism

design nine men and 11 women were studied when hyperthyroid due to Graves' disease and again after at least 3 months of euthyroidism

measurements The serum concentrations of free T3, free T4, TSH, sex hormone‐binding globulin (SHBG), LH, progesterone and free, non‐SHBG bound and total testosterone were determined

results For both sexes, hyperthyroidism was associated with significant elevations of the mean totat testosterone and sex hormone‐binding globulin (SHBG) levels and significant depressions of the mean percentage and concentration of non‐SHBG‐bound testosterone and the mean percentage of free testosterone. For women, the mean free testosterone concentration was significantly lower during hyperthyroidism than during euthyroidlsm; no Significant difference in mean free testosterone concentration was observed between hyperthyroid and euthyroid men. When the experimentally derived data were analysed according to a model based on the binding constants of testosterone with SHBG and albumin, the simulated results for each patient when hyperthyroid and euthyroid paralleled the actual results. However, the model consistently overestimated the actual amounts of non‐SHBG‐bound testosterone. There was a significant correlation between SHBG concentration and the severity of thyrotoxlcosis as measured by the change in thyroid hormone levels between eukhyroidlsm and hyperthyroldism

conclusions Our results support the following pathogenetic sequence: thyrotoxicosis leads to a rise in serum SHBG concentration which Is accompanied by an increase In testosterone concentration, a fall In the concentration of non‐SHBG‐bound testosterone and little or no change in the concentration of free testosterone
Contraceptives containing desogestrel or levonorgestrel have different effects on serum lipoproteins and post‐heparin plasma lipase activities
Authors: Kaupplnen‐Makelln Rltva , Kuusl Timo , Ylikorkala Olavl , Tlkkanen Mattl J.
Published: March 2008

objective We examined the effects of mono and polyphasic oral contraceptives containing desogestrel or levonorgestrel on serum lipoproteins, sex hormone binding globulin and post‐heparln plasma lipase activities

design The women took either desogestrel or levonorgestrel during the first menstrual cycle on days 15–28. They then received monophasfc ethlnyloestradiol plus either desogestrel or levonorgestrel for three cycles. After this, the women took sequential pills containing ethlnyloestradiol plus either desogestrel or levonorgestrel for the three following cycles. Fasting blood samples were drawn pretreatment and at the end of each treatment

patients The study group consisted of 30 apparently healthy women, aged 18–35. They were randomly divided Into desogestrel and levonorgestrel groups, each consisting of 15 women

measurements Cholesterol, triglyceride and phosphollplds were determined in whole serum and In all lipoprotein fractions (following isolation of lipoproteins by ultracentrifugatlon). Plasma apolipoproteln A‐l concentration, post‐heparln plasma lipase activities and serum sex hormone binding globulin were also measured

results Desogestrel (150 μ g/day) did not change serum total triglyceride concentration, whereas levonorgestrel (150 μ g/day) decreased it. Except for monophasic ethinyloestradiol plus levonorgestrel, the oestrogen‐containing combinations increased serum triglyceride level. Low density lipoprotein (LDL) cholesterol remained stable with all treatments, but the cholesterol/triglyceride ratio of LDL decreased during all combinations with ethinyloestradiol. Levonorgestrel reduced total high density lipoprotein (HDL) cholesterol and both progestins reduced HDL2 cholesterol concentration. Addition of ethlnyloestradiol reversed this change in the desogestrel but not in the levonorgestrel group. The polyphaslc ethinyloestradiol plus levonorgestrel combination did not change total HDL cholesterol. Hepatic lipase was activated with either progestln when administered alone but Its activity was suppressed below the baseline level when ethlnyloestradiol was added. Conversely, both progestins suppressed sex hormone binding globulln levels, but addition of ethlnyloestradiol caused marked Increases above baseline. These increases were greater in women taking desogestrel than in those taking levonorgestrel. No treatment affected lipoprotein lipase activity significantly.

conclusions Monophasic or polyphaslc combinations of ethlnyloestradiol and desogestrel do not have deleterious effects on serum lipoproteins. If levonorgestrel is used as the progestln component, polyphaslc ethlnyloestradiol plus levonorgestrel appears more favourable than monophasic ethlnyloestradiol plus levonorgestrel
Assessment of the risk of post‐menopausal osteoporosis using clinical factors
Authors: Ribot C. , Pouilles J. M. , Bonneu M. , Tremollieres F.
Published: March 2008

obfective We wished to assess the predictive value of the main clinical risk factors for osteoporosis over a low vertebral bone mineral density

design A cross‐sectional study was made of a cohort of peri and post‐menopausal women (mean age, 54 years)

patients One thousand, five hundred and sixty‐five normal white women were selected from among the women referred to our menopause clinic for screening and prevention of osteoporosis

measurements Each woman had replied to a detailed standardized questionnaire including the main clinical risk factors and had her bone density measured using dual photon absorptiometry

results The predictive value for a low vertebral bone mineral density (2 SD below the normal young adult value) was assessed for 15 historical and anthropometric vari‐ables. Among these, age, age at menarche, weight, height, menopause and its duration, were independant predictors of a low bone mineral density, in a multiple logistic regression analysis. Odds ratios were calculated for each of these variables, weight, menopause and its duration being the three most influential variables. At best this model makes it possible to correctly classify 73% of women with a low bone mineral density and 66% of those with a normal bone mineral density. If this model Is used for screening, it could possibly save 25% of bone denslto‐metry examinations

conclusions Direct bone densitometry remains indispensable to assess osteoporosis risk, since risk factors alone are not sufficient for accurate delineation of either low or normal bone mineral density
Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome
Authors: Adams M. , Nagaya T. , Tone Y. , Jameson J. L. , Chatterjee V. K. K.
Published: March 2008

objective We wished to ascertain whether a mutation in the thyroid hormone receptor β gene was present in a family with generalized thyroid hormone resistance syndrome and to characterize the functional properties of this mutant receptor.

design Blood samples were obtained from family members for hormone assays and genomic DNA was isolated from leucocytes for genetic analyses

patients Three members (B, C, E) of a family with possible thyroid hormone resistance and two normal family members (A, D) were studied

measurements Basal thyroid function tests together with serum sex hormone binding globulin (SHBG) levels were measured. The thyroid hormone receptor β gene was amplified using the polymerase chain reaction and the receptor mutation identified by sequence analysis. The ability of mutant receptor to bind T3, interact with a specific DNA sequence and to modulate target gene expression was tested. The effects of mutant receptor on co‐expressed wild type receptor action were determined.

results Patients with resistance had raised levels of T4 and T3 together with inappropriately normal serum TSH and SHBG whereas unaffected individuals had a normal hormone profile. A single nucleotide substitution corresponding to a giycine to serine mutation at codon 340 (G340S) in the hormone binding domain was identified in one of the two β receptor gene alleles in patients with resistance, but not in the normal family members. When expressed in vitro, this receptor protein (G340S), as well as a related (G340R) mutant identified in another family, retained the ability to bind to a specific DNA sequence but were unable to bind ligand or to activate or repress target gene expression. in addition both receptor mutants were capable of Inhibiting the function of wlld type thyroid hormone receptor in a co‐expression assay but differed In their inhibitory potential.

conclusions We report a second type of mutation (Gly to Ser) in codon 340 of hTRβ in a family with generalized thyroid hormone resistance. Mutations at thls slte ellminate T3 blndlng, causing a loss of hormone‐stimulated receptor functlon. However, the mutant receptors retain the abllity to block normal receptor action. The occurrence of different mutations at the same site suggests that alterations in this region of the receptor may be Important for generatlng the clinical phenotype of thls disorder.
Preserved thyroidal secretion of thyroxione in acromegalic patients with suppressed hypophyseal secretion of thyrotrophin
Authors: Yoshinari Motolaka , Tokuyama Takashi , Kuroda Takeo , Sato Kaori , Okazawa Kaeko , Mizokami Tetsuya , Okamura Ken , Fujishima Masatoshi
Published: March 2008

objective We have assessed the mechanisms which maintain euthyroidism in acromegalic patients despite the suppression of thyrotrophin (TSH) secretion

materials Fourteen untreated patients with acromegaly were analysed. Ten patients were also studied after pituitary surgery

methods Thyroid hormones, growth hormone (GH), Insulin‐like growth factor‐I (IGF‐I) and thyroidal uptake of radioactive iodine, thyrotrophin releasing hormone (TRH) test and basal metabolic rate (BMR) were measured before and after pituitary surgery

results Nine patients had paipable goitres. The TSH response to TRH stimulation was suppressed in eight patients, who maintained normal serum levels of total T3, T4 and free T4. The patients with normal TSH response had lower levels of free and total T4 than controls. The response of TSH to TRH correlated inversely with the serum level of total and free T4, and also with the plasma level of IGF‐I (r=–0·74, P > 0·05, n= 9). After pituitary surgery, the serum levels of total and free T4 were elevated for at least up to 6 months, with a decrease in the T3/T4 ratio and the BMR.

conclusion GH may have a direct stimulatory action on the thyroid secretion of T4 possibly via increased IGF‐I, despite suppressed TSH secretion. The post‐operative elevation of serum T4 suggests the persistent secretion of T4 from the thyroid gland, in spite of instantaneous normalization of the accelerated conversion of T4 to T3, even after reduction of excess GH secretion
The incidence of late‐onset congenital adrenal hyperplasia due to 3β‐hydroxysteroid dehydrogenase deficiency among hirsute women
Authors: Mathieson J. , Couzinet B. , Wekstein‐Noel S. , Nahoui K. , Turpin G. , Schaison G.
Published: March 2008

objective The present study was designed to determine the incidence of 3β‐hydroxysteroid dehydrogenase deficiency (3β‐HSD) in adult women with hyperandrogenism.

design and patients In 78 hirsute patients and 30 normal women in the same age range, an ACTH stimulation test was performed on day 5 of the cycle by administration of a single bolus of 0·25 mg ACTH‐(1– 24) at 0800 h

measurements The following steroids were measured before, 30 and 60 minutes after ACTH Injection: Δ5‐pregnenolone (Δ5‐P), 17‐hydroxy‐Δ5‐pregnenolone (17‐OHΔS‐P), dehydroeplandrosterone (DHEA), Δ5‐androstenediol, progesterone (P), 17‐hydroxyprogesterone (17‐OHP), androstenedione (A), testosterone (T) and cortisol

results Maximum ACTH‐stimulated values of ΔS‐steroids were in excess of the 90% confidence limits of the control group in 19 hirsute women. Ten patients had an isolated increase in Δ5‐P, 17‐OHΔ5‐P, DHEA or Δ5‐androstenediol. Nine patients had an increase in two Δ5 steroids and none had increased values of three or four Δ5 steroids. The ratios of 17‐OHΔ5‐P to 17‐OHP, DHEA to A, Δ5‐P to P and Δ5‐androstenediol to T were increased in 5, 1, 1 and 1 patients respectively. No patient had elevated values of more than one ratio

conclusions Using stringent diagnostic criteria, partial 3 β‐HSD deficiency was excluded in all 78 patients and therefore appears to be a rare disorder.
Investigation of adrenal function in women with oligomenorrhoea and hirsutism (clinical PCOS) from the north‐east of England using an adrenal stimulation test*
Authors: Turner Elaine I. , Watson Malcolm J. , Perry Leslie A. , White Michael C.
Published: March 2008

objective To determine the prevalence of adrenal enzyme dysfunction in women presenting with oligomenorrhoea and hirsutism, two clinical features of polycystic ovary syndrome (PCOS)

design A prospective study of women attending outpatient clinics with these complaints. Androstenedione, dehydroepiandrosterone (DHEA), 17‐hydroxyprogesterone (17‐OHP), 11 ‐deoxycortisol and cortlsol were measured before and after overnight dexamethasone suppression and at 60 minutes after adrenal stimulation by ACTH injection

subjects Fifty women with clinical features of PCOS and 37 control women with regular cycles and normal hair distribution from the catchment area of the Royal Victoria infirmary which includes Newcastle upon Tyne, Co. Durham, Cleveland, Cumbria and Northumberland

measurements Number of women with steroid responses to ACTH beyond the normal range, as defined by the responses of the control group and in previous studies

results Nineteen women (38%) were found to have some abnormality. One woman (2%) was identified with 21‐hydroxylase (21‐OHase) deficiency and a second (2%) had an increase in 17‐OHP compatible with the heterozygote state for 21‐OHase deficiency. Four women (8%) had isolated elevations in the DHEA response consistent with minimal 3β‐hydroxysterold dehydrogenase (3β‐HSD) deficiency. Thirteen women (26%) showed increases in both androstenedione and DHEA, or androstenedione alone, compatible with enhanced 17–20 lyase activity.

conclusions Twelve per cent of the group showed evidence consistent with an adrenal enzyme deficiency; 26% had results in keeping with increased adrenal androgen production without an enzyme deficiency. These findings may be of relevance both in the pathogenesis of the features of PCOS and in determining appropriate treatment for individual patients
Nelson's syndrome following partial pituitary microadenomectomy and pregnancy
Authors: Igoe D. , Pidgeon C. , Dlnn J. , McKenna T. J.
Published: March 2008

We report for the first time the development of Nelson's syndrome in a patient who had previously undergone unsuccessful pituitary microadenomectomy and subsequently bilateral adrenalectomy. The removal of a 3‐mm portion of a microadenoma did not protect against the development of Nelson's syndrome within 3 years which was closely related to pregnancy, a previously noted association. This report suggests that the development of Nelson's syndrome depends not on the size of the initial pituitary tumour but rather on its individual potential for proliferating once free of the inhibitory effects of glucocorticold excess