ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8260837.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00828.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The present study was designed to determine the prevalence of 11β‐hydroxylase deficiency in adult women with hirsutism in a Turkish population.DESIGN AND PATIENTS One hundred and twenty‐four consecutive unselected hirsute patients were studied. An ACTH stimulation test was performed in the midfollicular phase of the cycle on the patients and 20 age‐matched controls by administration of a single bolus of 0.25 mg ACTH (1–24) at 0900 h.MEASUREMENTS Serum 11‐deoxycortisol levels were measured before, 30 and 60 minutes after ACTH injection. Basal free testosterone (fT), SHBG, cortisol and androstenedione (A) were also measured. The diagnosis of 11β‐hydroxylase deficiency has been presumed when the serum 11‐deoxycortisol response to ACTH stimulation exceeded three times the 95th percentile of controls.RESULTS Basal hormone levels including fT and A were significantly higher in the hirsute women than in the healthy women. SHBG was significantly lower in the hirsute patients. Basal and ACTH stimulated 11‐deoxycortisol levels were found to be significantly increased in the patients compared with the controls. Eight patients (6.5%) had an 11‐deoxycortisol response higher than three times the upper normal limit.CONCLUSIONS Using stringent diagnostic criteria, we have found that 6.5% of the hirsute women in a Turkish population could be presumed t

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8150825.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Despite improved diagnostic facilities and advancedin vitrostudies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. A defect in the regulation of GH secretion has been suggested in PCOS but the available data are limited and the underlying mechanisms remain unknown. In recent years considerable attention has been devoted to non‐classic GH secretagogues and, in particular, to the series of hexapeptides of which GH‐releasing peptide (His‐D‐Trp‐Ala‐Trp‐D‐Phe‐Lys‐NH2, known as GHRP‐6) is the most representative. GHRP‐6 seems to be a promising tool for exploring GH secretory mechanisms and it has been reported that GHRH+GHRP‐6 is a powerful stimulus to GH secretion. Our aim was to investigate the GH responses to GHRH, GHRP‐6 and the administration of GHRH+GHRP‐6 in two groups of patients (normal weight and obese) with PCOS in comparison with matched control groups.DESIGN All subjects were studied three times on different days with GHRH (100 μg i.v.), GHRP‐6 (90 μg i.v.) and GHRH+GHRP‐6 (100μg+90μg).PATIENTS Sixteen women with PCOS and 22 healthy controls were studied. They were divided into four groups according to BMI: Group A (non‐obese PCOS,n=6, age 21.8±1.7 years, BMI 22.1±0.8 kg/m2); Group B: (obese PCOS,n=10, age 12.7±1.3 years, BMI 32.9±2.1 kg/m2); Group C (non‐obese healthy women,n=13, age 26.8±1.5 years, BMI 21.8±0.6 kg/m2) and Group D (obese healthy women,n=9, age 29.4±4.2 years, BMI 35.7±1.3 kg/m2).MEASUREMENTS Serum GH was measured using a time‐resolved fluoroimmunoassay (Delphia, Pharmacia).RESULTS After GHRH administration significant differences were found between GH peaks in Groups A and B (82.4±16.4vs20±4.8 mU/lP<0.05) and in AUC for GH between Groups A and B (4667±1061vs847±236,P<0.05) while there were no differences between the same groups in GH peak or AUC after GHRP‐6 administration. There were no significant differences in peaks or AUC for GH after GHRH between Groups A and C, nor between Groups B and D. There were significant differences in GH peaks after combined administration of GHRH+GHRP‐6 between Groups A and B (211±26.4vs108±17.6,P<0.05) as well as between GH AUC in Groups A and B (12068±2323vs5997±1342,P<0.05). There were no differences in GH peaks or AUC for GH after GHRH+GHRP‐6 administration between Groups A and C or Groups B and D.CONCLUSIONS The impaired GH response to GHRH found in obese PCOS patients is a consequence of obesit

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8380848.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The GH responses to the insulin tolerance test (ITT) and growth hormone‐releasing hormone (GHRH) may yield different results in patients with pituitary lesions. The GH responses to these stimuli were compared in patients with untreated non‐functioning pituitary macroadenomas, who represent an important cause of GH deficiency.DESIGN Analysis of peak GH to ITT and to 100 μg GHRH in relation to an elevated PRL level (> 200 mIU/l for males and> 600 mIU/l for females) as an indication of hypothalamic‐pituitary dysregulation, as well as in relation to other anterior pituitary hormone deficiencies. A peak GH < 5 μg/l in either test indicated GH deficiency.PATIENTS Twenty females and 14 males (median age 52 (23−77) years) evaluated preoperatively in a university hospital setting.RESULTS In the whole group the median peak GH to GHRH (3.6 (0.9−26.3) μg/l) was higher than to ITT (1.6 (0.2−7.8) μg/l,P < 0.001). This difference was seen only in 19 patients with concomitant hyperprolactinaemia (P < 0.001). When hyperprolactinaemia was present, an insufficient GH peak was demonstrated by ITT in 16 cases and by GHRH stimulation in 7 cases (P < 0.01). The frequency of an insufficient GH peak by ITT (13 cases) and by GHRH (14 cases) was similar in the normoprolactinaemic patients. In addition, 9 of 10 patients with an impaired response to ITT and a normal response to GHRH were hyperprolactinaemic compared to 7 of 19 patients with GH deficiency as assessed by both stimuli (P < 0.02). Peak GH to ITT was lower in 24 patients with, compared to 10 patients without, other hormonal deficiencies (1.4 (0.2−5.6)vs3.0 (1.0−7.8) μg/l,P < 0.02), but was not related to elevated PRL. In contrast, GHRH‐stimulated GH was higher in hyperprolactinaemic than in normoprolactinaemic patients (5.9 (1.6−26.3)vs2.9 (0.9−5.4) μg/l,P < 0.001) and was not related to the presence of other pituitary hormone deficiencies. Analysis of covariance confirmed that peak GH to ITT was negatively associated with the presence of other pituitary hormone deficiencies (P < 0.01), whereas peak GH to GHRH was positively related to an elevated PRL level (P < 0.02). Basal GH was positively correlated with PRL (Rs = 0.36,P < 0.05).CONCLUSIONS This study demonstrates that ITT and GHRH tests cannot be used interchangeably in diagnosing GH deficiency in patients with non‐functioning pituitary macroadenoma and hyperprolactinaemia. If the ITT is considered to be the reference test, GH deficiency as assessed by GHRH can be missed in patients with hyperprolactinaemia. This disparity is probably due to a different mechanism of action of these stimuli. Hyperprolactinaemia may be associated with a diminished somatostatin

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8210831.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Elderly patients with hypothalamic‐pituitary disease exhibit a reduction in GH secretion distinct from the decline in GH secretion related to age. GH deficiency in young adults causes a change in body composition, with increased fat mass (FM) and reduced fat free mass (FFM), similar to that seen as a result of the normal ageing process. The aim of this study was to determine whether organic GH deficiency in elderly patients may cause changes in body composition beyond those due to ageing.SUBJECTS Twenty‐one patients (15 male) with documented pituitary disease and 24 controls (17 male) matched for age, height, weight and BMI, all over the age of 60, in whom GH status had been defined by a 24‐hour GH profile and an arginine stimulation test.MEASUREMENTS Serum was taken for fasting IGF‐I and IGFBP‐1 estimations. Total and regional FM and FFM were determined using dual‐energy X‐ray absorptiometry.RESULTS FM (median (range)) was increased in the patients, 27.76 (19.25–50.24)vs21.23 (8.81–49.15) kg in the controls (P < 0.005). FM was significantly increased in the arms, legs and trunk in the patients compared with the controls. The proportion of fat deposited centrally did not differ significantly between the two groups (57.0% (47.6–65.1) in the patientsvs55.3% (44.1–63.8) in the controls,P = 0.25). There was an inverse relation between total FM and serum IGFBP‐1 present in the patients, ρ = −0.632,P < 0.005, and in the controls ρ = −0.467,P < 0.05, but the relation between total FM and area under the GH profile was significant only in the controls (ρ = −0.651,P < 0.001) and not in the patients.FFM (51.19 (26.96–69.18) kg in the patientsvs51.55 (32.35–60.53) kg in the controls,P = 0.99) and serum IGFBP‐1 levels did not differ significantly between the two groups.CONCLUSION Organic growth hormone deficiency causes changes in body composition beyond the changes associated with the ageing process. These changes differ from those seen in younger GH deficient adults in that they are limited to an increase in FM with no change in FFM. These findings indicate that even in the elderly, in whom GH secretion is normally very low, the additiona

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8310842.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Previous studies of surgical treatment for acromegaly have used varied criteria for ‘cure’, but elevated GH levels are considered to be associated with continuing disease activity. We wished to analyse the results of transsphenoidal pituitary surgery for acromegaly and assess the longer‐term outcome for patients not offered further treatment when post‐operative levels of GH < 5 mU/l were achieved.DESIGN We studied a retrospective group of patients who underwent transsphenoidal surgery for acromegaly at St Bartholomew’s Hospital between 1985 and 1993.PATIENTS One hundred consecutive patients (53 male, mean age 46 years, range 18–68 years) undergoing transsphenoidal surgery for acromegaly were assessed. The patients were followed for a mean of 3.8 years (range 0.5–8 years) after operation.MEASUREMENTS GH levels are represented as a mean value from a four‐point day curve taken at 0830, 1300, 1700 and 1900h. ACTH reserve was assessed basally and, if this was normal, with the insulin tolerance or glucagon tests. TSH, T4, PRL, LH, FSH, testosterone or oestradiol and plasma and urine osmolality were also measured.RESULTS Post‐operatively, 42% of patients achieved a mean GH level of< 5 mU/l. The success of surgery was related to the preoperative GH level; 65% of the patients with preoperative GH levels 100 mU/l achieved post‐operative GH values< 5mU/l. In addition, tumour size influenced the outcome of surgery with 61% of patients with a microadenoma but only 23% of patients with a macroadenoma achieving post‐operative GH levels of< 5 mU/l. Of the 42 patients considered in remission postoperatively (mean GH < 5 mU/l), 32 were available for long‐term follow‐up and were not offered any further treatment: only one of these has shown evidence of mild biochemical recurrence after a mean follow‐up of 3.8 years (range 0.5–8).  There were no peri‐operative deaths. Two patients required surgical repair for CSF leaks and there were eight documented cases of meningitis. Permanent diabetes insipidus was noted in eight patients post‐operatively. New anterior pituitary deficiency occurred in 21% of patients following surgery; 73% had unaltered pituitary function and in 6% recovery of partial hypopituitarism was noted.CONCLUSIONS The stated outcome of surgery depends on the criteria adopted. Safe GH levels (mean levels< 5 mU/l) can be achieved in 42% of an unselected series of patients with acromegaly and if the tumour is a microadenoma this figure rises to 61%. Based on the current evidence it is safe not to offer f

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8370847.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Previous studies have shown that somatostatin analogues such as octreotide and lanreotide are effective in suppressing GH and IGF‐I levels in acromegaly, but the mode of administration and the frequency of injections were inconvenient for the patients. We have evaluated the effects of a new slow‐release (SR), long‐acting formulation of lanreotide, a somatostatin analogue, on clinical, biochemical and safety responses in acromegaly.DESIGN We studied the effects of SR‐lanreotide 30mg administered intramuscularly twice or three times monthly for 6 months. Ten patients were studied, in whom acromegaly was confirmed by clinical features,mean GH>5 mU/l, and failure to suppress GH to<2 mU/l after a 75‐g oral glucose load.MEASUREMENTS Subjective improvement in clinical symptoms of acromegaly was graded and recorded. Any adverse reactions were noted. Plasma GH levels were measured every 10min for one hour from 0830–0930h; fasting IGF‐I levels were determined at 0830h; GH, glucose and insulin responses to oral glucose loading were measured at 0,30,60,90 and 120minutes from 0930 to 1130h. Baseline measurements were carried out and repeated at 3 and 6 months. Biliary ultrasonography was performed at baseline and 6 months.RESULTS GH levels in the10 patients decreased from 26.8±12.0 (mean SEM) to 12.7±7.0 mU/l at 3 months (P=0.04) and 9.8±5.0 mU/l at 6 months (P=0.06). Fasting IGF‐I levels decreased from 123.2±27.0 to 73.5±13.0nmol/l at 3 months (P=0.01), and increased slightly to 97.4±31.0nmol/l (P=0.05) but remained below baseline levels at 6 months. Five patients achieved good control (GH<5 mU/l) at 3months. In the remaining 5 patients the dose frequency was increased to every 10 days and one achieved good control. IGF‐I levels normalized in 3 and 5 patients at 3 and 6 months, respectively. Fasting insulin levels and peak insulin after an oral glucose load did not change significantly at 3 months but decreased from 11.7±2.0 to 7.8±3.3 mU/l (P=0.05) and 106.2±24.6 to 53.3±14.3 mU/l (P=0.04) at 6 months, respectively. There was no significant change in fasting glucose at 3 or 6 months. Most patients reported clinical improvement in acromegalic symptoms. No major adverse events were reported, but mild to moderate gastrointestinal symptoms were recorded after the initial injections. One patient developed asymptomatic gallstones at 6 months.CONCLUSIONS This slow‐release formulation of lanreotide given either twice or thrice monthly was well tolerated, more convenient for patients, effective in controlling and alleviating the symptoms of acromegaly, as well as suppressing GH and IGF‐I levels, and had no detr

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8270836.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Recombinant IGF‐I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF‐I on soft connective tissue and bone metabolism in a group of patients with this disorder.PATIENTS AND DESIGN Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF‐I for 3 years with daily doses of 150–200 μg/kg. The adult LS patients were treated for 9 months with daily doses of 50–120 μg/kg. Blood samples for procollagens were collected before, during and at the end of IGF‐I treatment.MEASUREMENTS Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross‐linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF‐I administration.RESULTS Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF‐I treatment increased significantly the PIIINP levels in children from 7.2 ± 2.8 (SD) to 12.5 ± 2.2 μg/l (P < 0.001), and in adults from 2.7 ± 1.0 to 8.4 ± 3.6 μg/l (P < 0.001); serum PICP increased from 243 ± 123 to 384 ± 190 μg/l (P < 0.087) in children, and in adults from 43.4 ± 8.1 to 135.8 ± 41.9 μg/l (P < 0.001). ICTP levels in children increased from 9.7 ± 3.7 to 14.3 ± 5.9 μg/l (P < 0.001) and in adult patients levels increased from 3.6 ± 0.9 to 5.5 ± 2.2 μg/l (P < 0.001) during treatment and returned to basal values after stopping IGF‐I administration.CONCLUSIONS Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF‐I provide evidence that IGF‐I plays an important role in bone and soft connective tissue metabolism and that serum procollag

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.7990809.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE FSHcauses a dose‐related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase.DESIGN Normal volunteers were treated with a single injection of LH‐free FSH (Metrodin, 150 units) or saline as control, during the early, mid‐ or late luteal phase of the cycle, with subsequent hormone measurements.PATIENTS The 21 volunteers were aged 19–29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1–4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the mid‐luteal phase, 5–9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase.MEASUREMENTS Oestradiol (E2), progesterone (P), and INH were measured by previously described radioimmunoassays.RESULTS In both the early and mid‐luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid‐luteal 1553 to 2090 U/l) and E2(early 371 to 545 pmol/l, mid‐luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2or P.CONCLUSIONS It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly di

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8010811.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY