bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone responses to GH‐releasing peptide (GHRP‐6) in hypothyroidism
Authors: Pimentel‐Filho Fernando R. , Ramos‐Dias João C. , Ninno Fernanda B. D. , Façanha Cristina F. S. , Liberman Bernardo , Lengyel Ana‐Maria J. 
Published: November 2003

OBJECTIVE Both spontaneous and stimulated GH secretion are reduced in patients with hypothyroidism. The mechanisms involved in these alterations are not yet fully understood. GHRP‐6 is a synthetic hexapeptide that releases GH both in vivo and in vitro. Its mechanism of action is unknown, but there is evidence that this peptide acts as a functional somatostatin antagonist at pituitary level. The aim of this study was to evaluate the GH response to GHRP‐6 in patients with primary hypothyroidism and in normal controls.DESIGN Patients with hypothyroidism and normal controls were randomly submitted to 3 tests with GHRH (100 μg i.v.), GHRP‐6 (1 μg/kg i.v.) and GHRH + GHRP‐6, on separate days.PATIENTS Eleven patients with primary hypothyroidism were compared with 10 control subjects.MEASUREMENTS GH, TSH and free T4 were measured by immunofluorometric assay and IGF‐I by radioimmunoassay.RESULTS Hypothyroid patients had markedly lower peak GH values (mean ± SE μg/l) after GHRH administration (4.1 ± 0.9) compared to control subjects (24.9 ± 5.1). After GHRP‐6 injection hypothyroid patients had a significantly higher GH release (12.6 ± 1.9) than that obtained with GHRH, while in control subjects GH values were similar (22.1 ± 3.6). No significant differences in peak GH responses were observed following the administration of either GHRP‐6 alone (controls 22.1 ± 3.6; patients 12.6 ± 1.9) or in combination with GHRH (controls 77.4 ± 15.0; patients 52.8 ± 10.9), despite the trend to smaller responses in hypothyroid patients.CONCLUSION We have shown that patients with primary hypothyroidism have higher GH responses to GHRP‐6 than to GHRH, which are markedly blunted. When GHRP‐6 was associated with GHRH, a significant increase in the GH response was observed in these patients, which could suggest a role for somatostatin in this process. Our data suggest that thyroid hormones modulate GH release induced by GHRH and GHRP‐6 through different mechanisms. However, additional studies are necessary to further elucidate this hypothesis.
Treatment of macroprolactinoma with cabergoline: a study of 85 patients
Authors: Ferrari C. I. , Abs R. , Bevan J. S. , Brabant G. , Ciccarelli E. , Motta T. , Mucci M. , Muratori M. , Musatti L. , Verbessem G. , Scanlon M. F. 
Published: November 2003

OBJECTIVE Cabergoline is now established as an effective and well‐tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro‐, as opposed to micro‐, prolactinoma. We have therefore reviewed the efficacy and safety of cabergoline in the treatment of patients with prolactin‐secreting macroadenomas treated on a compassionate basis.STUDY DESIGN AND PATIENTS Eighty‐five patients with prolactin‐secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given in one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty‐five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists.Pretreatment prolactin levels ranged between 80 and 8300 μg/l and tumour maximum diameters were between 11 and 42 mm.MEASUREMENTS Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3‐month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n=62).RESULTS Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin‐lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment.CONCLUSIONS Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well‐tolerated treatment for macroprolactinoma patients.
The relationship between overnight GH levels and insulin concentrations in adolescents with insulin‐dependent diabetes mellitus (IDDM) and the impact of recombinant human insulin‐like growth factor I (rhIGF‐I)
Authors: Cheetham Tim D. , Connors Matthew , Clayton Kharen , Watts Angie , Dunger David B. 
Published: November 2003

OBJECTIVE We examined the relationship between GH concentrations and free insulin concentrations, used as an index of insulin sensitivity, before and after recombinant human insulin‐like growth factor I (rhIGF‐I) administration in adolescents with insulin‐dependent diabetes mellitus (IDDM).DESIGN AND PATIENTS Growth hormone concentrations were assessed by a peak detection programme (Pulsar) on a control night (2000 h–0800 h) and a night when rhIGF‐I was administered in a subcutaneous dose of 40 μg/kg at 1800 h to 16 adolescent subjects. Stable euglycaemia was maintained by a continuous intravenous insulin infusion and changes in free insulin levels on the two nights were compared with growth hormone data.RESULTS Mean overnight GH concentrations (2000 h–0800 h) on the control night were positively related to glycated haemoglobin (HbA1) concentrations (r=0.63; P<0.01) and were reduced following rhIGF‐I administration (24.9±3.6 mU/l on the control night versus 17.4±2.2 mU/l after administration, P=0.01). The mean GH pulse amplitude on the control night was related to the change in GH levels after rhIGF‐I (rs=−0.66, P<0.001). Multiple regression analysis revealed that mean GH pulse amplitude was the only determinant of free insulin concentrations (0500 h–0700 h) on both study nights (P<0.01). The percentage change in mean growth hormone pulse amplitude between the two nights was related to the percentage reduction in free insulin concentrations (r=0.53, P=0.03).CONCLUSIONS Growth hormone pulse amplitude is related to early morning insulin sensitivity in adolescents with IDDM on control nights and after rhIGF‐I administration. The reduction in insulin levels following rhIGF‐I may be linked to the change in GH pulse amplitude and not just to direct insulin‐like actions. Individuals with the higher GH (and thus HbA1 levels) were most sensitive to the GH‐suppressive effects of rhIGF‐I.
Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess
Authors: Colombo P. , Passini E. , Re T. , Faglia G. , Ambrosi B. 
Published: November 2003

OBJECTIVETo assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushing's disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing.DESIGN AND SUBJECTSPlasma ACTH and serum cortisol levels were evaluated after the administration of desmopressin (10 μg i.v.), CRH (1 μg/kg i.v.) and saline on different days in 17 patients with Cushing's disease, 1 with occult ectopic ACTH syndrome, 5 with Addison's disease, 3 who had been bilaterally adrenalectomized for Cushing's syndrome and 4 normal subjects. After pituitary adenomectomy desmopressin and CRH were administered again to 13 of the patients who had undergone pituitary surgery for their Cushing's disease.RESULTSIn 16 patients with Cushing's disease with microadenoma a positive ACTH/cortisol rise occurred in 11 patients after both desmopressin and CRH, 2 other patients were responsive only to desmopressin and 2 only to CRH, while in 1 patient equivocal responses to both tests were found. The persistence of a hormonal response to desmopressin after pituitary adenomectomy for Cushing's disease correlated with unsuccessful surgery, while, contrary to CRH, absent ACTH/cortisol rises were found in cured patients 1 and 12 months after operation. In 1 patient suspected for ectopic ACTH hypersecretion, desmopressin and CRH administration did not cause any ACTH/cortisol rise. Significant ACTH rises occurred after both desmopressin and CRH testing in patients with Addison's disease. All the 3 patients adrenalectomized for Cushing's syndrome showed a rise of ACTH levels after CRH, while a similar response after desmopressin occurred in only one of them.CONCLUSIONSDesmopressin is able to stimulate ACTH and hence cortisol release in Cushing's disease. It may be a useful test in patients with doubtful responses to CRH test, in those exhibiting responses to CRH indistinguishable from those of normal subjects and in the postoperative follow‐up of Cushing's disease. In some patients with abolished or reduced cortisol feed‐back at hypothalamic–pituitary level the sensitivity of normal corticotrophs to desmopressin is enhanced.
An Assessment of Optimal Hydrocortisone Replacement Therapy
Authors: Howlett Trevor A. 
Published: November 2003

OBJECTIVE To assess the management of hydrocortisone replacement therapy in one institution, and derive recommendations for optimum starting and maintenance replacement therapy with hydrocortisone.DESIGN Retrospective survey of clinical management using a clinical information system and the patient case notes.PATIENTS Using the department’s clinical information system, 210 patients were identified who had been treated with hydrocortisone. Case notes were reviewed and 130 patients were identified whose records contained the results of at least one valid hydrocortisone day curve. Data on 174 day curves performed on these patients (65 on twice daily and 109 on thrice daily hydrocortisone regimes) formed the basis of this analysis.METHODS Hydrocortisone day curves had been performed as part of routine clinical management: patients collected a 24 h urine for free cortisol on the day prior to the test and took their morning hydrocortisone at the normal time, at home, on wakening. During a day‐case attendance serum cortisol was then measured at 0900 h, 1230 h (prior to any lunchtime dose) and 1730 h (prior to the evening dose). ‘Optimal replacement’ was arbitrarily defined as that dose which achieved a UFC and 09:00h cortisol within the reference range for the normal population (to avoid over‐replacement) combined with 1230 h and 1730 h cortisol above 50 nmol/l, and ideally above 100 nmol/l (to avoid under‐replacement). Raw data from all hydrocortisone day curves was analysed in an Excel spreadsheet to determine the effect of different dose regimens on the percentage of patients achieving each and all of these 4 criteria, and on an overall ‘quality score’ (comprising 1 point for each of the 4 criteria attained).RESULTS Patients on twice daily hydrocortisone regimes achieved optimal replacement in 15% of cases compared to 60% on thrice daily regimes (P < 0.001 by χ2); mean overall ‘quality scores’ for these regimens were 2.72 and 3.49 respectively (P < 0.001 by t‐test). Of individual dose regimens with sufficient cases for valid comparison, a dose of 10 mg/5 mg/5 mg (rising/lunch/evening) achieved optimal replacement in 66% and mean ‘quality score’ of 3.62 (n = 53), compared to 50% and 3.32 for 10 mg/10 mg/5 mg (n = 28) and 10% and 2.48 for 20 mg/–/10 mg (n =29).CONCLUSIONS The use of arbitrary, but logical, criteria to assess the quality of hydrocortisone replacement regimens indicates that optimal replacement is achieved with thrice daily hydrocortisone regimens, and that the traditional twice daily regime results in a 0900 h cortisol above normal in one‐third, and late afternoon cortisol below 50 nmol/l in one‐half of patients thus treated. An appropriate starting dose of hydrocortisone of 10 mg/5 mg/5 mg (rising/lunch/evening) is suggested, with subsequent individual adjustment based on simple hydrocortisone day curves.
Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience
Authors: Premawardhana L. D. K. E. , Hughes I. A. , Read G. F. , Scanlon M. F. 
Published: November 2003

OBJECTIVE The outlook for fertility and attaining full adult height is poor in women with congenital adrenal hyperplasia. Such outcomes have followed treatment regimes with variable ages at onset, compliance rates and monitoring. We review final height, vaginal anatomy, ovulation rates and fertility in a group of adult females with the disease.DESIGN AND PATIENTS Sixteen adult females first diagnosed in infancy or early childhood were reviewed (age range 17–33 years; 11 with salt‐wasting disease; five with simple virilizing disease). Case note and clinical review were combined with daily saliva progesterone and weekend 17‐hydroxyprogesterone estimation in three consecutive menstrual cycles in a subgroup of eight patients in the ovulation study.MEASUREMENTS AND ANALYSIS Daily saliva progesterone concentrations were transformed into a cumulative sum curve using a computer program. T95 (defined as the number of days from the start of the luteal phase saliva progesterone rise, in which 95% of total saliva progesterone for the menstrual cycle was obtained) and log C95 (where C95 was defined as 95% of total saliva progesterone for the same cycle) were plotted for each cycle on a boundary diagram obtained from a normal reference population. Weekend saliva 17‐hydroxyprogesterone concentrations were compared with published nomograms.RESULTS The majority of patients attained a final height below the parental target. Mean standard deviation scores (±SEM) and ranges were −1.49 (±0.34) and −4.2 to 0.8 for the patients and −0.38 (±0.24) and −1.89 to 0.97 for their parents. Of the combined group two‐thirds had regular menses and one‐third hirsutism; 94% had reconstructive genital surgery with 50% requiring second procedures; 77% had an adequate vaginal introitus (of them 84% in the salt‐wasting group and 75% in the simple virilizing group were sexually active). Three of five patients with salt‐wasting disease and 2/3 with simple virilizing disease who had both an adequate introitus and were sexually active conceived, resulting in eight pregnancies. In the ovulation study, a 40% ovulation rate was observed with good correlation between plasma testosterone concentrations and degree of control as assessed by weekend 17‐hydroxyprogesterone concentrations.CONCLUSIONS Our study highlights the potential for improved fertility in female patients with congenital adrenal hyperplasia, who are treated early, comply with long‐term treatment and have adequately reconstructed external genitalia. Attaining full adult height potential remains a problem.
An account of the quality of life of patients after treatment for non‐functioning pituitary tumours
Authors: Page Renee C. L. , Hammersley Margaret S. , Burke Chris W. , Wass John A. H. 
Published: November 2003

OBJECTIVE Studies assessing quality of life in GH‐deficient adults have shown varying results. This may be due to a number of factors including varying causes of GH deficiency, the use of radiotherapy in treatment and patient selection. We aimed to assess whether anterior pituitary hormone deficiency or external pituitary radiotherapy influenced the quality of life of patients with non‐functioning pituitary tumours.PATIENTS We studied 48 patients treated and under follow up for non‐functioning pituitary tumours on standard hormone replacement therapy excluding GH. There were 21 females and 27 males with a mean age of 59±12 years. We also studied 42 control patients who had undergone mastoid surgery and were followed at least annually. There were 17 females and 25 males with a mean age of 61±14 years.DESIGN All patients attended a research clinic and completed the Short Form 36 (SF36) and General Well Being Schedule (GWBS) to assess quality of life. Thyroid function tests, IGF1 and IGFBP3 were measured on all patients. Gonadotrophin and cortisol measurements were made on the patients with pituitary disease where appropriate.RESULTS IGF1 and IGFBP3 levels were lower in the pituitary patients compared with controls: 104±98 vs 143±37 μg/l (P<0.0001) and 2.9±0.75 vs 3.3±0.52 mg/l (P<0.004). There were no significant differences in the quality of life scores between the pituitary patients and the control subjects. There was also no difference in quality of life between pituitary patients with two or more hormone deficiencies (n=29) compared with controls. Patients who had received radiotherapy (n=18), when compared with controls, had a decreased mental health score using the SF36 71±21 vs 81±17 (P<0.05) and decreased total GWBS score 70±20 vs 82±17 (P<0.05). Subscore analysis of GWBS showed this to be due to depression and decreased control of emotions.CONCLUSIONS We found that the quality of life of patients treated and under follow up for non‐functioning pituitary tumours was similar to that of patients treated by mastoid surgery and under similar follow up. The pituitary patients deficient in two hormones and thus most likely to be GH deficient were also similar to the controls. These results suggest that adding GH replacement in this patient group may not be routinely indicated for improvement in quality of life and needs careful assessment. Patients who had received radiotherapy were more depressed and anxious than controls. Further investigation into the psychological and psychomotor effects of radiotherapy in this group of patients is required.
The basal rate of cell proliferation in normal human parathyroid tissue: implications for the pathogenesis of hyperparathyroidism
Authors: Wang Q. , Palnitkar S. , Parfitt A. M. 
Published: November 2003

BACKGROUND The basal rate of cell proliferation in the human parathyroid gland is generally believed to be low, but has never previously been measured directly, although, as in other tissues, it is relevant to the pathogenesis of neoplasia.METHODS We retrieved embedded tissue blocks of parathyroids removed at autopsy from 39 patients without hypercalcaemia or abnormal renal function, aged 18 to 76 years (mean 47.6). New sections were cut and examined for expression of Ki‐67, a cell‐cycle marker, using the MIB‐1 antibody with microwave antigen retrieval, and tonsil as positive control. Using an eyepiece graticule with unbiased square‐counting frame, positively labelled chief cells were counted in large squares and total chief cells in small squares in fields selected by systematic random sampling from multiple regions. A minimum of 15 ×103 chief cells were accumulated in each case. The prevalence of Ki‐67 positive cells per 104 cells (label index or LI) was converted to cell birth rate assuming that the duration of Ki‐67 expression was 24 hours. In ten cases, the entire section was examined; a map of the distribution of the positive cells was reconstructed, and divided into outer and inner regions.RESULTS The geometric mean value for LI was 1.44/104, and multiplicative SD 2.54. The corresponding geometric mean cell‐birth rate was 5.24%/year and 95% confidence interval 0.81–33.8%/year. We found no significant effect of age, sex, race, or duration of tissue storage. The distribution of cells conformed to a Poisson distribution, and there was no difference between central and peripheral regions.CONCLUSIONS (1) Our results establish the human parathyroid gland as a conditionally renewing tissue with very low basal cell‐birth rate; other reports of much higher LI values are probably due to selective and consequently biased sampling. (2) Since the total number of cell divisions is a major determinant of the total number of mutations, our results place some constraints on possible mechanisms for parathyroid neoplasia.
Abnormal effect of cigarette smoking on pituitary hormone secretions in insulin‐dependent diabetes mellitus
Authors: Chiodera P. , Volpi R. , Capretti L. , Speroni G. , Necchi‐Ghiri S. , Caffarri G. , Colla R. , Coiro V. 
Published: November 2003

OBJECTIVE We observed the effect of smoking two cigarettes on GH, AVP and cortisol secretion in patients with diabetes and normal subjects.DESIGN AND PATIENTS We tested 10 male smokers with insulin‐dependent diabetes mellitus (IDDM) and 10 normal smokers. On a different occasion, normal and diabetic smokers were tested with an insulin (0.15 U/kg body weight) tolerance test (ITT).MEASUREMENTS Hypoglycaemia‐induced hormonal responses in smokers were compared with those observed in 10 diabetic and 10 normal non smokers.RESULTS All subjects showed similar basal GH, cortisol and AVP levels. In the normal subjects, cigarette smoking induced a significant increase in circulating GH, AVP and cortisol levels, with mean peaks 3.3, 3 and 1.58 times higher than baseline, respectively. Smoking‐induced hormonal responses were significantly higher in diabetics (mean peak was 5.2 times higher than baseline for GH, 4.0 for AVP and 1.83 for cortisol). Insulin induced a similar hypoglycaemic nadir in all subjects at 30 minutes, even though the diabetic subjects had a delayed recovery in blood glucose levels. GH and AVP responses to hypoglycaemia were significantly higher in diabetic (mean peaks 11.5 and 3.2 times higher than baseline, respectively) than in normal (mean peaks 7.3 and 1.9) non‐smokers, whereas these groups showed similar cortisol responses (mean peak 2.3 times higher than baseline). Smoking did not change any hypoglycaemia‐induced hormonal rise in the normal controls, whereas it significantly enhanced GH, AVP and cortisol levels (mean peaks 14.5, 4 and 3.8 times higher than baseline, respectively) in diabetics.CONCLUSIONS In patients with IDDM, cigarette smoking not only elicits higher GH, AVP and cortisol responses than in normal subjects, but also enhances the counter‐regulatory hormone responses to insulin‐induced hypoglycaemia. These findings suggest interactions between nicotine inhaled with cigarette smoking and diabetes‐induced neuroendocrine alterations.