bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone and prolactin are secreted more irregularly in patients with Cushing's disease
Authors: Veldman Ronald Groote , Frölich Marijke , Pincus Steve M. , Veldhuis Johannes D. , Roelfsema Ferdinand 
Published: March 2003

OBJECTIVETo investigate whether the spontaneous secretion of growth hormone and prolactin in adult patients with pituitary‐dependent Cushing's disease is decreased.PATIENTSFourteen adult patients (9 women, 5 men; age: 34 ± 3.4 years, mean ± SEM) with pituitary‐dependent Cushing's disease and 14 controls matched for age, gender and body mass index were studied.METHODSBlood samples were withdrawn at 10 minutes intervals starting at 0900 h for 24 h. GH and PRL release were quantified with deconvolution methods. The regularity of GH and PRL release was measured with approximate entropy statistics.RESULTSThe number of GH secretory events per 24 h was higher in patients than in controls: 19 ± 1.3 vs. 14 ± 1.5 peaks per 24 h, respectively (P = 0.020). GH secretion rate was about one quarter lower in patients (ns), and the 24 h secretion of PRL was unchanged. Total GH production correlated negatively with the urinary excretion of free cortisol (R = 0.729, P = 0.005) and with the plasma cortisol production rate (R = 0.613; P = 0.026).The orderliness of GH and PRL secretion was appraised with the approximate entropy statistic (ApEn). For GH secretion ApEn(1,20%) in patients was 0.952 ± 0.084 vs. 0.404 ± 0.047 in controls, P = 1.17 × 10−4, pointing to a markedly disordered secretion in patients. Similar results were obtained for PRL secretion: patients: 1.586 ± 0.063 vs. 1.003 ± 0.068 in controls, P = 3.67 × 10−5. No statistically significant differences in secretory dynamics were demonstrated between the 10 patients with a microadenoma and the four with a macroadenoma.CONCLUSIONThe amount of GH released spontaneously into the circulation in adult patients with pituitary‐dependent Cushing's disease is inversely related to the degree of cortisol hypersecretion. However, except for severe hypercortisolism, GH secretion is relatively preserved. In addition, secretion of GH and PRL is remarkably disordered in patients with Cushing's disease. Since we could not detect differences in GH and/or PRL secretory dynamics between patients with a microadenoma and those harboring a macroadenoma, we speculate that an intrapituitary paracrine mechanism and/or elevated cortisol feedback effects may be responsible for the evident disruption of GH and PRL secretion patterns.
The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism
Authors: Soule Steven , Van Zyl Smit Cathy , Parolis Gerry , Attenborough Shaun , Peter Debbie , Kinvig Sue , Kinvig Tanya , Coetzer Elizna 
Published: March 2003

OBJECTIVEThe 1 μg ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic–pituitary–adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 μg ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease.DESIGNA prospective analysis of the performance of the 1 μg ACTH stimulation test in a group of patients with pituitary disease.PATIENTSThe cortisol response to 1 μg ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11‐deoxycortisol response to overnight metyrapone: normal (11‐deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11‐deoxycortisol < 200 nmol/l).MEASUREMENTSIn both controls and patients, blood was sampled for cortisol at − 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 μg synthetic ACTH (Synacthen®). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11‐deoxycortisol.RESULTSThe 65 patients with pituitary disease were categorized according to the 11‐deoxycortisol response to metyrapone as follows: 53 normal (11‐deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 μg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut‐off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%.CONCLUSIONSThe normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 μg ACTH stimulation test, like the 250 μg‐test, lacks sensitivity for the diagnosis of ACTH deficiency.
Effects of successful parathyroidectomy on altered arterial reactivity in patients with hypercalcaemia: results of a 3‐year follow‐up study
Authors: Neunteufl Thomas , Heher Sandra , Prager Gerhard , Katzenschlager Reinhold , Abela Claudette , Niederle Bruno , Stefenelli Thomas 
Published: March 2003

OBJECTIVESerum calcium was found to be an independent, prospective risk factor for myocardial infarction. We have previously shown that altered arterial reactivity in the course of primary hyperparathyroidism, a disease characterized by hypercalcaemia, may predominantly involve the arterial media and not the endothelium as observed in patients with various stages of atherosclerosis. The present study was performed to test whether successful parathyroidectomy can improve vascular reactivity in patients with primary hyperparathyroidism.SUBJECTS AND DESIGNEndothelium‐dependent, flow‐mediated and endothelium‐independent, nitroglycerin‐induced dilatation were assessed by brachial artery ultrasound (7 MHz) in 18 patients with primary hyperparathyroidism (mean ± SD; age, 55.1 ± 12.6) prior to and 3 years after successful parathyroidectomy.RESULTSParathyroidectomy resulted in significant decreases of PTH (242 ± 186 vs. 34 ± 24 ng/l, P = 0.0001) and serum calcium levels (2.8 ± 0.3 vs. 2.4 ± 0.1 mm/l, P = 0.00001) and in an increase of serum phosphate levels (0.78 ± 0.23 vs. 1.17 ± 0.18 mm/l, P = 0.00001). However, normalization of hormone and electrolyte levels did not lead to an improvement of flow‐mediated dilatation (12.1 ± 3.1 vs. 11.0 ± 5.4&, P = 0.49) or nitroglycerin‐induced dilatation (12.5 ± 3.1 vs. 13.2 ± 6.8%, P = 0.68) within the follow‐up period. No changes were observed with respect to the risk factor profile, vessel size and blood flow.CONCLUSIONThese data suggest that restoration of normocalcaemia by parathyroidectomy cannot improve vascular reactivity in patients with primary hyperparathyroidism but may prevent further progression of vascular disease within this period of time.
No advantage of the new combined octreotide‐GHRH test over established GH‐stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults
Authors: Schütz Florian , Wüster Christian , Heilmann Peter , Ziegler Reinhard , Hadji Peyman 
Published: March 2003

OBJECTIVETo evaluate the sensitivity and specificity of a combined octreotide (SMS)‐GHRH test we compared it with established GH stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults.DESIGNBecause there is no universally agreed gold standard for the diagnosis of GHD in adults it is difficult to define the relative merits of different tests in patients with structural pituitary disease. We have addressed this by grouping patients according to the degree of concordance between three established tests (insulin (IHT), arginine (ARG) and GHRH stimulation test (GHRH)) and serum IGF‐I levels and have subsequently analysed the frequency destribution of test results across defined groups: group 1, with complete GHD in all tests, group 2, with differences between tests with regard to the diagnosis of GHD and group 3, with normal GH response in all tests. The patients also underwent a new combined SMS‐GHRH test, the results of which were compared with IHT, ARG and GHRH.MEASUREMENTSFive hours after an octreotide injection GHRH was given intravenously and GH measured.RESULTSARG had the highest sensitivity (Se = 100%) and specificity (Sp = 100%) of the tests used. The IHT also diagnosed GHD with precision but showed false positive as well as false negative results (Se = 90%, Sp = 100%). Se and Sp of GHRH were lower than those of IHT and ARG (Se = 100%, Sp = 89%). The SMS‐GHRH worked well and was superior to GHRH but had less precision than IHT and ARG (Se = 88%, Sp = 100%).CONCLUSIONWe conclude that there is discordance between the three established tests and that the octreotide‐GHRH test does not have any advantages for diagnosing GHD in adults. IGF‐I levels can be used as a screening test only. The arginine test was the best conventional test in our study.
Panhypopituitarism associated with severe retroperitoneal fibrosis
Authors: Braun Jens , Schuldes Horst , Berkefeld Joachim , Zanella Friedhelm , Jonas Dietger , Usadel Klaus‐Henning , Badenhoop Klaus 
Published: March 2003

A 43‐year‐old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started.Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis.Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis ‘idiopathic retroperitoneal fibrosis’ is confirmed, fibrotic manifestations and complications involving extra‐retroperitoneal tissues including the endocrine system, should be sought.
Relationships with serum parathyroid hormone in old institutionalized subjects
Authors: Stein M. S. , Flicker L. , Scherer S. C. , Paton L. M. , O'Brien M. L. , Walton S. C. , Chick P. , Di Carlantonio M. , Zajac J. D. , Wark J. D. 
Published: March 2003

OBJECTIVE and BACKGROUND Old people in residential care are at the highest risk of any group for hip fracture. This may relate to their high prevalence of hyperparathyroidism. There are few data, however, on relationships with serum parathyroid hormone (PTH) in these individuals. This study therefore examined complex associations with serum PTH in nursing home and hostel residents.DESIGN Cross‐sectional analysis.PATIENTS One hundred and forty‐three nursing home and hostel residents of median age 84 years.MEASUREMENTS Serum PTH, 25‐hydroxyvitamin D (25OHD), 1,25‐dihydroxyvitamin D (1,25‐(OH)2D), plasma creatinine, phosphate, calcium, albumin, Bsm‐1 vitamin D receptor genotype, age, weight and use of frusemide or thiazide.RESULTS The statistical models determined accounted for half the interindividual variation in serum PTH. Heavier weight was associated with both the prevalence of secondary hyperparathyroidism and the serum concentration of PTH. Novel interactions with serum PTH were identified between: weight and 25OHD; 25OHD and phosphate; and phosphate and thiazide diuretic use. Plasma phosphate was associated with PTH independently of calcium and 1,25‐(OH)2D. There was no independent association between PTH and nuclear vitamin D receptor genotype.CONCLUSIONS Heavier weight is associated with both the prevalence and severity of secondary hyperparathyroidism and consistent with animal models of secondary hyperparathyroidism, phos‐phate may relate to serum PTH independently of 1,25‐(OH)2D or calcium.
In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A
Authors: Wessels H. T. , Hofland L. J. , Van Der Wal R. , Van Gastel L. , Van Koetsveld P. M. , De Herder W. W. , De Jong F. H. 
Published: March 2003

OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas.PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas.RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P < 0·05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0·56, P < 0·005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0·73, P < 0·0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0·79, P < 0·0005).CONCLUSIONS It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.
Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism
Authors: Karjalainen A. , Paassilta M. , Heikkinen J. , Bäckström A‐C. , Savolainen M. , Kesäniemi Y. A. 
Published: March 2003

OBJECTIVEConflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA1c have been studied only among diabetics. The objective of this studywas to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration.DESIGNThe effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17β‐oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double‐blind, double‐dummy study for six months.PATIENTSSeventy‐nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group.MEASUREMENTSOral glucose tolerance tests (OGTT) with blood glucose, serum C‐peptide and insulin determinations were performed. GHbA1c, IGF‐I and IGFBP‐1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT.RESULTSA small significant reduction in the GHbA1c concentration was observed during both peroral (P < 0·05) and transdermal oestrogen therapy (P < 0·05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C‐peptide decreased by 8% both in the peroral group (P < 0·05) and in the gel group (P < 0·01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF‐I and increased IGFBP‐1, but these findings were not associated with the changes in glucose metabolism.CONCLUSIONSNeither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.
Hypogonadism in patients with acromegaly: data from the multi‐centre acromegaly registry pilot study
Authors: Katznelson Laurence , Kleinberg David , Vance Mary Lee , Stravou Stavros , Pulaski Karen J. , Schoenfeld David A. , Hayden Douglas L. , Wright Margaret E. , Woodburn Carol J. , Klibanski Anne 
Published: March 2003

OBJECTIVEBecause acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi‐centre acromegaly patient registry.DESIGN AND MEASUREMENTSMedical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age.RESULTSInformation was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 ± 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0·0003). GH levels were higher in patients with hypogonadism (P = 0·03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively.CONCLUSIONWe developed a web‐based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia.
The biochemical and clinical course of postpartum thyroid dysfunction: the treatment decision
Authors: Stuckey Bronwyn G. A. , Kent G. Neil , Allen Janet R. 
Published: March 2003

To follow the clinical and biochemical course of a cohort of women who had postpartum thyroid dysfunction (PPTD) at 6 months postpartum and to examine the treatment practices of general practitioners and endocrinologists in the setting of PPTD.Prospective longitudinal study.Metropolitan, Perth, Australia.Eighty‐six Caucasian women who were identified to have PPTD at 6 months postpartum in a cross‐sectional study of 748 women.Characteristics of the clinical and biochemical course of PPTD and documentation of the treatment practices and factors influencing treatment of PPTD by general practitioners and endocrinologists.Sixteen of 86 women (19%) were receiving treatment at 9 months postpartum and by 30 months postpartum 27% of women had received treatment for PPTD. Fifty‐one percent of those not treated were biochemically euthyroid at 9 months, although, for those with hypothyroid biochemistry at 6 months, the median TSH at 18 months was at the upper limit of the reference range. Thyroid peroxidase antibody titre fell over the 2 years of follow‐up. There was no significant change in clinical parameters over the study. Forty‐nine percent of endocrinologists and 73% of general practitioners reported that they required clinical signs or symptoms before initiating treatment for hypothyroid PPTD.In a cohort of women with postpartum thyroid dysfunction, a quarter received treatment. Elevated TSH in untreated women does not completely return to the normal median. The role of clinical assessment in treatment decision‐making differs between primary care physicians and endocrinologists. A case is made for the early Institution of permanent thyroxine replacement in women with postpartum thyroid dysfunction, elevated TSH and positive thyroid antibodies.
The usefulness of quantitative orbital magnetic resonance imaging in Graves' ophthalmopathy
Authors: Prummel Mark F. , Gerding Martin N. , Zonneveld Frans W. , Wiersinga Wilmar M. 
Published: March 2003

BACKGROUNDTwo‐thirds of patients with Graves' ophthalmopathy (GO) respond to immunosuppressive treatment (prednisone or orbital irradiation), but one‐third do not respond. Responders are likely to be in the active, oedematous stage of the eye disease, nonresponders in the inactive fibrotic stage. Clinical distinction between the two stages can be difficult. Quantitative magnetic resonance imaging (MRI) might be helpful in this respect, as T2 relaxation times are longer in oedematous than in fibrotic tissues.STUDY DESIGNProspective study on quantitative orbital MRI in healthy subjects and patients with moderately severe GO, evaluating T2 relaxation time of extraocular muscles (EOM): (a) in patients vs. controls, and (b) in patients, as a predictor of outcome to orbital irradiation.SUBJECTS and MEASUREMENTSNine healthy volunteers and 64 consecutive patients with moderately severe untreated GO, who were euthyroid for ≥2 months and qualified for orbital irradiation. T2 relaxation times were measured at the site of the largest diameter in all eight EOM of each subject. Baseline T2 values in patients were related to outcome of radiotherapy, as assessed by an independent observer 6 months later according to predefined criteria.RESULTST2 relaxation times of the eight EOM were longer in GO patients than in controls: median [range] 126 [52–250]vs. 88 [50–126] msec; P = 0·003. Per subject the single eye muscle with the longest T2 time was selected to represent active inflammation (excluding the lateral muscles for technical reasons). Again patients were different from controls: 160 [68–250]vs. 103 [86–115] msec, P < 0·001. In the group of 34 responders to subsequent radiotherapy, these T2 times tended to be longer than in the 30 nonresponding patients: 168 [108–250]vs. 138 [68–216] msec, P = 0·07. Using a cut‐off value of 130 msec (derived from a receiver‐operator‐characteristics curve) a positive predictive value of 64% and a negative predictive value of 92% for the outcome of radiotherapy was calculated.CONCLUSIONQuantitative orbital magnetic resonance imaging was found to be less accurate in predicting succesful outcome of radiotherapy than expected. It seems more useful in detecting the fibrotic end‐stage than the active stage of Graves' ophthalmopathy. It is therefore of limited use in the decision whether or not to apply immunosuppression in patients with moderately severe Graves' ophthalmopathy.