bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOKINETICS OF ALDOSTERONE IN PATIENTS WITH ADDISON'S DISEASE: EFFECT OF RIFAMPICIN TREATMENT ON GLUCOCORTICOID AND MINERALOCORTICOID METABOLISM
Authors: SCHULTE H. M. , MÖNIG H. , BENKER G. , PAGEL H. , REINWEIN D. , OHNHAUS E. E. 
Published: March 2008

SUMMARYTreatment of tuberculosis with rifampicin in patients with pre‐existing adrenal failure has been reported to induce adrenal crisis due to alteration of Cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half‐life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6‐β‐hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P 450 dependent enzymes. Infusion of aldosterone at a constant rate of 0‐17 mg/h over 4‐5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean ± SD, 1649 ± 144 vs 1586 ± 80 pg/ml, respectively). The disappearance curve of IR‐aldosterone from plasma was biexponential. No change could be observed in the plasma half‐lives (α‐phase 29 ± 1.9 min vs 30 ± 1.5 min, β‐phase 129 ± 3.2 minra126 ± 4.3min), the MCR (1‐47 ± 0.1 1/h/kg vs 1.46 ± 0.1 1/h/kg vs), and the volume of distribution (9.9 ± 1.9 vs 10.2 ± 0.3 1). The antipyrine half‐life decreased significantly from 12.2 ± 2.6 h to 7.6 ± 0.9 h (P± 0.05) with a rise in antipyrine clearance from 0.38 ± 0.07 to 0.80 ± 0‐23 ml/min/kg (Plt;0.05) and no change in the volume of distribution. Urinary excretion of 6‐β‐hydroxycortisol increased from 711 ± 130 μg/24 h before to 1670 ± 387/μg/24 h (P < 0‐05) after 6 days of rifampicin treatment with no changes in urinary free Cortisol excretion.
THE MATERNAL OVARY IS NOT THE SOURCE OF CIRCULATING INHIBIN LEVELS DURING HUMAN PREGNANCY
Authors: McLACHLAN R. I. , HEALY D. L. , LUTJEN P. J. , FINDLAY J. K. , de KRETSER D. M. , BURGER H. G. 
Published: March 2008

SUMMARYThe concentration of immunoreactive inhibin in serum was measured in three pregnant women with premature ovarian failure involved in a donor oocyte in‐vitro fertilization programme. Inhibin was not detectable in peripheral serum prior to conception but rose within 2‐4 weeks of embryo transfer, whereafter levels rose gradually during pregnancy (< 20 weeks 1‐22 U/ml (0.85‐1.76) versus >20 weeks 2.28 U/ml (1.42‐3.67), P < 0.01; geometric mean ± 67% confidence interval) and were similar to those observed in 24 normal pregnant women. hCG rose in parallel with inhibin during early gestation, but declined after 3 months. FSH levels were elevated before conception and were suppressed during pregnancy. In conclusion (i) immunoreactive inhibin is detectable from early gestation in women with no endogenous ovarian function indicating that the maternal ovary does not contribute significantly to inhibin secretion during pregnancy; (ii) the trophoblast is the likely source of inhibin during pregnancy; (iii) the regulation of hCG and inhibin secretion differs throughout gestation; and (iv) inhibin may have a role in FSH regulation during pregnancy and/or a local role within the feto‐placental unit.
THE PITUITARY‐LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM
Authors: TSATSOULIS A. , WHITEHEAD E. , JOHN J. ST. , SHALET S. M. , ROBERTSON W. R. 
Published: March 2008

SUMMARYEighteen men (mean age 27, range 18‐30 years) treated for Hodgkin's disease with 6‐8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age‐matched men (n= 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 ± SD 6‐9 vs 2.0 ± 1.5 IU/1, P< 0‐0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10‐3 + 3‐9 IU/1) than in controls (3‐9+1‐9 IU/1, P<00001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n= 17, mean age 27, range 17‐43 years) and in a further age‐matched control group (n= 17). Bioactive and immunoreactive LH levels were significantly increased (P< 0‐005 and P< 0‐001, respectively) in the patient group. However, the biological: immunological (B:I) LH ratios were found to be similar in the patients (2.7 ± 0.6, mean ± SD) and controls (2.8 ± 0.7). There was a significant correlation between immunoreactive LH and FSH concentrations in the patient group (r = 0‐65, P<001), but not in the controls. In conclusion Leydig cell function, as judged by the steroidogenic responses to HCG stimulation, is normal in patients with chemotherapy‐induced spermatogenic damage. The biological activity of LH is not changed, but there is a resetting of the LHLeydig cell axis
STRUMA OVARII: A CASE REPORT
Authors: LAZARUS J. H. , RICHARDS A. R. , MACPHERSON M. J. , DINNEN J. S. , WILLIAMS E. D. , OWEN G. M. , WADE J. S. H. 
Published: March 2008

SUMMARYA patient with struma ovarii and hyperthyroidism is described. She was treated for Graves' hyperthyroidism at age 22 and received thyroxine for post‐operative hypothyroidism. Twenty years later she became thyrotoxic and was treated with antithyroid drugs and radioiodine. Diagnosis of struma ovarii was made by radioiodine profile scanning and an ovarian tumour was removed. This had the pathological features of struma ovarii and autoradiographic evidence of pre‐operatively administered 125I was seen in the lesion. The patient had positive results for long acting thyroid stimulator (LATS) and LATS‐protector (LATS‐P) pre‐ and post‐operatively. Bioassays for thyroid stimulators were positive post‐operatively but radioreceptor assays for TsAb were consistently negative. It is suggested that profile scanning is an appropriate investigation for diagnosis. It is not clear whether the lesion was autonomous or being stimulated by circulating thyroid stimulators.
GH FEEDBACK OCCURS THROUGH MODULATION OF HYPOTHALAMIC SOMATOSTATIN UNDER CHOLINERGIC CONTROL: STUDIES WITH PYRIDOSTIGMINE AND GHRH
Authors: ROSS R. J. M. , TSAGARAKIS S. , GROSSMAN A. , NHAGAFOONG L. , TOUZEL R. J. , REES L. H. , BESSER G. M. 
Published: March 2008

SUMMARYWe have studied the effect of increased cholinergic tone on the GH response to growth hormone‐releasing hormone (GHRH) and on GH feedback, using pyridostigmine, an acetylcholinesterase inhibitor. In six healthy male adult volunteers 120 mg oral pyridostigmine increased basal GH secretion compared to placebo and augmented the GH response to 100 μg i.v. GHRH (1‐29) NH2; the effect was more than the additive effect of pyridostigmine and GHRH when each was given alone. Pretreatment with 2 IU methionyl‐hGH given i.v. abolished the serum GH response to GHRH given 3 h later, demonstrating a negative feedback loop of GH on the response to GHRH; this inhibited response to GHRH was restored in subjects given pyridostigmine as well as methionyl‐hGH. The data demonstrate that enhanced cholinergic tone releases GH, augments the serum GH response to GHRH and unblocks the negative feedback effect of methionyl‐hGH pretreatment on the GH response to GHRH. These results suggest that GH negative feedback effects on its own secretion occur predominantly through increased hypothalamic somatostatin secretion; this somatostatin secretion is under inhibitory cholinergic control.
THE EFFECT OF ALPHA ADRENERGIC MANIPULATION ON THE 24 HOUR PATTERN OF CORTISOL SECRETION IN MAN
Authors: AL‐DAMLUJI S. , CUNNAH D. , PERRY L. , GROSSMAN A. , BESSER G. M. 
Published: March 2008

SUMMARYWe have studied the role of central alpha‐1 adrenoceptor mechanisms which stimulate Cortisol secretion throughout the 24 h period in man. Six normal subjects were given 24 h i.v. infusions of the alpha‐1 adrenoceptor agonist methoxamine, the alpha‐1 antagonist thymoxamine, and saline under double‐blind conditions. The only cardiovascular effects of these adrenergic manipulations was a slight bradycardia accompanying the methoxamine infusion. The methoxamine infusion was accompanied by higher concentrations of Cortisol than the saline infusion during waking hours and the food related secretory surges were exaggerated, while the converse held with thymoxamine. In contrast, the nocturnal surge of Cortisol secretion was unaffected by these adrenergic manipulations. These findings suggest that an alpha‐1 adrenoceptor mechanism contributes to the maintenance of Cortisol secretion during waking hours, but not at night.
NEUROPEPTIDE Y IN MULTIPLE ENDOCRINE NEOPLASIA: RELEASE DURING SURGERY FOR PHAEOCHROMOCYTOMA
Authors: CONNELL J. M. C. , CORDER R. , ASBURY J. , MACPHERSON S. , INGLIS G. C. , LOWRY P. , BURT A. D. , SEMPLE P. F. 
Published: March 2008

SUMMARYHigh plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal <3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak =1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50‐fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.
THE EFFECT OF SUBTOTAL THYROIDECTOMY WITH PROPRANOLOL PREPARATION ON ANTIBODY ACTIVITY IN GRAVES' DISEASE
Authors: STEEL N. R. , TAYLOR J. J. , YOUNG E. T. , FARNDON J. R. , HOLCOMBE M. , KENDALL‐TAYLOR P. 
Published: March 2008

SUMMARYThe effect of subtotal thyroidectomy on thyroid stimulating antibodies (TSAb), thyrotrophin binding inhibitory immunoglobulins (TBII) and antimicrosomal antibodies (MsAb) was studied in 26 patients with Graves' hyperthyroidism treated pre‐operatively with propranolol, but without antithyroid drugs. Following surgery, two patients relapsed in the first year and eight patients became hypothyroid. Eighteen patients (69%) had detectable TSAb at entry and no significant change in titre was seen during propranolol therapy. Following surgery TSAb levels fell within 24 h in eight patients, and at 6 weeks only seven patients had detectable TSAb. TSAb were still detectable in seven patients at 6 months. TSAb activity did not predict the late relapses. TBII were present in 13 patients (50%) before surgery and titres remained unchanged in all but two patients during the immediate postoperative period. At 6 weeks TBII had disappeared from the serum of only three patients. During the early postoperative period TBII became transiently detectable in five of the 13 patients initially TBII negative. The two patients who subsequently relapsed remained TBII positive throughout. Microsomal antibodies were present in the sera of 22 patients (85%). Surgery was followed by a decline in titre, which was substantial in only six of 13 patients studied in detail. Thus, in 92% patients hyperthyroidism was successfully eradicated. Propranolol treatment had no effect on antibody activity. TSAb and TBII disappeared from the circulation in 61 % and 46% patients, respectively. These data are compatible with the concept that lymphocytes within the thyroid are the major site of TSAb production but other important sites for synthesis of thyroidal autoantibodies probably exist. Although outcome from surgery could not be accurately predicted from TSAb or TBII status either pre‐ or post‐operatively, the two patients who relapsed had the most severe disturbances of thyroid autoimmunity; all patients in whom initially detectable TSAb or TBII disappeared remained in remission.
INAPPROPRIATE ACTH CONCENTRATIONS IN TWO PATIENTS WITH FUNCTIONING ADRENOCORTICAL CARCINOMA
Authors: LAW A. , HAGUE W. M. , DALY J. G. , HONOUR J. W. , TAYLOR N. , JEFFCOATE S. L. , HIMSWORTH R. L. , JOPLIN G. F. 
Published: March 2008

SUMMARYTwo female patients with functioning adrenocortical carcinomas had plasma ACTH detectable by RIA at presentation. In both patients there was evidence for biological activity of ACTH. There was no evidence for an ectopic source of ACTH, nor for a pituitary tumour. Urinary steroid analysis showed patterns of multiple hormone secretion characteristic of adrenocortical carcinomas. The finding of detectable ACTH concentrations in a patient with Cushing's syndrome does not exclude the presence of an adrenocortical tumour.
A DOUBLE‐BLIND CROSS‐OVER 12‐MONTH STUDY OF l‐THYROXINE TREATMENT OF WOMEN WITH ‘SUBCLINICAL’ HYPOTHYROIDISM
Authors: NYSTRÖM E. , CAIDAHL K. , FAGER G. , WIKKELSÖ C. , LUNDBERG P.‐A. , LINDSTEDT G. 
Published: March 2008

SUMMARYTwenty women, who had been randomly selected from women with subclinical hypothyroidism identified in a population study were treated with l‐thyroxine and placebo in a double‐blind cross‐over design during 2·6 months. Three women did not complete the study, one because she moved to another part of the country, and two because of nervousness and sense of tachycardia. None of these ‘drop‐outs’ had any objective signs of overtreatment; they had normal pulse rate and a serum T3 concentration within the reference interval. During l‐thyroxine treatment serum procollagen‐III‐peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised (P>0·001). Serum concentrations of procollagen‐III‐peptide then correlated with those of free thyroxine (P>0·01), total thyroxine (P>0·05), and reverse triiodothyronine (P>0·05). The same comparison revealed little or no effect on the concentrations of serum creatine kinase activity, transcortin or sex‐hormone binding globulin. Heart rate‐corrected preejection period and symptom score decreased (P>0·05). Four women starting with l‐thyroxine showed a marked and prolonged (4–6 months) rise in thyrotrophin concentration during the subsequent placebo period, but remained clinically euthyroid. Four women (of 17) improved during therapy as judged by psychometric testing and their own rating. We could not by pretreatment observations identify these four women apart from serum free and total 3,5,3′‐triiodothyronine concentrations in the lower part of the health‐associated reference interval. Subclinical hypothyroidism is common among middle‐aged and old women, and our findings indicate that approximately one woman in four with this ‘subclinical’ condition will benefit from L‐thyroxine treatment.
GROWTH AND GROWTH HORMONE RESPONSES TO OXANDROLONE IN BOYS WITH CONSTITUTIONAL DELAY OF GROWTH AND PUBERTY (CDGP)
Authors: CLAYTON P. E. , SHALET S. M. , PRICE D. A. , ADDISON G. M. 
Published: March 2008

SUMMARYThirteen boys with constitutional delay in growth and/or development aged 7.6 to 16 years received 2.5mg/day of oxandrolone for 3 months. Their growth response on treatment and in the subsequent 3 months was compared to that of 14 age‐matched untreated controls. Growth rates were analysed in groups arbitrarily defined by testicular volume at entry (>4ml prepubertal, >4ml pubertal). Growth velocities increased on oxandrolone (prepubertal, mean 4.4 to 7.5cm/year, P = 0.05: pubertal, mean 4.7 to 8cm/year, p>0.05). Over the next 3 months, the pubertal boys grew at 9.3cm/year, while the prepubertal group decelerated to 6.2cm/year. Both control groups showed no significant change in velocity over 6 months. GH responses to arginine and GRF, and to sleep in prepubertal boys, were unchanged throughout the study. However, in pubertal boys the mean GH levels (‘area under the curve’) during sleep at 3 and 6 months, had increased over baseline values, associated with a significant increase at 6 months in basal somatomedin‐C (140 to 214ng/ml, p>0.05). Oxandrolone does not alter the GH status of prepubertal boys, and thus probably promotes growth by a direct action at the growth plate. In contrast, the persistent growth acceleration of pubertal boys may be associated with increased GH and somatomedin‐C levels: in this group, oxandrolone has proved a useful stimulus to growth.
ANOMALIES IN THE ASSAY OF PARATHYROID HORMONE IN NORMOCALCAEMIC PATIENTS WITH RENAL STONE DISEASE
Authors: ASHBY J. P. , LOVERIDGE N. , BROWN R. C. , ZANELLI J. M. , RINSLER M. G. , WATTS R. W. E. 
Published: March 2008

SUMMARYA group of 22 normocalcaemic patients with renal stone disease were retrospectively studied using seven different immunoassays for parathyroid hormone (PTH). N‐terminal immunoradiometric assays and an intact hormone immunochemiluminometric assay sometimes gave results which fell above the normal range. These results were at variance with values obtained in three region‐specific radioimmunoassays and an immunoradiometric assay for the intact hormone. Since these atypical samples contained normal levels of biologically active PTH the elevated immunoassay results were not thought to relate to the normal circulating hormone but rather to interference in the immunometric assays. The interfering substance was thought to be a large molecule which could not be removed by charcoal and did not dilute out in parallel to the PTH standard curve.
CRF IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME: A COMPARISON WITH THE DEXAMETHASONE SUPPRESSION TEST
Authors: GROSSMAN A. B. , HOWLETT T. A. , PERRY L. , COY D. H. , SAVAGE M. O. , LAVENDER P. , REES L. H. , BESSER G. M. 
Published: March 2008

SUMMARYAccurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin‐releasing factor (CRF‐41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high‐dose dexamethasone suppression test (8 mg/day for 48 h).Of 20 patients with confirmed Cushing's disease (pituitary‐dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high‐dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF‐41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high‐dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high‐dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.
LACK OF EFFECT OF ALDOSTERONE ON INTRACELLULAR SODIUM AND POTASSIUM IN MONONUCLEAR LEUCOCYTES FROM PATIENTS WITH PSEUDOHYPOALDOSTERONISM
Authors: WEHLING M. , KUHNLE U. , WITZGALL H. , WEBER P. C. , ARMANINI D. 
Published: March 2008

SUMMARYIn three patients with pseudohypoaldosteronism the effects of aldosterone on intracellular sodium and potassium were studied and compared with normal controls in whom aldosterone prevents the loss of sodium and potassium in vitro. Mononuclear leukocytes were incubated with or without aldosterone (1.4 n M) in RPMI‐1640 for 1 h at 37°C. After two washes in isotonic MgCl2 the wet cell pellets were weighted and intracellular sodium and potassium determined by flame photometry, results are expressed as mmol/kg wet cells. In the patients intracellular sodium fell from 18,23 and 29 mmol/kg to 14,18 and 11 mmol/kg, respectively, in the absence of aldosterone. With aldosterone added to the incubation medium sodium was not different from values obtained without aldosterone (15,20 and 13 mmol/kg). Corresponding values for potassium were 89, 48 and 75 mmol/kg before and 68, 32 and 51 mmol/kg after incubation without and 69, 36 and 54 mmol/kg after incubation with aldosterone. Thus, incubation with aldosterone did not show an effect on intracellular sodium and potassium as seen in normals. Baseline values of sodium and potassium before the incubation were within the normal range. From these results it is concluded that in patients with pseudohypoaldosteronism the absent or decreased number of mineralocorticoid receptors in mononuclear leucocytes are accompanied by a lack of response of intracellular sodium and potassium to aldosterone in vitro. However, normal baseline intracellular electrolyte concentrations in these patients may indicate that mineralocorticoids are not involved in the maintenance of normal levels of intracellular sodium and potassium.
EPISODIC PULSATILE SECRETION OF FSH, LH, PROLACTIN, OESTRADIOL, OESTRONE, AND LH CIRCADIAN VARIATIONS IN POLYCYSTIC OVARY SYNDROME
Authors: VENTUROLI S. , PORCU E. , FABBRI R. , MAGRINI O. , GAMMI L. , PARADISI R. , FORCACCI M. , BOLZANI R. , FLAMIGNI C. 
Published: March 2008

SUMMARYPulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean ± SD. PCOS subjects had high LH mean values (27.9 ± 5.9 IU/1) (P< 0.005). LH pulse amplitude was higher than controls (11 6 ± 3.7 IU/1 versus 5.2 ± 1.8 IU/1; P<0.005) while no consistent changes in frequency or interpulse interval (62.0±10.7 min versus 65.8 ± 19.2 min; P= NS) were found. A mean of 4.8 ± 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 ± 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 ± 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 ± 14.4 min and the amplitude was 2.87 ± 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 ± 12.5 pg/ml) than controls (32.0 ± 9.9 pg/ml; P<002), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 ± 18.8 pg/ml and 37.7 ± 16‐1 pg/ml, respectively); 6‐0 ± 2.2 pulses and 6.0 ± 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 ± 27.1 min and 71.8 ± 11.1 min, respectively. Sixty‐five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 ± 15 min and 25 ± 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma