bluuebunny/crossref_metadata_2025_split huggingface dataset:
KINETICS OF PLASMA CORTICOSTEROIDS DURING METYRAPONE INFUSION IN MAN
Authors: LEJEUNE‐LENAIN C. , WOLTER R. , FRANCKSON J. R. M. 
Published: March 2008

SUMMARYThe effect of metyrapone on plasma kinetics of cortisol (F), 11‐deoxycortisol (S), corticosterone (B), 11‐deoxycorticosterone (DOC), aldosterone (Aldo) and 17 hydroxyprogesterone (17 OHP) was studied in ten normal prepubertal children intravenously infused with the drug (1 gm/1.73 m2 body surface area in 4 h).Similar falls in F, B and Aldo were observed during the first hour expressing similar sensitivity of the 11 hydroxylases to the drug. The effect of the compensatory increase of endogenous ACTH could be detected after 1 hour by the rise in 17 OHP. However the concentrations of the 11‐hydroxy compounds, F, B and Aldo, remained low throughout the infusion period.From the second hour onwards, facilitation of the synthesis of DOC was noticed.After the end of infusion, the levels of the precursors decreased and F and B were restored to initial values. Aldo remained low probably due to the inhibitory effect of the elevated DOC on the renin‐angiotensin system.
NON‐PROTEIN‐BOUND OESTROGENS IN PLASMA AND URINARY EXCRETION OF UNCONJUGATED OESTROGENS IN MEN
Authors: SPEIGHT ALISON C. , HANCOCK K. W. , OAKEY R. E. 
Published: March 2008

SUMMARYUnconjugated oestrone and unconjugated oestradiol‐17β were measured in 24 h urine specimens from twenty normal men. The concentrations of non‐protein‐bound oestrone and non‐protein‐bound oestradiol‐17β, in samples of blood obtained from these subjects during the time in which the urine was collected, were measured by equilibrium dialysis (using a correction for plasma dilution). The mean excretion of unconjugated oestrone (0.44 ± 0.36 nmol/24 h, mean ± SD) was significantly greater (P < 0.01) than that of unconjugated oestradiol‐17β (0.20 ± 0.13 nmol/24 h). The concentrations of non‐protein‐bound oestrone and non‐protein‐bound oestradiol‐17β in plasma were 5.52 ± 2.69 pmol/1 and 2.42 + 0.73 pmol/l, respectively.There was no correlation between the quantity of unconjugated oestrone excreted and the concentration of non‐protein‐bound oestrone in plasma (r= 0.27) nor between the quantity of unconjugated oestradiol‐17β in the urine and the concentration of non‐protein‐bound oestradiol‐17β in plasma (r= 0.05). Therefore in normal men, estimation of unconjugated oestrone or oestradiol‐17β in urine provides no guide to the concentration of the corresponding non‐protein‐bound oestrogen in plasma.
AMNIOTIC FLUID CONCENTRATIONS OF 3,3′,5′‐TRI‐IODOTHYRONINE (REVERSE T3), 3,3′‐DI‐IODOTHYRONINE, 3,5,3′‐TRI‐IODOTHYRONINE (T3) AND THYROXINE (T4) IN NORMAL AND COMPLICATED PREGNANCY
Authors: MEINHOLD H. , DUDENHAUSEN J. W. , WENZEL K. W. , SALING E. 
Published: March 2008

SUMMARYAmniotic fluid concentrations of 3,3′,5′‐tri‐iodothyronine (rT3), 3,3′‐di‐iodothyronine (3,3′‐T2), 3,5,3′‐tri‐iodothyronine (T3) and T4 were studied in 384 women during normal and complicated pregnancy. An inverse correlation was observed between decreasing rT3 and increasing 3,3′‐T2 concentrations in amniotic fluid with gestational age. The mean rT3 level in normal pregnancy was 2.81 nmol/l at 12–20 weeks and decreased significantly to 1.06 nmol/l at 36–42 weeks of gestation. The mean 3,3′‐T2 concentration was 49.1 pmol/l at 12–20 weeks increasing to 119 pmol/l at 36–42 weeks. The mean T4 value of 3.83 nmol/l at 12–20 weeks was about half that of later periods. The T3 concentration in a random sample of 45 amniotic fluids ranged from <28 to 370 pmol/1 (mean 102 pmol/l). The mean rT3, 3,3′‐T2 and T4 values measured in patients with intra‐uterine malnutrition, gestation diabetes, tocolysis, placental insufficiency and rhesus incompatibility at 31–40 weeks of gestation were not significantly different from those in uncomplicated pregnancy. Significantly decreased rT3 and T4 concentrations were found in toxaemia. From the results obtained in complicated pregnancy it may be concluded that measurements of iodothyronines, especially rT3, in amniotic fluid have insignificant diagnostic value in the recognition of intra‐uterine lesions with the probable exception of fetal hypothyroidism. The analysis of the dependence of iodothyronine concentrations on the gestational age showed a maximum of rT3 and T4 levels between 20 and 30 weeks of pregnancy. This marked rise of iodothyronine concentrations in amniotic fluid at mid‐gestation may be due to the onsetting maturation of the hypothalamic‐pituitary‐thyroid control system of the fetus.
RAPID ASSAY OF PLASMA 21‐DEOXYCORTISOL AND 11‐DEOXYCORTISOLIN CONGENITAL ADRENAL HYPERPLASIA
Authors: FUKUSHIMA D. K. , NISHINA T. , WU R. H. K. , HELLMAN L. , FINKELSTEIN J. W. 
Published: March 2008

SUMMARYPlasma assays using highly specific antisera to 21‐deoxycortisol, 21‐deoxycortisone and 11‐deoxycortisol were developed to provide a rapid means of diagnosis in patients with congenital adrenal hyperplasia (CAH). The assays were done on plasma extracts with and without Celite chromatography to compare the results of direct assays on plasma extracts and assays on purified plasma extracts. Both methods showed elevations of metabolites that permitted the correct diagnosis of the specific enzyme deficiency. Untreated patients with 21‐hydroxylase deficiency had elevated levels of 21‐deoxycortisol, 21‐deoxycortisone and 17‐hydroxyprogesterone. One of the untreated patients with 21‐hydroxylase deficiency had elevated levels of these metabolites due to inadequate glucocorticoid treatment. In one newborn patient, who developed a salt‐losing syndrome, a combined deficiency of 11‐ and 21‐hydroxylase appeared to be present based on elevations of plasma concentrations of 11‐deoxycortisol (2.7 μg/dl), 21‐deoxycortisol (10.3 μg/dl), 21‐deoxycortisone (8.6 μg/dl), and 17‐hydroxyprogesterone (> 20 μg/dl). After treatment was begun the levels of all four metabolites returned to normal. This patient had XX/XO karyotype and ambiguous genitalia. Fourteen normal neonates were studied as controls for this subject. Normal neonates all had low plasma levels of these compounds. Their 21‐deoxycortisol concentrations were all less than 0.5 μg/dl and their 11‐deoxycortisol concentrations were all less than 0.1 μg/dl. The study shows that accurate, rapid plasma diagnosis is possible in patients with congenital adrenal hyperplasia, using specific radioimmunoassay procedures.
SELECTIVE INHIBITORY EFFECT OF PORCINE FOLLICULAR FLUID ON FOLLICLE STIMULATING HORMONE SECRETION IN ANTERIOR PITUITARY CELLS IN CULTURE
Authors: LAGACÉ LISETTE , LABRIE FERNAND , LORENZEN JANICE , SCHWARTZ NEENA B. , CHANNING CORNELIA P. 
Published: March 2008

SUMMARYIncubation of rat anterior pituitary cells in culture with porcine follicular fluid (treated with charcoal to remove steroids) led to a marked inhibition of spontaneous FSH release while no effect was observed on basal LH secretion. The inhibitory effect of follicular fluid was, however, less specific on LHRH‐induced gonadotropin release. Although more potent on FSH than LH release, a significant inhibition of LH release induced by the neurohormone was also observed. This inhibitory activity is mainly associated with material of MW 10000 daltons.
DISTURBED MINERAL METABOLISM IN HYPERTHYROIDISM: GOOD CORRELATION WITH TRMODOTHYRONINE
Authors: MANICOURT D. , DEMEESTER‐MIRKINE N. , BRAUMAN H. , CORVILAIN J. 
Published: March 2008

SUMMARYMineral metabolism is frequently disturbed in hyperthyroidism. In a group of seventy‐two patients with hyperthyroidism, we observed an increase in serum diffusible calcium in 50% of the cases, elevated inorganic phosphorus in 30% and elevated alkaline phosphatase in 44% of the cases. Correlations existed between the values of diffusible calcium, inorganic phosphorus, alkaline phosphatase and certain indices of thyroid function (T4, FT4I, T3, FT3I), of which that with T3 was the best (P < 0.001). Our results suggest that the magnitude of the disturbances of mineral metabolism depends on the severity of the hyperthyroidism and that it is the T3 level that constitutes the best index of that seventy.
COMPARISON OF LONG‐ACTING ANALOGUES OF LUTEINIZING HORMONE RELEASING HORMONE IN MAN
Authors: WASS J. A. H. , BESSER G. M. , GOMEZ‐PAN A. , SCANLON M. F. , HALL R. , KASTIN A. J. , COY D. H. , SCHALLY A. V. 
Published: March 2008

SUMMARYCurrently, LHRH, when used therapeutically, is given by parenteral injection every 8 h. We have looked at the release of LH and FSH induced by five analogues of LHRH and compared this with gonadotrophin release after synthetic LHRH. The analogues were substituted in position 6 or in positions 6 and 10 and were given intravenously, intranasally or subcutaneously in three separate studies. After intravenous administration of 100μg, all analogues caused greater release of LH and FSH than did synthetic LHRH. Given intranasally in a dose of 500 μg, three of the four analogues tested caused greater LH and FSH release than did LHRH. With tryptophan substitution in position 6 (D‐TRP6‐LHRH), mean LH levels in five subjects were still above the normal range 24 h after a single intranasal dose. The intranasal administration of selected analogues of LHRH has great potential in the treatment of conditions associated with deficient gonadotrophin secretion, provided that pituitary overstimulation, which may eventually lead to a decrease in LH and FSH output by the anterior pituitary, is avoided.
PROPRANOLOL, TRIIODOTHYRONINE, REVERSE TRIIODOTHYRONINE AND THYROID DISEASE
Authors: FEELY JOHN , ISLES T. E. , RATCLIFFE W. A. , CROOKS J. 
Published: March 2008

SUMMARYPropranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1–2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranolol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.
THE HORMONAL STATUS OF PATIENTS WITH BENIGN PROSTATIC HYPERTROPHY: FSH, LH, TSH AND PROLACTIN RESPONSES TO RELEASING HORMONES*
Authors: HAMMOND G. L. , LUKKARINEN O. , VIHKO P. , KONTTURI M. , VIHKO R. 
Published: March 2008

SUMMARYIn order to determine whether the benign prostatic hypertrophy (BPH) adenoma is responsible for low serum LH levels in patients with this disease, we measured FSH, LH and prolactin in sera collected from patients before and 0.8–2.2 years after retro‐pubic prostatectomy, but found no change in their levels. Pituitary stimulation tests were therefore conducted to evaluate the pituitary hormone reserve in normal elderly men, and BPH patients before and after removal of the BPH adenoma. Blood was drawn 20 min before and during the administration of 100 μg LHRH and 200 μg TRH, as a single intravenous injection, and after 20, 60 and 120 min. Serum FSH, LH, TSH and prolactin were estimated by radioimmunoassays. Prior to prostatectomy, patients with BPH had significantly lower levels of serum LH, but not FSH, TSH or prolactin, as compared to normal men 20 min before the test. Serum LH in the BPH group after prostatectomy (1–2.75 years) was not statistically different from that of normal age‐matched men, but the mean level more closely resembled that of the untreated BPH group. Although there were no significant differences in serum levels of FSH or prolactin between subject groups during stimulation, levels of LH and TSH in untreated BPH patients' serum were significantly lower than those of normal men. The BPH patients after prostatectomy resembled the normal men under these circumstances, and the serum levels of TSH in these ex‐BPH patients were significantly higher than in untreated BPH patients. Similarly, the maximum LH and TSH responses to the hypothalamic releasing hormones were also significantly lower in the BPH patients as compared to normal age‐matched men, and evidently return to normal 1–2.75 years after prostatectomy. No statistically significant differences were observed in the FSH and prolactin responses to LHRH and TRH between groups. The results suggest that a factor originating from the BPH adenoma, such as 5α‐dihydrotestosterone, may be responsible for the suppression of pituitary LH and TSH responses to LHRH and TRH, respectively. It also appears that the pituitary of BPH patients does not regain its full secretory potential after the BPH adenoma has been removed, or that an additional factor may regulate pituitary LH secretion in the untreated and ex‐BPH patients at the hypothalamic level.
PLASMA CYCLIC‐AMP RESPONSE TO PARATHYROID HORMONE IN TURNER'S SYNDROME AND ALBRIGHT'S HEREDITARY OSTEODYSTROPHY
Authors: ASHBY J.P. , RENTON W. B. , MACPHERSON J.N. , PRICE W. H. , ABBOTT S. R. 
Published: March 2008

SUMMARYPurified bovine parathyroid hormone (BPTH) given by injection to five patients with Turner's syndrome, and seven healthy volunteers produced a significant rise in plasma cyclic AMP reaching a maximum within 10 min. In a pseudohypoparathyroid patient there was no increase. Urinary excretion of cyclic AMP exceeded the normal in three out of four patients with Turner's syndrome. Thus, if there is a relationship between Turner's syndrome and Albright's osteodystrophy it is with the incomplete form known as pseudo‐pseudohypoparathyroidism.
PITUITARY MICROADENOMA: DIAGNOSTIC STUDIES
Authors: PINEDA GUSTAVO , VALDES MARIO , CASTRO MARIO , STEVENSON CARLOS 
Published: March 2008

SUMMARYForty‐one women with oligo‐menorrhoea and/or galactorrhoea were subjected to hypothalamic pituitary‐thyroid testing in an attempt to establish the presence or absence of an underlying pituitary microadenoma. They were divided into two groups in accordance with the serum level of prolactin (PRL): Group I (N = 25, mean ± SE 17.6 ± 1.5 ng/ml) and Group II (N = 16, 102.8 ± 29.7 ng/ml). The dynamic tests performed were a TRH test, a stimulation test with metoclopramide (MCP) and a suppression test with bromocriptine. The results of these tests were compared with those obtained in nine normal women and eleven patients with surgically proved pituitary microadenoma. Radiologically abnormal pituitary fossas were found in ten subjects from Group I and in fourteen from Group II. All patients were euthyroid.A persistently elevated serum TSH in response to TRH was observed in patients of Group II suggesting an hypothalamic abnormality and a progressive decrease in the 120‐min use of serum T3 was noted with increasing evidence of the existence of a pituitary tumour. A negative correlation was found between the basal serum PRL and the rise of serum PRL with TRH.Patients from Group II showed a lower PRL response to MCP when compared to Group I and again a negative correlation between basal level of serum PRL and the change after MCP was observed. No clear difference in the 4‐h response to bromocriptine was found between the different groups of subjects.In conclusion, none of the three tests analysed permitted us to establish which of the patients had an underlying pituitary microadenoma.
FREE‐RUNNING CIRCADIAN PLASMA CORTISOL RHYTHM IN A BLIND HUMAN SUBJECT
Authors: ORTH D. N. , BESSER G. M. , KING P. H. , NICHOLSON W. E. 
Published: March 2008

SUMMARYThe plasma cortisol rhythm in man has been presumed to be an endogenous circadian rhythm, synchronized by some external stimulus to an exact 24‐h period. Sleep/wake and ‘social activity’ cycles have been considered as candidates for this synchronizer. Previous studies have suggested that the dark/light phase shifts associated with the sleep/wake cycle may be the external synchronizer, rather than the sleep/wake cycle itself. A totally blind, but otherwise normal subject was studied for a period of 50 days. Her hourly sleep/wake status and hourly integrated mean plasma cortisol concentrations were determined, and the data were subjected to non‐parametric mathematical analysis. The subject was found to have a free‐running rhythm in plasma cortisol with a period of approximately 24.5 h. Her sleep/wake rhythm, determined by similar analysis, had a period of exactly 24 h. In addition to the dominant 24.5‐h cortisol rhythm, there appeared to be a minor 24‐h cortisol rhythm with a peak that coincided approximately with the time of awakening. It was not possible to determine whether this sleep/wake‐related peak represented a minor component of the circadian rhythm, synchronized by some stimulus associated with sleep/wake activity, or merely an acute response to awakening itself. Nevertheless, the two rhythms exhibited ‘beating’ behaviour, resulting in maximal peak cortisol concentrations when they were in synchrony and minimal peak concentrations when they were not. It is concluded that environment dark/light phase shifts are the dominant synchronizer of the circadian rhythm in plasma cortisol concentrations in man, as they are for a variety of circadian rhythms in other living things.
OESTROGEN MODULATION OF GONADOTROPHIN AND PROLACTIN RELEASE IN WOMEN WITH ANOVULATION AND THEIR RESPONSES TO CLOMIPHENE
Authors: KANDEEL F. R. , BUTT W. R. , RUDD B. T. , LYNCH S. S. , LONDON D. R. , EDWARDS R. LOGAN 
Published: March 2008

SUMMARYAn LHRH test was performed before and at both 44 and 92 h after the administration of 2.5 mg oestradiol benzoate in eleven patients with hyperprolactinaemia, eight with idiopathic secondary amenorrhoea and seven with oligomenorrhoea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4–6). Mean basal concentrations of oestradiol in each group of patients and oestrone in those with hyperprolactinaemia were significantly lower than in the normal subjects. The mean concentration of prolactin in women with secondary amenorrhoea remained lower than in the normal women throughout the tests (P < 0.05). The LH and FSH responses to LHRH before oestrogen in patients with hyperprolactinaemia and of FSH in those with secondary amenorrhoea, were greater than in the normal subjects (P < 0.001). After oestrogen treatment the responses were similar in all groups except in those with oligomenorrhoea where LH and FSH responses at 44 h (P < 0.05 and P < 0.01 respectively) and LH responses at 92 h (P < 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification) but the amplification at 92 h and at 44 h compared to the pre‐treatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinaemic group of patients there was a negative correlation between the basal prolactin concentration and the gonadotrophin amplifications at 92 h (P < 0.01), and a positive correlation between the basal oestrone levels and the amplifications at 92 h (P < 0.01). The results of the oestrogen amplification test in eleven of the non‐hyperprolactinaemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal oestrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotrophin (HCG) as well as clomiphene to ovulate. The other three showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinaemic patients to clomiphene were poor and there was a negative correlation between prolactin concentration and oestrogen production (P < 0.01). All ten hyperprolactinaemic patients treated with bromocriptine ovulated and eight conceived. The oestrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non‐hyperprolactinaemic anovular women.
RAPID CONVERSION OF CARBIMAZOLE TO METHIMAZOLE IN SERUM; EVIDENCE FOR AN ENZYMATIC MECHANISM
Authors: NAKASHIMA TOSHIRO , TAUROG ALVIN 
Published: March 2008

SUMMARYCarbimazole (CBZ) is one of the major drugs currently used for the treatment of Graves' disease. It is a carbethoxy derivative of methimazole (MMI), originally developed in the hope of obtaining a longer acting drug than methimazole. In the present study we have demonstrated that carbimazole is rapidly converted to methimazole in vitro by serum from rats and humans, and we have obtained evidence that this conversion is enzymatic. Experiments with [35S] CBZ in rats showed that the drug is so rapidly transformed to MMI after i.v. injection (within 3 min) that very little of the unchanged drug would be expected to reach the thyroid gland. The antithyroid action of CBZ in rats, therefore, can be ascribed entirely to the MMI to which it is rapidly converted. Although no experiments were performed with human subjects in vivo, the very rapid conversion of CBZ to MMI by human serum in vitro suggests that the antithyroid action of CBZ in humans can also be attributed to MMI. The original expectation of a longer acting drug has, therefore, not been met by CBZ. On the basis of the studies reported here there appears to be no advantage in using CBZ in preference to MMI for the treatment of Graves' disease.Although the in vivo action of CBZ must be attributed to its rapid conversion to MMI, the drug does possess inherent antithyroid activity. This was shown in the present study by the finding that CBZ is as potent as MMI in blocking thyroid peroxidase‐catalysed iodination of thyroglobulin.
MODE OF ACTION OF CARBIMAZOLE IN GRAVES' DISEASE
Authors: WISE P. H. , MARION M. , PAIN R. 
Published: March 2008

SUMMARYIn a series of hyperthyroid subjects treated with a high dose ‘block‐replace’ regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub‐total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio‐iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti‐thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormonogenesis, but more definitively by affecting thyroid hyperstimulation at a prebiosynthetic level.The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a ‘block‐replace’ regime, further suggests that current concepts of ‘suppressibility’ are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary‐thyroid axis, but rather a direct influence of prolonged therapy with anti‐thyroid drugs on the natural history of the disease.