bluuebunny/crossref_metadata_2025_split huggingface dataset:
ON THE SITE OF ACTION OF THE ANTI‐ADRENAL STEROIDOGENIC EFFECT OF ETOMIDATE AND MEGESTROL ACETATE
Authors: LAMBERT A. , FROST J. , MITCHELL R. , WILSON A. U. , ROBERTSON W. R. 
Published: March 2008

SUMMARYThe sites of action of the anti‐steroidogenic action of etomidate and megestrol acetate have been established with a novel in vitro approach based upon the inhibition of cortisol (Co) secretion by dispersed guinea‐pig adrenal cells. The cells were challenged with the Co precursor steroids (all at 10−5 mol/l) pregnenolone (Pe), 17‐hydroxy‐pregnenolone (17‐Pe), progesterone (Po), 17‐hydroxyprogesterone (17‐Po), 21‐deoxycortisol (21‐DOC) and 11‐deoxycortisol (11‐DOC), or 1‐24 adrenocorticotrophin (ACTH, 100 ng/l) in the presence or absence of either etomidate, megestrol acetate, metyrapone or trilostane (all at 5 ± 10−5 mol/l). In the absence of drug, the steroid precursors or ACTH provoked a cortisol secretion of > 14 times that secreted by cells incubated in their absence. ACTH‐stimulated Co secretion was inhibited by > 85% by all the drugs employed. In the presence of trilostane and megestrol acetate, Co secretion provoked by the Δ4 3‐keto steroids (Po, 17‐Po, 21‐DOC and 11‐DOC) was similar to the controls. However, with the Δ5, 3β‐hydroxy steroids, 17‐Pe and Pe, Co secretion was inhibited by > 57% in the presence of these drugs. In contrast, etomidate and metyrapone inhibited Co secretion by >60% when 11‐deoxycortisol was employed, indicative of a block at 11 β‐hydroxylase, the final step in the cortisol biosynthetic pathway. Similar results were seen with Pe, 17‐Pe, Po and 17‐Po, all of which are converted to cortisol via a biosynthetic route which includes catalysis by 11 β‐hydroxylase. In contrast the transformation of 21‐deoxycortisol to Co, a step which proceeds directly via 21‐hydroxylase, was unaffected by the presence of any of the drugs. The site of action for etomidate was confirmed by a second method. Adrenal cells were incubated for 90 min with ACTH (1–24, 100 ng/l) and 14C‐pregnenolone in the presence and absence of either etomidate or trilostane. 11‐DOC and Co were extracted from the incubates and assayed by thin‐layer chromotography. The ratio of 11‐DOC to Co was 0.20, 0.27 and 1.64 for the control, trilostane and etomidate incubations respectively. We conclude that trilostane and megestrol acetate are 3a‐hydroxysteroid dehydrogenase, A5‐A4 isomerase inhibitors, whereas metyrapone and etomidate act at the level of 1 la‐hydroxylase.
A PREALBUMIN VARIANT WITH AN INCREASED AFFINITY FOR T4 AND REVERSE‐T3
Authors: LALLOZ M. R. A. , BYFIELD P. G. H. , HIMSWORTH R. L. 
Published: March 2008

SUMMARYA euthyroid adult female (LC) was found to have persistently raised concentrations of total T4 (159 nmol/l) and rT3 (500 pmol/l) in her serum in association with a normal T3 (2–1 nmol/l). Serum concentrations of all three T4‐binding proteins were within normal limits. A variant prealbumin with an increased affinity for T4 was found to be responsible for the raised serum level of T4. Unlike normal prealbumin, the variant also bound appreciable amounts of rT3. The affinity constant for T4 binding to prealbumin LC was 5.5 × 108 l/mole which is sevenfold higher than that obtained for normal prealbumin (8.5 × 107 l/mole). The affinity constant for the binding of rT3 to prealbumin LC was 2.0 × 106 l/mole while that for the normal protein was unmeasurable by our method. The T4‐binding capacity of prealbumin LC in serum was within the normal range indicating that there is no new additional T4‐binding site on the protein. Prealbumin LC has the same molecular size as the normal protein, hence it is likely that the tetrameric structure has been preserved. The electrophoretic mobility of prealbumin LC was normal indicating no alteration in charge. It is postulated that the increased affinity for T4 (and presumably for rT3) results from a hydrophobic amino‐acid substitution in the prealbumin monomer.
EFFECT OF ‘PHYSIOLOGICAL’ DOSES OF TRIIODOTHYRONINE REPLACEMENT ON THE HORMONAL AND METABOLIC ADAPTATION TO SHORT‐TERM SEMISTARVATION AND TO LOW‐CALORIE DIET IN OBESE PATIENTS
Authors: PASQUALI R. , BARALDI G. , BISO P. , PIAZZI S. , PATRONO D. , CAPELLI M. , MELCHIONDA N. 
Published: March 2008

SUMMARYIn four groups of obese patients matched for Body Mass Index (BMI), we studied the effects of different 3‐week semi‐starvation treatments followed by an 8‐week hypocaloric (1008 kcal, protein 20%, carbohydrate 40%) diet with or without low doses of T3 therapy. Dietary intake (formula diet) in the semi‐starvation period was 480 kcal, with 66 g protein (P) and 51 g carbohydrate (CHO) in groups I and III and with 33 g P and 84 g CHO in groups II and IV. Moreover, groups III and IV were given low doses (20 μg twice a day) of T3 while groups I and II received a placebo. During semi‐starvation periods, a similar fall in BMI values was found in all groups, while during the low‐calorie diet, T3‐treated patients showed the greater BMI reduction. During semi‐starvation, nitrogen balance was significantly more negative in low‐protein than in high‐protein‐treated groups; differences between T3‐treated (III and IV) and control (I and II) groups were not significant over this relatively short treatment period. No differences in 24 h urinary 3‐methylhistidine or alanine excretion were evident between the four groups. During the entire period of study, daily urine creatinine excretion did not change in any group. In conclusion, in our study low‐dose T3 therapy was seen to favour weight loss during low‐calorie diet although negative effects on protein metabolism were not excluded, particularly when relatively small amounts of protein were administered.
TWENTY‐FOUR HOUR VARIATIONS OF THYROID HORMONES AND THYROTROPHIN CONCENTRATIONS IN HYPOTHYROID INFANTS TREATED WITH L‐THYROXINE
Authors: CZERNICHOW P. , WOLF B. , FERMANIAN J. , POMAREDE R. , RAPPAPORT R. 
Published: March 2008

SUMMARYThe 24 hour plasma profile of T4, FT4, T3 and TSH was measured in a group of infants treated for congenital hypothyroidism with an oral aqueous preparation of L‐T4 (5‐7.5 μ g/kg) given as a single dose at 0800 h. Mean basal plasma T4 was 8.4 ± 2.0 μ g/dl (mean ± SD) and remained constant during the study while mean serum FT4 increased significantly from 1.64 ± 0.50 ng/dl to a maximum of 2.08 ± 0.63 ng/dl 4 h after medication. Plasma T3 decreased significantly from 241 ± 48 ng/dl to 202 ± 36 ng/dl 6 h after drug administration. Finally, plasma TSH decreased significantly from a mean of 24.2 ± 18.8 μU/ml to 14.8 ± 10.5 μU/ml 6 h later. Therefore during treatment of congenital hypothyroidism with L‐T4 no specific schedule for T4 sampling is required. However, TSH determination 4 to 8 h after medication could slightly underestimate mean levels. In addition, any attempt to monitor treatment by FT4 determination should take into consideration variations of plasma values in the hours following L‐T4 absorption.
AUTO‐IMMUNE ADDISON'S DISEASE ASSOCIATED WITH HYPERPROLACTINAEMIA
Authors: LEVER E. G. , McKERRON C. G. 
Published: March 2008

SUMMARYFour cases of auto‐immune Addison's disease are reported in association with hyperprolactinaemia. Two of the females had galactorrhoea. In three cases complete resolution of hyperprolactinaemia occurred with corticosteroid replacement, but it was only partial in the fourth. We suggest that hyperprolactinaemia was due to Cortisol deficiency operating directly or indirectly at the level of the pituitary. These data support the animal and in vitro evidence for the influence of corticosteroids on prolactin release.
RENAL 1,25‐DIHYDROXYVITAMIN D, PHOSPHATURIC, AND CYCLIC‐AMP RESPONSES TO INTRAVENOUS SYNTHETIC HUMAN PARATHYROID HORMONE‐(1‐34) ADMINISTRATION IN NORMAL SUBJECTS
Authors: SLOVIK D. M. , DALY MARGARET A. , POTTS J. T. , NEER R. M. 
Published: March 2008

SUMMARYThe exogenous administration of bovine parathyroid hormone or parathyroid extract has been used to differentiate states of parathyroid hormone resistance and parathyroid gland secretory failure, and in recent years to test renal 1,25‐dihydroxyvitamin D (1,25‐(OH)2‐D) secretion. We evaluated the effect of synthetic human parathyroid hormone (hPTH‐(1–34)) administration on the renal 1,25‐(OH)2‐D, phosphaturic and cyclic‐AMP responses in eleven normal young adults. The intravenous administration of 200 units of hPTH‐(1–34) over 10 min produced a 1.3‐5.4 fold increase (P <0.01) in renal phosphate clearance and a 19–75 fold increase (P < 0.0001) in urinary cyclic‐AMP excretion. Serum 1,25‐(OH)2‐D levels showed a small and insignificant change at 2‐5 h and a significant (P <0.05) but small (21 ± 24 pmol/1) increase at 7 h after the first injection. In eight subjects a second injection of hPTH‐(1–34) was given at 7 h. In these individuals serum 1,25‐(OH)2‐D levels at 24 h were 40 ± 14 pmol/1 (44%) higher than baseline (P <0.01), but were variable over the 24 h period. The present study shows that hPTH‐(1–34) produces renal phosphaturic and cyclic‐AMP responses in normals similar to those produced by bovine PTH preparations. However, the serum 1,25‐(OH)2‐D response to one or two intravenous injections of hPTH‐(1–34) is small, variable, and inconsistent and, therefore, will not provide a consistent way of stimulating renal 1,25‐(OH)2‐D secretion.
TREATMENT OF PRECOCIOUS PUBERTY WITH LHRH ANALOGUE IN COMBINATION WITH CYPROTERONE ACETATE—FURTHER EXPERIENCE
Authors: KAULI R. , PERTZELAN A. , BEN‐ZEEV Z. , LEWIN R. PRAGER , KAUFMAN H. , SCHALLY A. M. COMARU , SCHALLY A. V. , LARON Z. 
Published: March 2008

SUMMARYSix girls and one boy with precocious puberty were treated with a superactive LHRH analogue (D‐TRP6‐LHRH) for periods ranging from 1 year to 2 years and 3 months. In the first phase of the treatment it was administered in combination with cyproterone acetate (CyA) to counteract an early stimulatory effect until inhibition of gonadotrophin secretion was achieved. The gonadotrophin‐dependent signs i.e. gonadarche, showed sustained arrest and even regression. Gonadal sex steroids decreased but the adrenal androgens were unaffected. In four patients who showed progression of the angrogen‐dependent signs (adrenarche), despite suppression of gonadotrophins, increasing the dosage of the LHRH analogue was ineffective and combined therapy with CyA was reinstituted in three of them because of accelerated growth and bone maturation. It is concluded that at present the treatment of choice for precocious puberty is the daily administration of a superactive LHRH analogue such as D‐TRP6‐LHRH, together with CyA in the initial stage, and at a later state if adrenarche progresses too rapidly.
RECOVERY OF ADRENAL FUNCTION AFTER TREATMENT OF ADRENOCORTICAL CARCINOMA WITH o,p’‐DDD
Authors: GREIG F. , OBERFIELD S.E. , LEVINE L. S. , GHAVIMI F. , PANG S. , NEW M. I. 
Published: March 2008

SUMMARYThe adrenolytic agent, 2,2‐bis [2‐chlorophenyl‐4‐chlorophenyl] 1,1 dichloroethane (o.p'‐DDD), was used over a 20‐month period following surgery in a 2 3/12‐year‐old girl for treatment of adrenocortical carcinoma. The child remained free of disease and was maintained on glucocorticoid and mineralo‐corticoid supplements for 7 years. Hormonal evaluation was undertaken at 9 9/12 years of age to determine remaining adrenal steroidogenic capacity. Following discontinuation of both hydrocortisone and 9α‐fludrocortisone, she remained stable and asymptomatic. Immediately after discontinuing 9α‐fludrocortisone, the adrenal glomerulosa was able to respond to stimulation by the renin‐angiotensin system as shown by the ability to achieve renal sodium conservation on a restricted sodium intake (< 10 mEq/d for 5 d). The response of the adrenal fasciculata to ACTH stimulation showed a slower recovery. Baseline levels of cortisol were in the low normal range, but there was no increase in plasma cortisol or urinary 17‐hydroxysteroids following stimulation with ACTH. The responses of cortisol, deoxycorticosterone, and corticosterone to ACTH stimulation gradually improved to achieve normal stimulated levels 18 months after stopping medications. Serum testosterone and δ4‐androstenedione were initially increased for level of puberty, while levels of dehydroepian‐drosterone were prepubertal. Testosterone and δ4‐androstenedione did not suppress with dexamethasone (2 mg/d for 2 d; 4 mg/d for 2 d), and dehydroepiandrosterone decreased only slightly. However, administration of norethindrone (Norlutin) (10 mg orally, three times a day for 3 d) resulted in suppression while human chorionic gonadotrophin (hCG; 5000 U i.m. daily for 3 d) produced stimulation of testosterone, δ4‐androstenedione and dehydroepiandrosterone. Thus the androgens were felt be predominantly of ovarian origin. Dehydroepiandrosterone rose to low normal levels by 18 months after discontiution of hydrocotesone. We thus demonstrate for the first time that both the adrenal glomerulosa and fasiculata have the capacity to recover normal function following treatment with o,p'‐DDD. Further, we suggest that early exposure to excess adrenal androgens may result in mild alteration of gonadal function.
HOW EFFECTIVE IS EXTERNAL PITUITARY IRRADIATION FOR GROWTH HORMONE‐SECRETING PITUITARY TUMOURS?
Authors: FEEK C. M. , McLELLAND J. , SETH J. , TOFT A. D. , IRVINE W. J. , PADFIELD P. L. , EDWARDS C. R. W. 
Published: March 2008

SUMMARYForty‐six patients with GH‐secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty‐patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (± SD) serum GH in the former group was 74.3 ± 74.8 mU/1 before treatment, falling by 28% per year over 0–5 years and by 16% per year over 0–20 years. The mean (± SD) serum GH in the latter group was 265.4 ± 209.3 mU/1 before treatment, falling by 76% in the first year—a direct result of surgical removal of tumour—then by 30% per year over 1–5 years and 16% per year over 1–20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH‐secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.
THYROID FUNCTION IN PATIENTS WITH HOMOZYGOUS β‐THALASSAEMIA
Authors: PHENEKOS C. , KARAMEROU A. , PIPIS P. , CONSTANTOULAKIS M. , LASARIDIS J. , DETSI S. , POLITOU K. 
Published: March 2008

SUMMARYThyroid function was evaluated in 20 patients aged 8‐30 years who were suffering from homozygous β‐thalassaemia. All patients have been receiving frequent blood transfusions and treated for the resulting transfusional iron overload with intramuscular injections of Desferrioxamine. Total thyroxine (T4), T3‐uptake, total triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured. In addition a standard TRH stimulation test was performed and blood samples were checked for the presence of thyroid antibodies. It was found that total T4 was significantly lower in the patients than in the controls. Total T3 and rT3 levels were similar in both patients and controls and all patients were negative for thyroid antibodies. T3 uptake in the patients was also statistically different from the controls resulting in significantly lower free thyroxine index (FTI). Basal TSH values were not different from the controls but the TSH increase following TRH stimulation was significantly higher in the patients suggesting, together with the low total T4 and FTI, a state of compensated hypothyroidism.
PLASMA ARGININE VASOPRESSIN IN DEHYDRATED ELDERLY PATIENTS
Authors: KIRKLAND J. , LYE M. , GODDARD C. , VARGAS E. , DAVIES I. 
Published: March 2008

SUMMARYPlasma arginine vasopressin was assessed by radioimmunoassay in dehydrated elderly patients and healthy young and elderly control subjects. The elderly control subjects' AVP levels were higher than the young control subjects (Kruskal‐Wallis rank sums z= 3.29; P <0.001). Despite similar plasma osmolalities, after correction for the osmotic contribution of urea, the patients' AVP levels were higher than the elderly controls (z= 4.16; P <0.001) and were in the range reported to evoke a maximal antidiuretic response. It is concluded that the dehydration which often accompanies acute illness in the elderly is not primarily a consequence of inadequate AVP release.
CHANGES IN PLASMA LEVELS OF PROLACTIN, IN RELATION TO THOSE OF FSH, OESTRADIOL, ANDROSTENEDIONE AND PROGESTERONE AROUND THE PREOVULATORY SURGE OF LH IN WOMEN
Authors: DJAHANBAKHCH O. , McNEILLY A. S. , WARNER PAMELA M. , SWANSTON I. A. , BAIRD D. T. 
Published: March 2008

SUMMARYPlasma samples were obtained at 8 hourly intervals around the preovulatory surge of LH in three groups of women with spontaneously ovulatory menstrual cycles, in order to clarify the hormonal events around the time of ovulation. In 21 of 25 women in whom samples were collected every 8 hours the start of the LH surge occurred between midnight and 0800. In 16 of these women the concentration of LH, FSH and progesterone was measured every 8 hours around the pre‐ovulatory surge of LH. A progressive increase in progesterone started with the onset of the LH surge, with a transient fall after 32‐40 h at a time coincident with that of ovulation. In 10 women oestradiol, androstenedione and prolactin were measured 8 hourly around the pre‐ovulatory surge of LH beginning at 0800 h. Prolactin showed a sustained increase in levels beginning at the start of and lasting for the duration of the pre‐ovulatory LH surge; oestradiol levels did not rise around this time, and declined by 24 h after the onset of the LH surge. These results suggest that (1) the pre‐ovulatory LH surge begins between midnight and 0800 h in the majority of women, (2) luteinization of the granulosa cells within the pre‐ovulatory follicle occurs in response to the LH surge, (3) the increase in prolactin at the time of the LH surge is not directly related to increasing levels of oestradiol but may be due to a decrease in hypothalamic inhibition of prolactin secretion which occurs coincident with the release of LHRH associated with the preovulatory LH surge.
IODIDE ORGANIFICATION DEFECT IN A COLD THYROID NODULE: ABSENCE OF IODIDE EFFECT ON CYCLIC AMP ACCUMULATION
Authors: DEMEESTER‐MIRKINE N. , SANDE J. VAN , DOR P. , HEIMANN R. , COCHAUX P. , DUMONT J. E. 
Published: March 2008

SUMMARYA follicular adenoma of the thyroid was ‘hot’ one hour after 99mTc pertechnetate administration, but ‘cold’24 h after 131I iodide administration. Incubation of the tissue in vitro demonstrated a defect in iodide binding to proteins that was abolished by addition of an H2O2 generating system. In this tissue iodide failed to inhibit TSH‐induced cyclic AMP accumulation. The results show that iodide oxidation is required for its inhibitory action on cyclic AMP accumulation in human thyroid.
THE EFFECT OF BROMOCRIPTINE IN THE POLYCYSTIC OVARY SYNDROME
Authors: SPRUCE BARBARA A. , KENDALL‐TAYLOR PAT , DUNLOP W. , ANDERSON A. J. , WATSON M. J. , COOK D. B. , GRAY CHRISTINA 
Published: March 2008

SUMMARYThe effect of chronic administration of bromocriptine to 20 patients with the polycystic ovary syndrome (PCOS) was studied. All patients had normal serum prolactin levels. Bromocriptine 7‐5 mg daily was administered for up to 1 year and the biochemical and clinical responses assessed at 3‐monthly intervals. Over a period of 3 to 12 months significant reductions in serum LH levels, LH/FSH ratios and in plasma testosterone were observed. In 14 patients, blunting of the previously enhanced LH response to LHRH was observed. Clinical improvement also occurred, most notably in menstrual function. In 12 out of 20 patients a monthly cycle was established and in a further three there was an increase in the frequency of menstruation towards normal. Eleven out of 20 patients ultimately noted a subjective improvement in hirsutism. We conclude that bromocriptine, given to patients with polycystic ovarian disease, inhibits LH hypersecretion, leading to restoration of cyclic ovarian function and reduced androgen synthesis.
WHICH TESTOSTERONE REPLACEMENT THERAPY?
Authors: CANTRILL J. A. , DEWIS P. , LARGE D. M. , NEWMAN M. , ANDERSON D. C. 
Published: March 2008

SUMMARYThree different forms of testosterone (T) replacement therapy were compared; they were the intramuscular injection of mixed testosterone esters 250 mg; the subcutaneous implantation of 6 x 100 mg pellets of fused testosterone; and the oral administration of testosterone undecanoate (TU) 80 mg twice daily. Six hypogonadal males were treated with oral TU for an eight week period, during which time serial serum hormonal estimations were performed over 10 h at the initiation and after four and eight weeks of therapy. Serum T levels showed marked variability both between subjects and within the same subject on different occasions. We attribute this to variability in absorption of TU, which is formulated in oleic acid. The overall mean T level calculated from the areas under the profiles of TU was 120 nmol/1. Hormone responses to injected T esters were studied in nine hypogonadal males. Serum T rose to supraphysiological peak concentrations (mean 71 nmol/1) 24‐48 h after an injection, followed by an exponential decay to reach baseline concentrations after 2‐3 weeks. The overall calculated mean T level in subjects receiving testosterone esters 250 mg every three weeks was 27‐7 nmol/1. Subcutaneous implantation of testosterone in six hypogonadal men produced a gradual rise in serum T followed by a slow decline, with T levels remaining within the normal range for 4‐5 months. The calculated overall mean T level over 21 weeks after implantation was 170 nmol/1. Serum oestradiol (Ej) levels remained within the normal male range throughout the study periods on both TU and T implant therapy but showed a supraphysiological peak (mean 347 pmol/1) 24‐48 h after a T injection. 5α‐dihydrotestosterone (DHT) levels appeared to parallel those of T on the three forms of therapy, with DHT:T ratios being highest for TU therapy. This was also true for the target organ metabolite 5α‐androstane‐3α, 17β‐diol. At the doses studied drug costs were similar for T implantation (every 5 months) and T ester injections (every 3 weeks), but were 7‐8 times higher for TU (80 mg twice a day). We conclude that T implantation remains overall the most physiological form of androgen replacement therapy, is generally well accepted and attended by few side effects; TU may have a useful role in the initial phases of therapy.