bluuebunny/crossref_metadata_2025 huggingface dataset:
TRANSIENT THYROTOXICOSIS IN ENDEMIC GOITRE PATIENTS FOLLOWING EXPOSURE TO A NORMAL IODINE INTAKE
Authors: LIMA N. , MEDEIROS‐NETO G.
Published: March 2008

Twenty‐three endemic goitrous subjects (goitre grade: III and IV) that were living in a chronic iodine‐deficient area (iodine intake: less than 40 μg I/d) were submitted to clinical and laboratory evaluation within 3–8 weeks of arrival at the metropolitan area of São Paulo, where daily iodine intake is estimated to be 150–200 μg I/d. Eight patients developed a mild thyrotoxic state (T4 = 14.7 ± 2.3 μg/dl, T3 = 279 ± 55 ng/dl, no TSH response to TRH). Five additional subjects, although euthyroid, had a blunted TSH‐response to TRH, and the remaining ten patients were euthyroid and had a normal TSH response to TRH. Thyrotoxicosis was associated with larger goitres (mean thyroid weight: 133 ± 46 g), with high thyroid uptake of RAI (mean 24 h 131 I uptake: 40 ± 15%) but not with increased urinary iodine excretion. Serum Tg levels were more elevated in the first two groups of patients (respectively, geometric means 68 and 72 ng/ml), than in the euthyroid, TRH‐responsive group (52 ng/ml). Thyrotoxicosis resolved spontaneously after three to six months without the need for any specific medication. It was concluded that a relatively small and normal iodide intake due to regular consumption of iodized salt and industrialized foods may induce a transient form of thyrotoxicosis in endemic goitre patients arriving into urban areas.
EFFECT OF SODIUM SALICYLATE ON HORMONAL RESPONSES TO HYPOGLYCAEMIA IN TYPE II DIABETICS
Authors: BRASS E. P. , HALTER J. B. , ENSINCK J. W. , ROBERTSON R. P.
Published: March 2008

Prostaglandins and prostaglandin synthesis inhibitors are known to influence the secretion of a number of hormones. More specifically, sodium salicylate is known to increase insulin secretion in Type II diabetics in response to a glucose stimulus. To challenge the hypothesis that prostaglandins may be instrumental in a generalized defect of glucose recognition in Type II diabetics, the effect of sodium salicylate on the hormonal counter‐regulatory response to insulin‐induced hypoglycaemia was examined. Before salicylate treatment, seven Type II diabetics had brisk increases (mean ± SEM) in circulating adrenaline (time 0 = 50 ± 7 pg/ml; peak = 1630 ± 330 pg/ml), noradrenaline (time 0 = 260 ± 46 pg/ml; peak = 770 ± 140pg/ml), glucagon (time 0 = 38 ± 6 pg/ml; peak = 75 ± 10 pg/ml) and pancreatic polypeptide (time 0 = 149 ± 30 pg/ml; peak = 1170 ± 180 pg/ml) in response to insulin‐induced hypoglycaemia. In contrast to previous studies in normal subjects, treatment with sodium salicylate failed to augment hypoglycaemia‐induced secretion of adrenaline, noradrenaline or pancreatic polypeptide in Type II diabetics. The glucagon response to hypoglycaemia was augmented by sodium salicylate when the data were expressed as the incremental area under the glucagon vs. time curve, but not when peak response was used for analysis. These results are inconsistent with a prostaglandin‐related generalized defect in glucose recognition in Type II diabetics and suggest that augmentation of hormone secretion in these patients by sodium salicylate may be specific for glucose‐induced insulin secretion.
GROWTH HORMONE RESPONSIVENESS TO HUMAN PANCREATIC GROWTH HORMONE RELEASING FACTOR IN ACROMEGALY: MODULATORY EFFECTS OF BASAL HORMONE LEVELS AND OF CONCOMITANT SOMATOSTATIN ADMINISTRATION
Authors: PIETERS G. F. F. M. , SMALS A. E. M. , HERMUS A. R. M. M. , SMALS A. G. H. , BENRAAD J. , KLOPPENBORG P. W. C.
Published: March 2008

Human pancreatic growth hormone releasing factor 1–44 (hpGRF), 100 μg was administered as an i.v. bolus injection to eleven patients with acromegaly. The mean serum growth hormone (GH) levels rose (P < 0.001) from 54 ± 20 ng/ml to 215 ± 126 ng/ml (± SEM) 20 min after the injection. Although the maximum response of GH levels was highly variable it correlated positively with the individual GH levels (P<0.01, Rs=±0.80). Thus the higher the GH levels, the greater the responsiveness to hpGRF. Administration of somatostatin (SRIF), 300 μg/h, lowered basal GH levels from 76 ± 38 ng/ml to 13 ± 5 ng/ml (P < 0.01) after 1 h. hpGRF administration during concomitant SRIF infusion also led to highly variable growth hormone responses. The maximum GH responses again correlated positively with the GH level before hpGRF after 1 h of SRIF administration (P<0.05, Rs=±0.79). GH responses to hpGRF were completely blocked by SRIF in three out of four patients whose GH levels decreased to normal levels during SRIF infusion. Our data illustrate that the pituitary in acromegaly is normally responsive to both SRIF and hpGRF but at a higher setting of basal GH levels.
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

The 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

A 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

In 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

The 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

Four 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

The 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

Six 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

The 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

Forty‐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

Thyroid 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

Plasma 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

Plasma 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

A 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

The 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

Three 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.
DISCORDANT SERUM α‐SUBUNIT AND FSH CONCENTRATIONS IN A WOMAN WITH A PITUITARY TUMOUR
Authors: CHAPMAN A. J. , MACFARLANE I. A. , SHALET S. M. , BEARDWELL C. G. , DUTTON J. , SUTTON M. L.
Published: March 2008

We have studied a women who presented at the age of 51 with a large FSH and a‐subunit producing pituitary adenoma. Following insertion of ventriculo‐peri‐toneal shunts and external pituitary irradiation there was no change in the elevated serum concentrations of FSH, and α‐subunit over a four year period although she developed both ACTH and TSH deficiency. Various drugs, however, did alter the FSH and α‐subunit concentrations and these changes suggest possible mechanisms controlling FSH secretion. Ethinyloestradiol 0.03 mg daily for three weeks suppressed serum FSH to 77% of the basal level (240 ± 35 i.u./l to 184 ±20 i.u./l) but α‐subunit rose to 130% of basal level (281±50 ng/ml to 366±40 ng/ml). On ethinyloestradiol 01 mg daily, FSH suppressed to 17% of basal (40 ±11 i.u./l) with no change in a‐subunit concentration, while on 0.2 mg daily suppression of FSH was similar but α‐subunit fell to 59% of basal (190 ±28 ng/ml). Dexamethasone, 3 mg daily for one week reduced FSH to 53% of the initial concentration and α‐subunit to 74% while bromocriptine 7.5 mg daily for three months, reduced FSH to 39% and α‐subunit to 66% of basal. Neither thyroxine, 0‐2 mg daily for four weeks, nor an LHRH analogue, (Buserelin, Hoechst) 200 μg, three times daily for three months elicited any effect. Chromatography on Sephadex G100 showed that serum FSH and α‐subunit both had Kav values somewhat lower than those of their standard counterparts (FSH, 0‐20 vs 0‐25; α‐subunit 0‐35 vs 045). We conclude that the dissociation between changes in FSH and α‐subunit after giving oestrogen, bromocriptine and dexamethasone suggests that these drugs inhibit the synthesis of both a and β‐subunits of FSH with the latter being more sensitive to their effects. The results seem inconsistent with the alternative possibility of impaired release of both subunits or impaired α‐β combination as the mechanism causing the fall in FSH secretion.
CONTRACEPTION WITH AN LHRH AGONIST: EFFECT ON GONADOTROPHIN AND STEROID SECRETION PATTERNS
Authors: KUHL H. , JUNG CLAUDIA , TAUBERT H.‐D.
Published: March 2008

Chronic treatment with the LHRH agonist d‐Ser(TBU)6‐LHRH (l‐9)‐EA (buserelin) has been suggested as a contraceptive method since it has been shown to inhibit ovulation. To elucidate the mechanism of this paradoxical action, we investigated the pattern of gonadotrophin and steroid secretion after the daily intranasal application of 300 μg of the agonist. Ten volunteers with ovulatory cycles received the analogue from Day 1 to Day 22 and 5 mg norethisterone acetate from Day 16 to Day 22. Blood samples were taken on Day 1,15, and 21 every 15 min for 6 h after the application of the agonist. LH secretion was increased nine‐fold on the first treatment day as compared to Day 2 of the preceding control cycle. Thereafter, it decreased slowly but was still elevated five‐fold on Day 21 of treatment. FSH release increased three‐fold on Day 1 but decreased thereafter to values similar to those of the controls. During treatment with the analogue, the LH/FSH ratio changed from 1‐3 (controls) to 3‐8 on Day 1 and to 5‐5 on Day 15 and 21 of treatment. Although the ovary retained follicular activity, ovulation was inhibited in every treatment cycle. This seemed to be due to an impairment of follicular steroid synthesis as indicated by a significant increase of 17α‐hydroxyprogesterone and testosterone levels for several hours after the application of the analogue. It appears that at least during the first treatment cycle of daily administration of buserelin the abolishment of pulsatile gonadotrophin release, and the abnormally increased ratio of LH/FSH secretion may possibly impair follicular maturation and thus contribute to the inhibition of ovulation.
LACK OF INHIBITION OF ANTERIOR PITUITARY HORMONE RELEASE DURING CHRONIC TREATMENT WITH CALCIUM ANTAGONISTS
Authors: D'ARMIENTO M. , PONTECORVI A. , BIGI F. , CRISTOFARO A. M. DE , REDA G. , GRECO V.
Published: March 2008

Calcium antagonists are widely used for the treatment of cardiovascular disorders, especially ischaemic heart disease. It has been demonstrated that these drugs, either in vitro or acutely administered in humans, inhibit the basal and stimulated secretion of pituitary hormones by blocking calcium influx through slow calcium channels. To see if a similar effect could be detected after their chronic administration, we studied the basal, TRH‐ and LHRH‐stimulated TSH, PRL, LH and FSH release in 18 male subjects with chronic stable angina before and on the 30th day of oral treatment with verapamil (n=8; 80 mg three times a day) or with nifedipine (n=10; 10 mg three times a day). Neither drug had any effect on basal TSH, PRL, LH and FSH values or on their response to the specific hypothalamic‐releasing hormones. These results suggest that the chronic administration of calcium antagonists, at the usual therapeutic doses, does not effect the process of stimulus‐secretidn coupling of anterior pituitary hormones, ruling out any impairment of the related target glands which have been expected on the basis of previous studies.
MATERNAL THYROID HORMONE LEVELS IN PREGNANCY AND THE SUBSEQUENT COGNITIVE AND MOTOR PERFORMANCE OF THE CHILDREN
Authors: PHAROAH P. O. D. , CONNOLLY K. J. , EKINS R. P. , HARDING ANN G.
Published: March 2008

Serum levels of thyroxine and triiodothyronine during pregnancy were measured in women from a severely iodine deficient region in the highlands of Papua New Guinea. Subsequently the children born to these women were examined when aged 10‐12 years and measures made of intellectual ability and motor competence. A significant correlation between these measures in the children and the maternal thyroxine but not maternal triiodothyronine level was observed. It is speculated that maternal thyroxine and not triiodothyronine may be essential for normal neurological maturation of the fetus before the fetal thyroid becomes functional.
CIRCULATING CATECHOLAMINE, THYROTROPHIN, THYROID HORMONE AND PROLACTIN RESPONSES OF NORMAL SUBJECTS TO ACUTE COLD EXPOSURE
Authors: O'MALLEY B. P. , COOK N. , RICHARDSON A. , BARNETT D. B. , ROSENTHAL F. D.
Published: March 2008

The responses of circulating catecholamines, TSH, thyroid hormones and prolactin to 30 min of acute cold exposure (4°C) were measured in eight normal volunteers over a 2 h period. There was a rise in circulating noradrenaline, TSH, T4 and T3 levels and a fall in circulating prolactin in the subjects studied, but no change in circulating adrenaline levels nor any alteration in the T4/T3 ratio. The thyroid axis of normal individuals can respond rapidly to acute cold exposure. In addition, the increased plasma noradrenaline levels accompanied by unaltered adrenaline levels suggest that the stimulus exerted by cold does not evoke a generalised stress response, but rather that the sympathetic nervous system is selectively stimulated.
BIOLOGICALLY ACTIVE PARATHYROID HORMONE IN FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA
Authors: ALLGROVE J. , SANGAL A. K. , LOW D. C. , WELLER P. H. , LOVERIDGE N.
Published: March 2008

Biologically active PTH (bio‐PTH) has been assayed by the cytochemical bioassay in five members (three affected) of a family with typical features of familial hypocalciuric hypercalcaemia (FHH). Carboxy‐terminal immunoreactive PTH was undetectable and bio‐PTH was within the normal range in all the subjects regardless of whether or not they were hypercalcaemic. These results suggest that increased biological activity of circulating PTH cannot account for the hypercalcaemia of FHH.
ARGININE INFUSION INCREASES PERIPHERAL PLASMA SOMATOSTATIN IN MAN
Authors: SKARE S. , HANSSEN K. F. , KRIZ V. , TORJESEN P. A.
Published: March 2008

A somatostatin (SRIF) radioimmunoassay is described, using an antiserum raised in rabbit, reacting more with SRIF‐14 than ‐28. Glass tubes were employed for the assay because our tracer, 125I 1‐Tyr‐SRIF, was adsorbed to plastic (23% non specific binding). Vycor extraction was used, and following Sephadex G‐50 chromatography, the plasma extract showed two forms, coeluting with SRIF‐28 and ‐14. Fifteen healthy subjects, eight women and seven men, 21‐39 years old, received an infusion of arginine chloride (2‐38 mmol/kg) for 20 min, or saline. An immediate rise in plasma SRIF from the mean basal level at 2 min was shown. Maximal value was 240±30 pmol/1 (P <: 001) after 10 min followed by a rapid descent towards the basal level after the infusion. A temporal relationship was observed between the SRIF, insulin and glucagon responses following arginine infusion, while the GH levels increased only after the SRIF levels had declined, indicating an inhibition of GH. This is further supported by the high degree of correlation (r=0‐87) between SRIF‐ and GH increments. It is suggested that plasma SRIF measurement during arginine infusion gives an estimate of the pancreatic SRIF releasing capacity.
A RADIOIMMUNOASSAY FOR GnRH AGONIST ANALOGUE IN SERUM OF PATIENTS WITH PROSTATE CANCER TREATED WITH D‐Ser (tBu)6AZA Gly10 GnRH
Authors: CLAYTON R. N. , BAILEY L. C. , COTTAM J. , ARKELL D. , PERREN T. J. , BLACKLEDGE G. R. P.
Published: March 2008

A radioimmunoassay is described for D‐Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I‐118630 as the label, and an anti‐GnRH serum, the specificity of the assay is directed to the N‐terminal end of the peptide, and putative degradation products have < 6% cross‐reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 μg, has a half‐time of disappearance from the serum of 4·9 ± 0·4 h and a volume of distribution of 13·7 ± 0·8 litres. Continuous subcutaneous infusion of 120 μg 118630/d gave stable serum concentrations of between 2–3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the ‘peak and trough’ pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3·6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6–8 ng/ml 15 d after the implant and fell to < 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3·6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long‐acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.
THE EFFECT OF VASOPRESSIN INFUSION ON GLUCOSE METABOLISM IN MAN
Authors: SPRUCE B. A. , MCCULLOCH A. J. , BURD J. , ØRSKOV H. , HEATON A. , BAYLIS P. H. , ALBERTI K. G. M. M.
Published: March 2008

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down gly‐cogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4±9 ± 0±1 to a peak of 5±70±2 mmol/1 (P<0<001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3‐hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11±9 ± 0±43 to 13±38 · 0±63 μmol/kg/min (P < 0·001). Infusion of AVP also increased plasma glucagon concentrations from 38 ± 8 to 79 ± 20 pg/1 (P < 0·01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.
A CASE OF PITUITARY DEPENDENT CUSHING'S DISEASE WITH CLINICAL AND BIOCHEMICAL FEATURES OF THE ECTOPIC ACTH SYNDROME
Authors: HALE ANN C. , MILLAR J. B. G. , RATTER SALLY J. , PICKARD J. D. , DONIACH I. , REES LESLEY H.
Published: March 2008

A case of atypical pituitary dependent Cushing's disease is reported. The patient presented with clinical symptoms similar to those of the ectopic ACTH syndrome; notably a marked hypokalaemic alkalosis, widely fluctuating plasma cortisol levels, greatly elevated plasma ACTH levels, and failure to suppress both plasma cortisol and ACTH levels following high dose oral dexamethasone. However, a large aggressive pituitary tumour was detected by skull X‐ray and computed tomography. Removal of the pituitary tumour led to full remission of the patient's Cushing's syndrome. Pro‐opiomelanocortin (POMC) related peptides in the plasma and tumour tissue extract of this patient have been characterized by gel‐filtration and Concanavalin‐A Sepharose affinity chromatography, indicating processing of POMC in a manner more usually associated with ectopic tumours.
ABNORMAL VITAMIN D METABOLISM IN PAGET'S DISEASE OF BONE
Authors: GUILLARD‐CUMMING D. F. , BEARD D. J. , DOUGLAS D. L. , JOHNSON S. K. , LAWSON‐MATTHEW P. J. , RUSSELL R. G. G. , KANIS J. A.
Published: March 2008

We have studied several biochemical indices of bone turnover and vitamin D metabolism in 32 untreated patients with Paget's disease and in 32 age‐matched control subjects. Patients with Paget's disease, as expected, were characterized by high bone turnover, as judged by alkaline phosphatase and urinary excretion of hydroxyproline. Serum values of 24,25‐dihydroxyvitamin D3 (24,25(OH)2D3) and the ratio of 24,25(OH)2D3 to 25‐OHD were significantly lower in patients than in control subjects. Serum concentrations of 1,25(OH)2D3 were normal in Paget's disease. The distribution of values for 24,25(OH)2D3 was log normal. On the basis of the normal range computed from control subjects, patients were divided into those with low or normal values for 24,25(OH)2D3. Disease activity, as judged by biochemical indices was significantly higher in the patients with the lower values of 24,25(OH)2D3. We conclude that Paget's disease is characterized by low circulating concentrations of 24,25(OH)2D3, particularly in patients with more extensive or severe disease.
‘CHEMICAL HYPERTHYROIDISM’: THE SIGNIFICANCE OF ELEVATED SERUM THYROXINE LEVELS IN l‐THYROXINE TREATED INDIVIDUALS
Authors: RENDELL M. , SALMON D.
Published: March 2008

We have previously reported that l‐thyroxine treated patients may often have elevated serum T4 concentrations and yet show no clinical signs of hyperthyroidism. We found that such patients had normal serum T3 concentrations. The present study explored the relationship between serum T3 and T4 and dosage of l‐thyroxine. Retrospective analysis of 99 patient records was performed. There was an increase of serum T4, serum T3 resin uptake (T3R), and T3 with increasing dose of l‐thyroxine. The T3/T4 ratio decreased with increasing dose of l‐thyroxine and with increasing T4. This phenomenon was analysed prospectively by starting 23 individuals on l‐thyroxine and progressively incrementing the dose until either symptoms of hyperthyroidism developed or T4 levels exceeded the upper unit of the normal range. Once again, there was a progressive increase in serum T4, T3R, and T3 with increasing dose of l‐thyroxine. At even the lowest dose of l‐thyroxine (0.05 mg), there was a marked fall in T3/T4 ratio as compared to untreated individuals. The T3/T4 ratio fell further with increasing dose but with a fairly weak correlation. The decrease in T3/T4 ratio showed a much stronger correlation with serum T4. Of the 23 individuals, all exceeded the upper limit of the normal range of serum T4. No individual with elevated T4 developed clinical signs of hyperthyroidism unless serum T3 was also elevated beyond the normal range. Of eight individuals who reached elevated T3 levels, six demonstrated clinical signs of hyperthyroidism. We conclude that l‐thyroxine treated individuals may show elevated T4 levels and yet be clinically euthyroid as a consequence of a relative decrease in T3 levels. Serum T3 appears to be the most reliable indicator of possible hyperthyroidism in l‐thyroxine treated patients.
PROLONGED FOLLICULAR PHASE AND DEPRESSED GONADOTROPHINS FOLLOWING HYSTERECTOMY AND CORPUS LUTE‐ECTOMY IN WOMEN WITH PREMENSTRUAL TENSION SYNDROME
Authors: BÄCKSTRÖM T. , SMITH S. , LOTHIAN H. , BAIRD D. T.
Published: March 2008

In an attempt to obtain further information on the aetiology of premenstrual syndrome (PMS), the endocrine changes following enucleation of the corpus luteum in the mid‐luteal phase of the cycle were studied in seven patients with PMS, and the results compared to details of seven control patients undergoing hysterectomy for menstrual problems. In the luteal phase, before surgery, the concentration of progesterone and FSH was lower, while that of oestradiol was slightly higher, in women with PMS. Following enucleation of the corpus luteum, follicular development and ovulation recommenced more slowly in women with PMS compared to controls (time to ovulation: 21 (range 18–24, vs 19(14–20) d, P < 0.01). During the follicular phase there was no difference between the two groups in the concentration of oestradiol. The rise in concentration of FSH following enucleation was delayed in patients with PMS, and the serum FSH concentration was significantly lower during the late follicular phase of the cycle, but not during the mid follicular phase. The results suggest that these women with PMS have a more sensitive ‘feed‐back’ than the controls, resulting in a lower preovulatory FSH level even though the oestradiol levels were not different. The results also suggest that the abnormalities described during the preoperative luteal phase are associated with the delay in the initial FSH rise.
THE ASSESSMENT OF OVULATION BY A COMBINATION OF ULTRASOUND AND DETAILED SERIAL HORMONE PROFILES IN 35 WOMEN WITH LONG‐STANDING UNEXPLAINED INFERTILITY
Authors: PETSOS P. , CHANDLER C. , OAK M. , RATCLIFFE W. A. , WOOD R. , ANDERSON D. C.
Published: March 2008

We have examined for the presence of subtle hormonal abnormalites in women with long‐standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26–32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of ≥ 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of > 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.
BONE METABOLISM IN ACUTE PARATHYROID CRISIS
Authors: CUNDY T. , DARBY A. J. , BERRY H. E. , PARSONS V.
Published: March 2008

Studies on bone metabolism described in a fatal case of acute parathyroid crisis, occurring in a 48‐year‐old woman in whom serum immunoreactive parathyroid hormone levels were very high, and a 5 g parathyroid adenoma was found at operation. The histological and biochemical findings suggested a massive and acute increase in bone resorption. There was, however, no evidence of any compensatory increase in bone formation, indicating that acute parathyroid crisis is characterized by a marked dissociation between bone resorption and formation. It is suggested that a sudden fall in oestrogen levels may contribute to the pathogenesis of this disorder.