bluuebunny/crossref_metadata_2025 huggingface dataset:
THE DIAGNOSTIC VALIDITY OF LOCAL AND TOTAL BONE MINERAL MEASUREMENTS IN POSTMENOPAUSAL OSTEOPOROSIS AND OSTEOARTHRITIS
Authors: NILAS LISBETH , GOTFREDSEN A. , RIIS B. J. , CHRISTIANSEN C.
Published: March 2008

Assessment of different forms of prevention and treatment of bone mineral loss depends upon valid and precise methods to assess bone mass. We have here studied four groups of women: 45 healthy premenopausal women, 37 healthy postmenopausal women, 21 women with osteoarthritis and 20 with hip fractures. Bone mass was measured in the spine and total body by dual photon absorptiometry and in two forearm sites (proximal and distal bone mineral content (BMC) by single photon absorptiometry. The long‐term (1 year) reproducibility was 1.2% for proximal BMC, 1.6% for distal BMC, 5.5% for spinal BMC, and 21% for total body bone mass (TBBM). In the early postmenopausal years bone mass was mainly reduced in areas with a high content of trabecular bone. In elderly postmenopausal women and women with hip fractures bone mass was almost identical in all four sites studied. The osteoarthritic patients had an 18% reduction of bone mass in the forearms and in TBBM, whereas the spinal bone mass was only reduced by 6%. In all subgroups TBBM could be predicted from the forearm measurements with standard errors of estimates of 9–13%. When the osteoarthritic women were excluded spinal bone mass could be predicted from both forearm measurements with a standard error of 15% (r= 0.74). The distal forearm BMC seems to be a more accurate estimate of spinal bone mass than does the proximal measurement. Of the 20 patients with hip fracture 16 had a distal forearm value below the premenopausal normal range, whereas spinal bone mass was subnormal in only eight (P < 005). We conclude that bone loss is universal in patients with hip fracture and measurements of forearm bone mass will meet most clinical and research demands.
DOES SHORT‐TERM FASTING DESENSITIZE HUMAN SOMATOTROPHS TO ORAL L‐DOPA STIMULATION?
Authors: RÖJDMARK S.
Published: March 2008

To investigate whether short‐term fasting influences hormone release from human somatotrophs and lactotrophs, two oral L‐dopa tests, using 0.5 g L‐dopa, were carried out in seven normal subjects. The first test was performed after an overnight fast (8 h), the second after an additional 48 h of total food withdrawal. Basal blood glucose declined by 21 ±2% (mean ± SEM) between the two tests (P < 0001). Free T3 in serum (FT3) fell by 32 ±4% (P < 0001). GH responsiveness to L‐dopa—as reflected by the GH incremental area (ng/ml ± min)—decreased from 588 ± 162 to 24 ± 240 (P < 0.02). The latter response area did not even differ significantly from zero. Food deprivation failed to affect the lactotrophs, inasmuch as similar PRL decremental areas (ng/ml ± min) were obtained in response to L‐dopa before (704 ± 165) and after (686 ±128) the prolonged fast. In order to prevent blood glucose from falling significantly during the period of food deprivation eight additional normal subjects were given 9 small oral doses of glucose (each dose 0.5 g/kg) at regular intervals between the two L‐dopa tests. This resulted in similar FT3 concentrations before and after the prolonged fast. Furthermore, glucose supplementation restored normal GH responsiveness to L‐dopa, as evidenced by similar GH incremental areas before and after the glucose fast. These results imply that short‐term fasting desensitizes human somatotrophs to exogenous L‐dopa. The finding that the decreased GH responsiveness returns to normal if a decline in FT3 is prevented by oral glucose supplementation, suggests that changes in FT3 might contribute to the abolished GH responsiveness to L‐dopa in fasting.
RELATIONSHIP BETWEEN HUMAN PROSTATIC EPITHELIAL CELL PROTEIN SYNTHESIS AND TISSUE DIHYDROTESTOSTERONE LEVEL
Authors: GELLER J. , LIU J. , ALBERT J. , FAY W. , BERRY C. C. , WEIS P.
Published: March 2008

To evaluate the role of small amounts of prostatic tissue dihydrotesterone (DHT) as a stimulus to epithelial cell protein synthesis, we studied tissue from 27 patients given various androgen‐blocking drugs for 1 week before transurethral resection of the prostate (TURP) and measured epithelial protein synthesis and DHT levels in the tissue specimens. Test drugs before TURP included megestrol acetate 160 mg per day, with and without Tamoxifen 40 mg per day, or ketoconazole 1200 mg per day. The tissue was processed immediately and epithelial cells separated by digestion of tissue with 0.5% collagenase. After separation, epithelial cells were labelled with either 3H‐leucine or l‐35S‐methionine. The DHT level was measured in whole prostatic tissue. Megesterol acetate alone and with tamoxifen significantly decreased both the incorporation of 3H‐leucine into protein and the tissue concentration of DHT; megestrol acetate plus ketoconazole significantly decreased l‐35S‐methionine incorporation into protein and the DHT level. When the data correlating DHT with protein synthesis using both labelling techniques were combined, the curves were parallel and a strong correlation was noted between DHT and protein synthesis over a wide range of values (P < 0–001). These results suggest that in hormone‐dependent prostatic cancer even small amounts of prostatic DHT such as may occur from adrenal androgens following castration may significantly stimulate protein synthesis of the tumour epithelial cells.
HYPERMINERALOCORTICOIDISM DUE TO ADRENAL CARCINOMA: PLASMA CORTICOSTEROIDS and THEIR RESPONSE TO ACTH and ANGIOTENSIN II
Authors: ISLES C. G. , MACDOUGALL I. C. , LEVER A. F. , FRASER R.
Published: March 2008

A 47‐year‐old female presented with hypertension, hypokalaemia, low plasma renin, high plasma aldosterone and was found to have a left adrenal tumour 4 cm in diameter by computerized tomography. Detailed biochemical studies showed high plasma levels of 11‐deoxycorticosterone and corticosterone in addition to aldosterone and 18‐hydroxycorticosterone, Basal 11‐deoxycorticosterone levels were particularly high. Corticosterone, 18‐hydroxycorticosterone and aldosterone concentrations were abnormally sensitive to infusions of ACTH and angiotensin II. Plasma Cortisol and assays for sex hormones were normal although there was evidence that Cortisol derived from the neoplasm. At operation a well‐differentiated adrenocortical carcinoma weighing 50 g (56 × 30 × 36 mm) was removed. There was no evidence of metastases following surgery. Adrenal function returned to normal. Review of the literature suggests that adrenocortical carcinoma should be suspected in patients who otherwise have typical features of Conn's syndrome, but whose tumours are more than 3 cm in diameter. Measurement of steroids such as 11‐deoxycorticosterone in addition to aldosterone is recommended since abnormally high values may also help to distinguish between hyperaldosteronism due to adenoma and carcinoma. Previously reported cases of isolated aldosterone production by a carcinoma cannot be substantiated.
DETERMINATION OF ENOLASE ISOZYMES IN VARIOUS ADRENAL GLAND TUMOURS
Authors: YONEDA M. , TAKATSUKI K. , YAMAUCHI K. , OISO Y. , TOMITA A. , MIZUNO S. , KATO K.
Published: March 2008

Enolase isozymes (α enolase and γ enolase) in the extracts of adrenal tumours (phaeochromocytoma, adenoma of primary aldosteronism and Cushing's syndrome, and neurinoma) were determined by means of enzyme immunoassay systems. The mean ± SEM, respectively, of α and γ enolase levels were 2.5 ± 0.37 μg/mg protein and 3‐2 ± 0–69 μg/mg protein for 9 phaeochromocytomas, 15.2 + 3.1 μg/mg protein and 0.65 ± 0.18 μg/mg protein for three adenomas with primary aldosteronism, 10.8 ± 3.0 μg/mg protein and 0.23 ± 0.02 μg/mg protein for five adenomas causing Cushing's syndrome, and 3.8 ± 0.88 μg/mg protein and 0.30 ± 0.15 μg/mg protein for three neurinomas. Thus, the γ enolase concentration in the extract of phaeochromocytoma was higher than that of other adrenal tumours. The serum level of γ enolase was determined in 36 patients with adrenal tumours and 26 normal controls by radioimmunoassay. The mean + SEM of γ enolase level was 5.4 ± 0.3 ng/ml in normal controls, 91 ± 0.9 ng/ml for 10 patients with phaeochromocytoma, 6.3 ± 0.3 ng/ml for 11 with primary aldosteronism, 5.5 ± 0.4 ng/ml for 11 with Cushing's syndrome, and 5.1 ± 0.7 ng/ml for four with neurinoma. Thus, patients with phaeochromocytoma had a significantly higher serum γ enolase levels than did those with tumours derived from adrenal cortex and normal controls. In patients with phaeochromocytoma, serum γ enolase levels showed a significant positive correlation with urinary adrenaline levels (P<0.05), and after resection the elevated level of γ enolase fell significantly (P<0.05) and returned to normal. These results indicate that γ enolase in serum may be a useful marker for the differential diagnosis of adrenal tumours and therapeutic monitoring of phaeochromocytoma.
CYPROTERONE ACETATE, AN ALTERNATIVE GESTAGEN IN POSTMENOPAUSAL OESTROGEN/GESTAGEN THERAPY
Authors: RIIS B. J. , JENSEN J. , CHRISTIANSEN C.
Published: March 2008

Seventy‐six healthy, early postmenopausal women (aged 45–54 years) were allocated to 2 years of treatment with a cyclic combination of 2 mg oestradiol valerate (21 d) and 1 mg cyproterone acetate (11 d) or placebo. Sixty‐five women (86%) completed the study. In the placebo group the bone mineral content in the forearms (measured by single photon absorptiometry) and the bone mineral content in the lumbar spine and total skeleton (measured by dual photon absorptiometry) decreased significantly and at the same magnitude (P < 0001), whereas all bone mass measurements remained unchanged in the hormone‐treated group. In the hormone‐treated group there was a significant decrease in biochemical estimates of bone turnover (serum alkaline phosphatase, serum phosphate, fasting urinary calcium and hydroxyproline), whereas these values were unchanged in the placebo treated group. We conclude that treatment with a cyclic combination of 2 mg oestradiol valerate and 1 mg cyproterone acetate is effective as prophylaxis of postmenopausal bone loss.
THE PLASMA ARGININE VASOPRESSIN RESPONSE TO INSULIN‐INDUCED HYPOGLYCAEMIA IN CHILDREN WITH SHORT STATURE IS RELATED TO AGE AND THE ONSET OF PUBERTY
Authors: SECKL J. R. , DUNGER D. B. , HUEN K. , LIGHTMAN S. L.
Published: March 2008

The plasma arginine vasopressin (AVP) response to insulin‐induced hypoglycaemia was investigated in 27 children with short stature. None had diabetes insipidus. Six patients were excluded from further analysis because of hypothalamo‐pituitary dysfunction. Of the remainder, 14 were prepubertal (Tanner 1) and seven were pubertal (Tanner 2–4). Both groups had similar height velocity retardation. There was a significant rise of AVP of 3.4±1.3 pmol/1 at 30 min in the pubertal group (P < 0.05) but no significant change in prepubertal patients. There was a significant relationship between chronological age and AVP response 30 min after insulin (r= 0.45, P < 0.05) and a closer correlation between bone age and AVP response (r= 0.62, P < 0.01). The data suggest that insulin‐induced hypoglycaemia does not reliably stimulate AVP secretion in children and that this response is related to age and pubertal stage.
EVIDENCE FOR GONADAL DESENSITIZATION AFTER PULSATILE THERAPY IN WOMEN WITH AMENORRHOEA?
Authors: GLASIER A. , BAIRD D. T. , McNEILLY A. S.
Published: March 2008

Sixteen women with primary and secondary amenorrhoea were treated with pulsatile GnRH administered subcutaneously. Ovulation was successfully induced in 6/8 women with hypogonadotrophic hypogonadism; and in 2/2 women with idiopathic hyperprolactinaemia; but in only 3/6 women with amenorrhoea associated with an elevated LH:FSH ratio. Using serial blood sampling, we were unable to demonstrate the establishment of a physiological pattern of gonadotrophin secretion in the presence of an apparently normal menstrual cycle. Nor did we observe a consistent relationship between injection of GnRH and the resultant gonadotrophin response. A reduction or total cessation of both pituitary and gonadal sensitivity to GnRH was observed in four women. Possible reasons for these findings are discussed.
INCOMPLETE MASCULINIZATION DUE TO A DEFICIENCY OF 17β‐HYDROXYSTEROID DEHYDROGENASE: COMPARISON OF PREPUBERTAL AND PERIPUBERTAL SIBLINGS
Authors: WILSON S. C. , HODGINS M. B. , SCOTT J. S.
Published: March 2008

Incomplete masculinization due to a deficiency of 17β‐hydroxysteroid dehydrogenase (17β‐HSD) was investigated in siblings aged 4 years (Case 1) and 12 years (Case 2). Diagnosis was based on increased ratios of androstenedione (A) to testosterone (T) in blood, and impaired reduction of A to T by 17β‐HSD in vitro in the testes. Impairment was total in Case 2 but partial in Case 1. Case 2 also showed deficient conversion of dehydroepiandrosterone (DHA) to androstenediol and of oestrone to oestradiol by 17β‐HSD which were normal in Case 1. Oxidation of T to A by 17β‐HSD and conversion of 17α‐hydroxyprogesterone to A by 17,20 desmolase were normal in the testes of both siblings. 3β‐HSD conversion of DHA to A was normal in Case 1, but markedly increased in Case 2. In contrast to testicular findings, 17β‐HSD reduction of A to T in genital skin fibroblasts from Case 2 was normal and diagnosis would not have been possible from studies of measurements of this enzyme in skin. The severity of the testicular 17β‐HSD deficiency in the peripubertal compared with the prepubertal sibling suggests either considerable intra‐familial variation in the extent of the enzyme defect or that puberty may aggravate this disorder. The normal reductive action of 17β‐HSD in skin, despite impaired action in testes, suggests involvement of more than one iso‐enzyme.
INTRINSIC PULSATILITY OF ACTH RELEASE FROM THE HUMAN PITUITARY IN VITRO
Authors: GAMBACCIANI M. , LIU J. H. , SWARTZ W. H. , TUEROS V. S. , RASMUSSEN D. D. , YEN S. S. C.
Published: March 2008

An in‐vitro perifusion system was used to investigate spontaneous ACTH release from human fetal (21–23 weeks gestation) and adult pituitaries. The pattern of ACTH release from fetal pituitaries (n= 7) exhibited a remarkable pulsatile character with a mean (± SEM) pulse interval of 11.3 ± 0.8 min. The mean pulse amplitude was 49.7 ± 6.3 pg, with a nadir to peak increment of 90.7 ± 10.4%. The mean ACTH release rate was 87.2±13.3 pg/2 min. Addition of the calcium chelator EGTA (4 nM) to the perifusion medium induced a significant (p±0.01) decrease in both ACTH release rate (from 102.0 ± 8.5 to 52.0 ± 9.9 pg/2 min) and ACTH pulse amplitude (from 57.7 ± 2.8 to 31.3 ± 4.6 pg) (n= 3). Administration of either 2 nM corticotrophin releasing factor (CRF) or 56 mM KCl induced 10‐ and 2‐fold increases in ACTH secretion, respectively (n= 2). Quarters of adult human pituitaries (n– 6) also secreted ACTH in a pulsatile fashion, with a pulse interval of 14.8±1.7 min, pulse amplitude of 86.7± 10.0 pg, nadir to peak increment of 84.5 ± 9.8%, and overall release rate of 167.2 ± 8.8 pg/2 min. These studies demonstrate that ACTH release from the isolated human pituitary in vitro is characterized by high frequency/low amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium‐dependent pulsatile ACTH release apparently reflects the activity of an intrinsic intrapituitary pulse‐generating mechanism.
ROLE OF GONADAL STEROIDS IN THE SEROTONINERGIC CONTROL OF PROLACTIN SECRETION IN MEN
Authors: FORESTA C. , INDINO M. , SCANDELLARI C.
Published: March 2008

The physiological regulation of PRL secretion seems to involve the central serotonin system, since plasma PRL levels are enhanced by serotoninergic agonists and serotonin re‐uptake blockers. The aim of this study was to evaluate whether the influence of oestrogens on PRL is mediated by the hypothalamic serotonin system. The PRL response to fenfluramine, a serotonin agonist that releases the amine and inhibits its re‐uptake, was assessed in 10 normal men (aged 18–25 years) and in six castrated men (aged 18–24 years). In both groups, the effect of fenfluramine on PRL secretion was also evaluated on the sixth day after receiving clomiphene citrate, an oestrogen antagonist and partial agonist. In castrated men, fenfluramine administration was also performed on the seventh day after the last dose of testosterone enanthate (200 mg i.m. every 3 weeks for 4 months). Our results demonstrate that in normal men fenfluramine treatment significantly enhances plasma PRL levels, and clomiphene citrate treatment significantly reduces this effect. In castrated men, fenfluramine is also able to enhance PRL secretion but to a lesser extent; after clomiphene citrate treatment the increase of plasma PRL levels induced by fenfluramine rises to the normal range. We therefore suggest that in man oestrogens and aromatizable androgens influence PRL secretion at least in part by involving the activation of the hypothalamic serotonin system.
KINETICS OF INSULIN DISAPPEARANCE FROM PLASMA IN CORTISONE‐TREATED NORMAL SUBJECTS
Authors: ELLEMANN K. , THORSTEINSSON B. , FUGLEBERG S. , FELDT‐RASMUSSEN B. , ANDERSEN O. O. , GRÖNBÆK P. , BINDER C.
Published: March 2008

The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1–5 mU/kg/min) was used to achieve different levels of steady state plasma insulin concentrations; normoglycaemia was preserved by a glucose clamp technique. The experimentally determined data were compared using a previously validated model of saturation kinetics. The amount of glucose required to maintain normoglycaemia during the insulin infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered insulin resistant by short‐term cortisone treatment.
FOOD‐INDUCED CORTISOL SECRETION IS MEDIATED BY CENTRAL ALPHA‐1 ADRENOCEPTOR MODULATION OF PITUITARY ACTH SECRETION
Authors: AL‐DAMLUJI S. , IVESON T. , THOMAS J. M. , PENDLEBURY D. J. , REES L. H. , BESSER G. M.
Published: March 2008

Food ingestion stimulates Cortisol secretion in man, but the mechanism of this effect is unknown. We have investigated the possible role of adrenoceptors in the mediation of this effect. Six normal males were given continuous 3 h i.v. infusions of normal saline, methoxamine (alpha‐1 adrenoceptor agonist) and thymoxamine (alpha‐1 adrenoceptor antagonist). Methoxamine enhanced and thymoxamine attenuated the ACTH and Cortisol responses to a standard meal given 60 min after commencement of the infusion. The drugs had no effect on nutrient absorption. Four patients with recent onset of pituitary ACTH deficiency and normally responsive adrenal glands showed no ACTH or Cortisol rises after the standard meal, demonstrating that postprandial Cortisol secretion is mediated by pituitary rather than gut ACTH. Our previous investigations have demonstrated that alpha‐1 adrenoceptors stimulate pituitary ACTH secretion in man by an action within the blood brain barrier. We therefore conclude that postprandial Cortisol secretion is mediated by central stimulant alpha‐1 adrenoceptors modulating pituitary ACTH secretion.
REMISSION OF HYPOPARATHYROIDISM DURING LACTATION: EVIDENCE FOR A PHYSIOLOGICAL ROLE FOR PROLACTIN IN THE REGULATION OF VITAMIN D METABOLISM
Authors: CUNDY T. , HAINING S. A. , GUILLAND‐CUMMING D. F. , BUTLER J. , KANIS J. A.
Published: March 2008

We studied a young woman with surgical hypoparathyroidism who, on her usual maintenance dose of calcitriol, developed hypercalcaemia 9 d postpartum when lactation was established. Serum values of 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) values were very high (127 pg/ml). The patient remained without exogenous calcitriol treatment for 40 d, during which time serum 1,25(OH)2D3 levels remained within the normal range and serum calcium fell with a half‐time of 27 d. The requirements for calcitriol increased to antepartum levels when lactation had ceased. There was a close negative correlation between requirements for calcitriol and serum PRL values. After weaning, an episode of hypercalcaemia was induced by increasing the dose of calcitriol. On stopping calcitriol the serum 1,25(OH)2D3 fell to low values (4 pg/ml) within 2 d and serum calcium fell with a half‐time of 3 d, necessitating the early reintroduction of calcitriol. We conclude that in hypoparathyroidism exogenous vitamin D requirements fall during lactation because of enhanced endogenous production of 1,25(OH)2D3. The lactation‐associated increase in circulating 1,25(OH)2D3 concentrations thus results from a parathyroid hormone‐independent mechanism, possibly by an effect of PRL on the la‐hydroxylase.
ACID THYROGLOBULIN PROTEASE ACTIVITIES IN HUMAN DISEASED THYROID GLANDS
Authors: YOSHINARI M. , OKAMURA K. , SHIROOZU A. , NAKASHIMA T. , INOUE K. , FUJISHIMA M.
Published: March 2008

The lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome‐rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimoto's thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14‘cold’ adenomas, four‘hot’ adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimoto's thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The‘hot’ adenomas had higher protease activity than‘cold’ ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.
THE DEFINITION OF TRUE RECURRENCE OF PITUITARY‐DEPENDENT CUSHING'S SYNDROME AFTER TRANSSPHENOIDAL OPERATION
Authors: LAMBERTS S. W. J. , KLIJN J. G. M. , de JONG F. H.
Published: March 2008

Two patients are described with pituitary‐dependent Cushing's syndrome who had successful transsphenoidal selective removal of basophil microadenomas. After a period of adrenal insufficiency the clinical signs and the Cortisol secretion rate became normal after 12–18 months, together with the return of a normal feedback response to glucocorticoids (dexcamethasone suppression), a normal diurnal rhythm of plasma Cortisol, and a normal response to stress (increase of plasma Cortisol to insulin‐induced hypoglycaemia). However, pituitary‐dependent Cushing's syndrome recurred 38 and 56 months after operation. This was preceded by gradual changes of the results of the dexamethasone tests, disappearance of the diurnal rhythm of Cortisol, and of the responses of plasma Cortisol to hypoglycaemia.‘True recurrence’ should be defined as the return of the clinical and biochemical characteristics of Cushing's syndrome after a successful transsphenoidal operation, with a normal hypothalamic‐pituitary‐adrenal axis as evidenced by a normal response to dexamethasone, a normal diurnal rhythm of Cortisol and a normal increase of plasma Cortisol with insulin‐induced hypoglycaemia.
CLINICAL USEFULNESS OF A HIGHLY SENSITIVE ENZYME‐IMMUNOASSAY OF TSH
Authors: MORI T. , IMURA H. , BITO S. , IKEKUBO K. , INOUE S. , HASHIDA S. , ISHIKAWA E. , OGAWA H.
Published: March 2008

Using a recently developed sensitive enzyme immunoassay (EIA) for TSH, serum TSH levels in normal subjects and patients with various thyroid disorders were measured. The minimum detectable concentration was less than 0.005 mU/l. An excellent correlation was observed between TSH values measured by EIA and by sensitive radioimmunoassay (r= 0.932). In 26 normal subjects, serum TSH ranged from 0.30 to 2‐65 mU/l (geometric mean 0.97 raU/l). In 27 untreated hyperthyroid Graves' patients, serum TSH was detected in all but one, ranging from 0.005 to 0.19 mU/l (geometric mean 0.040). These values were proved to be specific for human TSH by absorption, recovery, cross‐reactivity and dilution studies; non‐specific serum effects were also ruled out. In 10 patients with destructive thyroiditis, similar TSH values (0.005‐0.20 mU/l, mean 0.032) were observed. However, no significant correlations between TSH and circulating thyroid hormone levels were observed in these thyrotoxic conditions. Furthermore, 9 untreated Graves' patients did not respond to a single i.v. injection of TRH. In 13 hypothyroid patients with hypothalamopituitary disorders, 10 had basal TSH levels of less than 0.4 mU/l, and TRH tests in five gave peak TSH values of more than 0.8 mU/l, which were associated with significant increases in serum T3. In three patients with Sheehan's syndrome, elevated basal TSH levels were observed. Two of them responded to TRH, but these TSH elevations were not associated with T3 increases. In conclusion, this sensitive EIA could measure TSH levels in most patients with thyrotoxicosis and central hypothyroidism. However, the true significance of these measured values needs to be elucidated by future studies.

The conventional radioimmunoassay (RIA) for TSH cannot fully discriminate low TSH levels from those of euthyroid subjects, but recently developed sensitive RIA and immunoradiometric assay (IRMA) have been reported to be able to discriminate between them (Pekary et al., 1975; Smith et al., 1979; Mori et al., 1983; Seth et al., 1984). However, even these assays cannot detect serum TSH in patients with thyrotoxicosis. Detectable amounts of TSH have been observed in the pituitary of hyperthyroid Graves' patients (Kumahara et al., 1967; Mori, 1973). We could expect them, therefore, to secrete some TSH into the circulation, but to detect low TSH levels, it is necessary to apply a very sensitive assay. Cytochemical bioassay of TSH has been reported to be of sufficient sensitivity (Bitensky et al., 1974). However, the assay is not suitable for routine use, and is known to be interfered with by certain non‐specific serum effects (Condliffe & Weintraub, 1979).

We have recently reported the development of a highly sensitive enzyme immunoassay (EIA) for TSH which could detect 0.005 mU/l or even less (Inoue et al., 1986). This paper deals with clinical application of the EIA, and discusses the significance of TSH values measured in cases of decreased TSH secretion.
ORBITAL COBALT IRRADIATION COMBINED WITH RETROBULBAR OR SYSTEMIC CORTICOSTEROIDS FOR GRAVES' OPHTHALMOPATHY: A COMPARATIVE STUDY
Authors: MARCOCCI C. , BARTALENA L. , PANICUCCI M. , MARCONCINI C. , CARTEI F. , CAVALLACCI G. , LADDAGA M. , CAMPOBASSO G. , BASCHIERI L. , PINCHERA A.
Published: March 2008

Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side‐effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty‐four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20‐30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5‐9; the final score was 3‐2, with a change of ‐ 2.7 (P< 0001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra‐ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side‐effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment. The results obtained in the group receiving systemic corticosteroids were more satisfactory both clinically (excellent and good responses being observed in 60% vs 30% of cases) and in terms of changes of the OI (mean decrease 3.5 vs 2.6, P<0.02). In conclusion, the combination of orbital irradiation with retrobulbar corticosteroids may be used in the treatment of severe Graves' ophthalmopathy, but appears to be less effective than orbital irradiation used with systemic corticosteroids. Thus, the use of retrobulbar corticosteroids should be limited to patients with contra‐indications to systemic steroids.
NEW FINDINGS IN APPARENT MINERALOCORTICOID EXCESS
Authors: DIMARTINO‐NARDI J. , STONER E. , MARTIN K. , BALFE J. W. , JOSE P. A. , NEW M. I.
Published: March 2008

We report two female siblings (ages 4 and 9 years) and one 8‐year‐old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. The deficiency of 11β‐hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of Cortisol (F) to cortisone (E). As a result, the serum Cortisol half‐life (T½) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of Cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in Cortisol action or metabolism results in Cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME.
THE RELATIONSHIPS BETWEEN SERUM T3 INDEX, THYROID VOLUME, AND THYROID STIMULATING, TSH RECEPTOR BINDING AND THYROID GROWTH STIMULATING ANTIBODIES IN UNTREATED GRAVES' DISEASE
Authors: BLIDDAL H. , HEGEDÜS L. , HANSEN J. M. , BECH K. , VAN DER GAAG R. , DREXHAGE H. A.
Published: March 2008

This study represents an international double‐blind collaborative study of abnormal immunoglobulin activity in untreated Graves' disease. Laboratories in two countries participated in a comparison of thyrotrophin binding inhibiting (TBII), thyroid stimulating (TSAb), and growth stimulating (TGI) immunoglobulins with clinical data, including ultrasonically measured thyroid size. The correlation between TGI and thyroid volume (n= 25, Rs= 0.54, P < 0‐05) and the fact that 9 of 10 patients with high range TGI values had large goitres establish the relationship between TGI and goitre, confirming that the in‐vitro activity of these antibodies is related to an in‐vivo action. In addition, both TBII and TSAb correlated with serum free T3 indices (TBII: n= 60, Rs= 0.46, P < 0.001, and TSAb: n= 60, Rs= 0.64, P<0001). Moreover, both TBII and TSAb correlated with thyroid volume (TBII: n= 60, Rs= 0.37, P< 0.01, and TSAb: n= 60, Rs= 0.41, P < 0001) suggesting that these antibodies are also important in development of goitre in Graves' disease. Finally, some correlation between the antibodies was observed. TBII correlated with TSAb (n= 60, Rs= 0.47, P < 0.001), and in the 16 patients with positive TGI results, this activity correlated with TBII (Rs= 0.54, P <0.05), but not with TSAb. Also some cases were found with corresponding high range TBII and TGI, while negative for TSAb, suggesting a close relationship between the in‐vitro measurement of TSH binding and TGI.
AN ASSESSMENT OF POSTERIOR PITUITARY FUNCTION IN PATIENTS WITH SHEEHAN'S SYNDROME
Authors: JIALAL I. , DESAI R. K. , RAJPUT M. C.
Published: March 2008

Antidiuretic hormone (ADH) function was assessed in a group of 16 patients with Sheehan's syndrome and 17 controls. All patients were on adequate cortisone and thyroxine replacement therapy before testing. During the dehydration test the patients revealed an impairment of ADH function. The maximum urine osmolalities and the urine‐plasma osmolality ratios were significantly lower in the patients with Sheehan's syndrome compared to controls (maximum urine osmolalities 633 ± 38 (SEM) and 873 ± 29 (SEM) mOsm/kg, respectively, P <0.001; urine‐plasma osmolality ratios 2.15 ± 0.14 (SEM) and 3.01 ± 0.10 (SEM), respectively, P < 0.001). Plasma osmolalities were significantly higher in the patients (296.1 ± 1.2 (SEM) and 290 ± 0.9 (SEM), respectively, P < 0.001). The patients took a longer period to achieve these maximum urine osmolalities. Three of the patients with Sheehan's syndrome were diagnosed as having diabetes insipidus since their maximum urine osmolalities were below 600 mOsm/kg and following desmopressin all three had an increment in urine osmolality which exceeded 9%. In addition these three patients had a maximum urine‐plasma osmolality ratio below 1‐9. Thus, it appears the patients with Sheehan's syndrome have an impairment of ADH function which manifests in some as diabetes insipidus.
THE PLACE OF INTRAVENOUS GHRH 1–40 STUDIES IN THE THERAPY OF GROWTH HORMONE‐DEFICIENT CHILDREN WITH GHRH
Authors: SMITH P. J. , BROOK C. G. D.
Published: March 2008

We studied GH responses to i.v. GH releasing hormone (GHRH) (1 jug/kg) before and during the treatment of 11 GH deficient children with s.c. nocturnal pulsatile GHRH 1‐10; seven for 9 months and four for 6 months. Each subject demonstrated GH stimulation at each i.v. study. There was a wide variation of response between subjects and in each subject on different occasions. Significant growth acceleration following s.c. GHRH was demonstrated in eight of 11 patients (73%). The sensitivity or true positive rate of the index GHRH study to predict a clinical response to s.c. treatment, regardless of the GH response achieved, was also 73%. When an index GH ‘cut‐off’ response of < 10 mU/1 was employed, the probability of an increase in growth rate to s.c. GHRH fell to 0‐50 (sensitivity 80%). The GHRH study was unhelpful, and in fact misleading, when assessed as a method of monitoring clinical progress and the outcome of pulsatile s.c. GHRH treatment. The growth response of a child to s.c. GHRH therapy is of far greater importance than the GH response following an i.v. bolus of GHRH. The index study gave no useful indication of either the potential GH pituitary reserve or which subjects would respond to treatment. Pretreatment and repeated GHRH studies are of limited value and should be interpreted with caution.
PREVALENCE, NATURAL HISTORY AND SURGICAL TREATMENT OF EXOPHTHALMOS
Authors: STREETEN D. H. P. , ANDERSON G. H. , REED G. F. , WOO P.
Published: March 2008

The 95% confidence limits of exophthalmometer measurements have been defined by a single observer in 105 individuals who had no known thyroid disease, and found to be 10.5‐18.8 mm. Measurements in 308 patients with thyrotoxicosis have shown that exophthalmos (>19 mm) of one or both eyes was present in 21‐3% of the patients. Among the 122 thyrotoxic patients whose exophthalmometer measurements could be performed annually for 3‐19 years after correction of the thyrotoxicosis (usually with 131I), exophthalmos remained stable in 78.7%, worsened in 15.6% and became less severe in 5.7% of the patients. Transantral decompression of the orbits was performed in 15 patients with rapid subjective improvement in all and reduction in exophthalmometer measurements of 3.6 ± 0.5 (mean ± SEM) mm, and no serious side‐effects. In view of these findings, transantral decompression should be considered more frequently in the treatment of severe or cosmetically damaging exophthalmos.
THE COEXISTENCE OF MALE PSEUDOHERMAPHRODITES WITH 17‐KETOSTEROID REDUCTASE DEFICIENCY AND 5α‐REDUCTASE DEFICIENCY WITHIN A TURKISH KINDRED
Authors: IMPERATO‐McGINLEY J. , AKGUN S. , ERTEL N. H. , SAYLI B. , SHACKLETON C.
Published: March 2008

Two distinct enzyme defects affecting androgen production and resulting in male pseudohermaphroditism were found in a Turkish kindred from a small isolated village in the Taurus mountains of southern Turkey. Pedigree analysis revealed the inter‐relationships of 9 male pseudohermaphrodites. Six affected subjects had adequate steroid hormone analysis. Two adult male pseudohermaphrodites had 17‐ketosteroid reductase deficiency with elevated concentrations of plasma androstenedione relative to testosterone, and elevated concentrations of urinary androsterone (A) and etiocholanolone (E) relative to tetrahydrocortisol (THF), 5α‐tetrahydrocortisol (5α‐THF) and tetrahydrocor‐tisone (THE). Four affected males (three adults, one child) had 5a‐reductase deficiency (elevated ratios of plasma testosterone/dihydrotestosterone and urinary 5β/5αC19 and C21 steroid metabolites). The homozygous state for both enzyme deficiencies was not demonstrable in the same affected subject, suggesting that the enzyme deficiencies are segregating separately within this kindred. Whether the mutant genes are segregating on allelic chromosomes or other autosomes cannot be determined from this study.
REDUCED GROWTH HORMONE RESPONSE TO GROWTH HORMONE‐RELEASING HORMONE IN CHILDREN WITH SIMPLE OBESITY: EVIDENCE FOR SOMATOMEDIN‐C MEDIATED INHIBITION
Authors: LOCHE S. , CAPPA M. , BORRELLI P. , FAEDDA A. , CRINÒ A. , CELLA S. G. , CORDA R. , MÜLLER E. E. , PINTOR C.
Published: March 2008

We have evaluated the plasma GH response to a single injection of 1μg/kg of GH‐releasing hormone (GHRH)‐40 in 15 obese children and 15 age‐matched control children. Most of the obese children showed a subnormal plasma GH response to GHRH and the mean plasma GH integrated area (IC‐GH) following stimulation was significantly smaller in obese than control children. Plasma somatomedin‐C (SM‐C) levels were significantly higher in obese than control children, and were negatively correlated with the peak plasma GH levels (r=−0.616, P<001) and the IC‐GH (r=−0.554, P<0.02) after GHRH. Non‐esterified fatty acids (NEFA) and fasting plasma insulin levels were also elevated in obese children, but did not correlate with the extent of plasma GH response to GHRH. These data confirm previous observations on the refractoriness of obese children to release GH after GHRH, and imply that it may be due to the feedback inhibition operated by the elevated plasma levels of SM‐C.
STILBOESTROL PRETREATMENT OF CHILDREN WITH SHORT STATURE DOES NOT AFFECT THE GROWTH HORMONE RESPONSE TO GROWTH HORMONE‐RELEASING HORMONE
Authors: ROSS R. J. M. , GROSSMAN A. , DAVIES P. S. W. , And M. O. SAVAGE , BESSER G. M.
Published: March 2008

Oestrogens are known to enhance both basal and stimulated GH secretion. To examine whether this effect is mediated through the hypothalamus or the pituitary we performed insulin tolerance and GH‐releasing hormone (GHRH) tests with and without oestrogen priming in a group of 14 short children. Pretreatment with stilboestrol increased basal levels of GH and both peak and incremental levels during insulin hypoglycaemia. In contrast, there was no effect of stilboestrol priming on the GH response to either an i.v. bolus of 100 μg or 0.1 μg/kg (range 2‐6 μg) of GHRH. The children had significantly higher GH responses to an unprimed GHRH than unprimed insulin tolerance test. We conclude stilboestrol priming acts through the hypothalamus presumably by increasing endogenous GHRH release, and that short children with a subnormal GH response to insulin hypoglycaemia show a greater response to GHRH; this suggests the presence of a hypothalamic cause for their decreased GH secretion.
ERYTHROCYTE OUABAIN BINDING IN PATIENTS RECEIVING THYROXINE
Authors: WILCOX A. H. , LEVIN G. E.
Published: March 2008

Thyroid hormone action at the cellular level was investigated in euthyroid women who were receiving replacement thyroxine, and whose plasma T4 levels were above the upper reference limit for healthy subjects. There is evidence that erythrocyte sodium pump sites are reduced in number in patients with hyperthyroidism. These sites were measured by the ouabain binding capacity. Plasma T4, free T3 and TSH were also measured, the latter by a high sensitivity fluoroimmunoassay. Three groups of women were investigated; 30 patients receiving T4 with elevated plasma T4 concentrations, 30 age‐matched healthy women, and 10 untreated thyrotoxic patients. Erythrocyte ouabain binding was significantly reduced in the thyroxine treated patients, although not to the degree observed in the thyrotoxic patients. Plasma free T3 concentration was increased in 12 of 30 treated patients. TSH was undetectable in 23 of 30 treated patients. The ouabain binding results provide some evidence for increased thyroid hormone action at cellular level in the thyroxine treated patients.
THE HUMAN LEUCOCYTE SODIUM PUMP IN ADRENOCORTICAL INSUFFICIENCY
Authors: NG L. L. , EVANS D. J. , BURKE C. W.
Published: March 2008

In view of the known effects of Cortisol and related compounds on sodium balance, we examined leucocyte 22Na+ efflux in patients with adrenocortical insufficiency. The ouabain‐sensitive 22Na+ efflux rate constant, which reflects sodium pump activity, was lowered in secondary hypoadrenalism (mean 1.95 ± SD 0.25 vs 2.33 ± 0.45 h‐1, P< 0.002, n= 6). Patients with hypoadrenalism also had higher intracellular sodium content (mean 34.9 ± SD 3.5 vs 27.8 ± 9.5 mmol/kg dry weight, P< 0.008) and lower intracellular potassium to sodium ratios (mean 9.7 ± SD 0.7 vs 12.9 ± 3.6, P<0.001). These defects in cellular sodium balance were corrected following replacement therapy with Cortisol, prednisolone or dexamethasone. In‐vitro incubation of normal leucocytes with 5‐20 nmol/1 dexamethasone led to an increase in the Na+/K+‐ATPase activity. The effect of Cortisol and related compounds on the distribution of sodium between intra‐ and extra‐cellular fluid may be mediated by their action on the sodium pump.
PHOSPHOLIPASE C ACTIVITY IN HUMAN ENDOMETRIUM: ITS SIGNIFICANCE IN ENDOMETRIAL PATHOLOGY
Authors: BONNEY R. C. , FRANKS S.
Published: March 2008

Phospholipase C activity was measured in human endometrium using an assay based on the release of total labelled water soluble products (inositol, inositol phosphates) from L‐3‐phosphatidyl‐[2‐3H] inositol. The enzyme was shown to be calcium dependent and to have an optimum pH of 5.5. There was no difference between proliferative phase and secretory phase endometrium with respect to phospholipase C activity either in women with normal menstrual blood loss (proliferative phase: 3.7 ± 0.7 (mean ± SD), secretory phase: 4.5 ± 2.0 nmol/mg protein/min) or in those complaining of severe menorrhagia (proliferative phase: 5.8 ± 2.8, secretory phase: 7.0 ± 2.8 nmol/mg protein/min). However, women complaining of severe menorrhagia had significantly higher endometrial phospholipase C activity than those in the normal group (P<0.01 and P<0.02 for proliferative and secretory phases respectively). Endometrial phospholipase C activity was also elevated in the presence of other gynaecological disorders, e.g. dysmenorrhoea, adenocarcinoma of the cervix and endometrial hyperplasia. The results indicate that phospholipase C activity in human endometrium is not related to the stage of the menstrual cycle but that in the presence of menorrhagia and other gynaecological disorders, activity is increased. Phospholipase C could be implicated in the generation of arachidonic acid for prostaglandin synthesis which may in turn be associated with these abnormalities.
IMMUNOMODULATORY EFFECT OF THE TREATMENT OF GRAVES’DISEASE ON ANTIGEN‐SPECIFIC MONOCYTE PROCOAGULANT ACTIVITY PRODUCTION
Authors: IITAKA M. , IWATANI Y. , GERSTEIN H. C. , ROW V. V. , VOLPÉ R.
Published: March 2008

The monocyte procoagulant activity (PCA) production assay has been shown to be a good parameter of cell‐mediated immunity. We have studied antigen‐specific PCA production in peripheral blood mononuclear cells from patients with Graves’disease to determine the effect of the treatment on the cell‐mediated immune response. Peripheral blood mononuclear cells from patients with untreated or relapsed Graves’disease produced significantly greater PCA with thyroid antigen stimulation than those from normal subjects. Patients both on antithyroid drugs in the hyperthyroid state and within 3 months post‐131I therapy also produced significantly larger amount of PCA than normal subjects. However, there was no significant difference in PCA production with thyroid antigen stimulation between normal subjects and patients on anti‐thyroid drugs in the euthyroid state, or patients over 3 months post‐131I therapy. The ratio of positive to negative PCA production in patients on anti‐thyroid drugs in the euthyroid state or over 3 months post‐131I therapy was significantly lower than in untreated or relapsed Graves’disease patients. Mononuclear cells from patients on propylthiouracil responded to propylthiouracil in vitro by production of PCA. Cells from normal subjects, untreated Graves’disease patients, or patients with Hashimoto's thyroiditis did not produce PCA with propylthiouracil stimulation. Mononuclear cells from patients who were on propylthiouracil for more than 3 months produced greater PCA than those on the drug for less than 3 months, suggesting sensitization of lymphocytes to propylthiouracil during the course of treatment. However, after 131I therapy, they gradually became unresponsive to propylthiouracil. This study has shown that the activity of the antigen‐specific response assessed by PCA production in mononuclear cells from Graves’disease patients declined after treatment, suggesting that the treatment exerted immunomodulatory effects.
LONG‐TERM TREATMENT OF HYPERPROLACTINAEMIA WITH BROMOCRIPTINE: EFFECT OF DRUG WITHDRAWAL
Authors: WANG C. , LAM K. S. L. , MA J. T. C. , CHAN T. , LIU M. Y. , YEUNG R. T. T.
Published: March 2008

Fifty‐one patients with hyperprolactinaemia (23 with macroadenoma, 23 with microadenoma, and five with idiopathic hyperprolactinaemia) were treated with bromocriptine for 2‐12 years (4.9 ± 2.9 years, mean ± SD). During therapy, the serum PRL levels were suppressed into the normal range in all but five patients. In these five patients, despite the high circulating PRL, gonadal function returned to normal in three, while in the other two gonadotrophin reserve was impaired even before therapy. Gel chromatography showed that one of these patients had a high proportion of a large molecular weight form of PRL. Twenty‐four patients received bromocriptine as the sole method of treatment for over 2 years (3.4 ± 2.3 years). In five out of the 24 subjects (21 %), serum PRL remained normal with no clinical symptoms after prolonged drug withdrawal (1‐4 years). Twenty‐one patients received radiotherapy in conjunction with bromocriptine therapy. Of these 11 had prior surgery. After a follow‐up of 6.0 ± 3.0 years after radiotherapy, serum PRL remained within the normal range in 6 out of 21 subjects (29%), 1‐4 years after bromocriptine withdrawal. One of the patients had impaired GH response to insulin hypoglycaemia developing after radiotherapy. We conclude that prolonged bromocriptine treatment is an effective treatment for prolactinomas.