bluuebunny/crossref_metadata_2025 huggingface dataset:
HYPERTHYROIDISM AND THE IMPALPABLE THYROID GLAND
Authors: GREENWOOD R. M. , DALY J. G. , HIMSWORTH R. L.
Published: March 2008

A retrospective analysis of 594 unselected cases of hyperthyroidism from one district was made to determine whether the thyroid gland had been palpable on presentation. The thyroid had been diffusely palpable in 374 patients (63%), nodular in 110(19%) and impalpable in 96 (16%); there was no clinical record in 14 (2%) cases. Under 40 years of age a diffuse gland was usual, being present in 86% of cases. The proportion of nodular and impalpable glands both increased progressively with age comprising 30% and 48% respectively in patients older than 70 years. Graves's ophthalmopathy was present in 13% of hyperthyroid patients with diffuse glands, in 12% of those with impalpable glands, but in only 1·5% of those with nodular thyroids. Thyroid autoantibodies were found with a similar frequency in all three groups. There was a very good correspondence between clinical assessment of shape and nodularity of thyroid and the results of isotope scanning; the majority of patients with impalpable glands (86%) had a diffuse uptake of isotope. In the elderly hyperthyroid patient an impalpable thyroid gland is common and is not a factor to weigh against the diagnosis.
INFLUENCE OF ENDOGENOUS AND EXOGENOUS OESTROGENS ON POSTERIOR PITUITARY SECRETION IN WOMEN
Authors: WILLIAMS T. D. M. , EDWARDS A. , FAIRHALL K. M. , ROBINSON I. C. A. F. , McGARRICK G. M. , LIGHTMAN S. L.
Published: March 2008

Four normally mestruating subjects were studied throughout the menstrual cycle to investigate changes in plasma LH, arginine vasopressin (AVP), oxytocin (OT) and oxytocin associated neurophysin (NPOT). A clear mid‐cycle LH peak was observed in each subject. Mean levels of AVP, OT and NPOT were 2·2 pmol/1, 1·1 pmol/1 and 39 pmol/1, respectively. There were no significant differences between plasma levels during follicular, mid‐cycle and luteal phases for each of these. Two further subjects with anovulatory cycles were studied in a similar way. In the first subject, with polycystic ovarian disease, posterior pituitary peptide levels were in the normal range, whereas the other subject, recovering from anorexia nervosa, had raised plasma levels of all posterior pituitary peptides (AVP 8·1 pmol/1, OT 1·8 pmol/1, NPOT 131 pmol/1, mean values) despite a normal osmolality. Administration of ethinyl oestradiol, 100 μg or 500 μg, had no effect of either AVP or OT, but 100 μg caused a marked rise in NPOT levels in all cases within 12 h (from mean 64 pmol/1 to mean 196 pmol/1) and the levels remained elevated for 3 d.
ESTIMATION OF 1,25 DIHYDROXYVITAMIN D BY CYTORECEPTOR AND COMPETITIVE PROTEIN BINDING ASSAYS WITHOUT HIGH PRESSURE LIQUID CHROMATOGRAPHY
Authors: NICHOLSON G. C. , KENT J. C. , GUTTERIDGE D. H. , RETALLACK R. W.
Published: March 2008

Using two different cultured rat osteosarcoma cell lines (UMR 106 and ROS 17/2·8) we have investigated the recently described cytoreceptor assay for 1,25‐dihydroxyvitamin D (1,25‐(OH)2D). The assay method is relatively simple and sensitive to 2·4 fmole per tube. Using either cell line, assay of serum samples, whose only preparation consisted of extraction and purification on a disposable diatomaceous earth column, produced variable values for serum 1,25‐(OH)2D. Additional purification, using a disposable silicic acid minicolumn to remove other vitamin D metabolites resulted in consistent values and additional HPLC resulted in no further decrease in the values obtained. Our results show that a single two stage non‐HPLC column can purify serum samples for assay in the cytoreceptor assay. The method is also applicable to the competitive protein binding assay employing calf thymus cytosol and the correlation between values obtained by both methods is highly significant. It is a sensitive, simple, and accurate method with technical advantages which allow greater sample throughput than other 1,25‐(OH)2D assays.
EFFECTS ON GROWTH HORMONE SECRETION FOLLOWING INTRAVENOUS AND SUBCUTANEOUS INJECTIONS OF GROWTH HORMONE‐RELEASING FACTOR (hGRF‐44 NH2): COMPARISON OF IMMUNOREACTIVE PLASMA GRF LEVELS
Authors: SASSOLAS GENEVIÈVE , BIOT‐LAPORTE SYLVIANE , COHEN R. , CHARFI A. ELM , FERRY S. , BORSON FRANÇOISE
Published: March 2008

The effects of subcutaneous administration of three doses of human growth hormone‐releasing factor (hGRF‐44 NH2 or hGRF) at doses of 100, 300 and 600 μg were studied in six normal young men. GH responses obtained with 100 and 300 μg were negligible. In contrast, the 600 μg dose gave a profile of response comparable in timing and magnitude to that obtained with i.v. hGRF at maximal effect doses (20, 80, 100 μg). Plasma immunoreactive hGRF levels (IR‐hGRF) were compared after s.c. and i.v. hGRF. Mean maximal plasma concentrations were comparable with s.c. 600 μg and i.v. 20 μg. Peaks occurred earlier with i.v. hGRF (5 min as opposed to 15 min): however, return to undetectable values was obtained between 90 and 120 min after s.c. or i.v. injections. These data suggest a great loss of the peptide between the subcutaneous space and blood, without delayed absorption. High variability in plasma IR‐hGRF concentrations between the subjects after the same s.c. doses was observed.
EFFECT OF CALCITONIN ON GASTROINTESTINAL REGULATORY PEPTIDES IN MAN
Authors: STEVENSON J. C. , ADRIAN T. E. , CHRISTOFIDES N. D. , BLOOM S. R.
Published: March 2008

A major physiological role of calcitonin in humans appears to be regulation of skeletal turnover. It has been suggested that another function of calcitonin is to prevent post‐prandial rises in calcium, particularly in animals, but the importance of such a function in man remains to be determined. Although it is known that calcitonin has an inhibitory effect on the secretion of gastrin and insulin, its actions on other gut and pancreatic hormones have not previously been studied. To investigate interrelations between calcitonin and gastrointestinal regulatory peptides, 0·5 mg synthetic human calcitonin was administered to 10 fasting patients. No changes in the plasma concentrations of glucose, somatostatin, neurotensin, enteroglucagon, vasoactive intestinal polypeptide or bombesin were observed. In contrast, profound falls in the circulating levels of gastrin, insulin and pancreatic glucagon were seen, reaching a maximum shortly after the peak of plasma calcitonin concentration. Marked changes were also observed in the levels of motilin, pancreatic polypeptide and, to a lesser extent, gastric inhibitory polypeptide, but the maximal falls occurred about 40 min later, coinciding with a significant fall in serum calcium. It is possible that the effect of calcitonin on these hormones was direct, perhaps receptor‐mediated. The falls in levels of motilin and pancreatic polypeptide could have been further enhanced by changes in extracellular calcium ion concentrations. Whether any of these effects of calcitonin occur physiologically remains to be determined. However, these findings suggest new therapeutic possibilities for calcitonin.
PROLACTIN SECRETION AND BIOLOGICAL ACTIVITY IN FEMALES WITH GALACTORRHOEA AND NORMAL CIRCULATING PROLACTIN CONCENTRATIONS AT REST
Authors: JOHNSTON D. G. , HAIGH J. , PRESCOTT R. W. G. , HEATON A. , KENDALL‐TAYLOR P. , BAYLIS P. , ALBERTI K. G. M. M. , ROWE R. , FRIESEN H. , COOK D. , WATSON M.
Published: March 2008

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1·5 to 8·5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone > 20 nmol/1) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean ± SEM prolactin, 288 ± 36 mU/1, patients, n= 7; 291±21 mU/1, controls, n= 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin‐releasing hormone, 200 μg (at 20 min, 2417 ± 658 mU/1, patients, n= 7; 2113 ± 424 mU/1, controls, n= 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 ± 536 mU/1, patients, n= 7; 5858 ± 460 mU/1, controls, n= 8) and insulin‐induced hypoglycaemia (at 60 min, 1441 ± 551 mU/1, patients, n= 7; 1298 ± 183 mU/1, controls, n= 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in‐vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 ± 43 mU/1, n= 10; controls 348 ± 64 mU/1, n= 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean ± SEM glucose, 5·47 ± 008 mmol/l, patients; 5·05±0·14 mmol/1, controls; P < 0·05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean ± SEM, 0·044±;0·004 versus 0·058±0·004 mmol/1, P <0·05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.
COMPARISON BETWEEN BIOACTIVITY AND IMMUNOREACTIVITY OF SERUM PROLACTIN IN URAEMIA
Authors: MOORADIAN A. D. , MORLEY J. E. , KORCHIK W. P. , MA K. W. , HARTFEL M. A. , PARSONS J. A.
Published: March 2008

The lactogenic potency of sera from 24 male uraemic patients on regular haemodialysis and 14 control subjects was measured by Nb2 node rat lymphoma cell bioassay, and was compared to serum prolactin levels measured by radioimmunoassay. Sera with immunoreactive growth hormone levels exceeding 5 ng/ml were excluded from comparisons. The uraemic patients had a higher serum immunoreactive prolactin (48.2 ± 10.5 ng/ml) than controls (13.3 ± 1.3 ng/ml (P < 0.01). Similarly the lactogenic potency of uraemic serum was higher than that of the control sera (25.5 ± 3.9 vs 12.6 ± 1.4 ng/ml, P <0.02). The ratio of immunoreactive serum prolactin to the lactogenic potency of the serum was significantly higher in the uraemic group (1.80 ± 0.14 vs 1.10 ± 0.10, P < 0.01) suggesting decreased bioactivity of prolactin in uraemic serum. To examine whether low molecular weight inhibitory molecules were responsible for this discrepancy, the lactogenic potency of 8 uraemic sera was studied before and after 4 h of dialysis against 1 litre of haemodialysis medium. Two of the eleven sera studied showed a significant increment in lactogenic potency after dialysis (47% and 57%). We conclude that there is a disparity between the bioactive and the immunoreactive serum prolactin concentrations in patients with chronic renal failure and that a dialysable factor may be partly responsible for this discrepancy in some cases.
THE RELATIONSHIP BETWEEN SALIVARY ALDOSTERONE AND PLASMA FREE ALDOSTERONE CONCENTRATIONS
Authors: FEW J. D. , WALLIS P. J. W. , JAMES V. H. T.
Published: March 2008

The proportion of aldosterone in plasma not bound to proteins (% plasma free aldosterone, %PFA) was measured using an equilibrium dialysis technique and was found to lie predominantly in the range 25–40% although extremes of 20% and 60% were encountered. From this value and the total concentration of aldosterone in plasma (plasma aldosterone, PA) the concentration of free aldosterone in plasma (PFA) was calculated. Percentage PFA was not affected by the in‐vitro addition of aldosterone (up to the equivalent of 2000 pmol/1) but the incremental addition of cortisol (up to the equivalent of 550 nmol/1) resulted in a linear increase in % PFA from 26% to 34%. Percentage PFA was found to be significantly, negatively correlated with serum albumin concentration (r=−0·87; P< 0·001) but it was only when this was less than 15 g/1 that % PFA was abnormally high. Salivary aldosterone concentration (SA) was more highly correlated with PFA (r= 0·84) than with PA (r= 0·75), which indicates that even modest variance in %PFA has a discernible effect upon the overall SA‐PA relationship. We conclude that measurement of salivary aldosterone concentrations gives a useful estimate of plasma free aldosterone level. Variations in the latter are determined more by changes in the total concentration of aldosterone in plasma than by variations in the degree of binding by plasma proteins.
EFFECT OF ORAL CONTRACEPTIVES ON SERUM PROLACTIN: A LONGITUDINAL STUDY IN 126 NORMAL PREMENOPAUSAL WOMEN
Authors: HWANG P. L. H. , NG C. S. A. , CHEONG S. T.
Published: March 2008

A prospective longitudinal study was carried out in 126 normal premenopausal women aged 18–34 years to determine the effect of oral contraceptives containing less than 50 μg of oestrogen on serum prolactin concentration. The mean prolactin concentration in patients receiving oral contraceptives (n= 80) rose from a control level of 8·9 ng/ml to 10·2 ng/ml at 3 months (P < 0·05) and 10·9 ng/ml at 12 months (P < 0·001). In a parallel group of patients (n= 46) who used intrauterine devices for contraception, no significant change in serum prolactin concentration was observed over the same period. It is concluded that currently available oral contraceptives have a small but significant stimulatory effect on prolactin secretion in normal women.
DOES GROWTH HORMONE RELEASING FACTOR DESENSITIZE THE SOMATOTROPH? INTERPRETATION OF RESPONSES OF GROWTH HORMONE DURING AND AFTER 10‐HOUR INFUSION OF GRF 1–29 AMIDE IN MAN
Authors: DAVIS J. R. E. , SHEPPARD M. C. , SHAKESPEAR R. A. , LYNCH S. S. , CLAYTON R. N.
Published: March 2008

It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10‐h infusion of the equipotent 1–29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1–29). Four normal adult males received an intravenous infusion of 1–29 GRF (1 μg/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 μg intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0·5 mU/1) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/1) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 μg GRF bolus increased mean (± SEM) GH from 0·82 ± 0·21 mU/1 to a peak of 59·0 ± 44·8 mU/1 (P < 0·002). Following 10‐GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6·4 and 7·2 rising to peak values of 11·2 and 23·0 mU/1 respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak.

The loss of GRF responsiveness after GRF infusion may be due to ‘desensitization’. However the response of GH to GRF bolus injection appears to be partly related to the timing of the bolus with the pulses of GH induced by the previous infusion. Caution is needed in the interpretation of acute GRF tests following a period of GRF exposure.
STUDIES OF PROLACTIN SECRETION IN POLYCYSTIC OVARY SYNDROME
Authors: MURDOCH A. P. , DUNLOP W. , KENDALL‐TAYLOR P.
Published: March 2008

In order to investigate the postulated relationship between hyperprolactinaemia and polycystic ovary syndrome (PCOS) we have studied 62 patients with PCOS. Only two patients had persistent prolactin (PRL) concentrations greater than the normal range on both random sampling and after blood sampling from intravenous cannula over 2 hours. Twenty‐eight of the remaining patients had basal PRL secretion studied in more detail. Samples were collected at 15 min intervals during a 6 h period in all 28 patients and hourly samples were collected overnight from four patients. Results failed to demonstrate differences from control subjects in mean basal PRL concentrations, in spontaneous fluctuations or in increments related to stress, food or sleep. Lactotroph response to thyrotrophin releasing hormone, luteinising hormone releasing hormone and insulin stress testing in PCOS were determined. Results confirm a previous observation that normal PRL increments occur after ovulation and a blunted response follows a period of anovulation. This study has failed to find a consistent abnormality of lactotroph function in patients with PCOS other than that associated with anovulation.
SELECTIVE REDUCTION OF ELEVATED FSH LEVELS IN INFERTILE MEN BY PULSATILE LHRH TREATMENT
Authors: HÖNIGL W. , KNUTH U. A. , NIESCHLAG E.
Published: March 2008

In order to investigate whether isolated elevated FSH levels in men with idiopathic oligospermia can be lowered by pulsatile LHRH therapy, six patients were treated for 6 weeks with 5 μg LHRH pulses every 2 h. The pulses were delivered from a portable minipump (Zyklomat) through a subcutaneously inserted needle. At the end of treatment prepulse serum LH levels were no different from the levels before treatment while serum FSH was significantly reduced in all patients (16·9±2·5 U/1 vs 11·3±1·9 U/1, mean±SEM; P < 0·01). The normal FSH range was reached in one of the six patients. The areas under the LH curves following the first and the last (i.e. 504th) pulse were no different, while the areas under the FSH curves were significantly smaller (2870±434 vs 1776 ± 237 U/l×min; P < 0·01). Serum testosterone and oestradiol were significantly higher at the end of treatment (11·0±1·2 vs 15·2±1·9 nmol/1 146±18 vs 214 ± 25 pmol, respectively). Thus increased FSH levels in men with idiopathic oligospermia can be selectively reduced by pulsatile LHRH treatment. If the increased FSH levels are not the result but rather a factor contributing to the pathogenesis of certain types of oligospermia these findings may have implications for the treatment of this condition.
LONG‐TERM RESULTS FROM GRADED LOW DOSE RADIOACTIVE IODINE THERAPY FOR THYROTOXICOSIS
Authors: GOOLDEN A. W. G. , STEWART J. S. W.
Published: March 2008

An analysis has been made of the results of treatment in a series of 261 consecutive patients given graded low dose radioactive iodine therapy for thyrotoxicosis. Of these patients, 140 (54%) became euthyroid after a single dose of 131I and a further 50 (19%) achieved a remission after supplementary treatment with an antithyroid drug; 45 patients (17%) required further treatment with 131I which was invariably curative. The incidence of hypothyrooidism was 10% at 1 year. The subsequent incidence of hypothyroidism in the whole group was 27% at 5 years, 40% at 10 years and 53% at 15 years. Patients continued to become hypothyroid at a constant rate of 3% per year. The incidence of early hypothroidism can be reduced to some extent by using low doses of 131I and by relating the dose to the size of the gland. Late hypothyroidism on the other hand is due to latent nuclear damage and is inherent in the method of treatment.
LATE INCREASE IN SERUM 1,25‐DIHYDROXYVITAMIN D ONE MONTH AFTER SURGERY FOR ADENOMATOUS HYPERPARATHYROIDISM
Authors: D'AMOUR P. , GILBERT F. , GASCON‐BARRE M. , BOUTIN J. M. , HAVRANKOVA J. , BELANGER R. , MATTE R.
Published: March 2008

This study was designed to follow the evolution of serum 1,25(OH)2D after surgery for primary hyperparathyroidism. Ten patients were studied before and for up to 85 d after removal of a single parathyroid adenoma. Blood and 24 h urine were obtained at various time points, for the measurement of serum or urinary phosphate and calcium indices. Before surgery, serum calcium (2·91 ± 0·06 mmol/l; mean ± SEM), parathyroid hormone (354 ± 47 pg/ml) and 1,25(OH)2D (61·2 ± 7·8 pg/ml) were elevated while serum phosphate (1·01 ± 0·07 mmol/l) tended to be low. Relative hypoparathyroidism was evident for up to 5 d after surgery with the lowest value for serum parathyroid hormone (41 ± 16 pg/ml) on day 1, serum calcium (2·12 & 0·06 mmol/l) on day 3 and highest value for serum phosphate (1·41 ± 0·13 mmol/l) on day 5. As expected, serum 1,25(OH)2D levels decreased to 35·9 ± 4·2 pg/ml 24 h after surgery. Stabilization of serum and urinary parameters to normal values was seen between day 5 and day 27; the only exception was serum 1,25(OH)2D, which increased again at day 27 to 57·6 ± 5·0 pg/ml, a value as high as that before surgery. It was still elevated at day 50 (58·3 ± 4·3 pg/ml), but returned towards normal values in three out of four patients (44 ± 3·9 pg/ml) by day 80. No variation in 25(OH)D or 24,25(0H)2D was seen throughout the study. 1,25(OH)2D values could be related to serum parathyroid hormone values before surgery (r= 0·659, P > 0·05) but not after. The secondary increase in serum 1,25(OH)2D could not be related to variations in serum calcium, phosphate, parathyroid hormone or diet. Further studies will be required to explain this phenomenon.
ABNORMAL CIRCADIAN RHYTHM OF MELATONIN IN DIABETIC AUTONOMIC NEUROPATHY
Authors: O'BRIEN I. A. D. , LEWIN I. G. , O'HARE J. P. , ARENDT JOSEPHINE , CORRALL R. J. M.
Published: March 2008

The circadian rhythm of melatonin secretion from the pineal body is entrained to the light‐dark cycle and is controlled via sympathetic fibres originating from the superior cervical ganglia. We have therefore examined plasma melatonin profiles in diabetics with and without evidence of autonomic neuropathy and in normal matched controls. The physiological increase in nocturnal plasma melatonin concentration was not observed in diabetics neuropaths. There was no consistent pattern in the diabetics without neuropathy; only three out of the eight subjects in this group had a sustained nocturnal increase in melatonin. Normal diurnal variation of plasma cortisol was present in all groups of subjects. The present study shows that diabetic patients with evidence of autonomic neuropathy lack the normal circadian changes of plasma melatonin concentration. This provides confirmation for the control of pineal function via the sympathetic nervous system in man. The impaired melatonin profiles observed in diabetic patients without apparent autonomic neuropathy suggest that a subclinical state of sympathetic denervation may exist in this group of diabetics.
THE EFFECTS OF EXOGENOUS MELATONIN ON ENDOCRINE FUNCTION IN MAN
Authors: WRIGHT J. , ALDHOUS M. , FRANEY C. , ENGLISH J. , ARENDT J.
Published: March 2008

At two different times of year (spring and autumn) an oral preparation of the pineal neurohormone melatonin, or placebo, was administered to 12 healthy volunteers (10 men and two women in spring: the same group minus one man in autumn) daily at 1700 h for 1 month (spring), or 3 weeks (autumn) using a double‐blind cross‐over protocol. The daily dose was 2 mg melatonin in 5 ml corn‐oil, and placebo consisted of the vehicle only. In spring the anterior pituitary hormones LH, PRL, GH together with T4, cortisol, testosterone and melatonin were measured at 1– to 6–h intervals for 24 h in plasma on the day following the last dose. In autumn PRL, cortisol and melatonin levels were measured on the last day of treatment. Subjective fatigue, mood and sleep records were kept throughout the studies. Melatonin increased early evening fatigue and actual sleep, but had no effect on mood: these results are reported in full elsewhere. Melatonin administration had no effect on the levels or 24‐h rhythm of LH, GH, T4, testosterone or cortisol. An earlier fall in the nocturnal PRL was observed on both occasions. Overall PRL levels were higher in spring than in autumn. In five of the subjects, the secretion of endogenous melatonin was advanced by 1–3 h in the presence of exogenous melatonin. These observations suggest that the potential therapeutic use of melatonin as a hypnotic or in the treatment of jet lag is unlikely to be complicated by undesirable endocrine effects.
HIGH ACTIVITY OF CYCLIC 3′,5′‐NUCLEOTIDE PHOSPHODIESTERASE IN SERA OF PATIENT WITH PHAEOCHROMOCYTOMA
Authors: NAKAI AKIRA , NAGASAKA AKIO , OHYAMA TAKAKO , AONO TOSHIHIRO , IWASE KATSUMI , HASEGAWA HARUHIKO , HAYAMI SHIRO , HIDAKA HIROYOSHI , TANAKA TOSHIO , NIINOMI MITSURO , NIHEI NORIYUKI , NAKAGAWA HIFUMI , OHTANI SUSUMU , MIYAKAWA SHUICHI , KAWASE KYOHEI
Published: March 2008

Our previous observations that serum cyclic 3′,5′‐nucleotide phosphodiesterase activity varied in thyroid disorders and was positively correlated with thyroid function stimulated us to investigate the phosphodiesterase levels in sera of patients with pituitary and adrenal disorders, and the response to glucagon in normal subjects. Both serum cyclic AMP phosphodiesterase (cyclic AMP‐PDE) and cyclic GMP phosphodiesterase (cyclic GMP‐PDE) activities were measured at a low substrate concentration. Serum cyclic AMP‐PDE activity was elevated in five patients with phaeochromocytoma and was not elevated in patients with Cushing's syndrome or acromegaly, compared to the level in normal subjects. Increased enzyme activities returned to normal after resection of the tumours. Intramuscular injection of glucagon to five healthy subjects elevated cyclic AMP levels and cyclic AMP‐PDE activity in plasma. These results imply that the increased cyclic AMP level by the activation of cyclase may have induced cyclic AMP‐PDE in the target organ and the soluble cyclic AMP‐PDE may leak into blood vessels from target organs.
LACK OF EFFECT OF MUSCARINIC CHOLINERGIC BLOCKADE ON THE GH RESPONSES TO GRF 1–29 AND TRH IN ACROMEGALIC SUBJECTS
Authors: JORDAN V. , DIEGUEZ C. , VALCAVI R. , ARTIOLI C. , PORTIOLI I. , RODRIGUEZ‐ARNAO M.D. , GOMEZ‐PAN A. , HALL R. , SCANLON M. F.
Published: March 2008

It is well known that muscarinic cholinergic blockade either reduces or abolishes stimulated GH release in normal subjects. In this study we have investigated whether cholinergic muscarinic blockade could reduce the GH responses to GRF 1–29 and TRH in acromegalic subjects. Eight acromegalic subjects underwent two GRF tests (GRF 1–29, 1 μg/kg i.v.) with and without pirenzepine (0.6 mg/kg, i.v.). A further four of these patients received TRH (200 μg/kg, i.v.) on separate occasions with and without pirenzepine (0.6 mg/kg, i.v.). Cholinergic muscarinic blockade did not alter the GH responses to GRF and TRH in patients with acromegaly. These findings are in contrast with previous data reported on the effects of cholinergic blockade on stimulated GH levels in normal subjects and in patients with type I diabetes mellitus and are compatible with the view that somatotroph adenomas are functionally disconnected from hypothalamic control mechanisms.
DISCORDANT RESPONSES OF PROLACTINOMA TO TWO DIFFERENT DOPAMINE AGONISTS
Authors: AHMED S. R. , SHALET S. M.
Published: March 2008

A 19‐year‐old woman presented with headaches, temporal lobe epilepsy and primary amenorrhoea. There was a family history of multiple endocrine adenomatosis. Investigation revealed normal visual fields and acuity, hyperpro‐lactinaemia (48 000 mU/l) and a very large pituitary tumour with extrasellar spread. Treatment with bromocriptine reduced the tumour size and the prolactin level to 2440 mU/1. Six months after the start of therapy, resistance to bromocriptine developed and the prolactin concentration progressively rose to pretreatment levels, despite increasing the dose of bromocriptine to 40 mg/d. At this stage treatment with a second dopamine agonist, pergolide, was effective in reducing the prolactin concentration to normal within four months. Serial CT scans at 1, 6 and 12 months on dopamine agonist therapy showed a progressive decrease in tumour size, which seemed to be maintained even during the period of rising prolactin concentrations due to bromocriptine resistance. This case illustrates that during dopamine agonist therapy a discrepancy may exist in the clinical response as judged by reduction in tumour size and decrease in the circulating prolactin level. Furthermore, in patients with prolactinomas, pergolide may induce a response when resistance to bromocriptine develops.
THE PREOPERATIVE AND POSTOPERATIVE INVESTIGATION OF TSH AND PROLACTIN RELEASE IN THE MANAGEMENT OF PATIENTS WITH HYPERPROLACTINAEMIA DUE TO PROLACTINOMAS AND NONFUNCTIONAL PITUITARY TUMOURS: RELATIONSHIP TO ADENOMA SIZE AT SURGERY
Authors: SCANLON M. F. , PETERS J. R. , SALVADOR J. , RICHARDS S. H. , JOHN R. , HOWELL S. , WILLIAMS E. D. , THOMAS J. P. , HALL R.
Published: March 2008

We report here our results of the pre‐ and post‐operative assessment of prolactin and TSH status in 41 hyperprolactinaemic patients who underwent pituitary surgery over a 5 year period. Preoperatively in patients with prolactinomas (n= 33) the TSH response to domperidone decreased with increasing adenoma size. When the data are expressed on a group mean basis the exaggerated TSH response to domperidone in preoperative prolactinoma patients was reduced significantly in patients rendered normoprolactinaemic by surgery but persisted in those who remained hyperprolactinaemic. Similarly the reduced preoperative PRL responses to domperidone and TRH were significantly increased by successful surgery. In contrast patients with stalk‐compression hyperprolactinaemia (n= 6) due to larger lesions which were not prolactinomas all showed reduced or absent TSH responses to domperidone. The PRL responses to domperidone and TRH were reduced or absent both in patients with prolactinomas and in those with stalk‐compression hyperprolactinaemia. All patients with stalk‐compression hyperprolactinaemia showed a delayed pattern of TSH response to TRH with 60 min values being greater than 20 min ones. In contrast a normal pattern of TSH response to TRH was observed in all patients with hyperprolactinaemia due to prolactinomas. Postoperatively TSH and PRL responses were largely unchanged in patients with stalk‐compression hyperprolactinaemia regardless of whether normoprolactinaemia was restored by surgery. In conclusion a reduced or absent PRL response to TRH or domperidone is not diagnostic of the presence of a prolactinoma since it occurs in hyperprolactinaemic patients with prolactinomas or stalk‐compression. In contrast, the TSH response to acute dopamine antagonism is exaggerated in most patients with small prolactinomas but not in those with stalk‐compression hyperprolactinaemia and we have found this to be helpful diagnostically since the presence of an exaggerated TSH response to dopamine antagonism is evidence against the presence of stalk‐compression hyperprolactinaemia. The observation of a delayed TSH response to TRH in a hyperprolactinaemic patient should alert the clinician to the possibility of stalk‐compression hyperprolactinaemia due to a large lesion which may not be a prolactinoma.
SOMATOSTATIN AND OXYTOCIN INFUSION INHIBITS THE RISE OF PLASMA β‐ENDORPHIN, β‐LIPOTROPHIN AND CORTISOL INDUCED BY INSULIN HYPOGLYCAEMIA
Authors: PETRAGLIA FELICE , FACCHINETTI F. , D'AMBROGIO G. , VOLPE ANNIBALE , GENAZZANI ANDREA R.
Published: March 2008

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress‐induced rise of beta‐endorphin (β‐END), beta‐lipotrophin (β‐LPH) and cortisol in the human. For this purpose somatostatin (4.1 μg/min for 120 min or oxytocin (0·4 μg/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0·1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress‐related effects on the different hormonal secretions under basal conditions. Plasma levels of β‐END, β‐LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for β‐END and β‐LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of β‐END, β‐LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin‐induced hypoglycaemia (P> 0·01). These results indicate that somatostatin and oxytocin may influence the β‐END, β‐LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.
IS HUMORAL THYROID AUTOIMMUNITY RELEVANT IN AMIODARONE IODINE‐INDUCED THYROTOXICOSTS (AIIT)?
Authors: MARTINO E. , MACCHIA E. , AGHINI‐LOMBARDI F. , ANTONELLI A. , LENZIARDI M. , CONCETTI R. , FENZI G. F. , BASCHIERI L. , PINCHERA A.
Published: March 2008

Amiodarone, an iodine containing drug, may induce thyrotoxicosis by an uncertain mechanism. In this study the role of thyroid autoimmunity was evaluated in 28 consecutive patients referred to us because they had become hyperthyroid during long‐term amiodarone administration. Titres of thyroglobulin and thyroid microsomal antibodies, TSH binding‐inhibitory and thyroid stimulating antibodies were evaluated. Underlying thyroid disorders were demonstrated in 20 patients (9 of them had toxic diffuse goitre, seven toxic multinodular goitre and four toxic adenoma), while eight patients did not show any apparent thyroid gland abnormality. Circulating thyroid autoantibodies could be found in all amiodarone iodine‐induced hyperthyroid patients with toxic diffuse goitre and in one with toxic multinodular goitre, whilst they were absent in the other patients. These studies suggest that thyroid autoimmunity has little if any role in the development of thyrotoxicosis in amiodarone treated patients without underlying thyroid disorders. Furthermore, in amiodarone‐iodine‐induced thyrotoxicosis associated with various thyroid diseases, the humoral markers of thyroid autoimmunity show an incidence similar to that observed in spontaneous hyperthyroidism.
LONG‐TERM EFFECT OF IODIZED OIL ON SERUM THYROGLOBULIN LEVELS IN ENDEMIC GOITRE PATIENTS
Authors: LIMA N. , KNOBEL M. , MEDEIROS‐NETO G.
Published: March 2008

Serum thyroglobulin (Tg) response to bovine TSH (bTSH) was evaluated in 44 goitrous patients (grades III and IV) living in conditions of chronic iodine (I) deficiency (iodine urinary excretion > 40 μg I/g) and in 26 normal subjects. After the initial clinical evaluation and laboratory tests (bTSH test, T4, T3, anti‐Tg and anti‐microsomal antibodies) all goitrous patients received 1 ml i.m. of iodized oil (I‐oil) and were followed up for 30 months. The bTSH test was repeated at 6, 12, 20 and 30 months after I‐oil in 21 subjects. A marked reduction in goitre size was observed in 85% of the patients with a concomitant significant increase in the mean serum T4 and T3 concentrations, a significant fall in the mean serum TSH level and a significant decrease in the T3/T4 ratio. Goitrous patients had elevated serum basal Tg levels (55 ± 8 SEM μg/l) and a significantly mean higher peak Tg value after bTSH (200 ± 65 μg/l) as compared with normal subjects (respectively, 11 ± 1·4 and 32 ± 3·4 μg/l). Larger goitres (grade IV) had a significantly higher mean peak Tg response as compared with grade III goitres. Treatment with I‐oil significantly reduced the mean peak Tg response to bTSH after 6 months (59 ± 10 μg/l) but at 12 and 20 months the peak Tg response after the injection rose, respectively, to 110 ± 19 μg/l and 92 ± 14 μg/l (P > 0·02 as compared with 6 months), returning to the normal range only at 30 months. (55 ± 10 μg/l). The absolute increment (ΔTg) was also reduced significantly at 6 and 30 months but not at 12 and 20 months after I‐oil. We conclude that two major factors may be involved in the increased secretion or release of Tg from the goitrous tissue: increased thyrotrophic stimulation and follicular derangement and necrosis. Both events seemed to be corrected with the long‐term action of I‐oil.
HYPOTHALAMIC HYPOPITUITARISM FOLLOWING CRANIAL IRRADIATION FOR NASOPHARYNGEAL CARCINOMA
Authors: LAM K. S. L. , WANG C. , YEUNG R. T. T. , MA J. T. C. , HO J. H. C. , TSE V. K. C. , LING N.
Published: March 2008

Eight patients, one male and seven females, with no pre‐existing hypothalamic‐pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF‐44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF‐41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF‐41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post‐irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.
THE EFFECT OF CHOLINERGIC BLOCKADE ON THE ACTH, β‐ENDORPHIN AND CORTISOL RESPONSES TO INSULIN‐INDUCED HYPOGLYCAEMIA
Authors: EVANS P. J. , DIEGUEZ C. , REES L. H. , HALL R. , SCANLON M. F.
Published: March 2008

To assess the effect of cholinergic blockade on the ACTH, β‐endorphin and cortisol responses to insulin‐induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at + 45 min (mean ± SEM, 223 ± 21 pg/ml vs 148 ± 15 pg/ml, P > 0·01) and at + 120 min (54 ± 11 pg/ml vs 29 ± 10 pg/ml, P > 0·05). β‐endorphin levels were significantly greater at + 30 min (170 ± 45 pg/ml vs 96 ± 32 pg/ml, P > 0·05) and at + 105 min (81 ± 14 pg/ml vs 54 ± 7 pg/ml, P > 0·01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and β‐endorphin responses to insulin‐induced hypoglycaemia without altering the cortisol responses.
LH PULSATILITY FOLLOWING ACUTE ETHANOL INGESTION IN MEN
Authors: BANNISTER P. , HANDLEY T. , CHAPMAN C. , LOSOWSKY M. S.
Published: March 2008

Alcohol abuse leads to impotence, infertility and feminisation. Patients with chronic alcoholism have impaired hypothalamic‐pituitary function, but the effect of acute alcohol intake on hypothalamic function is unclear. The present study investigated the effect of ethanol ingestion on the pulsatile release of LH.

Eight healthy male volunteers, aged 24–36 years, were investigated on a control day and a study day. Blood was sampled every 15 min for 8 h. On the study day ethanol was ingested, 1·5 ml/kg as an initial dose with supplements to maintain mean levels at 110–140 mg%. LH was measured on each sample by specific radioimmunoassay. Testosterone was measured at 0, 90 and 360 min. Data were analysed for pulsatile release by visual inspection, iterative computerized analysis and for longer period secretion by spectral analysis. Pulsatile release of LH was shown for all subjects on both days. Ethanol increased median LH levels (4·8 vs 5·55), but not by a significant amount. LH pulse amplitude was increased by ethanol ingestion, 3·7 vs 5·4 IU/I; P > 0.05. Spectral analysis demonstrated a release of LH with a wavelength of 240 min which was unchanged by ethanol administration. Testosterone levels were unchanged.
CHOLINERGIC MUSCARINIC RECEPTOR BLOCKADE WITH PIRENZEPINE ABOLISHES SLOW WAVE SLEEP‐RELATED GROWTH HORMONE RELEASE IN NORMAL ADULT MALES
Authors: PETERS J. R. , EVANS P. J. , PAGE M. D. , HALL R. , GIBBS J. T. , DIEGUEZ C. , SCANLON M. F.
Published: March 2008

Cholinergic pathways play an important role in the regulation of GH secretion from the anterior pituitary gland, and in this study we have investigated whether cholinergic muscarinic receptor blockade with pirenzepine displayed any inhibitory action on slow wave sleep‐related GH release in normal subjects. Six adult males (ages 24–37 years) were studied in a randomized order and fasted from 1800 h on each study day. All subjects showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 4–50 mU/l). In contrast, pirenzepine treatment (100 mg p.o. at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. These data demonstrate clearly that cholinergic muscarinic receptor blockade completely abolishes slow wave sleep‐related GH release in normal adult subjects. Because of the striking effects it is reasonable to conclude that acetylcholine plays an important stimulatory role in mediating slow wave sleep‐related GH release. This finding may have investigational and therapeutic applications in young patients with Type 1 diabetes mellitus since GH is implicated in some acute metabolic and chronic microvascular complications of this disease.
THE EFFECT OF PERIPHERAL CATECHOLAMINE CONCENTRATIONS ON THE PITUITARY‐ADRENAL RESPONSE TO CORTICOTROPHIN RELEASING FACTOR IN MAN
Authors: MILSOM STELLA R. , DONALD R. A. , ESPINER E. A. , NICHOLLS M. G. , LIVESEY J. H.
Published: March 2008

To evaluate the effect of changes in plasma catecholamines on the pituitary‐adrenal response to ovine corticotrophin releasing factor (CRF) in normal man, the response to CRF alone (10 subjects) was compared with responses after infusions of adrenaline (6 subjects), noradrenaline (6 subjects) and after oral administration of the α2 agonist clonidine (10 subjects). Compared to control levels, plasma adrenaline and noradrenaline concentrations were increased three‐ and four‐fold respectively by exogenous infusions, whereas plasma noradrenaline was significantly lowered by clonidine. Despite these changes in plasma catecholamine levels, the responses of plasma ACTH, cortisol and aldosterone to CRF did not differ significantly from control (CRF alone) in any of the three studies. Neither clonidine pretreatment nor catecholamine infusions altered basal levels of plasma ACTH, cortisol or aldosterone and no effect of CRF or catecholamine manipulations on plasma arginine vasopressin concentration was observed. These results show that modulation of peripheral plasma catecholamine levels within physiological limits does not affect CRF‐stimulated release of ACTH or the adrenal response in normal man.
HYPERSECRETION OF PROINSULIN DOES NOT EXPLAIN THE HYPERINSULINAEMIA OF PATIENTS WITH LIVER CIRRHOSIS
Authors: BALLMANN M. , HARTMANN H. , DEACON C. F. , SCHMIDT W. E. , CONLON J. M. , CREUTZFELDT W.
Published: March 2008

A radioimmunoassay using a proinsulin‐specific antiserum that does not react preferentially with the split forms of proinsulin has been used to compare the response of circulating proinsulin to low (25 g) and high (75 g) oral glucose loads in healthy subjects and in patients with liver cirrhosis. The patients were divided into two groups: Group A (n= 7) with normal glucose tolerance and Group B with diabetic (n= 5) and impaired (n=1) glucose tolerance. There was no apparent correlation between glucose tolerance and the results of quantitative liver function tests. In the fasted state, the concentrations of serum proinsulin did not differ significantly in patients of Group A (0·022 ± 0·002 nmol/1) or Group B (0±026 · 0±004 nmol/1) from those in healthy subjects (0·021 ± 0·002 nmol/l). After 75 g glucose, the rise in serum proinsulin to a maximum concentration of 0·082 ± 0·012 nmol/1 in patients of Group A and to 0·070 ± 0·019 nmol/1 in Group B was not significantly different at any time point up to 180 min from the rise in healthy subjects (to 0·063 ± 0·005 nmol/1). After 25 g glucose, the response of serum proinsulin in Group B patients (maximum concentration 0·035 ± 0·003 nmol/1) was not significantly different from that in healthy subjects (maximum concentration 0·032 ± 0·003 nmol/1) but a slightly enhanced release was observed in the Group A patients (maximum concentration 0·049 ± 0·003 nmol/1) that was significantly greater (P>0·05) at 60 min post‐glucose. In contrast, the concentrations of serum immunoreactive insulin and immunoreactive C‐peptide in all patients with cirrhosis were significantly elevated compared with healthy subjects both in the fasted state and at several time points following high and low oral glucose. In the fasted state, the serum proinsulin/C‐peptide molar ratio, an index of the relative state of secretion of proinsulin and insulin, was significantly lower (P>0·05) in both groups of cirrhotic patients than in healthy subjects. After high and low glucose, this ratio fell in all patients and in the healthy subjects. We conclude that cirrhosis of the liver is associated with a hypersecretion of insulin but hyperproinsulinaemia does not contribute appreciably to the elevated concentration of immunoreactive insulin in the peripheral circulation.
PATTERN OF PLASMA LEVELS OF CORTISOL, DEHYDROEPIANDROSTERONE AND PREGNENOLONE SULPHATE IN NORMAL SUBJECTS AND IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLAEMIA DURING ACTH INFUSION
Authors: BOIZEL R. , de PERETTI E. , CATHIARD A. M. , HALIMI S. , BOST M. , BERTHEZENE F. , SAEZ J. M.
Published: March 2008

The aim of this study was to determine whether patients with homozygous familial hypercholesterolaemia (FH) have impaired adrenal cortical function. Plasma levels of cortisol, dehydroepiandrosterone (DHA), pregnenolone sulphate (PS) and DHA sulphate (DHAS) were measured during an 8 h ACTH infusion in six controls and two patients with homozygous FH. The basal PS levels of both patients and the basal DHA level of one were abnormally low for age and pubertal stage. During ACTH infusion we observed in both patients: (1) a mild impairment of control response after sustained stimulation (P> 0·002); (2) a clear impairment of PS response (values less than 2 SD of those in controls); (3) a clear impairment of DHA response (values less than 2 SD) until 4 h in the boy who was at pubertal stage 4 and whose response could be compared to controls; no increase at all in the affected girl (pubertal stage 2) at a stage where normal subjects respond with significant increase. These results suggest that patients with FH lack cholesterol for corticosteroid biosynthesis under maximal ACTH stimulation and that mild chronic ACTH stimulation due to a deficit in the cholesterol supply to adrenal cells might increase the conversion of Δ5 to Δ4‐steroids. They provide further evidence to support the primordial role of low density lipoprotein (LDL)‐cholesterol in adrenal steroidogenesis in vivo.