bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TREATMENT OF CENTRAL PRECOCIOUS PUBERTY USING AN INTRANASAL LHRH ANALOGUE (BUSERELIN)
Authors: STANHOPE R. , ADAMS J. , BROOK C. G. D.
Published: March 2008

Eight girls and one boy with precocious puberty were treated with intranasal (d‐Ser6)‐LHRH (buserelin) for 0.5–2.3 years (mean 1.2 years). Treatment regimen varied between 17 and 40 μg/kg/d in the girls to 10 μg/kg/d in the boy in two or three divided doses. Gonadotrophin‐dependent clinical signs showed arrest or regression whereas those of adrenarche progressed. Serial pelvic ultrasound assessment was used to monitor treatment in four girls. Although peak stimulated gonadotrophins reduced to prepubertal levels, basal gonadotrophins became elevated on treatment. The mode of action of buserelin was the abolition of gonadotrophin pulsatility. Initial data suggest an improved growth prognosis. We concluded that intranasal therapy is an alternative route of administration of LHRH analogue in the treatment of precocious puberty.
SENSORY THRESHOLDS AND MOTOR RESPONSIVENESS IN THYROID DISEASE: THEIR RESPONSES TO TREATMENT AND WARMING
Authors: O'MALLEY B. P. , ABBOTT R. J. , TIMSON L. , BECK A. D. , ROSENTHAL F. D.
Published: March 2008

It has been our clinical observation that patients with hypothyroidism are relatively insensitive to the discomfort of venepuncture, whereas thyrotoxic patients seem to have a heightened sensitivity. In an initial study we have measured the sensory thresholds of perception along with motor responsiveness in hypothyroid, thyrotoxic and euthyroid subjects, employing a simple and readily reproducible technique. Sensory thresholds were elevated and motor responsiveness impaired in hypothyroid subjects as compared to euthyroid controls. In thyrotoxic subjects, motor responsiveness was significantly enhanced, but sensory thresholds did not differ from control values. In a subsequent study the threshold abnormalities of thyroid dysfunction were corrected by rendering the patients euthyroid with appropriate therapy. Warming a further group of untreated hypothyroid patients produced a similar improvement in motor responsiveness to that seen in the L‐thyroxine‐treated group, thus implying that this parameter is at least, in part, temperature dependent. Sensory thresholds would seem to be reliable reflectors of tissue thyroid status in hypothyroidism, whereas motor responsiveness seems the better guide to thyroid status across the whole spectrum of thyroid function.
HUMAN CHORIONIC GONADOTROPHIN AND SUBUNITS—HETEROGENEITY IN SERUM OF MALE PATIENTS WITH TUMOURS OF THE GENITAL TRACT
Authors: NORMAN R. J. , LOWINGS C. , OLIVER T. , CHARD T.
Published: March 2008

The pattern of secretion of human chorionic gonadotrophin (hCG) and its subunits in male subjects with tumours of the genital tract was examined by gel filtration, radioimmunoassay, immunoradiometric assay, bioassay and binding to Concanavalin A. The predominant form of hCG was the intact molecule but all patients had increased levels of free beta subunit. The intact hCG was active in a mouse Leydig cell bioassay and was normally glycosylated. High concentrations of free alpha subunit were not found and the ratio of alpha subunit: beta subunit was less than that in normal pregnancy. It is concluded that hCG‐secreting tumours of the male genital tract are similar to choriocarcinoma in the female in that large quantities of intact hormone are produced with a disproportionate increase in free beta sub‐unit.
RECIPROCAL CHANGES OF SERUM THYROGLOBULIN AND TSH IN RESIDENTS OF A MODERATE ENDEMIC GOITRE AREA
Authors: FENZI G. F. , CECCARELLI C. , MACCHIA E. , MONZANI F. , BARTALENA L. , GIANI C. , CECCARELLI P. , LIPPI F. , BASCHIERI L. , PINCHERA A.
Published: March 2008

Subjects living in iodine deficient areas were reported to have elevated serum thyroglobulin (Tg) concentrations. This finding was interpreted as related to thyroid stimulation. Discrepant results, however, were found when serum Tg concentrations were correlated either with serum TSH or with goitre size. In this study we investigated the relationships between goitre size, serum Tg and serum TSH in 488 unselected adult subjects living in an endemic area of North‐Western Tuscany (Garfagnana district). The control group comprised 352 subjects residing in a non‐endemic area. In the endemic area a high prevalence of goitre was found (80·1%), thyroid enlargement being slight to moderate in the majority of cases and very large only in six subjects. Serum Tg concentrations increased and serum TSH levels decreased with the size of goitre. Statistical analysis by the chi‐square cross correlation test showed that the converse changes of serum Tg and serum TSH in relation to goitre size were highly significant. These findings indicate that the increase of serum Tg occurring in endemic goitrous subjects may be related to factors other than TSH stimulation. Functional autonomy of the thyroid may account for the finding of low serum TSH and elevated serum Tg values in patients with large goitres. The present data do not exclude the possibility that the release of Tg is influenced by TSH stimulation, but indicate that other factors may be responsible for the increased levels of Tg found in endemic goitre.
UNALTERED STIMULATION OF PITUITARY ADRENOCORTICOTROPHIN SECRETION BY CORTICOTROPHIN‐RELEASING FACTOR FOLLOWING SODIUM VALPROATE ADMINISTRATION IN A PATIENT WITH NELSON'S SYNDROME
Authors: GOMI M. , IIDA S. , ITOH Y. , MORIWAKI K. , KANAYAMA S. , NAMBA M. , TARUI S.
Published: March 2008

A 53‐year‐old woman with Nelson's syndrome was treated with 600 mg sodium valproate daily. Her plasma ACTH was effectively decreased, whilst the response of plasma ACTH to corticotrophin‐releasing factor (CRF) was unaltered. The result of the CRF test suggested that sodium valproate, at least in the present patient, acted at the hypothalamic level.
PROLACTIN AND TSH RESPONSES TO BOTH DOMPERIDONE AND TRH IN NORMAL AND HYPERPROLACTINAEMIC WOMEN AFTER DOPAMINE SYNTHESIS BLOCKADE
Authors: GHIGO E. , GOFFI S. , MOLINATTI G. M. , CAMANNI F. , MASSARA F.
Published: March 2008

A study of the effect of α‐methyl‐1‐tryosine (metyrosine) blockade (2 g/d for 2 d) of dopamine (DA) synthesis on the PRL and TSH response to domperidone (DOM) and TRH in normal women and subjects with pathological hyperpro‐lactinaemia is reported.

In the normal subjects, there was a marked increase in basal PRL (51·7 ± 11·1 vs 5·7 ± 1·0 ng/ml) and the PRL and TSH responses to DOM were abolished. The PRL response to TRH was also reduced.

In the hyperprolactinaemic subjects, metyrosine had no effect on basal PRL nor on the virtually non‐existent PRL response to DOM, whereas it abolished the exaggerated TSH response.

The conclusion is drawn that the response of both PRL and TSH to DA receptor blockers is really dependent upon DA inhibitory tone. A fall in this tone can also be postulated as responsible for the hyporesponsiveness of PRL to DOM frequently observed in pathological hyperprolactinaemia. In addition, the fact that metyrosine also abolished the exaggerated TSH response to DOM shows that the latter is totally dependent on enhanced DA inhibition of the thyrotrophs. Lastly, the reduced PRL response to TRH after metyrosine indicates that DA partly determines the ability of the lactotrophs to respond to TRH.
SOMATOSTATIN AND WATER EXCRETION IN MAN: AN INTRARENAL ACTION
Authors: WALKER B. J. , EVANS P. A. , FORSLING M. L. , NELSTROP G. A.
Published: March 2008

Intravenous infusion of somatostatin in six water loaded normal human subjects produced a prompt reduction in urine flow accompanied by a rise in urine osmolality and a decrease in free water clearance. Plasma AVP levels did not change. Somatostatin would seem to exert an antidiuretic effect directly on the kidney.
EFFECT OF LOW‐DOSE DOPAMINE INFUSION ON BASAL AND STIMULATED TSH AND PROLACTIN CONCENTRATIONS IN MAN
Authors: CONNELL J. M. C. , BALL S. G. , BALMFORTH A. J. , BEASTALL G. H. , DAVIES D. L.
Published: March 2008

Dopamine (DA) infused at pharmacological doses in man inhibits thyrotrophin (TSH) secretion, although the physiological significance of this observation is unclear. The effect of low‐dose DA infusion (0·1 μg/kg/min) on TSH and prolactin (PRL) concentrations during stimulation with thyrotrophin releasing hormone (TRH) in normal male subjects is reported. Six subjects were given intravenous DA or placebo infusions for 165 min on separate days. A bolus of TRH (7·5 μg) was given at +90 min, followed by infusion of the tripeptide (750 ng/min) for 45 min during both DA and placebo studies. In all subjects TRH administration caused a small rise in TSH which was partially inhibited by DA (peak 5·73 ± 0·85 mU/1 vs 4·58 ± 1·09, P > 0·05). PRL response to TRH was almost totally inhibited by DA (620·164 mU/1 vs 234·96, P > 0·05); integrated TSH and PRL responses to TRH were similarly inhibited by DA. Circulating plasma DA concentration during infusion of the catecholamine was 3·46 ± 1·00 ng/ml, which is within the range reported in pituitary stalk plasma of other species. These data support the hypothesis that DA is a physiological modulator of TSH secretion in normal man. Major differences in the time course of TSH and PRL responses to TRH, and in the suppressive effect of DA on these responses suggest that there are fundamental differences in stimulussecretion coupling for TRH and the lactotroph and thyrotroph.
PROLACTIN AND GROWTH HORMONE DYNAMICS IN EPILEPTIC PATIENTS RECEIVING PHENYTOIN
Authors: ELWES R. D. C. , DELLAPORTAS C. , REYNOLDS E. H. , ROBINSON W. , BUTT W. R. , LONDON D. R.
Published: March 2008

Resting growth hormone and prolactin levels and dynamic responses to bromocriptine and metoclopramide have been measured in epileptic patients before treatment, and compared with a matched group taking phenytoin alone. Mean resting levels of prolactin were higher in patients taking phenytoin (untreated patients 204 mU/1, phenytoin treated patients 302 mU/1), but dynamic responses to metoclopramide and bromocriptine were unaffected. Mean resting levels of growth hormone were also higher in patients taking phenytoin (untreated patients 1·4 mU/1, phenytoin treated patients 6·0 mU/1) and paradoxical suppression was seen following bromocriptine. Phenytoin is unlikely to have any major action on the D2 receptor present on the lactotroph. The abnormalities in growth hormone may explain the well recognized effects of phenytoin on connective tissue.
THE INTERACTION OF HUMAN PANCREATIC GROWTH HORMONE RELEASING FACTOR 1–44 WITH SOMATOSTATIN IN VIVO IN NORMAL MAN
Authors: DAVIES R. R. , TURNER S. J. , ØRSKOV H. , JOHNSTON D. G.
Published: March 2008

The interaction between the stimulatory effects of hpGRF 1–44 and the inhibitory effects of somatostatin on GH release have been investigated in six normal male subjects receiving continuous 4 h infusions of these peptides alone and in combination. hpGRF 1–44 0·3 μg/kg/h alone produced a peak GH response of 27·0 ± 7·6 mU/1 (mean ± SEM). Somatostatin 1·0 μg/kg/h markedly inhibited the GH response to hpGRF 1–44 with mean levels > 4·0 mU/1 during the infusion, though a rebound rise in GH levels to 26·1 ± 9·0 mU/1 was observed at the end of the infusion period. Somatostatin 0·2 μg/kg/h inhibited the GH response to hpGRF 1–44 to a lesser degree (peak GH during the infusion 11·7 ± 2·5 mU/1) and the rebound rise in GH levels (maximum 13·2 ± 4·3 mU/1) was less than that observed with high dose somatostatin. During somatostatin 1·0 μg/kg/h alone GH levels were suppressed > 1·0 mU/1 followed by a rebound at the end of the infusion in only two subjects. These data demonstrate a dose‐dependent inhibition of hpGRF 1–44 by somatostatin in vivo in man.
LONG‐TERM EFFECTS OF HISTAMINE H2‐RECEPTOR ANTAGONISTS ON SERUM PARATHYROID HORMONE IN CHRONIC RENAL FAILURE
Authors: FIORE C. E. , LUNETTA M. , KANIS J. A.
Published: March 2008

We assessed the effects of ranitidine and cimetidine (histamine H2‐receptor antagonists) on the serum concentrations of parathyroid hormone (PTH) in 22 patients with end‐stage chronic renal failure. Treatment for 3 months induced a significant decrease in serum concentrations of PTH determined by radioimmunoassay directed at the mid portion of the PTH molecule. In contrast, significant increases were noted using an assay directed at the aminoterminal portion, whereas no change was noted with a carboxy‐terminal assay. No significant changes in serum calcium, phosphate and alkaline phosphatase were noted after treatment with either agent, but serum concentrations of osteocalcin increased significantly. We conclude the H2‐receptor antagonists do not favourably influence the natural history of hyperparathyroid bone disease in patients with end‐stage chronic renal failure.
LACK OF EFFECT OF THE TRH RELATED DIPEPTIDE HISTIDYL‐PROLINE DIKETOPIPERAZINE ON TSH AND PRL SECRETION IN NORMAL SUBJECTS, IN PATIENTS WITH MICROPROLACTINOMAS AND IN PRIMARY HYPOTHYROIDISM
Authors: PETERS J. , FOORD S. , DIEGUEZ C. , SALVADOR J. , HALL R. , SCANLON M. F.
Published: March 2008

We have studied the effects of the TRH related dipeptide histidyl‐proline diketopiperazine [cyclo (His‐Pro)] on basal and stimulated TSH and PRL secretion in normal volunteers, in patients with microprolactinomas and in patients with primary hypothyroidism. Cyclo (His‐Pro), 400 μg intravenously did not alter basal TSH or PRL levels in normal males and females and was also without effect upon the elevated basal TSH and PRL levels in patients with primary hypothyroidism and microprolactinomas respectively. The same dose of cyclo (His‐Pro) did not affect the TSH or PRL response to TRH (100 μg i.v.) in normal male volunteers. These data indicate that cyclo (His‐Pro) does not affect TSH and PRL secretion in man at this dosage. It is also unlikely that this molecule will be of any therapeutic benefit in states of hyperprolactinaemia.
OESTROGEN‐RELATED CHANGES IN SEX HORMONE BINDING GLOBULIN LEVELS DURING NORMAL AND GONADOTROPHIN‐STIMULATED MENSTRUAL CYCLES
Authors: DOWSETT M. , ATTREE S. L. , VIRDEE S. S. , JEFFCOATE S. L.
Published: March 2008

Previous studies have identified no consistent change in sex hormone binding globulin (SHBG) levels during normal menstrual cycles. This is despite marked cyclical changes in plasma oestradiol concentration, and the observation that SHBG level increases in pregnancy, and after administration of exogenous gonadotrophin or synthetic oestrogens. The level of SHBG was measured in 19 normal females at 2 d intervals from day −8 to + 10 where the preovulatory peak of oestradiol was designated as occurring on day 0. SHBG levels increased by a mean 15%±4 (SEM) between the follicular and luteal phases (P>0·001) and this was due entirely to an increment between day 0 and + 2. The change in SHBG levels was correlated with the change in oestradiol levels between days −8 and 0 (P>0·001). Fifty‐six infertile patients were also studied. Twenty‐seven received Pergonal alone whilst the other 29 received Pergonal after a preceding 5 d on Clomid. In both groups peak preovulatory oestradiol levels were < 3 times higher than in normal cycles. SHBG levels showed no change in the follicular phase but rose markedly during the luteal phase. These increases were significantly correlated with peak preovulatory oestradiol concentration but showed no relationship with mid‐luteal progesterone concentration. We conclude that supranormal levels of oestradiol cause marked increases in SHBG binding capacity and increases in SHBG level of a lower order occur shortly after the preovulatory peak of oestradiol in the normal menstrual cycle.
SUPPRESSION OF PARATHYROID SECRETION AFTER ADMINISTRATION OF WR‐2721 IN A PATIENT WITH PARATHYROID CARCINOMA
Authors: HIRSCHEL‐SCHOLZ S. , JUNG A. , FISCHER J. A. , TRECHSEL U. , BONJOUR J.‐P.
Published: March 2008

WR‐2721 is an organic thiophosphate, known as a radioprotective agent, which also inhibits parathyroid hormone (PTH) secretion and reduces the plasma calcium level in euparathyroid animals and human subjects. In this study we present evidence that WR‐2721 is also able to reduce an abnormal PTH secretion in a case of parathyroid carcinoma. The intravenous infusion of a single dose (750 mg/m2) of WR‐2721 was followed within 3 h by a reduction in the plasma concentration of PTH by 60%, and of Ca by about 0·45 mmol/l. These changes were associated with a diminution in urinary cAMP excretion. Based on this observation it appears that WR‐2721 merits further investigation as a possible agent for the medical treatment of hyperparathyroidism.
RELATIONSHIP BETWEEN THE CHANGES IN SERUM THYROID HORMONE LEVELS AND PROTEIN STATUS DURING PROLONGED PROTEIN SUPPLEMENTED CALORIC DEPRIVATION
Authors: KAPTEIN ELAINE M. , FISLER JANIS S. , DUDA MARYSIA J. , NICOLOFF J. T. , DRENICK E. J.
Published: March 2008

The relationship between the changes in serum thyroid hormone levels and nitrogen economy during caloric deprivation were investigated in ten obese men during a 40 d, 400 kcal protein‐supplemented weight‐reducing diet. This regimen induced increases in the serum levels of total T4, free T4 and total rT3, and decreases of total T3, while serum TSH remained unchanged. There were progressive decreases in total body weight and urinary losses of total nitrogen and 3‐methylhistidine, with the early negative nitrogen balance gradually returning towards basal values during the 40 days. Subjects with the largest weight loss had the most increase in the serum levels of total T4 and free T4 index and the greatest decrease in T3. The magnitude of the increase of the nitrogen balance from its nadir was correlated with the extent of the reduction of T3 and increase of T3 uptake ratio and free T4 levels. The decrease in the urinary excretion of 3‐methylhistidine correlated with the increase in free T4 and rT3 levels. Nadir serum transferrin values were directly related to peak rT3 values, and the lowest albumin concentrations occurred in subjects with the highest total T4 and free T4 index values. Further, the maximum changes in the serum thyroid hormone levels preceded those of the nutritional parameters. These relationships suggest that: (1) increases in serum rT3 and free T4 and reductions in T3 concentrations during protein supplemented weight reduction may facilitate conservation of visceral protein and reduce muscle protein turnover; and (2) the variation in the magnitude of these changes may account for the heterogeneity of nitrogen economy.
VARIATION IN OSMOREGULATION OF ARGININE VASOPRESSIN DURING THE HUMAN MENSTRUAL CYCLE
Authors: SPRUCE B. A. , BAYLIS P. H. , BURD J. , WATSON M. J.
Published: March 2008

Osmoregulation of vasopressin secretion was studied in eight healthy women in the follicular and luteal phases of the menstrual cycle. Basal plasma osmolality in the luteal phase was significantly lower than in the follicular period (282·4±0·6, 285·6 ± 1·1 mmol/kg, respectively, P<0·05). Plasma AVP (pAVP) and plasma osmolality (pOsm) were measured during the infusion of 850 mmol/1 saline in both phases of the cycle, and linear regression analyses of these data gave the following regression equations (i) follicular, pAVP = 0·43 (pOsm‐284), r=+0·93, (ii) luteal, pAVP = 0·31 (pOsm‐279), r=+0·95. Both the slope and abscissal intercept were significantly different (P<0·01). Osmotic threshold for thirst sensation in the luteal phase was lower than the follicular (293±2, 297±1 mmol/kg, P<0·005). We conclude that, in the luteal phase, the threshold for AVP release and the gain or sensitivity of the osmostat are reduced together with lowering of the thirst threshold, which account for the lower basal luteal plasma osmolality.
GONADOTROPHIN‐SECRETING PITUITARY TUMOUR: REPORT AND REVIEW
Authors: WHITAKER M. D. , PRIOR J. C. , SCHEITHAUER B. , DOLMAN L. , DURITY F. , PUDEK M. R.
Published: March 2008

A 34‐year‐old male with a pituitary adenoma was investigated and demonstrated to have hypersecretion of both gonadotrophins in the basal state. Immunocytochemical staining and electron microscopic examination were positive for tumour cells secreting FSH and LH. Presenting symptoms included visual disturbances, loss of libido, impotence, cold intolerance, frontal headaches, change in skin pigmentation and excessive weight gain. The patient denied alteration in hair distribution, had no acral features, galactorrhoea or gynaecomastia. Surgical extirpation resulted in complete amelioration of his symptoms over a three year follow‐up period. Basal and stimulated pituitary function testing results returned to normal post‐operatively. A review of the literature documents six other cases of pituitary tumour secreting both LH and FSH in the basal state. More commonly, the pituitary adenoma secretes FSH only. The literature is reviewed with regard to both types of tumour.
EVIDENCE FOR THE PARTICIPATION OF ENDOGENOUS OPIOIDS IN THE SYMPATHOADRENAL RESPONSE TO HYPOGLYCAEMIA IN MAN
Authors: BOULOUX P‐M. G. , GROSSMAN A. , LYTRAS N. , BESSER G. M.
Published: March 2008

The effects of the long acting met‐enkephalin analogue d‐Ala2‐MePhe4‐met‐enkephalin‐O‐ol (DAMME) and the opiate antagonist naloxone on the plasma catecholamine responses to insulin‐induced hypoglycaemia have been investigated in two separate studies. DAMME depressed basal noradrenaline and adrenaline at 15 min, and blunted both the noradrenaline and adrenaline responses to hypoglycaemia. Naloxone did not alter basal plasma catecholamines, but caused a significant enhancement of the adrenaline response to hypoglycaemia. Neither DAMME nor naloxone altered the blood glucose response to insulin‐induced hypoglycaemia. These data are consistent with an inhibitory modulation of endogenous opioids in the sympathoadrenal response to insulin‐induced hypoglycaemia in man.
EVIDENCE FOR DIFFERING DOPAMINERGIC ACTIVITY IN CHILDHOOD‐ OR ADULT‐ONSET OBESITY
Authors: CATANIA ANNA , CANTALAMESSA L. , VENEGONI EMANUELA , ORSATTI ALESSANDRA , BALDINI MARINA , ZANUSSI C.
Published: March 2008

In order to investigate dopaminergic activity in two types of human obesity, childhood‐ and adult‐onset, we have studied the responses of plasma TSH and prolactin to domperidone, a dopamine receptor antagonist, in 12 patients obese since early childhood, 12 patients with adult‐onset obesity, and in 12 lean controls. All subjects were females. In childhood‐onset obese patients the responses of plasma prolactin and TSH to antidopaminergic stimulation were lower than those of adult‐onset obese patients and lean controls. Conversely, the stimulus elicited a normal response of plasma prolactin and an exaggerated response of plasma TSH in adult‐onset obese patients. These data indicate the presence of differing dopaminergic tone in the two types of human obesity.
END‐ORGAN RESPONSES TO THYROXINE THERAPY IN SUBCLINICAL HYPOTHYROIDISM
Authors: BELL G. M. , TODD W. T. A. , FORFAR J. C. , MARTYN C. , WATHEN C. G. , GOW S. , RIEMERSMA R. , TOFT A. D.
Published: March 2008

We studied variables known to change with thyroid hormone status in 18 patients with subclinical hypothyroidism before and during treatment with thyroxine in a dose sufficient to restore the plasma TSH response to TRH to normal. There was an associated increase in both plasma total T4 and free T4 within the normal range but plasma total T3 and free T3 were unchanged. As a result of thyroxine treatment there was a small but significant increase (P < 0.05) in left ventricular ejection fraction (LVEF) with maximal exercise but no significant changes in LVEF at rest and moderate exercise, continuously monitored mean sleeping heart rate, day/night ratios of urinary sodium excretion, peripheral nerve conduction velocities, fasting serum triglycerides, total cholesterol (TC), high density lipoproteins (HDL) or TC/HDL ratios. On this evidence we do not consider that thyroxine replacement therapy is indicated in patients with subclinical hypothyroidism.
PITUITARY FUNCTION FOLLOWING MEGAVOLTAGE THERAPY FOR CUSHING'S DISEASE: LONG TERM FOLLOW UP
Authors: SHARPE G. F. , KENDALL‐TAYLOR P. , PRESCOTT R. W. G. , ROSS W. M. , DAVISON C. , WATSON M. J. , COOK D. B.
Published: March 2008

Eight patients who had received megavoltage therapy for Cushing's disease 5–12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic‐pituitary function. One patient showed clear evidence of relapse of Cushing's disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary‐adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic‐pituitary function follow mega‐voltage therapy and these may progress to overt hypopituitarism.
BROMOCRIPTINE THERAPY IN ACROMEGALY: EFFECTS ON PLASMA GH LEVELS, SOMATOMEDIN‐C LEVELS AND CLINICAL ACTIVITY
Authors: NORTIER J. W. R. , CROUGHS R. J. M. , THIJSSEN J. H. H. , SCHWARZ F.
Published: March 2008

Thirty‐one patients with active acromegaly were treated with 10–20 mg bromocriptine daily for a period of 6–9 months. The clinical response was evaluated both by a subjective ‘score of symptoms’, and by a combined subjective and objective ‘clinical and metabolic improvement score’(c‐m score). The biochemical response was evaluated both by measurement of the mean of four plasma growth hormone (GH) determinations during the day and by measurement of plasma somatomedin‐C (Sm‐C) concentration. The clinical response as assessed by both methods showed a better correlation with changes in plasma GH levels (respectively r= 0·33; r= 0·50) than with changes in Sm‐C levels (r= 0·20; r= 0·36). The study confirms that in some patients clinical improvement is not accompanied by a decrease of plasma GH concentration. However, it is not possible to identify a subgroup of patients who showed clinical improvement with a decrease of Sm‐C levels, but whose plasma GH levels remained constant. It is concluded that measurement of plasma GH levels still appears to be the most useful biochemical assessment of disease activity in bromocriptine‐treated acromegaly.
IN‐VIVO METABOLITES OF SPIRONOLACTONE AND POTASSIUM CANRENOATE: DETERMINATION OF POTENTIAL ANTI‐ANDROGENIC ACTIVITY BY A MOUSE KIDNEY CYTOSOL RECEPTOR ASSAY
Authors: ARMANINI D. , KARBOWIAK ISABELLA , GOI ANNA , MANTERO F. , FUNDER J. W.
Published: March 2008

We have established a sensitive and specific radioreceptor assay for androgen receptor active materials in plasma, using tritiated methyltrienolone ([3H]R 1881) as tracer, and spayed mouse kidney cytosol receptor as the binding species. On radioreceptor assay, plasma from mice chronically administered spironolactone contained ˜ 10 times higher levels of androgen receptor active material than from mice administered potassium canrenoate. In parallel bioassays (antagonism of the effect of testosterone on seminal vesicle weight), spironolactone was >4 times as potent an antiandrogen as potassium canrenoate. Administered potassium canrenoate circulates as canrenoic acid, in equilibrium with its lactonized congener canrenone. Since over 80% of administered spironolactone is irreversibly converted to canrenone/canrenoic acid, its much higher anti‐androgen activity on radioreceptor assay and bioassay may point to the generation of unidentified, minor metabolites with very high affinity for androgen receptors and/or a very long plasma half‐life.
DEMONSTRATION OF SEX HORMONE BINDING GLOBULIN IN HUMAN CEREBROSPINAL FLUID
Authors: FÄSSLER R. , SCHWARZ S. , POHL P.
Published: March 2008

This study demonstrates the existence of sex hormone binding globulin (SHBG) in human cerebrospinal fluid (CSF) by means of a highly sensitive radioligand saturation assay that has been recently described by us for measurement of SHBG in human plasma. The molecular similarity of this 5α‐dihydrotestoster‐one binding protein with plasma‐SHBG was substantiated by a number of experiments in which the CSF‐protein displayed the same properties as plasma‐SHBG with respect to thermolability, affinity, specificity and sedimentation rate. SHBG levels in the CSF of normal women were found to be 0·139 ± 0·04 nmol/l (mean ± standard deviation), and in normal men to be 0·083 ± 0·03 nmol/l respectively. CSF‐SHBG in patients with a variety of neurological diseases associated with different degrees of a blood‐CSF barrier disturbance, showed a good correlation with commonly determined parameters such as CSF‐albumin and CSF‐IgG that are known to be of plasma origin. The concept of CSF‐SHBG originating from plasma by restricted diffusion is strongly supported by the finding that the CSF/plasma ratio of SHBG is independent of the plasma‐SHBG concentration in the entire physiological range. Possible diagnostic and pathophysiological implications of this so far undetected CSF‐constituent are discussed with regard to neurological and endocrine abnormalities.
MUSCARINIC CHOLINERGIC MEDIATION OF LHRH‐INDUCED LH AND FSH SECRETION IN NORMAL MEN
Authors: CHIODERA P. , VOLPI R. , D'AMATO L. , PETROLINI R. , SALATI G. , FERRARI P. , FAVA A. , COIRO V.
Published: March 2008

LHRH (100 μg i.v. bolus) was given to six young healthy men under basal conditions and after the administration of pirenzepine (10, 20, 30 or 40 mg i.v. 10 min before LHRH), which is a selective blocker of muscarinic cholinergic receptors. Pretreatment with 10 mg of pirenzepine did not modify LH and FSH responses to LHRH, whereas larger amounts of the drug significantly reduced gonadotrophin responses to LHRH. A dose‐related effect of the drug was not observed, since a maximal reduction of LHRH‐induced gonadotrophin secretion was already present when 20 mg of pirenzepine were used. When the effect of pirenzepine (20 mg) on the basal concentrations of FSH and LH was studied in four additional sex and age matched subjects, no significant changes were observed for at least 120 min after the injection. These results demonstrate that LHRH‐induced LH and FSH secretion involves a muscarinic cholinergic mechanism.
HIGH MOLECULAR WEIGHT VASOPRESSIN: DETECTION OF A LARGE AMOUNT IN THE PLASMA OF A PATIENT
Authors: SMITZ S. , LEGROS J.‐J. , FRANCHIMONT P. , LE MAIRE M.
Published: March 2008

Using a sensitive and specific radioimmunoassay for arginine‐vasopressin, we have searched for the presence of high molecular weight (HMW) vasopressin in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and an oat cell carcinoma of the lung. After incubation in 8 mol/l urea, one millilitre of the plasma from this patient was fractionated on a Sephadex G‐50 column and the immunoreactive vasopressin content was evaluated before and after trypsin treatment of the eluted fractions. A wide peak of apparent mol. wt. 2500–6000 daltons was revealed only after tryptic digestion of each fraction. This peak contained the equivalent of 1900 pg of vasopressin. A tryptic digest of this peak, rechromatographed on Sephadex G‐25, gave two small peptides the major one eluting at a position identical to vasopressin. These results demonstrate the presence of a large amount of HMW vasopressin in the plasma of a patient with SIADH and oat cell carcinoma of the lung.
5α‐REDUCTASE ACTIVITY IN HUMAN PROSTATE CANCER IS RELATED TO THE HISTOLOGICAL DIFFERENTIATION OF THE TUMOUR
Authors: HABIB F. K. , BUSUTTIL A. , ROBINSON R. A. , CHISHOLM G. D.
Published: March 2008

We have measured the activities of two androgen metabolizing enzymes in tissue obtained from thirty‐nine patients with carcinoma of the prostate (CaP). The enzyme activities were correlated to the histological differentiation of the tumours based on the Gleason Score and also compared to the activities measured in fourteen age matched patients with nodular prostatic hyperplasia (BPH). Although the mean values for the 5α‐reductase in CaP (9·29 ± 1·47 pmol/mg protein/30 min) were found to be significantly lower than the corresponding values in BPH (16·26 ± 3·04 pmol/mg protein/30 min) (P < 0·05), there were nonetheless significant differences within the cancer group and these were totally dependent on the degree of differentiation of the tumour. A progressively suppressed enzyme activity was measured as the carcinomatous tissue became more anaplastic. No correlation was, however, observed between tumour bulk which was also estimated histologically and 5α‐reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5α‐reductase could be used as a biochemical marker for tumour differentiation.

We also measured the 3α(β)‐hydroxysteroid dehydrogenase activities in cancer of the prostate but our findings indicated no significant differences between the various stages of the cancer. Furthermore we were unable to correlate the activities of this enzyme with that of the 5α‐reductase. Nonetheless two interesting patterns relating to the 3α(β)‐hydroxysteroid dehydrogenase emerged. Whilst in BPH the activity of this enzyme was confined to a very narrow range (1·04 ± 5·27 pmol/mg protein/30 min), there was a wide spread in the activities of the cancerous specimens with the highest 3α(β)‐hydroxysteroid dehydrogenase activity being usually manifested in specimens with a low 5α‐reductase. Since the capacity of some cancerous specimens to metabolize
FAILURE TO SUPPRESS C‐PEPTIDE SECRETION BY EUGLYCAEMIC HYPERINSULINAEMIA: A NEW DIAGNOSTIC TEST FOR INSULINOMA?
Authors: YKI‐JÄRVINEN H. , PELKONEN R. , KOIVISTO V. A.
Published: March 2008

In order to study the suppression of C‐peptide secretion in 5 patients with insulin‐producing tumours or beta cell hyperplasia, we raised and maintained plasma insulin at a high physiological level and kept plasma glucose unchanged for 2 h with combined infusions of glucose and insulin (insulin clamp technique). No suppression of C‐peptide secretion was seen in any of the patients, in contrast with a 35‐65% decline seen in each of 17 healthy control subjects. In 3 patients surgical removal of beta cell adenoma normalized the response, whereas it remained unchanged in a patient with beta cell hyperplasia after partial pancreatectomy and in another with inoperable carcinoma. These results indicate that insulin secretion by insulinomas is characterized by lack of suppression by insulin. Measurement of the insulin‐insulin feedback loop by the clamp technique may provide a rapid test to reveal autonomous insulin secretion without the risk of hypoglycaemia.
CONGENITAL ADRENAL HYPERPLASIA DUE TO DEFICIENT CHOLESTEROL SIDE‐CHAIN CLEAVAGE ACTIVITY (20, 22‐DESMOLASE) IN A PATIENT TREATED FOR 18 YEARS
Authors: HAUFFA B. P. , MILLER W. L. , GRUMBACH M. M. , CONTE F. A. , KAPLAN SELNA L.
Published: March 2008

Two siblings, a 9‐week‐old female and an 18‐year‐old male pseudohermaphrodite are described with deficient cholesterol side‐chain cleavage activity. The female died untreated in 1954; the second sibling, a phenotypically female infant with 46 XY karyotype, was diagnosed at age 5 weeks. Massive adrenal hyperplasia was revealed by intravenous pyelography showing downward displacement of the kidneys. Secretion rates of cortisol, aldosterone, deoxycor‐ticosterone and corticosterone were unmeasurable. Urinary 17‐hydroxycorti‐costeroids (17‐OHCS), tetrahydrocortisol, 17‐ketosteroids (17‐KS), pregnanetriol, pregnanediol, and Δ5‐3β‐ol steroids were not detected during prolonged administration of ACTH. Plasma concentrations and urinary excretion of gonadotrophins were increased. Gonadal mitochondria did not convert radioloabelled cholesterol to pregnenolone. The gluccocorticoid and mineralo‐corticoid deficiencies have been controlled well by steroid replacement therapy. Plasma ACTH concentrations and plasma renin activity remained strikingly elevated even when supraphysiologic doses of glucocorticoids and mineralocor‐ticoids were given. Oestrogen replacement alone induced a pubertal growth spurt. The differential diagnosis, the effects of long‐term steroid replacement therapy, and comparison with previously reported findings are discussed.
DIETARY INTAKE IN THYROTOXICOSIS BEFORE AND AFTER ADEQUATE CARBIMAZOLE THERAPY; THE IMPACT OF DIETARY ADVICE
Authors: ALTON S. , O'MALLEY B. P.
Published: March 2008

Dietary intake, including actual nutrient and energy intake, was assessed in 21 successive thyrotoxic patients before and after adequate carbimazole therapy. Group A (10 subjects) received regular formal dietary advice whereas Group B (11 subjects) did not. An age and sex matched control group, comprising 23 normal individuals, was also studied. The mean energy intake of all the thyrotoxic subjects was significantly greater than that of the normal control group (P < 0·0025). There was a greater overall reduction in the energy intake of Group A as compared with Group B (P < 0·01) and the former gained less weight, when expressed as a percentage of pretreatment weight. The mean final weight of all the thyrotoxic subjects exceeded the mean ideal weight for the group, reflecting a degree of true obesity at this stage. The simple measure of incorporating dietary advice into the treatment programme of thyrotoxic patients will usually result in some reduction of energy intake, and thus weight gain, en route to euthyroidism.
THE RESPONSE OF OBESE SUBJECTS TO CONTINUOUS INFUSION OF HUMAN PANCREATIC GROWTH HORMONE‐RELEASING FACTOR 1–44
Authors: DAVIES R. R. , TURNER S. J. , COOK D. , ALBERTI K. G. M. M. , JOHNSTON D. G.
Published: March 2008

The growth hormone (GH) response of seven obese subjects to a 4 h continuous infusion of human pancreatic GH‐releasing factor, 0·3 μg/kg/h, has been compared with that obtained in seven sex and age matched controls. The pattern of response was normal in the obese but peak GH levels (mean ± SEM: 13·8 ± 1·9 compared to 30·9 ± 4·7 mU/l, P < 0·01) and integrated GH levels (mean ± SEM: 27·1 ± 3·6 compared to 62·0 ± 9·7 mU/l/h, P < 0·01) were reduced in obese subjects. There was a negative correlation between the integrated GH response and the percentage ideal body weight (r=−0·80, P < 0·05), but no significant correlation with somatomedin‐C levels (r=+ 0·72; P= 0·07). Obese subjects have an impaired GH response to infusion of GH‐releasing factor which is not related to negative feedback by somatomedins.
SELECTIVE α2RECEPTOR BLOCKADE FACILITATES THE INSULIN RESPONSE TO ADRENALINE BUT NOT TO GLUCOSE IN MAN
Authors: STRUTHERS A. D. , BROWN D. C. , BROWN M. J. , SCHUMER B. , BLOOM S. R.
Published: March 2008

The adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of α2adrenoceptors. A specific α2adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0·05 μg/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline‐induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific α1antagonist (prazosin) had no significant effect on either glucose tolerance, glucose‐induced insulin release or glucose‐induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory α2adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the α‐adrenergic system.
AUGMENTATION OF ANDROGEN‐RECEPTOR BINDING IN VITRO: STUDIES IN NORMALS AND PATIENTS WITH ANDROGEN INSENSITIVITY
Authors: EVANS B. A. J. , HUGHES I. A.
Published: March 2008

Using a simple whole‐cell binding assay, the effect of androgens on receptor binding activity was studied in genital skin fibroblasts (GSF) from normals and patients with either androgen insensitivity syndrome (AIS), isolated micropenis or hypospadias. Expressing the response as a ratio of augmented to basal specific dihydrotestosterone (DHT) binding, there was a 2.4±0.87 (mean±SD) increase following 20 h incubation with 2 nmol/1 [3H] ‐DHT in normal GSF. Mibolerone, a synthetic nonmetabolizable androgen, produced a similar response. Augmentation was temperature dependent, independent of androgen metabolism and suppressed by protein and RNA inhibitors. All patients with isolated micropenis and hypospadias demonstrated normal augmentation of receptor binding activity. There was no response in patients with complete AIS who were receptor negative. In the majority of patients with partial AIS, there was an in vitro response to androgens; those reared as males all virilized with androgen therapy. In contrast, a male patient with partial AIS who failed to respond to high‐dose androgen therapy, showed no augmentation of specific androgen binding in GSF preincubated with androgens. This technique may be a useful in vitro bioassay to predict androgen responsiveness in vivo in patients with androgen insensitivity, either soon after birth in the short‐term, or later at puberty.
ACCURATE LOCALIZATION OF INSULINOMA USING PERCUTANEOUS TRANSHEPATIC PORTAL VENOUS SAMPLING—USEFULNESS OF SIMULTANEOUS MEASUREMENT OF PLASMA INSULIN AND GLUCAGON LEVELS
Authors: KINOSHITA Y. , NONAKA H. , SUZUKI S. , KONDO T. , CHIHARA K. , CHIBA T. , FUJITA T. , KOTOURA Y. , YAMAMURA T.
Published: March 2008

By means of percutaneous transhepatic portal venous sampling (PTVS), plasma insulin and glucagon levels were determined simultaneously at various sites of the hepatic portal venous system in two patients with insulinoma and four patients without. In the two cases of insulinoma, an obvious rise of insulin concentration was observed at the vicinity of the tumour, while glucagon levels were not elevated in the blood samples showing an insulin peak. In the remaining four cases without evidence of insulinoma, significant step‐ups of plasma insulin occurred in the splenic vein as well, but were accompanied with concomitant elevation of plasma glucagon levels in the same blood samples. Thus, by measuring insulin alone, false positive data may frequently be obtained when PTVS is performed on patients with suspected insulinomas. The simultaneous measurement of insulin and glucagon might be helpful in avoiding such errors.
CLINICAL AND ENDOCRINE STUDIES ON PATIENTS WITH AMENORRHOEA ASSOCIATED WITH WEIGHT LOSS
Authors: NAKAMURA Y. , YOSHIMURA Y. , ODA T. , KATAYAMA E. , KAMEI K. , TANABE K. , IIZUKA R.
Published: March 2008

Two hundred and forty‐three patients with amenorrhoea associated with weight loss were studied. At the onset of amenorrhoea, regardless of percentage weight loss, basal levels of LH were low and LH responses to LHRH were impaired. However, both basal and stimulated levels of FSH were comparable to normal. With resumption of menstruation, the basal and stimulated levels of LH were found to rise to normal, while FSH responses continued to exceed normal. However, 16·6% of 66 unimproved cases had normal responses but remained amenorrhoeic. Furthermore, amenorrhoea persisted in 71% of 31 patients with complete recovery of body weight. No significant correlation was noted between percentage weight loss and responsiveness to LHRH, nor between recovery of body weight and resumption of menstruation. Return to normal weight is desirable for resumption of normal cyclic menstruation and hypothalamic‐pituitary function, but is not always effective.
FAILURE OF HIGH‐DOSE SUSTAINED RELEASE LUTEINIZING HORMONE RELEASING HORMONE AGONIST (BUSERELIN) PLUS ORAL TESTOSTERONE TO SUPPRESS MALE FERTILITY
Authors: MICHEL E. , BENTS H. , AKHTAR FATIMA BINT , HÖNIGL W. , KNUTH U. A. , SANDOW J. , NIESCHLAG E.
Published: March 2008

Previously we have demonstrated that sperm counts of normal young men decreased during constant subcutaneous infusion of the LHRH agonist buserelin (118 or 230 μg/d). In order to test whether azoospermia can be achieved with higher doses, seven young men received 450 μg buserelin subcutaneously daily for 12 weeks via extracorporeal osmotic minipumps. To avoid symptoms of androgen deficiency, oral supplementation with 80 mg/d testosterone undecanoate (TU) was initiated in week 5 and was increased to 120 mg/d by week 8. Follow‐up after treatment lasted for another 12 weeks. In order to evaluate possible psychotropic effects of treatment‐related endocrine changes, continuous psychometric testing was performed focusing on personality, emotions and sexuality. After an initial rise, both serum LH and FSH returned to normal. FSH was below normal during the 3rd–5th week following treatment. LHRH stimulation tests performed at the end of treatment showed pituitary desensitization. Serum T (always measured between 0800 and 1300 h at least 12 h after last TU) tended to decrease by week 7 and remained slightly depressed until the end of treatment while libido, potency and emotional well‐being remained unchanged. While testicular volumes showed a reduction from week 7 of treatment to week 10 post‐treatment, sperm counts decreased only insignificantly from 65 ± 10 to 44 ± 14 million per ml in week 12 post‐treatment. Severe oligo‐ or azoospermia was not observed in any of the seven men. It is concluded that full androgen substitution by TU can drastically delay if not abolish the antifertility effect of LHRH‐induced pituitary desensitization.
EFFECTS OF LH SUPPRESSION IN POLYCYSTIC OVARY SYNDROME
Authors: FLEMING R. , BLACK W. P. , COUTTS J. R. T.
Published: March 2008

A LH‐releasing hormone (LHRH) analogue was administered to subjects with elevated circulating LH concentrations and elevated androgens (polycystic ovary syndrome, PCO) and also to a control group with normal menstrual rhythm and normal LH and androgens. In both groups circulating LH concentrations were reduced to low and indistinguishable concentrations. Oestradiol, oestrone, androstenedione and testosterone levels were all reduced by treatment in both groups. However, the reduction in androgen concentrations was less marked in the patients with PCO. The oestrogen/androgen ratios remained relatively unaltered, but the testosterone levels remained slightly elevated in the PCO patients after treatment. The results suggest that patients with PCO syndrome show a disorder of androgen metabolism independent of elevated LH concentrations.
PREDICTION OF RESPONSE TO ENDOCRINE THERAPY IN PRONOUNCED CYCLICAL MASTALGIA USING DYNAMIC TESTS OF PROLACTIN RELEASE
Authors: KUMAR S. , MANSEL R. E. , HUGHES L. E. , EDWARDS C. A. , SCANLON M. F.
Published: March 2008

Many of the endocrine agents currently used to treat symptomatic benign breast disease modify the action or secretion of prolactin. We have compared the responses to hormonal therapy with dynamic assessment of prolactin control in 29 patients with cyclical mastalgia and in 7 patients with non‐cyclical mastalgia. The tests of prolactin release used were direct stimulation by TRH or dopaminergic blockade by domperidone. These were carried out before treatment in the mastalgic patients and also in 22 age‐matched asymptomatic controls. The response to treatment was assessed using a special pain chart and visual linear analogue scale. Patients with cyclical mastalgia could be divided into two groups: those in whom the peak prolactin release was exaggerated (>4000 mU/1) and those in whom the prolactin release was less marked and similar to control subjects and patients with non‐cyclical mastalgia. Patients in the cyclical mastalgia group with a high peak prolactin release responded to hormonal treatment significantly more frequently (90%) than those with a normal prolactin release (50%). Basal prolactin levels did not correlate with the response to treatment. In the non‐cyclical mastalgia group, no patient had peak prolactin release >4000 mU/1 and none responded to therapy. This study indicates that dynamic tests of prolactin release in cyclical mastalgia may be useful in predicting the subsequent satisfactory response to endocrine therapy if a high peak prolactin release is induced.