bluuebunny/crossref_metadata_2025 huggingface dataset:
TSH AND PROLACTIN STIMULATION BY THE DECARBOXYLASE INHIBITOR BENSERAZIDE IN PRIMARY HYPOTHYROIDISM
Authors: DELITALA G. , DEVILLA L. , LOTTI G.
Published: March 2008

200 mg of the I‐aromatic amino acid decarboxylase inhibitor benserazide were administered orally to five patients with primary hypothyroidism. Benserazide induced a significant increase in prolactin and TSH plasma concentrations in all subjects. Since the drug blocks the conversion of DOPA to dopamine, these hormonal changes may be due to a reduction in circulating and/or median eminence levels of dopamine.
FUNCTIONAL SIGNIFICANCE OF IDIOPATHIC ADRENAL CALCIFICATION IN THE ADULT
Authors: HOELDTKE R. D. , DONALD R. A. , NICHOLLS M. G.
Published: March 2008

Two young adults with idiopathic adrenal calcification are described. In one patient the calcification was probably secondary to adrenal haemorrhage in the neonatal period. Neither patient exhibited clinical features suggestive of adrenal cortical insufficiency, and baseline serum cortisol levels were normal. The corticosteroid responses to ACTH administration and to other provocative tests indicated that both glucocorticoid and mineralocorticoid reserve was normal. One patient showed an appropriate epinephrine response to insulin‐induced hypoglycaemia. We conclude that even extensive adrenal calcification may be compatible with completely normal adrenal function. Since, however, little is known of the natural history of this condition, lifelong follow‐up of such patients is advised.
THE IMPORTANCE OF PITUITARY TUMOUR SIZE IN PATIENTS WITH HYPERPROLACTINAEMIA IN RELATION TO HORMONAL VARIABLES AND EXTRASELLAR EXTENSION OF TUMOUR
Authors: KLIJN J. G. M. , LAMBERTS S. W. J. , JONG F. H. DE , DOCTER R. , VAN DONGEN K. J. , BIRKENHÄGER J. C.
Published: March 2008

In sixty‐two patients with hyperprolactinaemia and a pituitary tumour (without growth hormone excess) we studied the importance of the size of the sella turcica plus extrasellar tissue (if present) in relation to the prevalence of extrasellar extension and impaired hormonal reserve. A lateral tumour area, V of 3 cm2, turned out to be a critical value both in the development of extrasellar extension of the pituitary adenoma as well as in the development of insufficiency of the pituitary‐gonadal, ‐thyroidal and ‐adrenal axis. Extrasellar extension occurred in 44% of the patients. Below the value of 3 cm2 (n= 36) there was only one patient with radiologically detectable significant suprasellar extension. Above the value of 3 cm2 twenty‐four out of twenty‐six patients had significant extrasellar extensions at radiological and perimetrical examination. Taking the size of the sella only, extrasellar extension occurred in one third of the cases with a sellar size between 2 and 3 cm2. There was a strongly positive correlation between (log) tumour size and (log) basal prolactin level (P < 0·0005). LH, FSH, TSH and ACTH secretion were evaluated by the consecutive administration of LHRH, TRH and metyrapone. Negative correlations were observed between (log) pituitary tumour size and (log) basal LH, FSH and TSH (respectively P < 0·005, P < 0·005, P < 0·025) and between (log) tumour size and (log) Δ LH, Δ FSH, Δ TSH and the plasma Compound S concentration after metyrapone (respectively P < 0·0005, P < 0·005, P < 0·01, P < 0·025). Again the value of the index of tumour size (3 cm2) proved to be critical. Above 3 cm2 a highly significant increase in the incidence of insufficient responses to the stimuli mentioned was observed. Pituitary tumour size may be one of the most important indices used in the management of patients with hyperprolactinaemia and a pituitary tumour.
COXSACKIE B VIRUS ANTIBODY RESPONSES IN JUVENILE‐ONSET DIABETES MELLITUS
Authors: RAY C. G. , PALMER J. P. , CROSSLEY JEANETTE R. , WILLIAMS R. H.
Published: March 2008

A prospective serological study of patients with recently diagnosed juvenileonset diabetes mellitus was carried out to determine neutralizing antibody responses to Coxsackie B viruses. The sera were tested with and without staphylococcal protein A absorption, to selectively ascertain whether specific IgM or IgG antibody predominated. Of eleven patients studied, ten had reciprocal antibody titres of sixteen or greater to at least one serotype. Three patients showed no reduction in titre in at least one serum sample after protein A absorption, suggesting a predominant IgM‐specific primary response to a recent infection by a Coxsackie B virus. The findings support the possibility that at least some cases of juvenile‐onset diabetes mellitus are closely related to Coxsackie B virus infections.
ON INCUBATION OF LONG ACTING THYROID STIMULATOR WITH HUMAN THYROID AND ADRENAL HOMOGENATES
Authors: DANDONA P. , KABIR D. J. EL
Published: March 2008

In view of the ability of long acting thyroid stimulator (LATS) containing sera and IgG samples to stimulate the adrenal cortex of the mouse, it was decided to study the effect of incubation of LATS containing IgG with human thyroid and adrenal homogenates. Whereas incubation with human thyroid gland abolished (loss > 80%) both the thyroid and adrenocortical stimulatory effects of LATS, incubation with human adrenal gland resulted in a minimal loss (20%) of both of these stimulatory activities; the magnitude of this loss was no greater than that attributable to non‐specific absorption observed with liver and kidney homogenates by previous workers. It is suggested that a, human and mouse thyroid receptors for TSH/LATS are similar and that adrenocortical receptor for ACTH/LATS are different; and b, the inability of human adrenal homogenates to neutralize LATS explains the absence of hyperadrenocorticism in patients with Graves’disease.
BASAL GANGLIA CALCIFICATION IN POSTOPERATIVE HYPOPARATHYROIDISM
Authors: FORMAN M. B. , SANDLER M. P. , DANZIGER A. , KALK W. J.
Published: March 2008

The presence of bilateral basal ganglia calcification was sought in nine patients with post‐operative and two patients with primary hypoparathyroidism, using computerized axial tomography (CAT) and plain skull radiographs. Calcification was detected with CAT in seven patients; five with post‐operative and both with primary hypoparathyroidism, but in only one was it demonstrable on plain X‐ray films. The presence of calcificaton appeared to be related to the duration of the disease and possibly the degree of control of serum calcium. Six of the seven patients with cerebral calcification also had cataracts. The incidence of basal ganglia calcification in hypoparathyroidism is probably much greater than previously recognized, especially in post‐operative hypoparathyroidism.
EXCESS FREE ALPHA RELATIVE TO BETA SUBUNITS OF THE GLYCOPROTEIN HORMONES IN NORMAL AND ABNORMAL HUMAN PITUITARY GLANDS
Authors: KOURIDES IONE A. , LANDON MARK B. , HOFFMAN BETH J. , WEINTRAUB BRUCE D.
Published: March 2008

Extracts of thirteen normal pituitaries from five men, three premenopausal women, and five postmenopausal women were fractionated by Sephadex G‐100 chromatography; alpha subunit, TSH‐β, LH‐β, and FSH‐β, as well as complete TSH, LH, and FSH, were measured by radioimmunoassay (RIA) in each fraction collected. In spite of variability in subunit content among normal pituitaries, a consistent excess of free alpha subunits relative to the sum of all free pituitary beta subunits was demonstrated in each normal pituitary (P < 0·025); the alpha to beta subunit ratio ranged from 1·29–8·31. In addition, in normal pituitary extracts the ratio of free alpha to alpha combined with beta subunits in the complete glycoprotein hormones generally exceeded 1 (mean 1·57), although the free alpha to combined alpha excess was not statistically significant. In extracts of pituitaries from two hypothyroid and four hyperthyroid patients, the excess of alpha to all pituitary beta subunits persisted. Centrifugation of pituitary extracts at 35 000g, rather than 1500g, prior to gel chromatography decreased the small percentage of void volume immunoactivity in both complete glycoprotein hormone and subunit RIAs, suggesting that it may have been caused by adsorption to membrane components in the extracts. Different methods of preparing the pituitary homogenates did not change the amount or ratio of alpha to beta subunits extracted. Heterogeneity was observed in pituitary alpha and TSH‐β by gel chromatography, suggesting that differences in the amount of glycosylation existed among intrapituitary free alpha and TSH‐β subunits. These studies, as well as prior studies of de novo subunit biosynthesis and in vivo secretory rates, support the concept that the excess content of free alpha to all free beta subunits in the pituitary reflects greater synthesis of alpha subunits; beta subunit synthesis appears to be the limiting factor in the production of complete TSH, LH, and FSH.
INCREASED 18‐HYDROXYCORTICOSTERONE RESPONSES TO FRUSEMIDE IN ESSENTIAL HYPERTENSION
Authors: SEMPLE P. F. , MASON P. A. , FRASER R.
Published: March 2008

Plasma concentrations of angiotensin II (AII), aldosterone, 18‐hydroxycorti‐costerone and cortisol were measured in seven patients with benign essential hypertension and in seven age‐matched control subjects before, and at frequent intervals for 2 h after the intravenous injection of frusemide (40 mg). In the normal subjects, significant increases in the plasma levels of AII, aldosterone and 18‐hydroxycorticosterone were apparent from 15 min after diuretic administration. The integrated responses of each hormone to frusemide administration were calculated. Aldosterone and AII responses to the diuretic were closely related, although three hypertensive patients had normal integrated aldosterone responses despite subnormal increases in the plasma concentrations of AII. The integrated 18‐hydroxycorticosterone responses were greater in the hypertensive (median 970 nmol. h−1. l−1) than in the normal subjects (median 180 nmol. h−1. l−1), P < 0·05. Some patients with a raised blood pressure appear to have an enhanced adrenal corticosteroid response to frusemide; this probably reflects an increased sensitivity to angiotensin II.
SEQUENTIAL CHANGES IN SERUM THYROGLOBULIN (Tg) AND ITS AUTOANTIBODIES (TgAb) FOLLOWING SUBTOTAL THYROIDECTOMY OF PATIENTS WITH PREOPERATIVELY DETECTABLE TgAb
Authors: FELDT‐RASMUSSEN ULLA , PETERSEN P. HYLTOFT , DATE J. , MADSEN C. M.
Published: March 2008

The changes in serum concentrations of thyroglobulin antibodies (TgAb) were investigated in eight patients with various thyroid disorders before, during and after thyroid surgery. TgAb was measured by a radioassay using 125I‐thyroglobulin.

In six patients the TgAb decreased rapidly during operation. Of these patients, four had low concentrations pre‐operatively, and the decrease in TgAb resulted in undetectable concentrations for more than 2 days. Serum thyroglobulin (Tg), measured in the specimens with undetectable TgAb, i.e. immediately following surgery, showed concentrationvstime curves resembling curves from patients with no antibody present.

Furthermore, two of these patients had such a high concentration of TgAb pre‐operatively that the initial Tg release was not sufficient to remove the TgAb, resulting in detectable TgAb throughout the investigation period. Serum samples drawn during and after operation were chromatographed according to molecular size, showing measureable Tg corresponding to 19S Tg. TgAb was only measureable in fractions corresponding to 7S IgG. The expected presence of complexed Tg and TgAb could not be demonstrated, but the analytical methods might have been unable to reveal this. The remaining two patients with thyroiditis showed no decrease in TgAb. This was compatible with a low content of Tg in the thyroid measured in one of them.
SIZE REDUCTION OF A PROLACTIN SECRETING ADENOMA DURING LONG‐TERM TREATMENT WITH THE DOPAMINE AGONIST LISURIDE
Authors: CHIODINI P. G. , LIUZZI A. , VERDE G. , COZZI R. , SILVESTRINI F. , MARSILI M. T. , HOROWSKI R. , PASSERINI F. , LUCCARELLI G. , BORGHI P. G.
Published: March 2008

A 38–year‐old amenorrhoeic woman suffering from a prolactin (PRL) secreting adenoma, which had suprasellar extension as shown by carotid angiography and computed axial tomography (CAT), was treated with a dopamine agonist (lisuride). PRL levels were lowered and after 1 year of treatment CAT showed a marked reduction of the tumour size. After 2 years of treatment menstruation returned and CAT demonstrated a further reduction of the adenomatous tissue. This study supports the suggestion that dopamine agonists possess an anti‐pro‐liferative effect on tumoural lactotrophic cells of humans.
FETAL ORIGIN OF AMNIOTIC FLUID INSULIN IN THE HUMAN MOTHER
Authors: GRECO A. V. , REBUZZI A. G. , BELLATI U. , SERRI F. , ALTOMONTE L. , MANNA R. , GHIRLANDA G.
Published: March 2008

To investigate the origin of insulin in amniotic fluid amniocenteses were carried out in pregnancies with live, dead and anencephalic fetuses. Amniotic fluid insulin of pregnant women bearing live fetuses was 9.0 ± 2.1 μU/ml; in six women with dead foetuses amniotic fluid insulin was not detected. A significant positive correlation was observed between gestational age and the amniotic fluid concentration of insulin. In the amniotic fluid of the four women bearing anencephalic fetuses, the amount of hormone was within normal limits (10.0 ± 1.4 μU/ml). Intravenous glucose administration (0.33 g/kg body weight) to the mother does not influence levels of insulin in amniotic fluid, but brought about changes in amniotic fluid glucose concentration. These findings support the conclusion that human amniotic fluid insulin is of fetal rather than maternal origin.
ENDOCRINE FUNCTION IN THE PRADER‐WILLI SYNDROME
Authors: JEFFCOATE W. J. , LAURANCE B. M. , EDWARDS C. R. W. , BESSER G. M.
Published: March 2008

Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader‐Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous administration of LHRH was subnormal in seven. Repeat administration of LHRH after 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader‐Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities.
SERUM CONCENTRATIONS OF HUMAN CHORIONIC GONADOTROPHIN AND ITS ALPHA AND BETA SUBUNITS. 1. DURING NORMAL SINGLETON AND TWIN PREGNANCIES
Authors: REUTER AIMÉE M. , GASPARD U. J. , DEVILLE J‐L. , VRINDTS‐GEVAERT YVONNE , FRANCHIMONT P.
Published: March 2008

Homologous radioimmunoassays have been developed for native hCG and its α and β subunits. Their specificities were assessed by analysis of the inhibition curves and by gel filtration of purified preparations of native hCG, hCGα and hCGβ, and of sera from pregnant women, on Sephadex G 100. Gel filtration data indicated a true cross‐reaction of native hCG in the hCGβ and hCGα assays of 0.5 and 0.35%, respectively. After validation of the RIA procedures for unfiltered serum assays, we have demonstrated that in 311 maternal sera obtained in 207 normal singleton pregnancies, free circulating hCGα increases continuously, whereas free hCGβ and native hCG peak between the 8th‐10th week. The ratio (hCGβ/hCG) x 100 is greatest during the first trimester (2–3%) and decreases thereafter to around 1%. The ratio (hCGα/hCG) x 100 is < 1% at the beginning of pregnancy, 2% at 14 weeks and 15–20% from the 23rd week onwards. The levels of hCG and its subunits are higher in fifty‐two samples obtained throughout normal twin pregnancies than in corresponding single pregnancies, but the ratios subunit: hCG are the same, suggesting qualitatively similar placental secretion in both types of pregnancy. Analysis of pregnancy sera by gel filtration and assay of hCG and subunits in eluant fractions confirmed that free α and β subunits are present in the circulation and that hCGα rises while hCG and hCGβ fall in late pregnancy. Heterogeneity of the circulating hCGβ subunit is also demonstrated.
LEYDIG CELL TUMOUR OF THE TESTIS WITH GYNAECOMASTIA AND ELEVATED OESTROGEN, PROGESTERONE AND PROLACTIN LEVELS: CASE REPORT
Authors: PEREZ C. , NOVOA J. , ALCANIZ J. , SALTO L. , BARCELO B.
Published: March 2008

The successful surgical removal of a feminizing interstitial cell tumour of the testis is described. The high oestradiol, progesterone and prolactin levels fell after surgery and the suppressed testosterone, FSH and LH recovered. Oestrogen secretion by the tumour could explain most of the observed hormonal changes.
INFLUENCE OF TREATMENT WITH RADIOIODINE AND PROPYLTHIORACIL ON THYROID STIMULATING IMMUNOGLOBULINS IN GRAVES' DISEASE
Authors: And KARINE BECH , MADSEN S. NISTRUP
Published: March 2008

Thyroid stimulating immunoglobulins (TSAb) were measured in fifty‐four patients with Graves' disease before treatment with either radioiodine (seventeen patients) or propylthiouracil (PTU) (thirty‐seven patients), and followed during treatment. After radioiodine TSAb increased to levels exceeding pre‐treatment values, and became detectable in three of six originally TSAb negative patients.

In most patients TSAb decreased during treatment with PTU, and became undetectable after a mean of 12 months in patients above 40 years, and after a mean of 6 months in patients below 40 years. In order to eliminate the presumed causative agent in Graves' disease, antithyroid treatment should be at least 18 months in patients above 40 years, and at least 12 months in patients below 40 years of age. In twenty‐nine patients TSAb were measured at cessation of 2 years antithyroid drug therapy. Ten patients were TSAb positive and all except one relapsed. Five of nineteen TSAb negative patients relapsed. Although TSAb positivity predict relapse, it is not an ideal index of prognosis after antithyroid therapy.
ACTH, LPH AND RELATED PEPTIDES IN THE ECTOPIC ACTH SYNDROME
Authors: PULLAN P. T. , CLEMENT‐JONES VICKY , CORDER R. , LOWRY P. J. , BESSER G. M. , REES LESLEY H.
Published: March 2008

Adrenocorticotrophin. lipotrophin and the related peptides α‐MSH, CLIP, β‐endorphin and met‐enkephalin have been measured, and characterized chromatographically in tumour extracts from seven patients with the ectopic ACTH syndrome. Four of the seven tumours contained the complete family of peptides, although the proportion of one to another varied between tumours. In addition, large molecular weight forms of ACTH and met‐enkephalin were seen. The potential clinical importance of these observations is discussed.
AN EVALUATION OF SUPERVOLTAGE ORBITAL IRRADIATION FOR GRAVES' OPHTHALMOPATHY
Authors: TENG C. S. , CROMBIE A. L. , HALL R. , ROSS W. M.
Published: March 2008

Twenty patients with moderately severe ophthalmopathy due to Graves' disease or ophthalmic Graves' disease were treated by supervoltage orbital radiotherapy generated by a linear accelerator. Seven patients (35%) showed some response within 3 weeks of the treatment, four patients (20%) improved minimally while nine patients (45%) were unchanged. Improvement was noted mainly in soft tissue changes while proptosis decreased in only four patients. With one exception, ophthalmoplegia did not improve after the radiotherapy. The benefit obtained with the treatment was not impressive.
LIMITED ADRENAL RESERVE IN PARACOCCIDIOIDOMYCOSIS: CORTISOL AND ALDOSTERONE RESPONSES TO 1–24 ACTH
Authors: NEGRO G. DEL , MELO E. H. L. , RODBARD D. , MELO M. R. , LAYTON J. , WACHSLICHT‐RODBARD H.
Published: March 2008

Adrenal function in twenty‐three patients with paracoccidioidomycosis (South American Blastomycosis) has been assessed by measuring the response to adrenocortical stimulation with 1–24 ACTH. Two patients with overt Addison's disease showed very low basal levels and the complete absence of an increase in either cortisol or aldosterone secretion. Six patients showed probable diminished adrenal reserve in terms of cortisol and three patients showed diminished reserve in terms of aldosterone function. These findings indicate an incidence of significant hypoadrenalism in 44% of hospitalized patients with disseminated paracoccidioidomycosis.
EFFECT OF OESTROGEN TREATMENT ON TESTICULAR LH/hCG RECEPTORS AND ENDOGENOUS STEROIDS IN PROSTATIC CANCER PATIENTS
Authors: HUHTANIEMI I. , LEINONEN P. , HAMMOND G. L. , VIHKO R.
Published: March 2008

LH/hCG binding and concentrations of pregnenolone, progesterone, 17‐hydroxyprogesterone, androstenedione, testosterone and 5α‐dihydrotestosterone were measured in testicular tissue obtained from patients undergoing orchiectomy for prostatic cancer. One group of the orchiectomized patients had received an injection of 80 mg polyestradiol phosphate 1–9 days before the operation, another group were treated with monthly injections of the oestrogen for several months, and the remainder were not treated with oestrogen. In non‐oestrogen treated patients (n= 8) the hCG‐binding capacity was 28.0±15.0 (SD) ng/g and the equilibrium association constant of binding was 0.69±0.38 x 1010 M−1.The binding capacity was significantly (P<0.025) lower (10.3±8.7 ng/g) in patients (n= 6) receiving the first oestrogen injection 3–9 days prior to the operation. A further decline to the level of 1.77±1.03 ng/g occurred in patients (n= 3) treated over 3 months with the oestrogen injections. At the same time, no significant changes were observed in peripheral serum LH and FSH levels. In the testicular endogenous steroid levels, statistically significant decreases were seen 9 days after the oestrogen injection in pregnenolone (from 505±315 ng/g to 138±86 ng/g) and in testosterone (from 669±243 ng/g to 254±49 ng/g) whereas no significant changes could be seen in the levels of the other steroids analysed. This study gives further evidence for the direct inhibitory action of oestrogens on human testicular steroidogenesis and suggests that the loss of testicular luteinizing hormone receptors may be one facet of this inhibitory action.
PITUITARY‐OVARIAN FUNCTION IN NORMAL WOMEN DURING THE MENOPAUSAL TRANSITION
Authors: METCALF MARY G. , DONALD R. A. , LIVESEY J. H.
Published: March 2008

The excretion of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogens and pregnanediol was measured in weekly urine samples collected for 14–87 weeks (median, 43 weeks) from thirty‐one perimenopausal women aged 36–55 years (median, 50 years). The results were compared with those found in twenty‐two postmenopausal women aged 55·4 ± 5·4 years (mean ± SD), and in twenty premenopausal women aged 44·4 ± 3·4 years with regular, ovulatory, menstrual cycles. Women classed as perimenopausal had a recent history of irregular menstrual cycles following regular cyclicity. The hormone patterns observed in the perimenopausal women varied widely, both between individuals and from time to time in the same individual. They ranged from ovulatory cycles with low premenopausal levels of FSH, to transient episodes indistinguishable from those found in postmenopausal women with high levels of FSH and LH. Between these extremes were patterns rarely seen at other times in reproductive life: namely, (1) in fourteen women on thirty‐two occasions lasting 2–9 weeks, postmenopausal levels of FSH and LH occurred in association with high oestrogen levels; (2) in eighteen women on thirty occasions lasting 2–8 weeks, there was an elevation of LH (but not FSH) into the postmenopausal range; (3) in thirteen women on twenty‐six occasions lasting 1–2 weeks, there was an elevation of FSH (but not LH) into the postmenopausal range. These patterns were not seen in any of the premenopausal women. Typically, the approach of the menopause was marked by an increased incidence of high postmenopausal levels of FSH and LH. Ovulatory cycles were observed at all stages in the perimenopause, and occurred within 16 weeks of the last menstrual period in seven of the thirteen women who became postmenopausal during the study. It is concluded that the appearance of high levels of FSH and LH is characteristic of the perimenopause and often precedes the sustained loss of sex hormone secretion by the ageing ovary. Postmenopausal biochemical parameters are no guarantee of the postmenopausal state.
THE BASAL PLASMA GLUCOSE: A SIMPLE RELEVANT INDEX OF MATURITY‐ONSET DIABETES
Authors: HOLMAN R. R. , TURNER R. C.
Published: March 2008

The ‘basal’ plasma glucose, defined as the stable overnight concentration, has been assessed as an index of diabetes control by comparison with plasma glucose measurements during 24‐h profiles in diet‐treated maturity‐onset diabetic patients and normal subjects. The basal plasma glucose correlated with the total (r = 0·98) and incremental (r = 0·86) glucose areas, as well as the 24‐h M value (r = 0·90). In mild diabetes the basal value was more abnormal than the incremental glucose area after meals, since 3 h after meals ‘reactive hypoglycaemia’ lowered the plasma glucose to less than the basal value. Thus diabetics with a raised basal plasma glucose up to 8 mmol/1 can have a normal 3‐h post‐prandial value. A raised basal plasma glucose provides similar diagnostic information to conventional oral glucose tolerance tests and provides an apposite measure of diabetes control. Diabetics who come up to a clinic, or who exercise whilst fasting, have fasting plasma glucose and insulin concentrations slightly higher than their overnight ‘basal’ levels, whereas there is little change in normal subjects. This higher ‘stressed fasting’ plasma glucose needs to be taken into account when assessing fasting plasma glucose values.

This work was presented in part at the 13th Annual Meeting of the European Diabetes Association, Geneva, September 1977.
CORRELATIONS BETWEEN PROGESTERONE, OESTRADIOL AND ALDOSTERONE LEVELS IN THE PREMENSTRUAL SYNDROME
Authors: MUNDAY MADELEINE R. , BRUSH M. G. , TAYLOR R. W.
Published: March 2008

Levels of progesterone, oestradiol and aldosterone in the plasma of twenty women with premenstrual syndrome (PMS) were measured by radioimmunoassay and the results were compared with those from a control series of ten normal volunteers. All the PMS patients were apparently ovulatory but the pooled progesterone values from days −9 to −5 premenstrually were significantly lower than the control values (P < 0·05). The oestradiol levels in the PMS patients were higher than in control subjects over the last 4 days of the cycle (P < 0·01). There was no significance in aldosterone levels between the PMS and control groups. The relevance of these results to the aetiology of PMS is considered.
TESTICULAR FUNCTION IN PREPUBERTAL MALE PSEUDOHERMAPHRODITISM
Authors: CAMPO S. , MOTEAGUDO C. , NICOLAU G. , PELLIZZARI E. , BELGOROSKY A. , STIVEL M. , RIVAROLA M.
Published: March 2008

Testicular function was evaluated in forty‐one prepubertal patients with male pseudohermaphroditism by determinating serum concentrations of progesterone, 17‐hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone and dihydrotestosterone before and after stimulation with hCG and, in some instances, ACTH. Testosterone response to hCG was normal in all subjects. In one patient, a 4‐year‐old boy, a deficiency of 17,20‐desmolase activity was diagnosed based on the coexistence of elevated levels of pregnenolone, 17‐hydroxypregnenolone, progesterone and 17‐hydroxyprogesterone and low levels of dehydroepiandrosterone and androstenedione. In three other patients enzymatic blocks were suspected but not confirmed. Congenital deficiency of enzymes neccessary for testosterone biosynthesis is an uncommon aetiology of male pseudohermaphroditism.
GONADOTROPHIN LEVELS IN WOMEN WITH CUSHING'S SYNDROME BEFORE AND AFTER TREATMENT
Authors: WHITE M. C. , SANDERSON J. , MASHITER K. , JOPLIN G. F.
Published: March 2008

Basal serum concentrations of LH and FSH and their response to LHRH were studied in twelve pre‐ and ten post‐menopausal women with Cushing's syndrome before and after treatment. Subnormal basal concentrations of LH were found in twelve out of twenty‐two, and of FSH in ten of the twenty untreated patients. There was a correlation between the urinary free cortisol (UFC) and basal LH values, r =−0·59 (P < 0·05), and UFC and basal FSH values, r=−0·76 (P < 0·02) in the premenopausal women. All seven patients with a UFC value > 1080 nmol/24 h (normal range < 270) had both a subnormal basal gonadotrophin level and a subnormal response of at least one gonadotrophin to the releasing hormone. In those patients in whom successful remission was obtained and who did not require replacement therapy, subnormal basal gonadotrophins were usually restored towards or into the normal range. It is concluded that while gonadotrophin levels may be normal in women with Cushing's syndrome, they are subnormal in those with the highest cortisol values. This may be due to a direct suppressive effect of cortisol on the release of stored pituitary hormone, and/or on LHRH release from the hypothalamus.
ANDROGEN REPLACEMENT WITH ORAL TESTOSTERONE UNDECANOATE IN HYPOGONADAL MEN: A DOUBLE BLIND CONTROLLED STUDY
Authors: SKAKKEBAEK N. E. , BANCROFT J. , DAVIDSON D. W. , WARNER PAMELA
Published: March 2008

The effects of androgen withdrawal and replacement were investigated in six hypergonadotrophic and six hypogonadotrophic men with hypogonadism. A double blind cross‐over design was used comparing testosterone undecanoate (T.U., Organon International), 160 mg daily by mouth, with placebo. There was a significant effect of T.U. on all measures of sexual interest and behaviour. Sexual interest increased within the first week of T.U. administration, ejaculation usually returning within the second week. Behavioural responses were similar in the hyper‐ and hypogonadotrophic groups.

The rise in plasma testosterone during T.U. administration was modest, not reaching the normal range in several cases. 5α dihydrotestosterone rose more substantially. There was a significant fall in sex hormone binding globulin, a rise in oestradiol and no significant change in gonadotrophin concentrations during T.U. administration.
HIGH SERUM GASTRIN LEVELS IN THYROTOXIC PATIENTS
Authors: DAHLBERG P. A. , KARLSSON F. A. , LUNDQVIST G.
Published: March 2008

High gastrin levels were found in twenty‐one out of fifty‐six consecutive patients (38%) with thyrotoxicosis. Following return to euthyroidism gastrin levels generally fell, but twelve patients (21%) remained hypergastrinaemic. Six of these patients (11%) had achlorhydria indicating atrophic gastritis of the antrum sparing type. No correlation between gastrin and triiodothyronine values was found. It is suggested that gastrin levels should be measured in thyrotoxic patients after treatment, and further control instituted in patients with raised gastrin levels. The relationship between gastric function, gastrin release and thyroid function seems complex. The interactions may involve both a direct effect of thyroid hormone on gastric acid production, adrenergic influences on gastrin release and linked phenomena with development of thyroid and gastric auto‐immune diseases.
ALTERED DOPAMINERGIC REGULATION OF THYROTROPHIN RELEASE IN PATIENTS WITH PROLACTINOMAS: COMPARISON WITH OTHER TESTS OF HYPOTHALAMIC‐PITUITARY FUNCTION
Authors: SCANLON M. F. , RODRIGUEZ‐ARNAO M. D. , McGREGOR A. M. , WEIGHTMAN D. , LEWIS M. , COOK D. B. , GOMEZ‐PAN A. , HALL R.
Published: March 2008

This study was carried out to test the hypothesis that sustained hyperprolactinaemia in patients with prolactinomas stimulates hypothalamic dopaminergic activity via a short loop positive feedback effect of prolactin (PRL). The intensity of dopamine (DA) effects on the pituitary around the adenoma was evaluated by measuring thyroid stimulating hormone (TSH) responses to intravenous injection of domperidone (10 mg) a new DA receptor blocking drug that does not penetrate the blood‐brain barrier. TSH responses have been compared with those of PRL to the same agent. Eight females with prolactinomas showed greater TSH release after domperidone than nine normal females (sum of TSH increments over 120 min 17·5 ± 1·7 v. 8·9±1·5 mu/l, P < 0·001) whilst PRL release was reduced (sum of PRL increments over 120 min 5·9 ± 2·4 v. 21·8 ± 3·8 mu/l ± 10−3, P < 0·01). Amongst nineteen hyperprolactinaemic females with apparently normal pituitary fossae (plain skull X‐ray), ten showed an exaggerated TSH response (ΔTSH, 4·2 ± 0·6 mu/l, range 2·5–9·40 mu/l) and reduced PRL response to domperidone, comparable with established tumour cases. In the remaining nine normal fossa hyperprolactinaemic females, the TSH and PRL responses to domperidone were similar to normal females.

These results support the initial hypothesis and indicate the coexistence of a defect in the dopaminergic inhibition of PRL release and increased dopaminergic inhibition of TSH release in patients with prolactinomas. The presence of an exaggerated TSH response to DA antagonism in a euthyroid, radiologically normal (plain skull X‐ray), hyperprolactinaemic patient is compatible with the presence of an autonomously‐functioning, PRL secreting, pituitary microadenoma and the TSH changes seen in these patients after DA antagonist administration can be readily detected by sensitive TSH radioimmunoassay.
PITUITARY FUNCTION IN PROLACTINOMA. EFFECT OF SURGERY AND POSTOPERATIVE BROMOCRIPTINE THERAPY
Authors: PELKONEN R. , GRAHNE B. , HIRVONEN E. , KARONEN S‐L. , SALMI J. , TIKKANEN M. , VALTONEN S.
Published: March 2008

Forty‐five women and fifteen men with prolactinomas have been treated surgically. Patients with large tumours received pituitary irraditation and postoperative hyperprolactinaemia was treated with bromocriptine. The patients have been followed‐up for 6–36 months following the operation. The tumours were larger and the levels of production higher in men as compared with women. All women had amenorrhoea. Galactorrhoea was present in forty‐three women but not in the men. After surgery serum prolactin levels fell significantly in all women but remained above normal in thirty‐six; prolactin remained high in twelve men. Bromocriptine effectively decreased the postoperative hyperprolactinaemia. The surgical complications were oculomotor nerve paresis in one woman and one man. After surgery six (23%) women developed impaired GH secretion, six (15%) impaired thyroid function, eight (18%) impaired cortisol secretion and five (17%) impaired LH secretion in isolation or combination which had not been present preoperatively. Three patients relapsed.

Fifteen women menstruated after surgery and ten began to do so during the subsequent bromocriptine treatment. Thus, menstruation was restored in all six women with microadenomas, in sixteen of twenty patients with intrasellar macroadenomas and three of nineteen patients with suprasellar adenomas. The preoperative LH‐reserve proved to be an important prognostic indicator. Nine patients, i.e. 50% of patients desiring fertility became pregnant. In the men gonadal function deteriorated in four patients and did not improve in any without testosterone treatment.
SERUM LEVELS OF PROLACTIN AND MILK PRODUCTION IN WOMEN DURING A LACTATION PERIOD OF THIRTY MONTHS
Authors: HENNART P. , DELOGNE‐DESNOECK J. , VIS H. , ROBYN C.
Published: March 2008

Serum prolactin was measured in single blood samples collected from 219 nursing mothers of the Kivu region (Zaïre) during 30 post‐partum months. In addition the number of feeding episodes per day and the amount of milk given to the child in 24 h were recorded. The mean serum prolactin levels remained around 1000 mu/l during the first 15 months of lactation and fell during the next 3 months to 550 mu/l. A decline in milk production per day occurred during the second year, but it was less marked than that of prolactin. This decline seemed to be associated with the decline in suckling frequency as the quantity of milk given per feed remained almost unchanged throughout lactation. The average amount of milk given by mothers with serum prolactin levels in the range of values seen in non‐lactating and non‐pregnant women (about 500 mu/l) is nevertheless of some 35 g per feeding or 260 g per day. These results demonstrate that milk production can be maintained in women with normal levels of prolactin and suggest that prolactin plays a permissive role in established lactation.
STUDIES OF THE OPIATE CONTROL OF PROLACTIN, GH AND TSH
Authors: GROSSMAN A. , STUBBS W. A. , GAILLARD R. C. , DELITALA G. , REES LESLEY H. , BESSER G. M.
Published: March 2008

Opiate peptides are known to influence the secretion of several anterior pituitary hormones under basal conditions. Further studies on prolactin, GH and TSH have therefore been performed in normal subjects, under basal and stimulated conditions, using an opiate agonist and antagonist. Sixteen mg naloxone had no effect on the basal release of prolactin or GH, but lowered TSH. An infusion of the met‐enkephalin analogue DAMME (1 mg) increased GH, and produced an exaggerated response of both prolactin and TSH to 200 μg TRH i.v. The peak responses of both prolactin and GH to hypoglycaemia were unaffected by pretreatment with either low‐dose (0·4 mg) or high‐dose (25 mg) naloxone, or DAMME (0·25 mg). These results suggest that opiate peptides are unlikely to play a major role in the tonic or hypoglycaemia‐stimulated release of prolactin and GH, although they may be of importance in the control of TSH.
AUTONOMIC NEURAL CONTROL MECHANISMS OF SUBSTRATE and HORMONAL RESPONSES TO ACUTE HYPOGLYCAEMIA IN MAN
Authors: FRIER B. M. , CORRALL R. J. M. , RATCLIFFE J. G. , ASHBY J. P. , McCLEMONT ELIZABETH J. W.
Published: March 2008

The contributions of adrenergic and cholinergic mechanisms to recovery from acute hypoglycaemia induced by insulin (0·15 units/kg i.v.) were examined in eleven normal subjects, six subjects with a pre‐ganglionic sympathectomy (adrenergic denervation) and six sympathectomized subjects given atropine (combined adrenergic denervation and cholinergic blockade).

Blood glucose recovery was impaired only in the sympathectomized subjects given atropine. The blood lactate response was reduced and the rise in free fatty acids was delayed in both groups of sympathectomized subjects, in whom the normal rises of plasma cyclic AMP and noradrenaline were absent. The plasma pancreatic glucagon response was appropriate to the prevailing blood glucose concentrations in all three groups. The cortisol response was impaired and the pattern of ACTH secretion was abnormal in sympathectomized subjects given atropine. Growth hormone levels were higher in both sympathectomized groups.

Blood glucose homeostasis was impaired during combined adrenergic denervation and cholinergic blockade. Glucagon secretion was activated independently of vagal control. In the sympathectomized group given atropine, the rise in plasma cortisol was blunted despite a greater degree of hypoglycaemia. A blockade of central cholinergic receptors producing impaired activation of ACTH secretion at hypothalamic level may explain, at least in part, this delayed restoration of normoglycaemia.
PROLONGED REMISSION IN FLORID CUSHING'S SYNDROME FOLLOWING METYRAPONE TREATMENT
Authors: BEARDWELL C. G. , ADAMSON A. R. , SHALET S. M.
Published: March 2008

Two patients presenting with diabetes mellitus and hypokalaemia resulting from markedly increased ACTH and cortisol secretion are described. Neither patient showed any evidence of a tumour and both responded dramatically to treatment with metyrapone in that all abnormal clinical features disappeared, ACTH concentrations returned to normal and both patients showed prolonged remission after metyrapone treatment was stopped. One patient relapsed after a severe viral illness and the administration of dexamethasone and cortisone. It is suggested that these cases may represent an unusual form of Cushing's syndrome in which ACTH secretion is stimulated by increasing concentrations of cortisol. When these are reduced by metyrapone administration ACTH secretion falls in parallel and prolonged remission of disease may result.
ENDOCRINE ASSESSMENT OF THE SUBFERTILE MALE
Authors: WU F. C. W. , EDMOND P. , RAAB G. , HUNTER W. M.
Published: March 2008

Sixty‐three male (XY) patients attending a subfertility clinic with average sperm density under 40 million/ml were studied by testicular biopsy and multiple basal estimations of plasma LH, FSH, testosterone as well as LHRH (50 μg i.v.) stimulation. A further forty patients with similar sperm densities also had testicular biopsy but only single estimations of the three hormones. A single basal FSH was found to be the best discriminator of testicular histologies. Patients with testicular biopsies showing germ cell aplasia in some or all seminiferous tubules (grades 3 and 4) had significantly higher basal FSH than those with hypospermatogenesis, germ cell arrest or normal appearance (grades 1 and 2). Basal FSH also showed a linear trend rising with decreasing sperm density but only rose above the normal range when sperm densities fell below 1 million/ml. When basal FSH, testicular histology and sperm density were considered together in the whole group (n= 100), high levels of FSH accurately indicated the presence of germ cell aplasia in some or all seminiferous tubules in azoo‐ and oligospermic men with sperm density under 5 million/ml. Normal FSH and azoospermia is diagnostic of obstruction in the excurrent ducts, and further investigation is undertaken if surgical correction of the obstruction is contemplated. Hormone estimations are not helpful in oligospermic patients with average sperm density over 5 million/ml. On the basis of these findings it is suggested that there is little place for the LHRH test in the routine assessment of male subfertility. Testicular biopsy is indicated only in oligospermic patients with average sperm density under 5 million/ml and normal basal FSH.
THE PREDICTION OF RELAPSE AFTER DRUG TREATMENT OF GRAVES' DISEASE BY ASSAY OF LONG ACTING THYROID STIMULATOR‐PROTECTOR (LATS‐P)
Authors: HARDISTY C. A. , HANFORD LINDA , MUNRO D. S.
Published: March 2008

In a study of fifty‐two patients with Graves' disease followed for 1 year after stopping antithyroid drugs, a strong relationship has been found between serum LATS‐P and relapse. In those with serum LATS‐P activity on stopping therapy, twenty‐one (88%) out of twenty‐four relapsed. In those with no LATS‐P activity on stopping antithyroid drugs only eight (29%) out of twenty‐eight relapsed and in five LATS‐P was detectable at relapse. The overall prevalence of positive assays for LATS‐P at relapse (90%) was similar to that seen in untreated Graves' disease.
THE EFFECT OF FENCLOFENAC ON THYROID FUNCTION
Authors: KURTZ A. B. , CAPPER S. J. , CLIFFORD J. , HUMPHREY M. J. , LUKINAC L.
Published: March 2008

The non‐steroidal anti‐inflammatory agent fenclofenac competitively inhibits the binding of thyroxine (T4) and triiodothyronine (T3) by thyroxine‐binding globulin (TBG). Eight male volunteers completed a 4‐week study during which they took fenclofenac 600 mg twice daily. The concentration of fenclofenac in serum reached a plateau after 1 week of therapy after which the mean concentration (± SEM) of the drug in serum was 78–6 ± 6–2 mg/l. During the steady state period on treatment there were reductions of the mean serum concentrations of total T4 to 35% (P < 0·001), total T3 to 55% (P < 0·001), free T4 to 69% (P < 0·001) and free T3 to 90% (NS) of the respective pretreatment values.

There were also significant changes in the concentrations of thyrotrophin and reverse T3 in serum. After starting treatment with fenclofenac serum concentrations of thyrotrophin fell to a nadir after 2–4 days at which time the mean concentration was 34% (P < 0·01) of the pretreatment value, whilst reverse T3 values increased to a maximum of 136% (P < 0·001) of the pretreatment values over 1–2 days. There was subsequently an increase of the thyrotrophin and a reduction in reverse T3 concentrations to normal by 2 weeks of treatment. Transient pituitary suppression was also suggested by the response to thryotrophin‐releasing hormone (TRH): 7 days after starting fenclofenac the mean thyrotrophin response was 62% (P < 0·001) of the pretreatment value. After 4 weeks of fenclofenac the response of TRH had returned to normal. After discontinuing fenclofenac there was a transient increase in the mean concentration of thyrotrophin in serum, to 129% of the pretreatment value (P < 0·001), with a subsequent return to normal. Four weeks after discontinuing fenclofenac the serum concentrations of thyroid hormones and thyrotrophin were normal.
EFFECTS OF VALPROIC ACID, NALOXONE AND HYDROCORTISONE IN NELSON'S SYNDROME AND CUSHING'S DISEASE
Authors: ELIAS A. N. , GWINUP G. , VALENTA L. J.
Published: March 2008

Two patients with Nelson's syndrome and one patient after bilateral adrenalectomy for Cushing's disease, without any evidence of Nelson's syndrome, were studied with respect to the effect of hydrocortisone, naloxone and valproic acid (a GABA transaminase inhibitor) on ACTH secretion. Hydrocortisone suppressed plasma ACTH concentrations to normal in the patient without Nelson's syndrome, but failed to do so in the two patients with Nelson's syndrome. Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelson's syndrome, but produced no change in the patient without Nelson's syndrome. Secretion of ACTH may thus be influenced by both opiate peptides and by gamma aminobutyric acid, as well as by the cortisol concentrations, these agents may act at different sites to inhibit ACTH release by the tumour.
ABNORMAL REGULATION OF PROLACTIN SECRETION AFTER SUCCESSFUL SURGERY FOR PROLACTIN‐SECRETING PITUITARY TUMOURS*
Authors: SCHLECHTE JANET A. , SHERMAN B. M.
Published: March 2008

Patients with prolactin‐secreting pituitary tumours have a diminished prolactin (PRL) response after administration of a variety of stimulatory agents, including thyrotrophin‐releasing hormone (TRH), chlorpromazine (CPZ) and insulin‐induced hypoglycaemia. We examined responses to these agents in sixty‐seven women with PRL‐secreting tumours before and after trans‐sphenoidal surgery. Twenty‐nine of the women were cured as denned by restoration of normal serum PRL concentrations and resumption of regular menses. One year following trans‐sphenoidal surgery, patients with normal PRL concentrations and regular menses had normal PRL responses to TRH, while the responses to CPZ and insulin hypoglycaemia were not improved. The reversible impairment of PRL response to TRH reflects suppressed function of normal PRL‐secreting cells, and the persistence of abnormal PRL responses to provocative stimuli after successful tumour removal may reflect some fundamental defect in the regulation of PRL secretion in patients with PRL‐secreting adenomas.

When growth hormone (GH) reserve after insulin hypoglycaemia was represented as the mean absolute increment above the basal concentration and compared with normal subjects, women with PRL‐secreting tumours had a diminished response that returned to normal after successful surgery. This reversible impairment of GH secretion is not adequately reflected by standard criteria for GH response and suggests that PRL may have a role in the regulation of GH secretion.