bluuebunny/crossref_metadata_2025 huggingface dataset:
RELATIONSHIP OF CHANGES IN SERUM CONCENTRATIONS OF PROLACTIN AND TESTOSTERONE DURING DOPAMINERGIC MODULATION IN MALES*
Authors: NAKAGAWA KOJI , OBARA TAKAO , MATSUBARA MIYAO , KUBO MITSUMASA
Published: March 2008

To evaluate the effect of PRL on the male pituitary‐gonadal system, serum concentrations of PRL, testosterone, LH and FSH were determined in healthy young men daily before, during, and after 3‐day oral administration of bromocriptine, metoclopramide or sulpiride. Bromocriptine (2.5 mg as a single dose) caused, concurrently with a marked suppression of serum PRL, a significant increase of serum testosterone and a transient decrease of serum LH. The changes of PRL and testosterone were negatively correlated. With metoclopramide (10 mg q.i.d.) serum PRL was increased and testosterone inversely decreased. There was no change in LH and FSH. Sulpiride (50 mg q.i.d.) evoked the elevation of serum PRL and LH, but no change in testosterone. A significant increase in serum concentration of testosterone was also observed in a patient with PRL‐producing pituitary tumour and four out of seven patients with acromegaly during bromocriptine treatment. These results suggest an inhibitory effect of PRL on testosterone secretion at the gonadal level, or direct dopaminergic stimulatory control of testosterone secretion.
hCGβ PRODUCING PINEAL CHORIOCARCINOMA
Authors: WASS J. A. H. , JONES A. E. , REES LESLEY H. , BESSER G. M.
Published: March 2008

A patient is described with tumours in the region of the pineal gland and anterior hypothalamus associated with high levels of hCGβ in the serum and cerebrospinal fluid (CSF). He presented aged 19, with hypopituitarism, but persistent secondary sexual characteristics. LH immunoreactivity in serum was due to the hCGβ which probably caused the elevated level of testosterone. Following cranial irradiation the tumour became undetectable and hCGβ was eradicated from the serum and CSF. The patient later died because of an intramedullary metastasis of choriocarcinoma in the cervical spinal cord.

The endocrine details of six previously reported intracranial neoplasms which have been shown to secrete hCGβ are reviewed. Only two of these involved the pineal region. Chorionic gonadotrophin production by this tumour enabled early detection of its recurrence. It is unclear how often precocious puberty is caused by tumours producing hCGβ, but patients presenting either with that problem or a pineal tumour should have circulating hCGβ measured.
DOSE‐RESPONSE RELATIONSHIPS IN A CYTOCHEMICAL SECTION BIOASSAY FOR THYROID STIMULATORS
Authors: NEYLAN D. , SMYTH P. P. A.
Published: March 2008

The thyroid stimulators TSH and thyroid stimulating immunoglobulins (TSI) have previously been distinguished in a cytochemical section bioassay (CBA) by the different times at which they caused maximum increase of lysosomal membrane permeability within guinea‐pig thyroid follicular cells. The present study demonstrates that the times at which maximum stimulation occurs in the assay depends not only on the type (TSH or TSI) but also on the concentration of the stimulator. At higher concentrations of stumulator earlier times of maximum stimulation were observed for both TSH and TSI. When both stimulators were simultaneously present in plasma at higher concentrations a single peak of stimulatory activity occurred. Neutralization studies using specific antisera revealed that the single peak represented a merging of TSH and TSI peaks. These findings explain the lack of parallelism to the standard curve seen at higher concentrations of TSH or TSI in the CBA. They emphasize the necessity of measuring plasma samples at a variety of dilutions in order to achieve parallelism and to avoid intra‐assay interference between TSH and TSI. When these conditions are observed CBA can be used to detect TSH and TSI with extreme sensitivity even when both are simultaneously present in plasma.
RAPID COMMUNICATION: SERUM IMMUNOREACTIVE MELATONIN IN BOYS WITH DELAYED PUBERTY
Authors: HAY H. N. COHENI. D. , ANNESLEY T. M. , BEASTALL G. H. , WALLACE A. M. , SPOONER R. , THOMSON J. A. , EASTWOLD P. , KLEE G. G.
Published: March 2008

Serum immunoreactive melatonin was measured in thirty‐three male subjects with delayed puberty, thirty of whom had simple (idiopathic) delayed puberty (SDP) and three of whom were GH deficient. The results were compared with a control population of twenty‐six subjects. Significantly elevated values of serum melatonin were demonstrated in both groups of abnormal subjects as compared with the control population (P < 0.0001). No significant fall of serum melatonin was noted in the subjects with simple pubertal delay prior to the onset of puberty. However, there was a significant fall of serum melatonin in these subjects between mid and late puberty (P < 0.025). The results suggest that whilst melatonin may inhibit puberty, a fall in serum levels is not essential for the commencement of puberty in man.
A COMPARISON OF THREE GLUCOCORTICOID SUPPRESSIVE REGIMES IN ADULTS WITH CONGENITAL ADRENAL HYPERPLASIA
Authors: And P. M. HORROCKS , LONDON D. R.
Published: March 2008

We have compared three glucocorticoids, hydrocortisone (HC) (20 mg mane & 10 mg nocte), cortisone acetate (CA) (25 mg mane & 12.5 mg nocte), dexamethasone (DXM) (0.5 mg mane & 0.25 mg nocte), for their effect on the biochemical control of adult patients with congenital adrenal hyperplasia (CAH). Twenty‐four‐hour profiles of plasma concentrations of ACTH, 17‐hydroxyprogesterone (170HP) and androstenedione (Δ4A), and 09.00 h dehydroepiandrosterone sulphate (DHAS) plasma concentrations were used to assess control. The patients were studied after 2 weeks on each glucocorticoid. The areas under the curves, the heights of the morning peaks of each hormone, the midnight concentrations, and the concentrations of hormones just before the evening dose were analysed. The results show that all the indices, except the midnight concentrations which were uniformally low, were significantly lower on DXM than on either HC or CA. There were no significant differences between HC and CA for any of the indices. The DHAS concentrations were low on all three glucocorticoids but again significantly lower on DXM.

DXM (0.5 mg mane & 0.25 mg nocte) is therefore, in the short term, a better suppressor of the pituitary‐adrenal axis in adults with CAH than either HC or CA, and in the dose used did not suppress ACTH to undetectable levels, nor the steroids to below levels found in normal subjects.
AMENORRHOEA AND FAILURE TO VIRILIZE IN A PATIENT WITH A TESTOSTERONE SECRETING GRANULOSA CELL TUMOUR
Authors: TAYLOR H. C. , VELASCO M. E. , FLORES S. G. , And G. BERG , BROWN T. R.
Published: March 2008

A 39‐year‐old woman presented with secondary amenorrhoea in the absence of galactorrhoea, hirsutism or virilization. Investigation revealed a strikingly elevated serum testosterone, dihydrotesterone, free testosterone and LH level. At laparotomy a large granulosa cell tumour was encountered and totally removed. Analysis of the tumour revealed 127 ng of testosterone/mg of tumour tissue. The testosterone was localized immunocytochemically to the granulosa cells, which demonstrated typical ultrastructural characteristics of oestrogen rather than androgen secreting tissue. A study of androgen binding and metabolism prior to tumour resection revealed a normal androgen receptor as evidenced by normal maximum binding, dissociation constant and nuclear uptake. Removal of the tumour resulted in a return to normal of all abnormalities. We conclude that granulosa cell tumours may rarely secrete large amounts of testosterone and that in this situation their ultrastructure is unchanged. Furthermore, absence of LH suppression or hirsutism in an amenorrhoeic patient does not dismiss the possibility of a significant androgensecreting tumour. In this situation, the failure to virilize may be due to a post‐nuclear translocational defect.
TRILOSTANE AND THE NORMAL HYPOTHALAMIC‐PITUITARY‐ADRENOCORTICAL AXIS
Authors: SEMPLE C. G. , THOMSON J. A , STARK A. N. , And M. McDONALD , BEASTALL G. H.
Published: March 2008

Trilostane has been used to treat Cushing's syndrome and other adrenocortical disorders. To investigate its effect on the normal adrenal gland, trilostane (initially 240 mg/day) was given to ten healthy men, the dose increasing at weekly intervals by 240 mg/day up to a final dose of 960 mg/day. The drug was well tolerated although one subject withdrew after the first week because of gastrointestinal side effects. Trilostane had no significant effect on aldosterone levels or blood pressure. The mean 24‐h urinary free cortisol excretion rose from 14.2 to 22.0 μmol/mol creatinine (P < 0.01) before and after trilostane 240 mg/day but did not rise thereafter. Early morning serum cortisol and plasma ACTH levels did not change on trilostane. The mean increment in serum cortisol after the i.v. injection of 0.25 mg of ACTH was reduced from 398 nmol/l before trilostane to 287 nmol/l on 240 mg/day and to 291 nmol/l on 960 mg/day (P± 0.01). Insulin‐induced hypoglycaemia while on 960 mg/day produced a maximum increment in serum cortisol of 361 < 118 nmol/l (mean ± SD) although one subject had a subnormal increment of 180 nmol/l (normal > 200 nmol/l). Plasma ACTH rose with hypoglycaemia in all cases. We conclude that trilostane has only a minor effect on the normal hypothalamic‐pituitary‐adrenocortical axis.
FERTILITY AFTER CHILDBIRTH: ADEQUACY OF POST‐PARTUM LUTEAL PHASES
Authors: McNEILLY A. S. , HOWIE P. W. , HOUSTON M. J. , And A. COOK , BOYLE H.
Published: March 2008

Normal ranges of urinary pregnanediol and total urinary oestrogen were determined from weekly estimations in twenty‐seven cycles from seven normally menstruating control women and compared with the levels in the cycles of twenty‐seven breast feeding and ten bottle feeding mothers. During lactation, the luteal phase pregnanediol levels were within normal limits in thirteen of forty‐nine (27%) cycles, the remainder of the luteal phases being deficient (31%) or absent (42%). The proportion of normal luteal phases remained low during first cycles after lactation in six of twenty‐three (26%) but rose to twenty‐four of thirty‐one (77%) in subsequent cycles. In bottle feeding mothers, the luteal phases of first post‐partum cycles were deficient in two often (20%) and absent in eight of ten (80%). In second post‐partum cycles, the majority of luteal phases were deficient (eight often, 80%) and it was not until third post‐partum cycles that seven of eight (88%) had luteal phase pregnanediol levels in the normal range. Cycles during lactation and first cycles after lactation had significantly lower mean urinary pregnanediol and total urinary oestrogen levels than both the control cycles and the later cycles after lactation. Similarly, first post‐partum cycles in bottle feeders had lower urinary pregnanediol and total urinary oestrogen levels than controls. This study shows an increased frequency of abnormal luteal phases during the early post‐partum menstrual cycles of both breast and bottle feeding mothers which may be associated with defective development of the follicle.
EFFECTS OF ORAL AND INTRAVENOUS TRH AND METOCLOPRAMIDE ON PRL AND TSH SECRETION IN WOMEN
Authors: And ANTTI KAUPPILA , YLIKORKALA OLAVI
Published: March 2008

Pituitary secretion of PRL and TSH is under the control of inhibitory dopaminergic and stimulatory TRH‐mediated mechanisms. To evaluate the relationships between these regulatory systems, ten healthy women were treated with oral TRH (20 mg twice daily), a dopamine blocking drug, metoclopramide (MC) (10 mg t.d.s.) or placebo for 1 week (from 8th to 14th cycle day). Serum concentrations of PRL, TSH, T3 and T4 were determined before, at the end, and 3 days after the treatments. In addition, PRL and TSH responses to i.v. TRH (200 μg) or MC (10 mg) were studied at the end of the oral treatments. Oral TRH treatment was accompanied by increases in basal T3 and T4 concentrations, no change in PRL, and a decrease in TSH 3 days after the end of treatment. Oral TRH did not modify the PRL response to i.v. MC while it eliminated the TSH response to i.v. MC, possibly because of elevated concentrations of thyroid hormones. Oral MC treatment raised the concentrations of PRL, T3 and T4, and also potentiated the PRL response to i.v. TRH, whereas the TSH response remained unaltered. These results demonstrate that dopaminergic and TRH‐mediated mechanisms are related in the control of PRL and TSH secretions, perhaps directly or through thyroid hormones.
VITAMIN D METABOLISM IN HYPERTHYROIDISM
Authors: MACFARLANE I. A. , MAWER E. B. , BERRY J. , HANN J.
Published: March 2008

The serum concentrations of 25‐hydroxycholecalciferol (25 OH D3), 24,25‐dihydroxycholecalciferol [24,25(OH)2D3] and 1,25‐dihydroxycholecalciferol [1,25(OH)2D3] were measured in twenty‐one patients with untreated hyperthyroidism. Compared with control subjects, 25 OH D3 concentrations were not altered, 24,25(OH)2D3 concentrations were increased, although not significantly and 1,25(OH)2D3 concentrations were decreased (P= 0.01). Following oral carbimazole therapy, 24,25(OH)2D3 concentrations fell (P<0.01), 1,25(OH)2D3 concentrations increased (P<0.01) and 25 OH D3 concentrations were unchanged. The altered 1,25(OH)2D3 and 24,25(OH)2D3 concentrations found in hyperthyroidism are probably due to the effects of thyroid hormone on bone and mineral metabolism. Increased serum calcium and phosphate concentrations with secondary hypoparathyroidism result in stimulation of the renal 24‐hydroxylase and suppression of the 1‐hydroxylase enzymes. In addition, serum 24,25(OH)2D3 concentrations were significantly correlated with serum triiodothyronine levels (T3) (r= 0.66, P<0.002) before treatment. This may indicate a direct stimulatory effect of T3 on 24‐hydroxylase activity. No relationship was found between serum 1,25(OH)2D3 concentrations before therapy and serum T3.
EVIDENCE FOR INDEPENDENT REGULATION OF HUMAN ERYTHROCYTE AND ADIPOCYTE INSULIN RECEPTORS
Authors: BENSON EDWARD A. , GALES‐BENSON PATRICE , ELLIOTT ROBERT B. , HOLDAWAY IAN M.
Published: March 2008

Specific binding of [125I]‐insulin was measured in erythrocytes and fat obtained at the time of mastectomy in twenty‐three subjects. There was a significant negative correlation between the level of specific binding to fat and fasting insulin concentration (r= 0.55, P<0.05, n= 23) suggesting down‐regulation of fat insulin receptors by insulin. Insulin binding to erythrocytes did not correlate with insulin level nor was there any relationship between insulin binding to erythrocytes and fat from the same subject. Thus while the erythrocyte insulin receptor may be of interest in its own right, it may not be subject to the normal regulatory influences seen in classical insulin target tissues. Insulin binding to erythrocytes may therefore be invalid as a model to study down‐regulation of insulin receptors.
TWO CASES OF LYMPHOMA OF THE PAROTID GLAND FOLLOWING ABLATIVE RADIOIODINE THERAPY FOR THYROID CARCINOMA
Authors: WISEMAN J. C. , HALES I. B. , JOASOO A.
Published: March 2008

Two adult patients are described in whom 131I therapy for thyroid carcinoma was followed by the development of non‐Hodgkin's lymphoma in salivary glands. Histologically one was lymphocytic and the other histiocytic. The total doses of 131I given were 27 GBq (675 mCi) and 14 GBq (350 mCi), lymphoma presenting 10 and 3 years respectively after the initial therapeutic dose of 131I. We suggest that the relationship is a causal one, because of the rarity of salivary gland lymphoma and the high dose of radiation to the salivary glands with this mode of therapy.
INTRANASAL LHRH AGONIST TREATMENT FOR INHIBITION OF OVULATION IN WOMEN: CLINICAL ASPECTS
Authors: BERGQUIST CHRISTER , NILLIUS SVEN JOHAN , WIDE LEIF
Published: March 2008

Daily intranasal administration of the potent stimulatory LHRH analogue D‐Ser(TBU)6‐EA10‐LHRH was given to fifty healthy women for 3 months. Twenty‐six women received 400 μg LHRH agonist/day and twenty‐four women received 600 μg/day. Inhibition of ovulation occurred during 147 of the 150 treatment months. The three presumptively ovulatory cycles were probably the result of initial technical problems with the nasal spray. No pregnancies occurred. Reactivation of corpus luteum with slightly raised progesterone levels in serum at initiation of treatment was observed in six women. During 20 months of treatment the serum progesterone levels were slightly raised, indicating luteinization of follicles or defect luteal phases. Most of the women had menstrual‐like bleeding during treatment. Seventeen volunteers had regular bleeding and twenty‐three women had oligomenorrhoea. No dysfunctional uterine bleeding occurred, but three women reported spotting. The remaining ten women had amenorrhoea during treatment without any symptoms of oestrogen deficiency. After discontinuation of treatment the women regained ovulatory menstrual cycles after 31 days on average. The treatment was very well accepted by all the women.
THE DECREASED BASAL AND STIMULATED PROLACTIN LEVELS IN ISOLATED GONADOTROPHIN DEFICIENCY: A CONSEQUENCE OF THE LOW OESTROGEN STATE
Authors: SPITZ I. M. , ZYLBER‐HARAN E. A. , TRESTIAN S. , DICKSTEIN Y. , PALTI Z. , SCHENKER J. G.
Published: March 2008

Prolactin secretion has been evaluated in seven male and six female patients with isolated gonadotrophin deficiency (IGD). The subjects were challenged with the dopaminergic antagonist, metoclopramide (10 mg) and TRH (200 μg) before, during and after cessation of hormonal treatment. Five females received three consecutive 21‐day courses of ethinyl oestradiol (0·1 mg daily) at monthly intervals and the remaining subject conjugated oestrogens (Premarin 0·625 mg daily) according to a similar protocol. Treatment of the males with hCG (pregnyl) 5000 iu twice weekly led to a rise in oestradiol and testosterone levels. Two males were receiving pergonal (human menopausal gonadotrophin) in addition. In the untreated state in both males and females, basal oestradiol and PRL levels were decreased as were the PRL responses to metoclopramide and TRH as compared with normal controls. During treatment in both groups, there was an increase in basal PRL levels as well as PRL response to the two stimuli, which became indistinguishable from the controls. Cessation of treatment was associated with a rapid decrease in basal PRL levels and PRL elevation following metoclopramide and TRH. In contrast to the effect of hCG, the administration of two non‐aromatizable androgens (mesterolone and fluoxymesterone) had no effect on basal and TRH‐induced PRL secretion. The administration of clomiphene citrate during hCG treatment in one male IGD patient produced a decrease in the basal and stimulated PRL response.

It is concluded that the low basal PRL levels and impaired PRL responses to stimulation are not an inherent component of the syndrome of IGD, but a consequence of the abnormal steroid milieu.
INVESTIGATION OF URINARY STEROID PROFILES AS A DIAGNOSTIC METHOD IN CUSHING'S SYNDROME
Authors: PHILLIPOU GEORGE
Published: March 2008

Patients with Cushing's syndrome may be discriminated from normal subjects on the basis of their respective neutral urinary steroid profile. In the former group, evidence is presented that lowered levels of T3 secondary to hypercortisolism, decrease the liver enzymes associated with 5α‐ reductase and 11β‐hydroxy steroid dehydrogenase activity. As a result the metabolism of cortisol and androstenedione in Cushing's syndrome yields an unique pattern dominated by 5β and 11β‐hydroxy steroid metabolites.
CONTROL OF SECRETION OF PARATHYROID HORMONE IN SECONDARY HYPERPARATHYROIDISM
Authors: ADAMI S. , MUIRHEAD N. , MANNING R. M. , GLEED J. H. , PAPAPOULOS S. E. , SANDLER L. M. , CATTO G. R. D. , O'RIORDAN J. L. H.
Published: March 2008

The response of the parathyroids to an infusion of calcium has been studied in patients with secondary hyperparathyroidism due to either vitamin D deficiency or to chronic renal failure. Two specific homologous immunoradiometric assays for human parathyroid hormone (PTH) have been used to assess the response, one specific for the amino‐terminus (N‐PTH), the other specific for the carboxy‐terminus (C‐PTH) of the molecule.

In both the vitamin D deficient and the uraemic patients, in response to a 4 mg/kg/h infusion of calcium generally for 4 h, suppression of N‐PTH was similar, falling to around 20–30% of the initial value. In the uraemic subjects, the degree of suppression was inversely related to the initial plasma calcium (r= 0·9, P< 0·001). Measured with the C‐PTH assay, the response was generally less, particularly in the uraemic subjects in whom it was often preceded by an initial rise in C‐PTH.

In both groups of subjects, suppression of N‐PTH began as soon as the plasma calcium began to rise and before hypercalcaemia was produced. At the end of the infusion the concentration of N‐PTH rose quickly, although the plasma calcium was still high. In four uraemic subjects the rate of infusion of calcium was reduced after 1–1·5 h to limit the rise in plasma calcium. As the calcium approached a plateau, the concentration of N‐PTH was found to rise again.

These results indicate the importance of using PTH assays of well defined specificity to evaluate autonomy, and show that the degree of suppression achieved is dependent both on renal function and basal plasma calcium. In addition, these observations suggest that the direction and rate of change of plasma calcium are important in the control of secretion of parathyroid hormone.
ANTIGENICITY OF HUMAN CHORIONIC GONADOTROPHIN PREPARATIONS IN MEN
Authors: NIESCHLAG E. , BERNITZ S. , TÖPERT M.
Published: March 2008

The antigenicity of HCG was tested in twenty‐three young healthy men receiving two different HCG preparations (A and B). Each subject received 5000 i.u. HCG intramuscularly daily for three consecutive days, followed by another course, 3 weeks later, of 5000 i.u. HCG injections daily for 3 days. Two of the fifteen subjects treated with preparation A developed HCG antibodies in response to the HCG injections.

The results show that although HCG is of human origin and also occurs normally in men, it may induce antibody formation even after brief treatment.
TREATMENT OF POST MENOPAUSAL OSTEOPOROSIS. A CONTROLLED THERAPEUTIC TRIAL COMPARING OESTROGEN/GESTAGEN, 1,25‐DIHYDROXY‐VITAMIN D3 AND CALCIUM
Authors: JENSEN G. FINN , CHRISTIANSEN C. , TRANSBØL I.
Published: March 2008

A controlled therapeutic trial on seventy‐four 70‐year‐old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis. The bone mineral content (BMC) was measured by 125I‐photonabsorptiometry at two sites in the distal part of the forearms, where the trabecular/cortical ratio is 0·25 and 1·5, respectively. Radiographs were done on the right hand to measure the metacarpal bone mass (cortical area/total area = CA/TA).

After observing the spontaneous course of bone loss for 6 months the participants were allocated at random to 12 months’treatment with 1,25‐dihydroxycholecalciferol [1,25(OH)2D3] and oestrogen/gestagen, alone or in combination, and calcium. The groups treated with oestrogen/gestagen [with or without 1,25(OH)2D3] showed a highly significant increase in BMC. In contrast bone mineral remained unchanged or decreased in both the calcium and the 1,25(OH)2D3 groups with a tendency towards more pronounced negative bone balance in the 1,25‐(OH)2D3 group.

Seven out of nineteen patients on 1,25(OH)2D3 developed hypercalcaemia, which necessitated a reduction in dosage. It is concluded that the new vitamin D metabolite, 1,25(OH)2 D3, given in clinically acceptable doses, is without value in the treatment of post menopausal osteoporosis.
IMMUNOLOGICAL DISTURBANCES IN TOXIC MULTINODULAR GOITRE AND ACTIVE GRAVES’DISEASE
Authors: KIY Y. , REZKALLAH‐IWASSO M. T. , PERAÇOLI M. T. S. , MOTA N. G. S.
Published: March 2008

Cell‐mediated and humoral immunity were studied in seventeen patients with toxic multinodular goitre, ten with active Graves’disease and fourteen healthy controls. The study included determination of sheep erythrocyte and complement rosette‐forming cells in the peripheral blood, immunoglobulin levels, titres of microsomal antibodies and migration inhibition test using thyroid extract and phytohaemagglutinin. When compared with controls the patients showed a positive response to thyroid antigen in the leucocyte migration inhibition test. Microsomal antibodies were detected in seven out of ten active Graves’disease patients against two out of seventeen of those with toxic multinodular goitre. Significantly increased IgG and IgA and decreased IgM levels were found only in the toxic multinodular group. These data provide further evidence for immunological disturbances in toxic multinodular goitre.
RAISED PLASMA OESTROGENS IN INFERTILE MEN WITH ELEVATED LEVELS OF FSH
Authors: WU F. C. W. , SWANSTON I. A. , BAIRD D. T.
Published: March 2008

In twenty oligospermic or azoospermic patients with elevated plasma FSH, the mean concentrations of plasma oestrone sulphate (843 ± 233 pg/ml), oestrone (54 ± 10±4 pg/ml) and oestradiol (46±6 ± 12±6 pg/ml) were found to be significantly higher than in twenty‐one normal fertile men of comparable age (593 ± 220 pg/ml, 40±6 ± 8±8 pg/ml and 33±1 ± 10±9 pg/ml respectively). SHBG binding capacity was elevated in the infertile group (infertile 3±35 ± 0±82 × 10−8 M/l v. normal 2±76 ± 0±89 × 10−8 M/l) but the total plasma testosterone concentrations were comparable (infertile 5435 ± 1578 pg/ml v. normal 5046 ± 1102 pg/ml). Evidence was cited to support the view that Sertoli cells, in response to an unphysiological FSH stimulation, are a likely source of excessive oestrogen production. The possible significance of increased intra‐testicular and circulating oestrogen in the altered state of testicular steroidogenic function in men with primary seminiferous tubular defects was discussed.
THE INVOLVEMENT OF THE PENTOSE SHUNT IN THYROID METABOLISM AFTER STIMULATION WITH TSH OR WITH IMMUNOGLOBULINS FROM PATIENTS WITH THYROID DISEASE. II. THE REOXIDATION OF NADPH AND STIMULATION OF HORMONE SYNTHESIS
Authors: DREXHAGE H. A. , HAMMOND LINDA J. , BITENSKY LUCILLE , CHAYEN J. , BOTTAZZO G. F. , DONIACH DEBORAH
Published: March 2008

Reducing equivalents derived from the tissue re‐oxidation of NADPH (NADPH‐diaphorase) have been implicated in the peroxidation that is involved in the organification of iodine in the production of thyroid hormones. Immunoglobulin (Ig) fractions from patients with thyroid diseases and from normal controls, in a standard dose of 125 μg/ml and 0±3 μ/ml thyrotrophin (TSH) were incubated with segments of guinea‐pig thyroid gland maintained in vitro. A quantitative cytochemical study was made on how these fractions influenced the enzyme activity. A good correlation was found between the ability of such Ig fractions to stimulate the NADPH‐diaphorase activity and (1) the degree of hyperthyroidism in the patients and (2) the amount of T3 secreted by the thyroid segments in vitro.
HISTIDYL‐PROLINE DIKETOPIPERAZINE SUPPRESSES PROLACTIN SECRETION IN HUMAN PITUITARY TUMOUR CELL CULTURES
Authors: MELMED S. , CARLSON H. E. , HERSHMAN J. M.
Published: March 2008

Because histidyl‐proline diketopiperazine (HPD), a metabolite of TRH, has been shown to suppress prolactin (PRL) release by rat pituitary tumour cells, human pituitary tumour cells were exposed to this compound. Monolayer cell cultures were initiated from pituitary tissue removed by transsphenoidal surgery from two patients with prolactin‐secreting microadenomas. Tumour fragments were mechanically dispersed; cells were seeded into multiwell plates and incubated in Ham's F‐10 medium enriched with fetal calf serum (20%). HPD (7±5 ng/ml) suppressed PRL release by both tumour cell cultures. Theophylline reversed the inhibition of PRL release induced by HPD. The data raise the possibility that HPD may act as an endogenous prolactin‐inhibiting factor in man.
AN IMPROVED METHOD FOR THE RADIOIMMUNOASSAY OF FREE‐THYROXINE IN SERUM DIALYSATES
Authors: GILES A. F
Published: March 2008

A convenient, sensitive radioimmunoassay of free thyroxine in serum dialysates is described. The method utilizes a solid phase separation system (pre‐formed double antibody) and a relatively short incubation period (220 min) with a staggered addition of tracer. Blanks were low and consistent. The normal range for non‐pregnant euthyroid samples (n= 59) was 11–23 pmol/1. Third trimester pregnancy samples were mostly within the normal range but at the lower end. Patients on T4 replacement showed a much wider variation in free T4 levels with many samples in the hyperthyroid region. Some hypothyroid samples had undetectable free T4 levels and hyperthyroid samples were frequently greater than 80 pmol/l.
NOCTURNAL NATRIURESIS IN HYPERTHYROIDISM
Authors: BELL G. M. , SAWERS J. S. A. , TOFT A. D. , DOIG A.
Published: March 2008

We measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P < 0·05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24‐h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P < 0·005) and urinary flow (P < 0·05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0·73, P < 0·01). Twenty‐four hour urinary calcium output was significantly greater (P < 0·02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.
THYROID HORMONES AND THE REGULATION OF THYROID FUNCTION IN MEN WITH COELIAC DISEASE
Authors: FARTHING M. J. G. , REES LESLEY H. , EDWARDS C. R. W. , BYFIELD P. G. H. , HIMSWORTH R. L. , DAWSON A. M.
Published: March 2008

A specific pattern of thyroid hormone abnormalities was observed in twenty‐seven men with coeliac disease which differed from that observed in patients with non‐thyroidal illness (NTI). Serum free thyroxine (FT4) was reduced, but increased after gluten was withdrawn from the diet and jejunal morphology improved. Total T4 (TT4), total triodothyronine (TT3), free triiodothyronine (FT3) and reverse T3 (rT3) levels were unchanged, unlike the findings in nineteen men with Crohn's disease when TT3 fell, rT3 tended to rise but TT4, FT4 and FT3 levels were normal, except FT4 was significantly higher in a subgroup of patients who were more severely ill. The thyroid hormone changes in Crohn's disease are those expected in NTI. Basal serum thyrotrophin (TSH) was normal in all but one of the patients with coeliac disease but 45% of untreated coeliacs had exaggerated responses of TSH to thyrotrophin releasing hormone, an observation which cannot be explained as a feature of NTI. These changes in thyroid hormones in coeliac disease could not be attributed to abnormalities of thyroxine‐binding globulin or thyroxine‐binding prealbumin, and thyroid autoantibodies were not detected in these patients. Hence, different patterns of thyroid hormone abnormalities can occur in different diseases of the same organ in patients of equivalent nutritional status. Circulating gluten peptides may be involved in the hypothalamic‐pituitary disturbance of coeliac disease.
PROPRANOLOL VERSUS CARBIMAZOLE AS THE SOLE TREATMENT FOR THYROTOXICOSIS. A CONSIDERATION OF CIRCULATING THYROID HORMONE LEVELS AND TISSUE THYROID FUNCTION
Authors: O'MALLEY B. P. , ABBOTT R. J. , BARNETT D. B. , NORTHOVER B. J. , ROSENTHAL F. D.
Published: March 2008

Serum triiodothyronine (T3), thyroxine (T4) and reverse triiodothyronine (rT3) levels were measured in seven hyperthyroid patients during 2 months of propranolol therapy and subsequently during 2 months of carbimazole. In keeping with previous observations, there was a slight fall in serum T3 level accompanied by elevations of serum T4 and rT3 during propranolol. As a consequence of carbimazole treatment, serum T3 and T4 fell markedly and rT3 was undetectable.

Three parameters of tissue thyroid function, glucagon stimulated cyclic AMP levels, systolic time intervals (STI) and visual evoked response (VER) were monitored in parallel to the peripheral hormone changes. There was no real improvement in tissue function during propranolol treatment. During carbimazole administration there was significant improvement in STI and VER as compared to pre‐treatment values, and a significant improvement in glucagon stimulated cyclic AMP levels as compared to the levels attained after 2 months of propranolol therapy.

Thus, the small fall in serum T3 produced by propranolol does not result in improved tissue thyroid function in thyrotoxicosis, whereas carbimazole brings about a dramatic improvement in peripheral hormone levels, and tissue function alike. Moreover, propranolol therapy can be hazardous in thyrotoxicosis, two patients with no previous history of heart disease developing left ventricular failure soon after its commencement.
THE SIGNIFICANCE OF THE PORTAL INSULIN SECRETION IN INSULIN DEPENDENT PATIENTS WITH RESIDUAL β‐CELL FUNCTION: A SAFEGUARD AGAINST HORMONAL AND METABOLIC DERANGEMENT
Authors: MADSBAD S. , FABER O. K. , KURTZ A. , KRARUP T. , REGEUR L. , TRONIER B. , ØRSKOV H. , BINDER C. , ALBERTI K. G. M. M.
Published: March 2008

Seven insulin‐dependent patients without β‐cell function and eight with residual β‐cell function (evaluated by C‐peptide values 6 min after 1 mg of glucagon i.v.; mean 0·23, range 0·16–0·43 nmol/1) were studied during 12 h of insulin deprivation following maintenance of near‐normoglycaemia with intravenous insulin infusion. Significant differences between the two groups were found in blood glucose and 3‐hydroxybutyrate already after 3 and 4 h respectively. After 12 h the mean blood glucose concentration had reached 17·2 · SEM 1·3 mmol/l in the first group compared with 8·8 ± 1·4 mmol/l in the second group (P < 0·01) while 3‐hydroxybutyrate concentrations rose to 5·5 ± 0·5 mmol/l and 1·4±0·3 mmol/l in the two groups respectively (P<0·01).

The free insulin concentration in plasma was three‐fold higher in the group without β‐cell function just before discontinuing the insulin infusion as compared with the group with β‐cell function (P<0·05). During the first 10 h of insulin deprivation no significant difference in free insulin concentration was found between the two groups. However, after 12 h of insulin deprivation all the patients with residual β‐cell function had measurable amounts of free insulin in peripheral blood, whereas in the C‐peptide negative group only the three patients with the highest amount of insulin binding antibodies had measurable free insulin concentrations.

Glucagon concentrations although raised after 5 h of insulin deprivation were similar in the two groups.

Mean growth hormone concentrations were higher throughout the study in the C‐peptide negative patients, while cortisol levels were significantly higher (P<0·05) after 6 h. For all the patients final cortisol concentrations were directly correlated to final blood glucose (r=0·45, P<0·05) and final blood 3‐hydroxybutyrate (r=0·67, P<0·02).

The present study supports the metabolic importance of portal insulin supply to the liver and thus of residual β‐cell function. The data emphasizes the importance of the often minimal endogenous insulin reserve preserved in some insulin dependent diabetics in protection against rapid development of ketoacidosis both directly and through effects on cortisol and growth hormone secretion.
THE INTERRELATIONSHIPS BETWEEN PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING DOPAMINERGIC BLOCKAGE IN PATIENTS WITH MILD HYPERPROLACTINAEMIA WITHOUT ANY DEMONSTRABLE PITUITARY TUMOUR
Authors: SPITZ J. M. , HAAS M. , TRESTIAN S. , ZYLBER‐HARAN E. , SHILO S.
Published: March 2008

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 μg) and LHRH (100 μg). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non‐responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean±SD basal PRL levels were 68·5 ± 29·9 ng/ml in Group I and not different in Group II (40·6±12·0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2·4±0·7 μU/ml to a peak of 5·9±2·7 μU/ml (P<0·005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide.

In Group II females, PRL responsiveness to metoclopramide was associated with TSH non‐responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.
HYDROXY‐INDOLE‐O‐METHYLTRANSFERASE ACTIVITY IN HUMAN PINEALS: A COMPARISON OF CONTROLS AND SCHIZOPHRENICS
Authors: OWEN F. , FERRIER I. N. , POULTER M. , CROW T. J.
Published: March 2008

The activity of hydroxy‐indole‐o‐methyltransferase (HIOMT) has been assayed in pineal glands from fifteen controls and twenty‐three schizophrenics. There was no significant difference between the two groups in HIOMT activity and no significant effect of age, sex or neuroleptic treatment on the activity of the enzyme. A diurnal rhythm was not discernible in HIOMT activity and it is suggested that this may be the result of terminal illness. It is concluded that HIOMT activity in pineals of schizophrenics is unlikely to differ from controls.
GONADOTROPHIN RELEASING HORMONE PROVOKES PROLACTIN RELEASE IN HYPERGONADOTROPHIC HYPOGONADAL WOMEN: A RESPONSE NOT ALTERED BY DEXAMETHASONE
Authors: GEORGITIS W. J. , TREECE G. L. , HOFELDT F. D.
Published: March 2008

The prolactin response to 100 μg of intravenous gonadotrophin releasing hormone was studied in seven hypergonadotrophic hypogonadal and four eugonadal women. Prolactin rose from a mean basal level of 7·3 ± 1·6 ng/ml to a mean peak level of 20·8 ± 5·2 ng/ml in the hypogonadal women, and did not change significantly from a mean basal level of 7·7 ± 1·2 ng/ml in the eugonadal women. Dexamethasone suppression did not alter the gonadotrophin or prolactin response to GnRH.

Hypergonadotrophic hypogonadal women, like some patients with acromegaly, anorexia nervosa. and anovulatory disorders, show an augmented release of prolactin after GnRH administration.
THE EVIDENCE FOR THE REGULATORY ROLE OF ENDOGENOUS GIP AS A GLUCOSE DEPENDENT INSULINOTROPIC HORMONE IN PATIENTS WITH DUODENAL ULCER
Authors: TAKEMURA J. , SEINO Y. , YAMAMURA T. , YOSHIYA K. , ISHIKAWA Y. , ITOH N. , IMURA H.
Published: March 2008

In order to investigate the mechanism of GIP secretion and the role of endogenous GIP in the enteroinsular axis in duodenal ulcer patients, we have compared plasma GIP, insulin, and blood glucose responses to oral glucose ingestion in 10 duodenal ulcer patients, 5 patients with total gastrectomy, and 20 normal subjects. The mean basal level of plasma GIP in totally gastrectomized patients was significantly higher than in normal subjects, while in duodenal ulcer patients the value was not different from that of controls. Plasma GIP and insulin responses to oral glucose loading were significantly higher than normal in both groups. The degree of exaggerated plasma GIP and insulin secretions was more prominent and earlier in totally gastrectomized patients than in duodenal ulcer patients, and was positively correlated with the blood glucose increase during glucose ingestion. On the other hand, no significant change in GIP secretion during insulin‐induced hypoglycaemia was observed in normal subjects, duodenal ulcer patients, or patients with selective proximal vagotomy. These findings indicate that the exaggerated GIP response to oral glucose in duodenal ulcer patients may be due not to increased vagal tone, but to more rapid incoming load. We found also that the hypersecretion of GIP induced by glucose ingestion in patients with duodenal ulcer and total gastrectomy may be responsible for the hyperfunction of the enteroinsular axis in these patients.
THE INTERACTION OF HUMAN ENDOMETRIAL AND MYOMETRIAL STEROID RECEPTORS WITH DANAZOL
Authors: JENKIN G. , COOKSON C. I. , THORBURN G. D.
Published: March 2008

The affinity of danazol for oestrogen, androgen and progesterone receptors in human endometrium and myometrium was determined, to study the mechanism of action of this drug in the treatment of endometriosis.

The ability of danazol to combine with each of the three types of receptor was similar in both endometrium and myometrium. The capacity of danazol to compete with oestradiol‐17β for the oestrogen receptor was very low (1·72 ± 0·48 ± 10−3% cross reaction, mean ± SEM) and danazol, at the maximum concentration used, was unable to saturate the receptor; but danazol's ability to compete with progesterone for its receptor was considerably higher (8·41 ± 1·65% using progesterone, 1·95 ± 0·41% using R5020) and was saturable. Danazol was also able to displace dihydrotestosterone from the cytosol androgen receptor (6·29·1±82% cross reaction). The association constant of oestradiol for the endometrial and myometrial oestrogen receptors was 2·19 ± 109M‐1 and 7·45 ± 109M‐1 respectively, while that of progesterone and dihydrotestosterone for their receptors was similar in endometrium and myometrium (mean 0·25 ± 0·06 ± 109 M‐1 and 3·62·1±67·109 M‐1 respectively). Using R5020, the association constant for the myometrial progesterone receptor was 2·50 ± 0·73 ± 109 M−1. We conclude that, in view of the high circulating levels of danazol present in patients being treated for endometriosis, it is possible that danazol may bind to, and partly saturate, endometrial and myometrial oestrogen, progesterone and androgen receptors during treatment. An explanation may thus be provided for some of the diverse actions of this drug.
GRAVES' IMMUNOGLOBULINS PROTECT THE HUMAN TSH RECEPTOR: FURTHER EVIDENCE FOR TSH RECEPTOR ANTIBODIES IN GRAVES' DISEASE
Authors: DAVIES T. F. , PLATZER M.
Published: March 2008

We have investigated whether membrane‐bound TSH and Graves' immunoglobulins (Ig) were able to inhibit the action of the disulphide‐reducing agent dithiothreitol (DTT) which reduced the binding of 125I‐bTSH to thyroid membranes. Human thyroid (20000 g fraction) was incubated with increasing concentrations of cold bTSH, washed and resuspended in 10 mmol/1 DTT for 60 min at 37°C. After the DTT was removed, 70–80% of the receptor‐bound bTSH dissociated with 2 mol/l NaCl. In the absence of cold bTSH, 80% of the binding of receptor‐purified 125I‐bTSH was inhibited after membrane exposure to DTT but in the presence of bTSH‐occupied receptor sites there was a dose related protection of the receptors, with 100% protection following incubation with 30 mU/ml bTSH.

Like bTSH, immunoglobulin fractions from Graves' sera caused a time‐dependent reduction in 125I‐bTSH binding‐inhibition after incubation and washing of thyroid membranes prior to ligand binding. Approximately 25–40% of this reduction was reversible by exposure to 2 mol/l NaCl. After pre‐binding normal Ig to thyroid membranes, and subsequent incubation with DTT, there was no protection of TSH receptors. However, each of the Graves' Ig examined (n= 4) was able to provide protection of the TSH receptor binding sites in proportion to their derived TSH receptor occupancy.

Receptor‐bound bTSH was, therefore, able to protect the human TSH binding site from disulphide reduction. In addition, Graves' Ig, but not normal Ig, contained antibodies which were able to protect the TSH receptor binding sites in the same way as bTSH. These data provided evidence that Graves' Ig, but not normal Ig, contained antibodies which, when bound to the TSH receptor, appeared to affect the configuration of the TSH receptor in the same way as the binding of bTSH and protected the receptor from reduction by DTT.

This evidence was consistent with graves' sera containing antibodies directed towards the TSH receptor binding site.
OUTCOME OF PATIENTS WITH GRAVES' DISEASE AFTER LONG‐TERM MEDICAL TREATMENT GUIDED BY TRIIODOTHYRONINE (T3) SUPPRESSION TEST
Authors: YAMAMOTO M. , TOTSUKA Y. , KOJIMA I. , YAMASHITA N. , TOGAWA K. , SAWAKI N. , OGATA E.
Published: March 2008

The value of the T3 suppressed 20‐min uptake test for the prediction of post‐treatment outcome was studied in 193 unselected patients with GRAVES' disease treated with thionamide drugs and T3. One hundred and twenty‐nine of 193 patients were studied previously and followed thereafter (Group A). Sixty‐four were newly treated patients: thirty‐three (Group B) were treated at the same hospital as Group A; thirty‐one (Group C) were treated at another hospital.

In total, 126 patients out of 193 satisfied our criteria for suppression (total suppression rate, 65%). The suppression rate for new patients (55% in Group B, 52% in Group C) was similar to that for Group A in 1977 (49%) after comparable duration of treatment. The suppression rate for Group A increased with prolongation of the treatment period (49% in 1977 and 71% in 1981).

As to the time course of suppression, it was observed that about two‐thirds of the suppressed patients satisfied the criteria for suppression within 3 years of starting treatment. The number of suppressed patients per year decreased thereafter as the treatment periods increased. However, the yearly suppression rate did not decrease with time. The time course of suppression in each patient could not be predicted from the results of initial thyroid function tests.

The overall remission rate among the 120 suppressed patients followed for 1–13 (mean, 4) years was 96%, which was almost equal to the value obtained in Group A in 1977 (95%) with the average follow‐up period of 2 years. Among the 46 patients in Group A followed for 5–13 (mean, 7) years, no increase in relapse was observed with prolonged follow‐up periods. Examination on the relationship between the duration of treatment and the post‐treatment outcome