bluuebunny/crossref_metadata_2025 huggingface dataset:
OESTROGEN MODULATION OF GONADOTROPHIN AND PROLACTIN RELEASE IN WOMEN WITH ANOVULATION AND THEIR RESPONSES TO CLOMIPHENE
Authors: KANDEEL F. R. , BUTT W. R. , RUDD B. T. , LYNCH S. S. , LONDON D. R. , EDWARDS R. LOGAN
Published: March 2008

An LHRH test was performed before and at both 44 and 92 h after the administration of 2.5 mg oestradiol benzoate in eleven patients with hyperprolactinaemia, eight with idiopathic secondary amenorrhoea and seven with oligomenorrhoea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4–6). Mean basal concentrations of oestradiol in each group of patients and oestrone in those with hyperprolactinaemia were significantly lower than in the normal subjects. The mean concentration of prolactin in women with secondary amenorrhoea remained lower than in the normal women throughout the tests (P < 0.05). The LH and FSH responses to LHRH before oestrogen in patients with hyperprolactinaemia and of FSH in those with secondary amenorrhoea, were greater than in the normal subjects (P < 0.001). After oestrogen treatment the responses were similar in all groups except in those with oligomenorrhoea where LH and FSH responses at 44 h (P < 0.05 and P < 0.01 respectively) and LH responses at 92 h (P < 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification) but the amplification at 92 h and at 44 h compared to the pre‐treatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinaemic group of patients there was a negative correlation between the basal prolactin concentration and the gonadotrophin amplifications at 92 h (P < 0.01), and a positive correlation between the basal oestrone levels and the amplifications at 92 h (P < 0.01). The results of the oestrogen amplification test in eleven of the non‐hyperprolactinaemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal oestrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotrophin (HCG) as well as clomiphene to ovulate. The other three showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinaemic patients to clomiphene were poor and there was a negative correlation between prolactin concentration and oestrogen production (P < 0.01). All ten hyperprolactinaemic patients treated with bromocriptine ovulated and eight conceived. The oestrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non‐hyperprolactinaemic anovular women.
RAPID CONVERSION OF CARBIMAZOLE TO METHIMAZOLE IN SERUM; EVIDENCE FOR AN ENZYMATIC MECHANISM
Authors: NAKASHIMA TOSHIRO , TAUROG ALVIN
Published: March 2008

Carbimazole (CBZ) is one of the major drugs currently used for the treatment of Graves' disease. It is a carbethoxy derivative of methimazole (MMI), originally developed in the hope of obtaining a longer acting drug than methimazole. In the present study we have demonstrated that carbimazole is rapidly converted to methimazole in vitro by serum from rats and humans, and we have obtained evidence that this conversion is enzymatic. Experiments with [35S] CBZ in rats showed that the drug is so rapidly transformed to MMI after i.v. injection (within 3 min) that very little of the unchanged drug would be expected to reach the thyroid gland. The antithyroid action of CBZ in rats, therefore, can be ascribed entirely to the MMI to which it is rapidly converted. Although no experiments were performed with human subjects in vivo, the very rapid conversion of CBZ to MMI by human serum in vitro suggests that the antithyroid action of CBZ in humans can also be attributed to MMI. The original expectation of a longer acting drug has, therefore, not been met by CBZ. On the basis of the studies reported here there appears to be no advantage in using CBZ in preference to MMI for the treatment of Graves' disease.

Although the in vivo action of CBZ must be attributed to its rapid conversion to MMI, the drug does possess inherent antithyroid activity. This was shown in the present study by the finding that CBZ is as potent as MMI in blocking thyroid peroxidase‐catalysed iodination of thyroglobulin.
MODE OF ACTION OF CARBIMAZOLE IN GRAVES' DISEASE
Authors: WISE P. H. , MARION M. , PAIN R.
Published: March 2008

In a series of hyperthyroid subjects treated with a high dose ‘block‐replace’ regime, mean thyroidal technetium uptake was shown to fall progressively over an 18 month period. Furthermore, sub‐total inhibition of hormone biosynthesis could be demonstrated, without evidence of proportionate inhibition of organification, the regression of radio‐iodine on technetium thyroid uptake showing similar slopes in euthyroid, treated and untreated hyperthyroid subjects. Together with the reported differential in remission rates between propranolol and anti‐thyroid drugs, it is concluded that carbimazole does not act solely by inhibiting intrathyroid hormonogenesis, but more definitively by affecting thyroid hyperstimulation at a prebiosynthetic level.

The inability to demonstrate normal suppressibility of trapping in any subject in the present series despite extended therapy with a ‘block‐replace’ regime, further suggests that current concepts of ‘suppressibility’ are invalid, the progressive fall in technetium uptake being unlikely to represent spontaneous restoration of a normal pituitary‐thyroid axis, but rather a direct influence of prolonged therapy with anti‐thyroid drugs on the natural history of the disease.
SEX HORMONE BINDING GLOBULIN CAPACITY AS AN INDEX OF OESTROGENICITY OR ANDROGENICITY IN WOMEN ON ORAL CONTRACEPTIVE STEROIDS
Authors: MAKHZANCY M. N. EL , WYNN V. , LAWRENCE DAPHNE M.
Published: March 2008

Plasma sex hormone binding globulin capacity (SHBC) measurements were evaluated in 125 women with a pre‐treatment mean value of 41 ± 17 nmol/l SHBG and during 3 to 36 cycles of either combination oestrogen and progestagen oral contraceptives (OC) or low progestagen‘mini’pills. An oestrogenic effect or significant elevation of SHBC was noted on combination OC or ethiriyl oestradiol with megestrol acetate, comparable with pregnancy levels (305 t 47 nmol/l SHBC or Volidan), whilst megestrol acetate alone (500 μg) caused a smaller but still significant rise of SHBG. Combination of ethinyl oestradiol with norethisterone acetate (Minovlar Loestrin) produced increased SHBG but ethinyl oestradiol combined with d‐norgestrel (Ovranette) caused no change in mean SHBG. An androgenic effect or significant lowering of mean SHBG to 24 ± 11 nmol/l in women on dl‐norgestrel (75 μg) and a decrease of mean SHBG on norethisterone (350 μg) daily indicated that these 19‐norderivatives are contraindicated in women with low pre‐treatment levels of SHBG or any clinical manifestation or history of androgenic hyperactivity. Combined OC preparations causing some elevation of SHBG might be preferable. Conversely women with a high pre‐treatment SHBG level might be more suited to combination OC with d‐norgestrel or the 19‐norprogestagen‘mini’pills. The characteristic response to SHBC for the group of oral contraceptives used was maintained throughout medication but on discontinuing the SHBC levels returned to pre‐treatment values.
SENSITIVE RADIOIMMUNOASSAY FOR SOMATOSTATIN USING N‐[1251‐TYR‐SOMATOSTATIN AS LABELLED ANTIGEN
Authors: DUPONT ANDRÉ , COY DAVID H. , ALVARADO‐URBINA GABRIEL , CÔTÉ JEAN , MEYERS CHESTER A. , MCMANUS JAMES , BARDEN NICHOLAS , DE LÉAN ANDRÉ , LABRIE FERNAND
Published: March 2008

A sensitive radioimmunoassay for somatostatin using N‐[25I]‐Tyr‐somatostatin is described and compared with that using [125I]‐Tyr1‐somatostatin. The minimum detectable amount of somatostatin using N‐[1251]‐Tyr‐somatostatin as tracer was 0.1 to 0.5 pg, which is approximately 10‐fold lower than the lower detection limit of the RIA using [125I]‐Tyr1‐somatostatin. Moreover, it was found that the shelf‐life of N‐[1251]Tyr‐somatostatin was prolonged in comparison with labelled Tyr1‐somatostatin. Human pancreatic and gastric extracts displayed immunological similarity to synthetic somatostatin tetradecapeptide.
THE EFFECT OF SULPIRIDE INDUCED HYPERPROLACTINAEMIA ON GLUCOSE TOLERANCE AND INSULIN SECRETION IN NORMAL SUBJECTS
Authors: HAGEN CLAUS , PEDERSEN PETER BECK , JENSEN SØREN BUUS , KNUD OLE , JENSEN THYGE
Published: March 2008

Blood glucose concentration and insulin secretion expressed by peripheral plasma insulin (IRI) and C‐peptide levels were measured during saline and sulpiride infusion in five normal men. In another experiment the same variables were analysed in six normal males before and during oral sulpiride treatment for 5 days. The i.v. and oral administration of sulpiride resultedin a significant rise in serum prolactin levels. The stimulated serum prolactin concentrations were equivalent to those seen during stress.

The sulpiride induced hyperprolactinaemia did not change blood‐glucose, plasma IRI levels, hepatic insulin removal and glucose utilization during basal conditions or after i.v. glucose administration.
STANDARD DOSE 131I THERAPY FOR HYPERTHYROIDISM CAUSED BY AUTONOMOUSLY FUNCTIONING THYROID NODULES
Authors: TANG FUI S. C. NG , MAISEY M. N.
Published: March 2008

Thirty‐one patients with hyperthyroidism shown on scintigram to have autonomously functioning thyroid nodules were treated with a standard dose of 15 milli‐curies (mCi) of 131I. Of thirty patients who have been followed up for at least 6 months to over 3 years, all but one patient were euthyroid after a single dose. Repeat scintigram and Thyrotropin Releasing Hormone (TRH) test after therapy confirmed that twenty‐five patients were cured of the disease. Only one patient developed hypothyroidism. This simplified standard dose regimen of radioiodine is effective in the treatment of hyperthyroidism caused by autonomously functioning nodules and is not complicated by the high incidence of hypothyroidism that is observed following radioiodine therapy of Graves’disease.
THYROID BINDING ANTIBODIES AND OTHER IMMUNOLOGICAL ABNORMALITIES IN PATIENTS WITH GRAVES’OPHTHALMOPATHY: EFFECT OF TREATMENT WITH CYCLOPHOSPHAMIDE
Authors: WALL J. R. , STRAKOSCH C. R. , FANG S. L. , INGBAR S. H. , BRAVERMAN L. E.
Published: March 2008

Patients with Graves’ophthalmopathy were studied for a possible role of thyroid binding antibodies (TBAb) as measured by a radioreceptor assay, and for in vitro evidence of immunoreactivity to orbital antigens. The effect of cyclophosphamide (CY) treatment on the immunological parameters and the clinical course of the eye disease was also studied. The mean TBAb index for all patients with eye disease was significantly less than that for normals and for patients with Graves’hyperthyroid‐ism who lacked eye disease. The mean TBAb index for patients with ophthalmopathy and past or present hyperthyroidism was significantly less than for those patients with eye disease but no associated hyperthyroidism (‘euthyroid Graves’ disease). TBAb levels did not correlate with the severity or duration of the eye disease and did not change during treatment with CY. Significant titres of serum antibodies against human eye muscle extract or subcellular fractions, or macro‐phage inhibitory factor (MIF) production in response to human orbital tissue extract were not detected in patients with eye disease. The congestive changes improved in all patients treated with CY, although the degree of proptosis and eye muscle involvement improved in only 3 of 24 and 11 of 20 patients respectively with these abnormalities. TBAb are unlikely to play a role in the pathogenesis of Graves’ophthalmopatliy and the hyperthyroidism and eye disease should be considered separate autoimmune disorders. The apparently anomalous finding of a higher mean TBAb index in patients with eye disease and hyperthyroidism than in those with hyperthyroidiam alone may reflect a more severe defect of suppressor T cell function in the former group. Because evidence for specific immunoreactivity
THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN
Authors: DELITALA G. , WASS J. A. H. , STUBBS W. A. , JONES A. , WILLIAMS S. , BESSER G. M.
Published: March 2008

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclo‐pramide. These results suggest that lisuride acts as a long‐acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.
IN VITRO BIOSYNTHESIS OF 1 8‐HYDROXY‐l l‐DEOXYCORTI‐COSTERONE FROM DEOXYCORTICOSTERONE BY HUMAN ADRENAL GLANDS REMOVED FROM PATIENTS WITH HYPERCORTICISM
Authors: TOUITOU Y. , BOGDAN A. , LUTON J‐P.
Published: March 2008

The biosynthesis of 18‐hydroxy‐ll‐deoxycorticosterone (18‐OH‐DOC) was studied by in vitro incubations of human adrenals resected from patients with Cushing's syndrome, using deoxycorticosterone as precursor. 18‐OH‐DOC synthesis was similar in adrenals from normal subjects and in those derived from patients with different types of Cushing's syndrome (hyperplasia, adenoma, carcinoma). The in vitro addition of o,p'‐DDD (5 X 10‐3 M) to an adrenocortical carcinoma incubation did not alter 18‐OH‐DOC biosynthesis. By contrast, treatment of the patient with o,p'‐DDD prior to adrenalectomy resulted in a low production of 18‐OH‐DOC in vitro but only when cortisol synthesis was drastically decreased.
EVIDENCE FOR THYROID ANTIGEN‐REACTIVE T LYMPHOCYTES INFILTRATING THE THYROID GLAND IN GRAVES’DISEASE
Authors: TOTTERMAN T. H. , ANDERSSON L. C. , HÄYRY P.
Published: March 2008

We have investigated the relative distribution and some in vitro functions of thyroid‐infiltrating immunocompetent cells obtained at fine‐needle aspiration biopsy in twelve patients with Graves’disease and thirteen patients with Hashimoto's thyroid‐itis. In both disorders the predominant (5749%) thyroid‐infiltrating cell was a small lymphocyte. Significant numbers of plasma cells (10%) were seen only in Hashimoto's thyroiditis. Mononuclear phagocytes (monocytes plus macrophages) were present in similar numbers (12–18%) in both disorders. In both Graves’and Hashimoto's disease there was a relative reduction of (thymus‐dependent) lymphocytes in the thyroid gland as compared to the blood. Blood and thyroid‐infiltrating T lymphocytes were tested for in vitro cell‐mediated immunity (CMI) to thyroid antigen in the leucocyte migration inhibition test (LMT). CMI was readily demonstrated in the blood of most patients with Graves’and Hashimoto's disease. When the thyroid‐infiltrating lymphocytes were tested for CMI in the LMT, only the infiltrating cells from patients with Graves’disease displayed CMI, whereas the thyroid‐infiltrating lymphocytes in Hashimoto's disease were negative. Fractionation of the immunocompetent cells demonstrated that the thyroid antigen‐induced LMT response of blood and thyroid‐infiltrating lymphocytes in Graves’disease is a T lymphocytedependent phenomenon.
IDIOPATHIC OEDEMA: A STUDY OF THE EFFECTS OF BROMOCRIPTINE
Authors: DENT R. G. , EDWARDS O. M.
Published: March 2008

We have studied the effect of bromocriptine in seven patients with idiopathic oedema. Two patients were unable to tolerate the drug; the remaining five were maintained on doses of between 5 and 7.5 mg a day. Symptomatic improvement was noted in two patients and in both of these and one other there was a significant improvement in mean diurnal weight gain. The fall in free water and sodium clearance on standing was reduced by bromocriptine, but there was no significant change in the excessive fall in plasma volume.
METOCLOPRAMIDE STIMULATION: A TEST OF GROWTH HORMONE RESERVE IN ADOLESCENT MALES
Authors: COHEN H. N. , HAY I. D. , THOMSON J. A. , LOGUE F. , RATCLIFFE W. A. , BEASTALL G. H.
Published: March 2008

A comparison was made between the growth hormone (GH) response to meto‐clopramide (‘Maxolon’‐Beecham Laboratories) and insulin induced hypoglycaemia in thirty‐five short adolescent males. Both tests initially caused adequate release of GH from the pituitary gland in 86% of those subjects who had normal GH reserve. The peak growth hormone responses of the two tests were similar in magnitude and were strongly correlated (r = 0.80, P < 0.001). Both tests raised serum GH to a similar degree in twenty‐nine out of the thirty‐five boys (83%), but four boys who responded satisfactorily to hypoglycaemia failed to respond to metoclopramide (MCP) stimulation, and two boys who failed to respond to hypoglycaemia responded satisfactorily to MCP stimulation.

MCP stimulation does not require prior preparation of the patient and is relatively free of side effects. Consequently, it is suggested that MCP stimulation may be a useful 1 hour out‐patient test for growth hormone deficiency in this relatively common group of patients.
METOCLOPRAMIDE INDUCED GROWTH HORMONE RELEASE IN HYPOGONADAL MALES
Authors: COHEN H. N. , HAY I. D. , BEASTALL G. H. , THOMSON J. A.
Published: March 2008

The growth hormone (GH) response to 10 mg intravenous metoclopramide (MCP) (‘Maxo1on’‐Beecham Laboratories) was determined in ten hypogonadal adult males. All the subjects responded with a peak growth hormone level > 14 mU/1 within 1 hour of administration of MCP. Seven normal adult males did not respond to MCP administration. It is concluded that MCP stimulation may be a useful test for both prolactin and growth hormone reserve in hypogonadal males.
MODIFICATION OF THE NORMAL POSTURAL CHANGES IN PLASMA RENIN ACTIVITY BY THE APPLICATION OF POSITIVE PRESSURE TO THE LEGS
Authors: MCGIVERN D. , HARDCASTLE A. , MILLAR J. G. B. , WARREN D. J.
Published: March 2008

In six normal male subjects plasma renin activity (PRA) rose progressively on standing over a 2 hour period. PRA fell to basal levels after a further 2 hours of recumbency. The rate of rise of PRA on standing was largely abolised following the application of an anti‐gravity (‘G’) suit. Continuous monitoring of blood pressure (BP) heart rate (HR) and packed cell volume (PCV) suggest that it is the fall in effective blood volume which elicits the stimuli to renin release during changes in posture.
CONGENITAL GOITRE AND HYPOTHYROIDISM WITH IMPAIRED IODIDE ORGANIFICATION AND HIGH THYROID PEROXIDASE CONCENTRATION
Authors: MEDEIROS‐NETO G. A. , NAKASHIMA T. , TAUROG A. , KNOBEL M. , SIMONETTI J. P. , MATTAR E.
Published: March 2008

A sibship of thirteen subjects whose parents were first cousins was studied for a defect in thyroid hormone synthesis. Five sibs were goitrous and had congenital hypothyroidism. All but one showed a positive perchlorate discharge test (PDT). Three other subjects were goitrous and euthyroid (one with a positive PDT), and the remaining five sibs were euthyroid with a presumably normal thyroid. However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones. In two hypothyroid patients a normal serum T3, low serum T4 and a low reverse T3 were observed. Microscopic studies of thyroid tissue from three of the sibs disclosed marked cellular hyperplasia with no lymphocytic infiltration anywhere in the tissue.

Peroxidase activity was determined on tissue from three sibs by three different assay procedures. It was within the normal range in one patient and was significantly elevated in the other two. There was no evidence for a qualitatively defective peroxidase. The defect in thyroid function in this family does not appear to involve a peroxidase deficiency. Thyroglobulin isolated from the thyroid glands of two of the goitrous, hypothyroid subjects was poorly iodinated but was judged to be normal by immunoreactive and ultracentrifugation procedures. Although the nature of the thyroid metabolic defect in this family was not elucidated, the evidence suggests a genetic defect, probably involving a recessive gene.
PLASMA HORMONE LEVELS AND OESTROGEN PRODUCTION IN A POSTMENOPAUSAL WOMAN WITH ENDOMETRIAL CARCINOMA AND AN OVARIAN THECOMA
Authors: REED M. J. , HUTTON J. D. , BEARD R. W. , JACOBS H. S. , JAMES V. H. T.
Published: March 2008

Plasma hormone concentrations, the production rate of oestrone from androstenedione, and the total production rate of oestrone have been measured in a 57‐year‐old woman with an ovarian thecoma and endometrial carcinoma before and 2 months after hysterectomy and bilateral ovariectomy. The plasma concentration of oestradiol (184 pmol/l), but not oestrone (144 pmol/l), was elevated pre‐operatively and FSH secretion was suppressed (115.0 μg/l). Post‐operatively the plasma concentration of oestradiol was significantly reduced (80 pmol/l) and the concentration of FSH (571 μg/l) had increased to a postmenopausal level. The concentration of oestradiol in samples of plasma obtained simultaneously at operation from the ovarian vein of the ovary containing the thecoma (3.38 nmol/l) was fifteen times greater than in the periphery (228.0 pmol/l), and this confirmed that oestradiol was secreted by the thecoma. The total production rates of oestrone pre‐and post‐operatively were 101.3 nmo1/24 h and 29.2 nmo1/24 h respectively and the production rates of oestrone from androstenedione were 41.4 nmo1/24 h and 32.9 nmo1/24 h. Thus, postaperatively, all the oestrone was produced from circulating androstenedione, whereas pre‐operatively only 40% of the oestrone was produced by the extraglandular conversion of androstenedione; the remaining 60% presumably originated from the peripheral conversion of oestradiol secreted by the thecoma. It is concluded that the oestradiol secreted by the thecoma was probably the major factor which caused the development of endometrial carcinoma in this subject.
EFFECTS OF THE H2 RECEPTOR ANTAGONIST CIMETIDINE ON PITUITARY HORMONES IN MAN
Authors: DELITALA G. , STUBBS W. A. , WASS J. A. H. , JONES A. , WILLIAMS S. , BESSER G. M.
Published: March 2008

The effects of the histamine (H2) receptor antagonist cimetidine on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and cortisol were studied in five normal males. Cimetidine, when given by infusion at the dose of 100 mg/h for 5 h, did not alter adenohypophyseal secretion either basally or after pituitary stimulation with LHRH and TRH. However, 400 mg cimetidine given intravenously as a bolus injection significantly stimulated PRL release in all subjects, without affecting any other measured hormone. A dose‐response relationship existed, and 200 mg cimetidine seems to be the minimum PRL‐releasing dose when given as an intravenous bolus injection. These results suggest that cimetidine releases PRL and that this effect is dose‐related, but only when large intravenous injections are given.
PLASMA DOPAMINE‐β‐HYDROXYLASE ACTIVITY AND BLOOD PRESSURE VARIABILITY IN HYPERTENSIVE MAN
Authors: LEVY S. B. , FRIGON R. F. , STONE R. A.
Published: March 2008

It has been proposed that measurements of plasma dopamine‐β‐hydroxylase (DBH) may allow for assessment of adrenergic tone and may elucidate a possible neurogenic contribution to essential hypertension. We performed a series of measurements of DBH in fifty‐seven normotensive and fifty hypertensive black and white men in order (1) to compare DBH to selected blood pressure patterns and (2) to evaluate the influence of salt intake, posture and race on plasma DBH. Plasma DBH, measured on unrestricted salt intake with subjects supine, was 42 ± 4 Units/L in white normotensives, greater (P< 0.05) than black normotensives (26 ± 6 Units/L). White hypertensives had greater plasma concentrations of DBH than black (35 ± 3 vs. 24 ± 5, P< 0.05). Normotensives did not differ from hypertensives. Dietary salt restriction and upright ambulation increased plasma DBH activity in hypertensives. Although DBH did not correlate directly with blood pressure, high DBH values were associated with lability of blood pressure in hypertensives but not in normotensives. There are two possible explanations for our results: (1) multiple factors influence plasma DBH activity and plasma levels reflect more than adrenergic function, or (2) essential hypertension is a multifactorial disease and excess sympathetic neuronal activity alone is not sufficient to produce sustained hypertension.
THE EFFECT OF CLOMIPHENE ON UNCASTRATED AND CASTRATED MALE TRANSSEXUALS
Authors: GOH H. H. , CHEW P. C. T. , KARIM S. M. M. , RATNAM S. S.
Published: March 2008

Clomiphene was administered at a daily dose of 100 mg for 5 consecutive days to two groups of male subjects. There were three uncastrated male transsexuals (Group A) and nine castrated male transsexuals (Group B). In the uncastrated subjects Clomiphene enhanced the secretion of follicle‐stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) starting from day 3 of treatment. The magnitude of the increment ranged from 150%–250% over the mean basal plasma level for LH, 113%–262% for FSH and 12%–68% for T. In contrast, Clomiphene suppressed both FSH and LH in the castrated subjects. Equal suppression of both the gonadotrophins were observed. The levels of FSH and LH in plasma on day 3 were suppressed to 66.4% and 66.2% of their respective mean basal levels. Two days after the termination of treatment, suppressions were maintained. These results suggest that Clomiphene acts as an anti‐oestrogen in uncastrated male transsexuals and in castrated male transsexuals who have subphysiological levels of oestradiol it acts as a weak oestrogen.
PIRIBEDIL INHIBITION OF PROLACTIN RELEASE INDUCED BY MECHANICAL BREAST EMPTYING IN PUERPERAL WOMEN
Authors: ALAGNA S. , LODICO G. , DEVILLA L. , MASALA A. , DELITALA G. , ROVASIO P. P. , STOPPELLI I.
Published: March 2008

The effects of a 5 day course of Piribedil, a dopaminergic agonist, on prolactin release evoked by mechanical breast emptying in puerperal women, was investigated. A daily dose of 75 mg. caused a significant decrease in the prolactin response to mechanical breast stimulation. Piribedil also proved clinically useful in inhibiting lactation. The role of dopaminergic mechanisms in the regulation of prolactin release induced by mechanical breast emptying are discussed.
THE RATIO OF THYROXINE TO THYROXINE‐BINDING GLOBULIN IN THE ASSESSMENT OF THYROID FUNCTION
Authors: BURR W. A. , EVANS S. E. , LEE J. , PRINCÉ H. P. , RAMSDEN D. B.
Published: March 2008

Serum thyroxine (T4), thyroxine‐binding globulin (TBG) and T3 Uptake have been measured in 122 hospital inpatients, 116 healthy volunteers, 101 patients with thyrotoxicosis, thirty‐six patients with myxoedema, eighty‐five euthyroid subjects with high or low TBG concentration and ten patients on treatment with diphenylhdantoin (DPH). T4:TBG ratio and free thyroxine index (FTI = T4/T3Ux 100) were calculated for each individual. In euthyroid controls, TBG concentration was normally distributed, and was significantly greater in females (12.1 ± 1.6 mg/l, mean ± SD) than in males (10. 8 ± 2.9 mg/l). TBG was raised in myxoedema (14.7 ± 2.4 mg/l), and reduced in thyrotoxicosis (10.8 ± 2.4 mg/l) when compared with euthyroid females. There was a 24%, rise in TBG concentration during drug treatment of thyrotoxicosis (pre‐treat‐ment= 11.1 ± 2.5 mg/l, post treatment (3/12) = 13.8 ± 3.4 mg/l). In euthyroid persons, T4 was linearly correlated with TBG concentration (r = 0. 92), but there was a tendency towards a curvilinear relationship which may have been due to reduction in the concentration of thyroxine‐binding prealbumin (TBPA) at high concentrations of TBG. T4:TBG ratio and FTI were similar in their ability to distinguish between thyrotoxic, euthyroid and myxoedematous persons when TBG concentration was normal. T4:TBG ratio was found to have the considerable advantage of correcting for increases in TBG concentration over a five‐fold range, whereas FTI was misleading when TBG concentration was raised. Both FTI and T4:TBG gave unreliable results when TBG was low, and in such cases measurement of TBG should alert the clinician to the need for alternative tests. During DPH treatment, both indices tended to give‘myxoedematous’results. Retrospective analysis of T4:TBG ratio and FTI in 104 hospital in‐patients with T4< 110nmol/l and 40 in‐patients with T4<40nmol/l suggested that the T4:TBG ratio gave better diagnostic precision than FTI.
BROMOCRIPTINE TREATMENT OF OLIGOSPERMIA: A DOUBLE BLIND STUDY
Authors: HOVATTA O. , KOSKIMIES A. I. , RANTA T. , STENMAN U.‐H. , SEPPÄLÄ M.
Published: March 2008

A double blind controlled study of bromocriptine treatment of oligospermia was carried out. Out of fifty‐one men who originally volunteered to the study there were forty who took the drug for 12 weeks as requested. All the partners of these men had failed to conceive, and in each case the pretreatment sperm count had been below 40 million/ml on two or several occasions. The pretreatment serum prolactin concentrations were similar in patients given bromocriptine (N = 20) and placebo (N = 20). There were three men in either group whose pretreatment serum prolactin concentration was in excess of 30 μg/l, the highest value being 96 μg/l. While bromocriptine effectively decreased the serum prolactin concentration, it had no significant effect over placebo on sperm volume, motility and morphology. In the bromocriptine group, sperm count increased to or above 40 million/ml in five out of twenty men, while in the placebo group this occurred in nine out of twenty patients. The plasma testosterone and dihydro‐testosterone levels increased slightly during treatment in both groups, but no significant difference was observed between bromocriptine and placebo treated patients. One wife of a bromocriptine‐treated man and two wives of placebo‐treated men became pregnant during treatment. In this study bromocriptine was no more effective than placebo in the treatment of oligospermia.
HETEROGENEITY IN ADRENAL STEROIDOGENESIS IN NORMAL MEN AND WOMEN
Authors: CHILD D. F. , BU'LOCK D. E. , HILLIER V. F. , ANDERSON D. C.
Published: March 2008

Adrenal steroidogenesis has been studied in vivo in normal men and women. Serum levels of nine steroids on the biosynthetic pathway (the Δ5 3‐β‐hydroxy‐steroids, pregnenolone (Pe), 17α‐hydroxypregnenolone (17Pe), dehydroepian‐drosterone (DHEA), androstenediol (Adiol), and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxyprogesterone (17Po), androstenedione (Adione), and testosterone (T)) as well as cortisol were measured during adrenal suppression and stimulation. This study demonstrates a marked heterogeneity in adrenal steroid responses between different subjects in the normal population. Thus, in three subjects ACTH stimulation from a dexamethasone‐sup‐pressed state resulted in a far greater increment of 17Po than in the other nineteen normal subjects. These three individuals (designated Type 2 res‐ponders) may have a partial deficiency of 21‐hydroxylase activity. In the remaining nineteen subjects (designated as Type 1 responders) the women had a greater increment of Adiol (P<0.05) and a lower increment of Po (P<0.01) than the men, suggesting that adrenal 3‐β‐hydroxysteroid dehydrogenase/isomerase activity may be slightly lower in women than men.
ADRENAL STEROIDOGENESIS IN HETEROZYGOTES FOR 21‐HYDROXYLASE DEFICIENCY
Authors: CHILD D. F. , BU'LOCK D. E. , ANDERSON D. C.
Published: March 2008

Adrenal steroidogenesis has been studied in vivo in eight obligate heterozygotes (six men and two women) for 21‐hydroxylase deficiency and the results compared with twenty‐one normal subjects. Serum levels of nine steroids on the biosynthetic pathway (the Δ53β‐hydroxysteroids, pregnenolone (Pe), 17α‐hyd‐roxypregnenolone (17Pe), dehydroepiandrosterone (DHEA), androstenediol (Adiol), and their Δ4 3‐keto counterparts, progesterone (Po), 17α‐hydroxypro‐gesterone (17Po), androstenedione (Adione), testosterone (T)) as well as corti‐sol were measured following ACTH stimulation from a dexamethasone‐sup‐pressed state. There was evidence of reduced 21‐hydroxylase activity in the heterozygotes when the results were compared with the usual pattern of response seen in nineteen of twenty‐two normal subjects. Thus the increment at 1 h for 17α‐hydroxyprogesterone was greater in all the heterozygotes and three of them (one man, two women) also had a greater increment for progesterone. 17,20 desmolase activity may also be reduced in the heterozygotes for they had a lower increment than normal of dehydroepiandrosterone and androstenediol. The results were complicated by the finding that three additional subjects in the normal population tested have much greater 17Po and Po responses than the majority and clearly form a separate population. Our data suggest that there is a common variant within the normal population which may result from the heterozygous state of 21‐hydroxylase deficiency; alternatively other forms of 21‐hydroxylase may exist with reduced activity that even in the homozygous state may not produce clinical disease.
RADIOIMMUNOASSAY OF PLASMA 18‐HYDROXY‐ll‐DEOXYCORTICOSTERONE AND ITS RESPONSE TO ACTH
Authors: MAY C. N. , LEWIS P. S. , HORTH C. E.
Published: March 2008

A radioimmunoassay for the measurement of 18‐OH‐DOC in plasma was developed using an antiserum raised against the γ‐lactone derivative. The steroids with the greatest degree of cross reaction were 18‐OH‐corticosterone‐γ‐lactone and aldosterone‐γ‐lactone which showed cross‐reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH‐20. The lowest limit of detection of 18‐OH‐DOC in 1 ml of plasma corresponded to 33 pmol ‐1. The intra‐assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1‐1 respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol l‐1 respectively. The amount of 18‐OH‐DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240–1920 pmol 1‐1 could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18‐OH‐DOC in ten normal subjects was 172.1 ± 39.1 pmol l‐1 at 09.00 h, 100.9 ± 16 9 pmol l‐1 at 12.00 h and 95.8 ± 33.3 pmol l‐1 at 16.30 h. Plasma 18‐OH‐DOC and cortisol levels were measured after various intravenous doses of ACTH in three patients with essential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18‐OH‐DOC. These results confirm the ACTH dependancy of 18‐OH‐DOC secretion.
GLUCAGON METABOLISM IN NORMAL SUBJECTS AND IN CIRRHOTIC PATIENTS BEFORE AND AFTER PORTASYSTEMIC VENOUS SHUNT SURGERY*
Authors: ALFORD F. P. , DUDLEY F. J. , CHISHOLM D. J. , FINDLAY D. M.
Published: March 2008

The effect of portasystemic shunt surgery on basal immunoreactive glucagon (IRG) levels, metabolic clearance rate (MCR) and t ½ for glucagon decay, and basal systemic delivery rate (BSDR) of glucagon was investigated in paired studies in ten cirrhotic subjects. The degree of hepatocellular dysfunction and extent of portasystemic venous shunting was also recorded. Basal IRG levels were highest in the post‐shunt (meanSEM, 382 ± 73 pg/ml) as compared to the pre‐shunt (213±27 pg/ml; P<0.05) cirrhotic and control (53 ± 13 pg/ml; P<0.005) groups. The MCR of glucagon was similar in control (13.±1.3 ml/kg/min) and pre‐shunt cirrhotic patients (13‐3±1.7 ml/kg/min) but was significantly (P<0.02) decreased in the post‐shunt cirrhotics (7.6±1.3 ml/kg/min). The ½for glucagon decay was similar in the control and cirrhotic groups. The BSDR, an estimate of pancreatic A cell secretion, was increased four‐fold (P<0.01) in the pre‐shunt (3042±454 pg/kg/min) and post‐shunt (2518±535 pg/kg/min) cirrhotic groups, as compared to controls (750±244 pg/kg/min). It is concluded that (a) in the presence of cirrhosis, the magnitude of portasystemic shunting is important in determining the degree of hyperglucagonaemia; (b) in preshunt cirrhotics raised basal IRG levels are principally due to A cell hypersecretion of glucagon whereas in post‐shunt cirrhotics raised IRG levels reflect both A cell hypersecretion and delayed clearance of glucagon; and (c) acute shunting of splanchnic venous blood away from the liver reduces the clearance of glucagon, suggesting that, in man, the liver contributes to the clearance of circulating glucagon.
IMMUNOLOGICAL AND GENETIC MARKERS IN A FAMILY WITH HASHIMOTO'S DISEASE
Authors: GORDIN A. , MÄENPÄÄ J. , MÄKINEN TUULIKKI , TÖTTERMAN T. H. , TIILIKAINEN ANJA
Published: March 2008

A family with Hashimoto's disease in three generations is described. Seven persons (all female) had Hashimoto's disease and four of them were initially hypothyroid. Hashimoto's disease was the only thyroid disorder occurring in this family; no other autoimmune disease was observed. Circulating thyroid antibodies were detected in all seven subjects with overt thyroiditis in this family. Thyroid antibodies were also detected in low titres in about half of the healthy relatives. Evidence of thyroid antigen‐directed cell‐mediated immunity was demonstrated using the leucocyte migration inhibition test in four out of seven subjects with thyroiditis and also in about half of the relatives without clinical thyroid disease. The relative number of thyroglobulin‐binding circulating lymphocytes was elevated in six subjects with Hashimoto's disease. Again, the percentage of such cells was also increased in about half of the‘healthy’relatives. Thyroid‐stimulating immunoglobulins were detected by the radio receptor assay in three of the seven subjects with Hashimoto's disease and in four out of thirteen relatives without overt signs of thyroiditis. In conclusion, all subjects with Hashimoto's disease carried immunological markers of autoimmune thyroid disease in the circulation. In addition, most of the‘healthy’relatives were also positive for some or all of the markers sought in this study. The expression of these markers thus seems to be variable. No clear‐cut conclusion could be drawn regarding the inheritance of these markers. H LA genotypes were assayed for thirty‐five specificities of A, B and C loci and five of the D loci. There was no correlation between any individual antigen or HLA haplotype and overt Hashimoto's disease in this family.
EFFECTS OF RADIOIODINE ON THYROTROPHIN BINDING INHIBITING IMMUNOGLOBULINS IN GRAVES’DISEASE
Authors: McGregor A. M. , PETERSEN M. M. , CAPIFERRI R. , EVERED D. C. , REES SMITH B. , HALL R.
Published: March 2008

We have studied the effects of 131I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) in fifty‐five patients with Graves’disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves’disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131I there was a marked increase in the serum TBII activity during the 3 months following therapy, whereas drug‐treated patients showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131I treatment or during drug treatment provide insight into the basic defects responsible for the development of hyperthyroid Graves’disease and suggest that both the thyroid and immune system are involved.
THYROID FUNCTION, IODINE NUTRITION AND FETAL BRAIN DEVELOPMENT
Authors: HETZEL BASIL S. , HAY IAN D.
Published: March 2008

The clinical effects of congenital hypothyroidism on brain function have been well documented and the need for early diagnosis and treatment established. This is now possible through neonatal screening. Improved results may be expected but there is evidence of prenatal effects. More evidence of the effects of fetal hypothyroidism on brain development is required in order to determine the need for antenatal diagnosis. Experimental studies indicate significant effects of hypothyroidism on fetal brain development in the monkey and the sheep during the third trimester. In the rat, significant effects, particularly on the cerebellum, can be shown in the first 3 weeks postnatally, a period corresponding to the third trimester of the human pregnancy. Retardation of cerebellar nerve cell migration, differentiation, growth and arborization have all been demonstrated, together with persistence of the external granular zone and DNA polymerase activity. Such effects provide an explanation for the common occurrence of ataxia and nystagmus in congenital hypothyroidism. Severe iodine deficiency with an intake less than 20 μg per day and high goitre prevalence in endemic goitre areas is associated with the condition of endemic cretinism characterised in its fully developed form by mental deficiency, deaf mutism, spastic diplegia and squint with absence of clinical hypothyroidism. This condition does not respond to replacement therapy with thyroid hormones. Correction of the iodine deficiency prior to pregnancy will prevent the condition, but correction of the iodine deficiency in the latter half of pregnancy will not. This indicates the necessity of iodine for fetal brain development in man. Experimental studies in the guinea pig and sheep indicate an effect of severe iodine deficiency on brain growth early in pregnancy at the time of neuroblast multiplication. Such an early effect could provide an explanation for the irreversibility of the effects of severe iodine deficiency on brain development in man. The role of maternal and fetal hypothyroidism and iodine deficiency itself in these effects has still to be defined. It may be concluded that the relation
SERUM PREGNENOLONE, PROGESTERONE, 17α‐HYDROXYPROGESTERONE, ANDROSTENEDIONE, TESTOSTERONE, 5α‐DIHYDROTESTOSTERONE AND ANDROSTERONE DURING PUBERTY IN BOYS
Authors: PAKARINEN A. , HAMMOND G. L. , VIHKO R.
Published: March 2008

We have determined the concentrations of pregnenolone, progesterone, 17α‐hydroxyprogesterone, androstenedione, testosterone, 5α‐dihydrotestosler‐one and androsterone in serum samples collected from a total of seventy‐nine boys who were 8–18 years of age at the time the first blood samples were drawn. Additional samples were drawn from sixty‐six and forty‐four of these boys after 1 and 2 year intervals, respectively. The first increases in serum steroid concentrations were those of androstenedione and androsterone, thus supporting the hypothesis that an early activation of the adrenal cortex is the first hormonal change in puberty. This increase in serum androstenedione occurred 2 years earlier than the first significant increase in serum testosterone, which took place by 13 5 years, after the first signs of external genital development, but in concert with the onset of pubic hair growth. The serum concentrations of 5α‐dihydrotestosterone were closely related to those of testosterone, but the relative increases were smaller, the consequence of which is a decrease in the ratio of 5α‐dihydrotestosterone: testosterone throughout puberty. The main increase in serum androsterone tends to take place after that of 5α‐dihydrotestosterone and testosterone. In comparison with the four androgens, the serum concentrations of their C21precursors correlated rather poorly with the physical signs of advancing puberty. As in the case of androstenedione, the concentrations of pregnenolone and 17α‐hydroxyprogesterone were relatively high in the youngest age groups, which probably also reflects an early adrenal activation. In contrast to testosterone, the major increases in precursor steroids occur at a relatively late stage of puberty. It seems likely therefore that a major qualitative shift in the testicular secretion of steroids occurs during puberty in boys.
FAILURE OF NALOXONE TO ALTER GROWTH HORMONE AND PROLACTIN LEVELS IN ACROMEGALIC AND IN HYPERPROLACTINAEMIC PATIENTS
Authors: BLANKSTEIN J. , REYES F. , WINTER J. , FAIMAN C.
Published: March 2008

We examined the effects of high‐dose intravenous naloxone administration in four acromegalic patients (mean serum growth hormone level 72 ng/ml) and in seven hyperprolactinaemic women (mean serum prolactin level 59 ng/ml), in order to assess whether this opiate antagonist would be effective in lowering growth hormone and prolactin levels. No effect was observed. This lack of effect suggests that an opioid pathway is not involved in the maintenance of elevated growth hormone or prolactin secretion in these patients. However, conclusions regarding the possible role of endogenous opioids in regulation of pituitary function in normal individuals cannot be drawn from this study.
METABOLISM OF INTRAVENOUSLY ADMINISTERED CHOLECALCIFEROL IN MAN
Authors: BARRAGRY J. M. , FRANCE M. W. , BOUCHER B. J. , COHEN R. D.
Published: March 2008

Following intravenous injection of (3H) cholecalciferol into healthy subjects the disappearance of label from the plasma was followed by the reappearance (‘rebound’) of (3H) radioactivity associated exclusively with cholecalciferol. Lipoprotein fractionation of plasma revealed an increasing association of label with protein rather than lipoprotein during the rebound phase. We conclude that the rebound of plasma radioactivity reflects the transfer of label from lipoprotein to Vitamin D‐binding globulin in the liver followed by its release into plasma.