bluuebunny/crossref_metadata_2025 huggingface dataset:
RECOVERY OF PITUITARY FUNCTION FOLLOWING SURGICAL REMOVAL OF LARGE NONFUNCTIONING PITUITARY ADENOMAS*
Authors: ARAFAH BAHA'UDDIN M. , BRODKEY JERALD S. , MANNI ANDREA , VELASCO MANUEL E. , KAUFMAN BENJAMIN , PEARSON OLOF H.
Published: March 2008

Pituitary function was evaluated in eleven patients with large nonfunctioning pituitary adenomas before and 3 months after surgical adenomectomy. The longest anteroposterior dimension from the anterior wall to the dorsum of the sella on a lateral skull x‐ray ranged between 22 and 45 mm. All adenomas were confirmed histologically and had negative immunostaining for GH, PRL, ACTH and HCG.

Based on the pre‐ and post‐operative pituitary function, the patients were divided into two groups. Group I included eight patients who had hypopituitarism pre‐operatively of whom five had partial recovery of pituitary function while three had persistent hypopituitarism. Group II included three patients who had normal pituitary function pre‐ and post‐operatively. Five patients of group I had high normal or slightly elevated serum PRL levels while one had a normal level and two patients had low levels pre‐operatively. TRH but not perphenazine resulted in a variable but definite rise in serum PRL preoperatively in patients with normal or elevated PRL level.

In contrast, neither stimulus resulted in a rise in serum PRL in two patients with low basal levels. Serum PRL levels were normal in six patients and low in two others post‐operatively. Serum TSH levels were low in all eight patients with hypothyroidism. TRH resulted in a sustained release of TSH in three patients and was without effect in two patients pre‐operatively. Of eight patients with pre‐operative hypothyroidism, five recovered normal function and three remained hypothyroid. Of six patients with adrenal insufficiency pre‐operatively, two recovered normal pituitary—adrenal function while only two of eight patients recovered gonadal function post‐operatively. None of the eight patients recovered GH responsiveness to stimulation. All patients that recovered pituitary function had normal or slightly elevated serum PRL pre‐operatively. Our data indicate that recovery of pituitary function in patients with large pituitary adenomas and hypopituitarism may occur after surgical removal of the adenoma. One of the possible mechanisms of hypopituitarism in this setting would be interruption of the hypothalamic pituitary portal circulation by the large adenoma. An additional factor might be pressure necrosis and destruction of normal pituitary cells by the expanding adenoma. The extent of that might determine the degree of recovery of pituitary function.
LEVELS OF α‐MELANOTROPHIN IN THE HUMAN FETAL PITUITARY GLAND THROUGHOUT GESTATION, IN ADULT PITUITARY GLAND AND IN HUMAN PLACENTA*
Authors: F.WILSON J.
Published: March 2008

α‐Melanotrophin was detected by radioimmunoassay in the human fetal pituitary gland from 11 weeks of gestation. The peak hormone concentration of 3.4 nmol/g pituitary tissue was reached at 17–20 weeks. From 17 to 36 weeks of gestation the total gland content rose gradually from 28 to 102 pmol. During this latter period, the pituitary gland grew some 10‐fold, with the result that the α‐melanotrophin concentration declined steadily to 1–3 nmol/g. In the final month of gestation, both the total gland content and the concentration of α‐melanotrophin rose significantly to 254 pmol and 2.4 nmol/g respectively. The variations in pituitary gland content of α‐melanotrophin were consistent with a role for pars intermedia peptides in the fetus. α‐Melanotrophin‐like peptides were not demonstrated in human placental tissue.
PLASMA ANGIOTENSIN II AND ALDOSTERONE IN UNSELECTED DIABETIC PATIENTS
Authors: FERRISS J. B. , SULLIVAN P. A. , GONGGRIJP H. , COLE M. , O'SULLIVAN D. J.
Published: March 2008

The concentrations of angiotensin II and aldosterone in plasma were measured in 101 consecutive unselected out‐patient diabetic patients and in fifty‐three normal controls. The concentration of angiotensin II was similar in diabetics without complications and controls, but was significantly lower in patients with hypertension or peripheral neuropathy. In contrast, plasma aldosterone was not reduced in any sub‐group. The concentrations of angiotensin II and aldosterone were positively correlated in controls, in diabetics without complications and in hypertensive diabetics, but this relationship was not found in patients with peripheral neuropathy, retinopathy or nephropathy.

There was no evidence of overt hypoaldosteronism in any of the diabetic patients. No individual aldosterone concentration was below the range found in controls and no plasma potassium concentration was above the control range. It is concluded that when plasma angiotensin II concentration is reduced in patients with specific diabetic complications such as neuropathy, plasma aldosterone may be maintained by factors other than the renin‐angiotensin system. This would explain why hypoaldosteronism is rare among unselected diabetics.
FERTILITY AFTER CHILDBIRTH: POST‐PARTUM OVULATION AND MENSTRUATION IN BOTTLE AND BREAST FEEDING MOTHERS
Authors: HOWIE P. W. , McNEILLY A. S. , HOUSTON M. J. , COOK A. , BOYLE H.
Published: March 2008

The resumption of post‐partum menstruation and ovulation was studied in ten bottle feeding and twenty‐seven breast feeding mothers. First menstruation occurred at 8±1 weeks (± 1±0 SE) in bottle feeders and 32±5 weeks (±2±5 SE) in breast feeders (P < 0±001); first ovulation occurred at 10±8 weeks (±1±0 SE) in bottle feeders and 36±4 weeks (±2±5 SE) in breast feeders (P < 0±001).

In bottle feeders, ovulation preceded first menses in only 2/10 (20%) of mothers but was regularly established thereafter, occurring in 17/18 (94%) of second and subsequent cycles.

Breast feeding did not postpone ovulation indefinitely because 13/27 of the breast feeding mothers ovulated while still lactating; ovulation occurred in 9/27 (33%) of breast feeding mothers during the phase of lactational amenorrhoea but was followed by menstruation in every case. In breast feeding mothers, the frequency of ovular cycles progressively increased with time, ovulation being observed in 9/20 (45%) of first cycles during lactation, 20/30 (66%) of later cycles during lactation, 16/23 (70%) of first cycles after lactation and 26/31 (84%) of later cycles after lactation.

There was a disruption of menstrual rhythms during lactation, the mean interval between the first day of consecutive menstrual cycles being 37±0 days ± 3±3 SE during lactation compared with 29±8 days ± 1±0 SE after lactation and 29±5 days ± 1±0 SE in the bottle feeding mothers.

This study shows that bottle feeding is associated with an early resumption of post‐partum menstruation and ovulation. In breast feeding mothers, there is complete suppression of ovulation during the greater part of lactational amenorrhoea but ovulation will return in a proportion of mothers just before first menses. After the return of menstruation during lactation, the frequency of ovular cycles progressively increases but does not return to normal until complete weaning has taken place.
SUPPRESSED PROLACTIN BUT NORMAL NEUROPHYSIN LEVELS IN CIGARETTE SMOKING BREAST‐FEEDING WOMEN
Authors: ANDERSEN A. NYBOE , LUND‐ANDERSEN C. , LARSEN J. FALCK , CHRISTENSEN N. JUEL , LEGROS J. J. , LOUIS F. , ANGELO H. , MOLIN J.
Published: March 2008

The hormonal responses to breast‐feeding were studied during the first 3 post‐partum weeks in ten women smoking more than fifteen cigarettes/day and in a control group. Basal PRL levels were significantly lower in smokers compared with non‐smokers, but suckling induced acute increments in serum PRL and oxytocin‐linked neurophysin, which were not influenced by smoking. The lactational pattern was normal, but smokers weaned their babies significantly earlier compared with non‐smokers. Heavy cigarette smoking women have lower basal PRL levels and this may shorten the period of lactation.
OPIATE MEDIATION OF AMENORRHOEA IN HYPERPROLACTINAEMIA AND IN WEIGHT‐LOSS RELATED AMENORRHOEA
Authors: GROSSMAN A. , MOULT P. J. A. , McINTYRE H. , EVANS J. , SILVERSTONE T. , REES LESLEY H. , BESSER G. M.
Published: March 2008

Endogenous opiates are involved in the control of pituitary gonadotrophin and PRL secretion, and possibly of food intake. Both hyperprolactinaemia and weight loss (especially in anorexia nervosa) are frequently associated with amenorrhoea and an absence of gonadotrophin pulsatility. Since it has been suggested that increased endogenous opiate tone may operate in both conditions, we infused high‐doses of naloxone into twelve patients with amenorrhoea of whom five had hyperprolactinaemia and seven had weight‐loss related amenorrhoea. Eleven of the twelve patients had low levels of oestradiol (< 50 pmol/l). Naloxone induced a marked rise in both LH and FSH levels in all of the five hyperprolactinaemic patients. In contrast, the patients with weight‐loss amenorrhoea responded to naloxone with only a small or no rise in gonadotrophins. There was no consistent change in PRL in either group of patients. It is concluded that in hyperprolactinaemia, but not weight‐loss amenorrhoea, there is an important endogenous opiate‐mediated tonic inhibition of secretion of hypothalamic gonadotrophin releasing hormone.
THE DEFICIENT LUTEAL PHASE MAY REPRESENT AN ANOVULATORY CYCLE
Authors: COUTTS J. R. T. , ADAM A. H. , FLEMING R.
Published: March 2008

The luteinized unruptured follicle syndrome which has been observed in women at laparoscopy has been implicated as a contributory factor to female infertility. In this study estimation of progesterone indices during the luteal phase and ovarian ultrasonography throughout the cycle have shown a definite association between retained luteal phase cysts and the deficient luteal phase.
THE ROLE OF ANTENATAL OESTROGEN IN POST‐PARTUM HUMAN LACTOGENESIS: EVIDENCE FROM OESTROGEN‐DEFICIENT PREGNANCIES
Authors: MARTIN R. H. , OAKEY R. E.
Published: March 2008

Five women with severe ante‐partum oestrogen deficiency (in four due to placental steroid sulphatase deficiency and in one due to an unknown cause) had low concentrations of PRL in peripheral plasma at delivery and in the puerperium. These women were unable to establish lactogenesis as assessed from plasma α‐lactalbumin concentrations on day 4 post‐partum. It is concluded that ante‐partum oestrogen is required both to ensure adequate PRL secretion and to permit lactogenesis in breast tissue in response to PRL. A review of patients’records in another nine cases of placental steroid sulphatase deficiency indicates that failure to establish breast feeding is a common feature.
RAPID COMMUNICATION: DIURNAL VARIATION OF SERUM IMMUNOREACTIVE ERYTHROPOIETIN IN A NORMAL SUBJECT
Authors: COTES P. MARY , BROZOVIC B.
Published: March 2008

Marked diurnal variation in serum immunoreactive erythropoietin was seen in a healthy man both during a 4‐day control period and following acute loss of 450 g of blood by venesection. The highest concentrations of erythropoietin occurred around midnight and the lowest around noon. These findings emphasize the need to take account of diurnal changes in serum erythropoietin when assays for this hormone are used or assessed for their potential as diagnostic tools.
THE EFFECT OF ADRENERGIC AND CHOLINERGIC MECHANISMS ON THE SECRETION OF PANCREATIC POLYPEPTIDE AND GASTRIN FOLLOWING HYPOGLYCAEMIA IN MAN
Authors: FRIER B. M. , CORRALL R. J. M. , ADRIAN T. E. , BLOOM S. R.
Published: March 2008

The changes of plasma pancreatic polypeptide (PP) and plasma gastrin following acute insulin‐induced hypoglycaemia (0.15 U/kg) were examined in six normal subjects, six tetraplegic subjects (preganglionic sympathectomy) and six tetraplegic subjects given atropine (combined adrenergic denervation and cholinergic blockade).

Adequate hypoglycaemia was achieved in all three groups. The normal rise of plasma PP following hypoglycaemia was present in the tetraplegic group without atropine but was abolished in the tetraplegic subjects given atropine. There was no significant rise in plasma gastrin following hypoglycaemia except in the tetraplegic group given atropine.

These results confirm that the secretion of PP in response to acute hypoglycaemia is mediated via cholinergic activity, while gastrin secretion appears to be inhibited in normal subjects by a vagal cholinergic mechanism.
LIVER DAMAGE AND SEX HORMONES IN CHRONIC MALE ALCOHOLICS
Authors: VÄLIMÄKI M. , SALASPURO M. , HÄRKÖNEN M. , YLIKAHRI R.
Published: March 2008

The hormonal status of thirteen chronic male alcoholics with histologically proved alcoholic liver cirrhosis and that of sixteen non‐cirrhotic chronic alcoholics with a similar drinking history were studied after the abstinence of 7–14 days. Low levels of plasma testosterone and moderately elevated concentrations of plasma LH were seen in cirrhotics but not in non‐cirrhotics. In cirrhotics, testosterone values showed positive correlations with levels of serum albumin and plasma prothrombin. The responses of LH and FSH secretions to LHRH stimulation were similar in the two groups as were the basal FSH values. Plasma concentrations of oestradiol were within normal limits in all patients. In both groups however, basal levels of plasma PRL and oestrone were increased, significantly more so in cirrhotics than in non‐cirrhotics. The latter group was characterized by an exaggerated response of PRL secretion to TRH stimulation. SHBG concentrations were within normal range in both groups.

In conclusion, our results emphasize the role of alcohol‐induced liver damage in the pathogenesis of sex hormone disturbances of chronic male alcoholics without neglecting, however, the direct effects of alcohol abuse itself.
PITUITARY‐OVARIAN FUNCTION BEFORE, DURING AND AFTER THE MENOPAUSE: A LONGITUDINAL STUDY
Authors: METCALF MARY G. , DONALD R. A. , LIVESEY J. H.
Published: March 2008

The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri‐menopausal women aged 44–55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22–30 weeks after final menstruation. Amenorrhoea of > 2 years duration in association with a persistent elevation in gonadotrophin output was considered proof of the post‐menopausal state.

No clear hormonal change occurred at the time of the menopause. During the peri‐menopause there is a transition from the regular ovulatory cycles of pre‐menopausal women to the unvarying high gonadotrophin and low oestrogen excretion which is generally regarded as being characteristic of post‐menopausal women. In the group studied, post‐menopausal levels of FSH and LH were common before and episodes of high oestrogen excretion were not uncommon after final menstruation. Menstrual failure appeared to occur spontaneously at some stage during the transition from the pre‐ to the post‐menopausal state, and not to be associated with its conclusion. From the hormonal point of view the immediately post‐menopausal period could not be distinguished from the long cycles of peri‐menopausal women. This suggests that an endometrial rather than a hormonal event might determine the time at which menstruation stops during the menopausal transition.
HYDROTESTOLACTONE LOWERS SERUM OESTRADIOL AND PRL LEVELS IN NORMAL MEN: EVIDENCE OF A ROLE OF OESTRADIOL IN PRL SECRETION*
Authors: D'AGATA R. , ALIFFI A. , MAUGERI G. , MONGIOI A. , VICARI E. , GULIZIA S. , POLOSA P.
Published: March 2008

The effect on serum PRL levels of lowering serum oestradiol (E2) concentration by short‐term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E2 levels decreased from 68 ± 5±8 to 26 ± 2±5 pmol/1 (mean ± SE, P < 0±05). These E2 changes were accompanied by a significant decrease in mean 2‐h PRL levels from 11±2 ± 2±1 to 6±5 ± 1±6 ng/ml mean ± SE, P < 0±05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E2 may be one of the factors which control blood PRL concentrations in men.
EFFECT OF CYPROTERONE ACETATE‐ETHINYL OESTRADIOL TREATMENT ON ADRENAL FUNCTION IN HIRSUTE WOMEN
Authors: CHAPMAN M. G. , And S. L. JEFFCOATE , DEWHURST C. J.
Published: March 2008

Pituitary adrenal suppression has been assessed in twenty‐two patients receiving cyproterone acetate (100 mg) and ethinyl oestradiol (30 μg) for the treatment of hirsutism. Cortisol responsiveness to ACTH and to insulin induced hypoglycaemia, and diurnal variations of plasma cortisol levels were measured before and after 6 months of treatment. There was no evidence that adrenal suppression is a significant problem in this group of patients.
LHRH ANALOGUES CAN BE LUTEOTROPHIC
Authors: And R. FLEMING , COUTTS J. R. T.
Published: March 2008

Seven normally menstruating women were treated with consecutive daily supraoptimal doses of the LHRH analogue Hoe 766 initiated in the mid/late luteal phase. This treatment caused immediate increases in circulating levels of LH, FSH, oestradiol (E2) and progesterone. After a few days, the pituitary became unresponsive to Hoe 766 and LH and FSH levels returned to the normal luteal phase ranges while progesterone and E2 levels did not decline to their respective pre‐treatment levels until at least 24 h later. As a result of this treatment, the onset of the next menses was delayed in five of the seven women, indicating luteotrophism. These data show that the corpus luteum was responsive to increased LH/FSH during Hoe 766 therapy. Therefore, reported luteolytic effects of short‐term treatment with LHRH and/or its analogues were probably not caused by direct inhibitory ovarian action but by reduction of ensuing pituitary gonadotrophin levels.
BROMOCRIPTINE‐INDUCED PREGNANCIES IN WOMEN WITH LARGE PROLACTINOMAS
Authors: BERGH T. , NILLIUS S. J. , ENOKSSON P. , And S.‐G. LARSSON , WIDE L.
Published: March 2008

Fourteen women with large prolactinomas experienced a total of nineteen bromocriptine‐induced term pregnancies. None of the women had received prior pituitary tumour therapy. Post‐partum sellar X‐ray examinations showed signs of tumour enlargement in two women. Only one of them had clinical symptoms of tumour expansion with visual field defects during the pregnancy. The visual impairment improved when bromocriptine treatment was reinstituted and the pregnancy continued to term. The other twelve women had a total of seventeen uneventful pregnancies without symptoms or signs of pituitary tumour expansion. Thus, medical therapy with dopamine receptor agonists is the primary treatment for most infertile women with prolactinomas. The risk of serious pregnancy‐induced tumour expansion is very small in properly investigated and carefully supervised patients with large PRL‐secreting pituitary adenomas.
FAMILIAL THYROID PEROXIDASE DEFECT
Authors: MEDEIROS‐NETO GERALDO A. , OKAMURA KEN , CAVALIERE HUMBERTO , TAUROG ALVIN , KNOBEL MEYER , BISI HELIO , KALLAS WALLACE G. , MATTAR EMILIO
Published: March 2008

A congenitally goitrous, mentally retarded, hypothyroid child, whose parents were first cousins, was studied for the cause of a strongly positive (86–5%) perchlorate discharge test. The mother had a recidivant goitre after being thyroidectomized in 1971. Her perchlorate discharge test was negative, but she displayed an exaggerated TSH response to TRH administration. The father also showed a negative perchlorate discharge, but he had a large cold nodule in the left thyroid lobe. The father also presented with a retinitis pigmentosa, detected additionally in two of his brothers and three nephews.

Thyroid tissue, obtained from the three patients at surgery, was assayed for thyroid peroxidase (TPO) by three different assays:

iodination of goitre thyroglobulin;

oxidation of guaiacol;

oxidation of iodide.

In a standard iodination assay (100 μM I−) and in a standard guaiacol assay 4–7 mM guaiacol) the TPO activity in the son's tissue was extremely low. Preincubation with haematin did not restore activity. The father displayed a normal TPO activity, but that of the mother was somewhat low. In the iodide oxidation assay employing 12 mM I− in the incubation system, and in iodination and guaiacol assays employing elevated concentrations of substrate, the TPO activity in the son's tissue was quite appreciable and was much closer to that of the parents. Presumably, therefore, the defect in the son's thyroid did not involve an absence of TPO. Rather, the results suggest a qualitative defect in the son's TPO, involving an abnormality in the binding of substrate for oxidation.

Thyroglobulin was isolated from the thyroid soluble fraction by sucrose density gradient centrifugation and its protein and iodine content determined. Thyroglobulin from the son's thyroid tissue contained only 0–043% iodine, compared to 0–45% and 0–29% for mother and father, respectively. The very low iodine content of the son's thyroglobulin accords with the low thyroid peroxidase activity and with the clinical and laboratory findings.

The fact that the parents in the present study are first cousins and that both showed some type of thyroid abnormality suggests that the severely affected son (goitre, mental retardation, and hypothyroidism) is homozygous for a recessive mutant gene.
REDUCED DOPAMINERGIC INHIBITION OF THYROTROPHIN RELEASE IN STATES OF PHYSIOLOGICAL HYPERPROLACTINAEMIA
Authors: RODRIGUEZ‐ARNAO MARIA D. , WEIGHTMAN D. R. , HALL REGINALD , SCANLON MAURICE F. , CAMPORRO J. M. , GOMEZ‐PAN A.
Published: March 2008

We have tested the hypothesis that physiological puerperal hyperprolactinaemia may be secondary to reduced hypothalamic dopaminergic inhibition of prolactin (PRL) release. Nine post‐partum females with physiological hyperprolactinaemia (aged 19–40 years; mean basal PRL±SE, 2099±257 mU/l, range 1002–3762 mU/l) were studied and results compared with fourteen normoprolactinaemic females (basal PRL<400 mU/l; aged 18–36 years). Puerperal hyperprolactinaemic females showed a reduced TSH response to dopamine (DA) receptor blockade with metoclopramide (10 mg i.v.) compared with normal females over a 60‐min period following drug administration (total incremental TSH change, mean ±SE, mU/l; 0.5±0.3 v. 3.1±1.0, P<0.005). This finding of reduced dopaminergic inhibition of TSH release in females with physiological puerperal hyperprolactinaemia supports the view that an overall reduction in hypothalamic dopaminergic tone may contribute towards hyperprolactinaemia in post‐partum women.
PULSATILE SECRETION OF LH, FSH, PROLACTIN, OESTRADIOL AND PROGESTERONE DURING THE HUMAN MENSTRUAL CYCLE
Authors: BÄCKSTRÖM C. T. , McNEILLY A. S. , LEASK R. M. , BAIRD D. T.
Published: March 2008

The pulsatile secretion of gonadotrophins and ovarian steroids was studied in normal women at different stages of the menstrual cycle. The concentration of LH, FSH, Prolactin (PRL), oestradiol and progesterone were measured in samples of plasma collected every 15 min for 6 h and the frequency and amplitude of each episodic pulse of hormone estimated. Although significant fluctuations occurred in the concentration of each hormone, LH showed the most easily identifiable pulses the frequency of which increased significantly from the early follicular to the late follicular phase of the cycle (3.4±0.3 v. 4.4±0.2 pulses 6 h P<0.01). During the luteal phase the basal concentration of LH (5.6±0.9 U/l), pulse amplitude (7.4±1.7 U/l) and frequency (1.6±0.2/6 h) were much lower than at any stage of the follicular phase (P<0.001). The concentration of FSH and PRL showed a similar but less marked change to that of LH throughout the menstrual cycle with a significant decline in both basal concentration and pulse frequency in the luteal phase of the cycle. Although only 47% of all LH pulses were associated with a pulse of FSH, 70% of FSH and prolactin pulses occurred within 15 min of an LH pulse.

The basal concentration of oestradiol increased significantly from the early follicular to the late follicular phase of the cycle (P<0.001). There was evidence of episodic secretion of oestradiol with the frequency of pulses declining from a maximum of 4.3±0.6/6 h in the mid‐follicular phase to 1.8±0.5/6 h in the luteal phase (P<0.02). In the follicular phase 74–80% of LH pulses were followed within 100 min by a significant rise in the concentration of oestradiol. It is suggested that:

the secretion of LH, FSH, PRL, oestradiol and progesterone is episodic in nature;

a significant number of secretory episodes of FSH, LH and PRL are coincidental;

the increased secretion of oestradiol from the pre‐ovulatory follicle is associated with a rise in the frequency of episodic pulses of LH.
URINARY 6‐SULPHATOXY MELATONIN EXCRETION DURING THE HUMAN MENSTRUAL CYCLE
Authors: FELLENBERG A. J. , PHILLIPOU G. , SEAMARK R. F.
Published: March 2008

The excretion of 6‐sulphatoxy melatonin in urine has been shown to provide a reliable index of melatonin production in man. Daily measurements made in two healthy ovulating women showed that both the total amount excreted/day and the proportion excreted during the sleep period remained relatively constant for each subject throughout the menstrual cycle. These data do not support the view that there are changes in melatonin production which correlate with cyclical reproductive endocrine function in the human.
THE BEHAVIOURAL EFFECTS OF TESTOSTERONE UNDECANOATE IN ADULT MEN WITH KLINEFELTER'S SYNDROME: A CONTROLLED STUDY
Authors: WU F. C. W. , BANCROFT J. , DAVIDSON D. W. , NICOL K.
Published: March 2008

The behavioural effects of exogenous testosterone in men with marginally low circulating androgen levels were investigated. Four adult men with Klinefelter's syndrome, low normal testosterone levels and normal sexual activity and interest were given testosterone undecanoate (TU 160 mg daily by mouth; Organon International) and placebo using a double blind cross‐over design. A modest increase in sexual interest was observed during TU administration compared to placebo, though there were no effects on self‐reported mood or energy, or on erectile responsiveness in the laboratory. Increase in circulating hormone levels during TU administration was more marked for DHT than for testosterone. The possible implications of this are discussed.
LACK OF DIFFERENCE IN GROWTH STIMULATING EFFECT BETWEEN WEEKLY SINGLE AND MULTIPLE HUMAN CHORIONIC GONADOTROPHIN ADMINISTRATION IN BOYS WITH DELAYED PUBERTY
Authors: van den BOSCH J. S. G. , SMALS A. G. H. , VALK I. M. , KLOPPENBORG P. W. C.
Published: March 2008

Using a non‐invasive sensitive technique measuring ulnar length, short‐term growth was studied in two groups of boys with constitutional delay in growth. In one (group A) a protocol of multiple hCG injections weekly was used (3 × 1500 iu), whereas the other (group B) received a single dose of hCG weekly (1 × 1500 iu), both during 6 weeks. The two hCG protocols appeared to be equally potent in stimulating 3‐week Ulnar Growth rates (TUG‐rates), tripling the growth velocities from prepubertal to pubertal levels. After stopping hCG treatment the mean TUG‐rate decreased again to a post‐treatment level that, taking both groups together, was significantly higher than the mean pretreatment TUG‐rate. During hCG administration mean body growth rates also rose significantly in the two groups. The extent of the changes, however, only allowed evaluation for the whole group in contrast to the changes in TUG‐rates which far exceeded the limits of confidence in all but one boy. Serum alkaline phosphatase activities (APA) increased significantly during hCG treatment and almost paralleled the increase in TUG‐rates. The APA response (ΔAPA) in group A, however, was unexpectedly higher than in group B. After stopping hCG treatment the mean APA significantly decreased taking both groups together to an almost pretreatment level. The results showed that a weekly single dose hCG regimen was as effective as the weekly multiple injection protocol in stimulating TUG‐rates to pubertal levels in the groups of constitutionally delayed boys studied.
THYROTOXICOSIS AND DYSPNOEA
Authors: AYRES J. , REES J. , CLARK T. J. H. , MAISEY M. N.
Published: March 2008

Shortness of breath is a common symptom in thyrotoxicosis and it may have a number of causes. We have studied dyspnoea, skeletal muscle power and respiratory muscle power in eleven patients who had thyrotoxicosis with no evidence of heart failure.

Four patients (36·4%) had a marked improvement with treatment in the maximal inspiratory pressure developed at the mouth. All four were breathless and had a proximal myopathy before treatment. This confirms the existence of a group of thyrotoxic patients with a reversible respiratory muscle myopathy which may explain the frequent finding of breathlessness on exertion in such patients.
HYPOTHALAMIC–PITUITARY–ADRENOCORTICAL FUNCTION IN CHRONIC ALCOHOLISM
Authors: HASSELBALCH H. , SELMER J. , SESTOFT L. , KEHLET H.
Published: March 2008

Hypothalamic–pituitary–adrenocortical (HPA) function was assessed during normal daily work and family life in fifteen male brewery workers with a daily alcohol intake of 100 g or more for at least 10 years. Free urinary cortisol was determined during three baseline days and for 3 days during administration of dexamethasone 0·5 mg 6‐hourly. All subjects had normal basal urinary cortisol excretion and all except one suppressed normally upon dexame our subjects had Cushingoid‐like moon face and two of these also alo hump. There was no correlation between free urinary cortisol or dexamethasone suppression and the Cushingoid stigmata. These results suggest that chronic alcohol intake per se does not influence HPA‐function.
24‐HOUR PROFILES OF MELATONIN, CORTISOL, INSULIN, C‐PEPTIDE AND GIP FOLLOWING A MEAL AND SUBSEQUENT FASTING
Authors: ARENDT J. , HAMPTON S. , ENGLISH J. , KWASOWSKI P. , MARKS V.
Published: March 2008

Melatonin, free and total cortisol, insulin, C‐peptide and glucose‐dependent insulin‐releasing peptide (GIP) were measured in the plasma of twelve normal volunteers (eight women and four men), at hourly intervals for 24 h following a meal and subsequent fasting. One volunteer was excluded from calculations due to a possible effect of stress on melatonin secretion. Melatonin and cortisol showed the normal 24‐h variation with peak values at 0200–0500 h, and 0900 h respectively. Following post‐prandial stimulation, gut hormones remained basal throughout the sampling period. No significant relationship was found between 24‐h melatonin secretion and basal, or stimulated gut hormone secretion. Melatonin secretion did relate significantly to body weight, suggesting that data concerning pineal effects in endocrine physiology and pathology, and effective disease, should be reviewed in the light of these observations.
FAILURE OF POSITIVE FEEDBACK OF OESTRADIOL DURING CHRONIC INTRANASAL LUTEINIZING HORMONE‐RELEASING HORMONE AGONIST TREATMENT
Authors: BERGQUIST C. , NILLIUS S. J. , WIDE L.
Published: March 2008

An oestrogen provocation test was performed in five healthy women during chronic intranasal treatment with 400 or 600 μg of the superactive LHRH agonist D‐Ser(TBU)6‐EA10‐LHRH daily. Oestradiol benzoate 2±5 mg was administered intramuscularly after at least 3 months of LHRH agonist treatment. The serum levels of FSH and LH were not affected by the oestrogen injection. Failure of positive feedback of oestradiol may be one explanation for the inhibition of ovulation which occurs during chronic LHRH agonist treatment.
PULSATILE GONADOTROPHIN SECRETION IN HYPERPROLACTINAEMIC AMENORRHOEA AND THE RESPONSE TO BROMOCRIPTINE THERAPY
Authors: MOULT P. J. A. , REES LESLEY H. , BESSER G. M.
Published: March 2008

Serum gonadotrophin concentrations were measured every 15 min for 8 h in six patients before and at weekly intervals during initiation of bromocriptine treatment of hyperprolactinaemic amenorrhoea. Before treatment mean gonadotrophin levels were similar to those found in the normal follicular phase, but LH secretion was characterized by infrequent pulses of large amplitude. In three subjects the patterns of LH pulsatility and serum oestradiol levels returned to normal within 7 days of starting bromocriptine. The other three subjects responded with an increase in the frequency of LH pulses and mean LH levels, but little rise in oestradiol. Thus some hyperprolactinaemic subjects have a defect in the ovarian response to endogenous gonadotrophin stimulation, which may persist for a few weeks after return of prolactin levels to normal. The restoration of a normal rate of LH pulsatility with bromocriptine can occur without any change in serum oestradiol concentration.
PREDICTION OF OVULATION IN WOMEN USING A RAPID PROGESTERONE RADIOIMMUNOASSAY
Authors: FLEMING R. , COUTTS J. R. T.
Published: March 2008

A rapid (3‐h) radioimmunoassay of plasma progesterone has been developed and used successfully to predict the time of ovulation in women undergoing artificial insemination. The results obtained using progesterone levels to date the stage of the cycle were analysed retrospectively by (1) estimation of the length of the ensuing luteal phases and comparison of these with luteal phase lengths of a control group (2) comparison of the dating using progesterone levels with retrospective determination of LH values and (3) by analysis of the dating in cycles in which conception occurred.
ACID GLYCOSAMINOGLYCANS IN MYXOEDEMA
Authors: PARVING H‐H. , HELIN G. , GARBARSCH C. , JOHANSEN A.A. , JENSEN B. A. , HELIN P. , LUND P. , LYNGSØE J.
Published: March 2008

Acid glycosaminoglycans were measured in the tissues of a virtually untreated 83‐year‐old woman with myxoedema. Intercellular oedema was demonstrated histologically in the tongue, myocardium, striated muscles, and in the skin. Tissue oedema was absent in two female control patients. All tissues from the patient with myxoedema, apart from the stomach, showed high concentrations of hyaluronic acid, but there was no consistent elevation of chondroitin‐4,6‐sulphate, heparan sulphate or dermatan sulphate. The accumulation of hyaluronic acid might contribute to the oedema formation in myxoedema.
PROPRANOLOL IMPROVES THE IMPAIRED TSH RESPONSE TO TRH IN PATIENTS WITH AUTONOMOUSLY FUNCTIONING EUTHYROID MULTINODULAR GOITRE
Authors: ELTE J. W. F. , HAAK A. , WIARDA K. S. , FRÖLICH M. , VAN DER VELDE E. A. , VAN DER HEIDE D. , QUERIDO A.
Published: March 2008

Ten patients with autonomously functioning euthyroid multinodular goitre received propranolol (Inderal® Retard 160 mg daily) for 4 weeks in order to investigate whether normalization of the TRH test or an increased TSH response to TRH could be obtained by decreasing serum T3 levels.

Serum T3 decreased significantly after 2 and 4 weeks of propranolol administration. Serum T4 increased during this period, although the change was only significant after 4 weeks of propranolol. T3 resin uptake did not change. The TSH response to TRH increased significantly during the administration of propranolol. Mean Δ TSH basally was 1·0, range 0–3·9 mU/1, and mean Δ TSH after 4 weeks of propranolol was 2·4, range 0–9·3 mU/1. A strong correlation was found between the increase in Δ TSH and the decrease in serum T3 after 4 weeks of propranolol. After withdrawal, Δ TSH and T3 returned to premedication levels.

Our data suggest that T3 is an important factor in the impairment of the TSH response to TRH in our patients. Normalization of the TRH test was, however, not obtained. These findings support the concept of subclinical hyperthyroidism in ‘euthyroid’multinodular goitre with autonomous function.
ANALYSIS OF FACTORS IN HYPERTHYROIDISM, WHICH DETERMINE THE DURATION OF SUPPRESSIVE TREATMENT BEFORE RECOVERY OF THYROID STIMULATING HORMONE SECRETION
Authors: FISCHER H. R. A. , HACKENG W. H. L. , SCHOPMAN W. , SILBERBUSCH J.
Published: March 2008

In twenty‐three thyrotoxic patients a prospective study was undertaken to assess the time until restoration of TSH secretion. For several methodological reasons we chose to study a model in which the patients were deliberately continued on full dose treatment until biochemical hypothyroidism was established.

The period until reappearance of TSH secretion varied between 42 and 293 days. In this time FTI had become subnormal, while T3 and the clinical index remained in the normal range. The interval until TSH restoration was not correlated with the parameters of thyroid status from the initial evaluation with the exception of a negative correlation with log PB131I 48 h (r= 0·511; P < 0·02).

The average follow up period in our patients was 115 days during which FTI decreased exponentially to 19±7 ± 20±5. The disappearance of T3 followed a biphasic course in which after 2–4 weeks T3 decline practically ceased and concentrations remained normal.

Assuming that a FTI between 100 and 65 was the threshold value beneath which hypophyseal TSH synthesis and secretion could be expected, we were able to determine the interval between the corresponding date and the date of returning TSH secretion in twenty‐one patients. This latency time was 34 ± 9±7 days and proved completely independent of the total time until TSH reappearance. In contrast there was a highly significant correlation (r= 0·987; P<0·001) between the time to reach the assumed threshold level and the time to recovery of TSH secretion.

The disappearance of FTI, although widely variable from patient to patient, showed a constant rate throughout the full scale from elevated to practically absent concentrations. Thus, the initial part of the disappearance curve determines the length of time until restoration of TSH secretion. This is illustrated by the tight relationship (r= 0·92; P < 0·001) between FTI after 28 days of treatment and the time when TSH started to rise. Knowledge of the FTI on day 28 allows treatment to be tailored to the needs of the individual patient.
PROLACTIN STIMULATION BY INTRAVENOUS LABETALOL IS MEDIATED INSIDE THE CENTRAL NERVOUS SYSTEM
Authors: BARBIERI CRISTIANO , LAROVERE MARIA TERESA , MARIOTTI GIANCARLO , FERRARI CARLO , CALDARA ROBERTO
Published: March 2008

We have previously reported that labetalol infusion increases prolactin (PRL) secretion in hypertensive patients. In an attempt to investigate the site where labetalol stimulates PRL, the drug was infused intravenously (100 mg) into healthy subjects, both under basal conditions and after pretreatment with l‐dopa plus carbidopa (250 mg and 25 mg respectively every 6 h for 1 day), since this regimen has been reported to blunt the PRL responses to centrally acting stimuli. The effects of oral labetalol administration (100 and 200 mg) on PRL was also evaluated. Serum PRL concentration did not change after oral labetalol, whereas it was increased by intravenous drug administration. This effect was completely abolished by pretreatment with l‐dopa plus carbidopa. These findings, though they do not demonstrate the mechanism, suggest that the hyperprolactinaemia induced by labetalol is mediated inside the blood–brain barrier.
TSH RECEPTOR BINDING AND THYROID STIMULATION BY SERA FROM PATIENTS WITH GRAVES' DISEASE
Authors: GINSBERG J. , SHEWRING G. , SMITH B. REES
Published: March 2008

An investigation of the ability of TSH receptor antibodies to bind to the TSH receptor and stimulate thyroid function is described. Binding studies were carried out using 125I‐labelled TSH and detergent solubilised porcine TSH receptors, and the parameter of thyroid stimulation employed was 125I‐organifi‐cation in isolated porcine thyroid cells. Different GRAVES' sera were found to show different dose‐response relationships and three types of antibody activity were evident in the six samples studied. In two samples receptor binding and thyroid stimulating activities were approximately parallel. In two receptor binding was detectable at lower doses than stimulation while in the last two stimulation was detectable at lower doses than binding.

It is proposed that these characteristics are due to different populations of receptor antibodies which exhibit different degrees of TSH agonism. Furthermore one of the reasons for the relatively poor correlation between TSH receptor binding and thyroid stimulation observed in series of individual GRAVES' sera may be the presence of different populations of antibodies showing different dose‐response relationships with regard to binding and stimulation.
GONADOTROPHIN AND ALPHA SUBUNIT SECRETION BY HUMAN ‘FUNCTIONLESS’ PITUITARY ADENOMAS IN CELL CULTURE: LONG TERM EFFECTS OF LUTEINIZING HORMONE RELEASING HORMONE AND THYROTROPHIN RELEASING HORMONE
Authors: SURMONT D. W. A. , WINSLOW C. L. J. , LOIZOU M. , WHITE M. C. , ADAMS E. F. , MASHITER K.
Published: March 2008

The long‐term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post‐menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary ‘functionless’ adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.
SERUM CALCIUM CONCENTRATION IN HYPERTHYROIDISM AT DIAGNOSIS AND AFTER TREATMENT
Authors: DALY J. G. , GREENWOOD R. M. , HIMSWORTH R. L.
Published: March 2008

In a large, mainly outpatient, series of hyperthyroid patients who attended a district general hospital the serum concentrations of calcium and albumin were measured before and in many cases after treatment. The calcium level (mean ± SD) before treatment (2·41·0±21 mmol/1, n= 437) was significantly higher (P < 0·01) than afterwards (2·36 ± 0·15 mmol/1, n= 232) and the albumin level rose when the patients became euthyroid (from 40·5±3·1 g/1 to 44·0 ± 2·4 g/1; P < 0·01). After treatment neither value differed from those of an unselected group of out‐patients. The usual relation between the serum concentrations of calcium and albumin did not hold in the hyperthyroid subjects but reverted to normal on treatment; the variation, probably due to an increase in ionized calcium, leads to an overestimate of the ‘corrected calcium’ when conventional methods are used to calculate this figure. Thus, using a conventional formula 8·5% of our hyperthyroid patients would appear to have a calcium greater than 2·65 mmol/1 (normal mean plus 2 standard deviations) whereas using a correction factor specific for the hyperthyroid situation the figure is reduced to 5·7% which is only twice the expected proportion. The calcium level was significantly greater (P < 0·001) in those patients in whom initial T3 concentration was high (>7·2 nmol/1). There was no effect of T4 upon serum calcium which could not be accounted for by the action of T3. In this series of 437 patients there was no case of symptomatic hypercalcaemia. The maximum value was 2·80 mmol/1 in a patient with coincident primary hyperparathyroidism. Significant hypercalcaemia is rare in hyperthyroidism.
DOPAMINERGIC BLOCKADE OF THE RENIN‐ANGIOTENSIN‐ALDOSTERONE SYSTEM: EFFECT OF HIGH AND LOW SODIUM INTAKES
Authors: GORDON M. B. , MOORE T. J. , DLUHY R. G. , WILLIAMS G. H.
Published: March 2008

Recent investigations suggest that dopamine inhibits aldosterone secretion. To test the hypothesis that dopamine contributes to the reduced aldosterone secretion on a high sodium intake, eight normal subjects were studied in metabolic balance on both 200 and 10 mmol sodium diets. On each diet, the subjects received a constant 4 h intravenous infusion of the dopamine antagonist, metoclopramide (MCP). Although MCP significantly increased plasma aldosterone (PA) throughout the infusion on both diets, the maximum increment in PA was greater on the low (37 ± 5 ng/dl) than on the high (14 ± 4 ng/dl) sodium intake (P <0·02). The greater response on the low sodium intake could not be ascribed to changes in potassium, cortisol or ACTH. However, plasma renin activity (PRA) and angiotensin II (AII) levels were significantly (P <0·01) increased by MCP while on the low but not the high sodium intake.

We conclude that the rise in PA while on a high sodium intake reflects dopaminergic antagonism by MCP directly at the level of the adrenal gland. On the low sodium intake, the enhanced PA response to MCP probably reflects both a direct adrenal effect and an indirect effect mediated via activation of the renin‐angiotensin system.
CIRCANNUAL RHYTHMS OF PLASMA LUTEINIZING HORMONE, FOLLICLE‐STIMULATING HORMONE, TESTOSTERONE, PROLACTIN AND CORTISOL IN PREPUBERTY
Authors: BELLASTELLA A. , CRISCUOLO T. , MANGO A. , PERRONE L. , SINISI A. A. , FAGGIANO M.
Published: March 2008

For a period of four years we have been studying 106 healthy males and 66 healthy females, aged 6–10, by cross‐sectional design, to look for evidence of a circannual rhythm in LH, FSH, testosterone, PRL, and cortisol secretion. Plasma samples were taken at 0800 h and all hormones were measured by RIA. A cosine function was fitted to the single data to indicate any significant circannual (about 1 year) rhythm and to estimate its parameters: mesor, amplitude, and acrophase. Annual changes were validated in the secretion of: LH (annual crest time in January in both sexes), testosterone (studied only in males, annual crest time in July), and PRL (significant rhythm only in females with annual crest time in March). FSH and cortisol did not show an annual rhythm in both sexes. Our data suggest that sex influences the circannual hormonal rhythms from prepuberty onwards.
LACK OF EFFECT OF ETHANOL ON PLASMA CORTISOL IN MAN
Authors: DAVIS J. R. E. , JEFFCOATE W. J.
Published: March 2008

The effects of acute administration of ethanol were studied in a total of 18 normal male subjects. Sixteen men were given oral ethanol (2·5 ml/kg vodka or gin) and four received intravenous infusions of ethanol (1 ml/kg), at two times of day, 0900 h and 1800 h. Neither intravenous nor oral ethanol caused a specific rise in plasma cortisol, in contrast to previously reported work. There was no evidence for circadian variation in response.

Since ethanol does not release plasma cortisol in normal individuals, the pathogenesis of ‘alcohol‐induced pseudo‐Cushing's syndrome’ should be re‐considered.
THROMBOEMBOLIC COMPLICATIONS IN CUSHING'S SYNDROME
Authors: SMALL M. , LOWE G. D. O. , FORBES C. D. , THOMSON J. A.
Published: March 2008

Thromboembolic events are thought to occur with increased frequency in Cushing's syndrome due to the predisposing factors, obesity, hypertension, a raised haematocrit and major surgery plus a ‘hypercoagulable state’. To examine this postulate further we have studied 43 patients with Cushing's syndrome retrospectively and 10 patients prospectively to determine the incidence of arterial and venous thrombosis, both spontaneous and post‐operative.

Arterial events were noted in four cases (9%) and deep vein thrombosis or pulmonary thromboembolism (PTE) occurred in six cases (11%). Post‐operative PTE occurred in 2‐7% of all operations. These vascular complications tended to occur in the older patients with Cushing's syndrome.

In our series, clinically significant thromboembolic episodes appear no more common than expected and the indications for prophylactic anticoagulation (the older and more obese patients) may not be different from other patients undergoing major surgery. An incidental finding was of a greater frequency of hypertension in Cushing's patients due to an adrenal adenoma.