Showing papers in "Clinical Endocrinology in 1982"

Pulsatile secretion of LH, FSH, prolactin, oestradiol and progesterone during the human menstrual cycle.

Abstract: SUMMARY 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: 1the secretion of LH, FSH, PRL, oestradiol and progesterone is episodic in nature; 2a significant number of secretory episodes of FSH, LH and PRL are coincidental; 3the increased secretion of oestradiol from the pre-ovulatory follicle is associated with a rise in the frequency of episodic pulses of LH.

An improved radioreceptor assay for tsh receptor antibodies

Abstract: An improved receptor assay for TSH receptor antibodies is described in which detergent-solubilized TSH receptors and 125I-labelled TSH are used. Normal human serum and immunoglobulin concentrates from normal serum showed little effect on the interaction between labelled TSH and detergent-solubilized receptors whereas immunoglobulin concentrates from some Graves sera caused marked inhibition of TSH binding. Precipitation with polyethylene glycol was the most convenient way of preparing immunoglobulin concentrates and using this technique the assay could be completed in a few hours. The coefficient of inter assay variation at 51% inhibition of labelled TSH binding was 3.7% and analysis of serum samples from patients with Graves' disease (n = 42), Hashimoto's disease (n = 26), multinodular goitre (n = 9), rheumatoid arthritis (n = 10) and normal donors (n = 35) suggested that the assay could detect TSH receptor antibodies in about 80% of patients (treated and untreated) with Graves' disease.

Tissue Concentrations of Levonorgestrel in Women Using a Levonorgestrel-Releasing IUD

Abstract: Thirteen women who were scheduled for hysterectomy volunteered for the study. Nine women had a levonorgestrel-releasing intrauterine contraceptive device inserted between 36 and 49 days prior to surgery and four women were on oral levonorgestrel treatment for 7 days prior to surgery. After the surgical removal of the uterus, samples of endometrial, myometrial, fallopian tube and fat tissue were obtained. Methods for measuring tissue concentrations of levonorgestrel were developed and the uptake of levonorgestrel by fat tissue in vitro was studied. The concentrations of levonorgestrel in myometrial, fallopian tube and fat tissue were all of the same order, of between 1 and 5 ng/g of wet weight of tissue, in both the intrauterine device group and the orally treated group. In the endometrium the levonorgestrel concentrations were many-fold higher in the intrauterine device group. The in vitro experiments showed a rapid uptake of levonorgestrel and an unsaturability of the fat tissue by the steroid at the concentrations used. The fat tissue concentrations of levonorgestrel correlated with the plasma concentrations.

Dexamethasone suppression tests: usefulness of simultaneous measurement of plasma cortisol and dexamethasone

Abstract: The effect of oral dexamethasone on the plasma content of cortisol and dexamethasone was investigated in 175 patients suspected of having Cushing's syndrome. Plasma concentrations of cortisol and dexamethasone were measured by specific radioimmunoassays at 08.00 h following administration of either a low-low (0.5 mg), low (1.0 mg), high (4.0 mg) or high-high (8.0 or more mg) dose of dexamethasone at midnight. All seventeen patients with documented Cushing's syndrome exhibited resistance to the action of low-low and/or low dose dexamethasone on suppression of 08.00 h plasma cortisol content. Nine of twelve patients with pituitary dependent Cushing's syndrome had plasma cortisol values of less than 166 nmol/l following high-high dose testing. In 157 patients with suspected Cushing's syndrome, standard dexamethasone testing was considered unsatisfactory in at least 20%. After low-low or low dose tests 11% had supranormal cortisol values, but plasma cortisol content overlapped with values observed in patients with Cushing's syndrome only when plasma dexamethasone content was less than 5.6 nmol/l. Twelve per cent of patients suspected of having Cushing's syndrome had sufficient elevation of plasma dexamethasone values after low dose testing so that marked reduction of plasma cortisol might be expected even in patients with pituitary dependent Cushing's syndrome. Four patients receiving anticonvulsants had subnormal plasma levels of dexamethasone for the dose administered, but all exhibited normal suppression when plasma levels of dexamethasone and cortisol were correlated simultaneously. In summary, there is considerable variation in the plasma content of dexamethasone following oral doses. Simultaneous measurement of both plasma levels of dexamethasone and cortisol has proved most useful in identifying patients with unsatisfactory dexamethasone suppression tests.

Relationship of altered thyroid hormone indices to survival in nonthyroidal illnesses

Abstract: SUMMARY Although alterations of serum thyroid hormone indices are frequent in nonthyroidal illnesses, their relationship to survival is poorly defined. Consequently, the prevalence and prognostic relevance of alterations in thyroidal indices were evaluated prospectively in 195 patients requiring intensive medical therapy and in 75 critically ill patients with serum total T4 (TT4) levels below 3 μg/dl. In the 195 patients, serum total T3 (TT3) and TT4 levels were reduced in 69% and 43% respectively. Decreased TT4 levels had the highest correlation with mortality (P < 0·001) and correctly predicted outcome in 70% of patients. Other thyroidal indices, which were significantly different between survivors and nonsurvivors, correlated with TT4 and did not contribute independently to prediction accuracy when assessed by discriminant function analysis. In seventy-five patients with TT4 levels below 3 μg/dl, the nadir TT4 level appeared a median of 9 days (range 1–28) after hospital admission. The nonsurvivors lived a median of 6 days (range 0–42) and the survivors were discharged a median of 20 days (range 4–55) after the TT4 nadir. Only an increased free fraction of T4 (FFT4) was found to correlate significantly with mortality and contribute to prediction accuracy. An inhibition of serum T4 binding to carrier proteins could account for both the decreased serum TT4 and the increased FFT4 values. Serum TT4 and/or FFT4 levels may be useful in assessing the severity and predicting the clinical outcome of acute critical nonthyroidal illnesses.

Treatment of post menopausal osteoporosis. a controlled therapeutic trial comparing oestrogen/gestagen, 1,25‐dihydroxy‐vitamin d3 and calcium

Abstract: A controlled therapeutic trial on seventy-four 70-year-old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis. The bone mineral content (BMC) was measured by 125I-photonabsorptiometry at two sites in the distal part of the forearms, where the trabecular/cortical ratio is 0·25 and 1·5, respectively. Radiographs were done on the right hand to measure the metacarpal bone mass (cortical area/total area = CA/TA). After observing the spontaneous course of bone loss for 6 months the participants were allocated at random to 12 months’treatment with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and oestrogen/gestagen, alone or in combination, and calcium. The groups treated with oestrogen/gestagen [with or without 1,25(OH)2D3] showed a highly significant increase in BMC. In contrast bone mineral remained unchanged or decreased in both the calcium and the 1,25(OH)2D3 groups with a tendency towards more pronounced negative bone balance in the 1,25-(OH)2D3 group. Seven out of nineteen patients on 1,25(OH)2D3 developed hypercalcaemia, which necessitated a reduction in dosage. It is concluded that the new vitamin D metabolite, 1,25(OH)2 D3, given in clinically acceptable doses, is without value in the treatment of post menopausal osteoporosis.

Reduced nocturnal melatonin secretion in chronic schizophrenia: relationship to body weight.

Abstract: Melatonin was estimated by RIA in samples taken at 24.00 h and 08.00 h from twenty-one male chronic schizophrenics and twelve age--sex matched controls and subsequently in more frequent nocturnal samples from nine of the chronic schizophrenics. The 24.00 h melatonin level and the 24.00/08.00 h melatonin ratio were significantly reduced in the chronic schizophrenic patients. Similar results, with no evidence of subsidiary peaks of melatonin secretion, were obtained in those patients who were retested. No relationships between melatonin secretion and age or anterior pituitary hormone secretion were demonstrated, but an effect of body weight was noted which accounted, in part, for the difference between schizophrenics and controls. These results suggest that the low levels of melatonin noted in studies on depressed patients may not be specific and that body weight must be controlled in subsequent studies of melatonin secretion in patients with psychiatric disease.

Fertility after childbirth: post‐partum ovulation and menstruation in bottle and breast feeding mothers

Abstract: The resumption of postpartum menstruation and ovulation was studied in 10 bottlefeeding and 27 breastfeeding mothers. 1st menstruation occurred at 8.1 weeks (+or- 1.0 SE) in bottlefeeders and 32.5 weeks (+or- 2.5 SE) in breastfeeders (P<0.001); 1st ovulation occurred at 10.8 weeks (+or- 1.0 SE) in bottlefeeders and 36.4 weeks (+or- 2.5 SE) in breastfeeders (P<0.001). In bottlefeeders ovulation preceded 1st menses only in 2/10 (20%) of mothers but was regularly established thereafter occurring in 17/18 (94%) of 2nd and subsequent cycles. Breastfeeding did not postpone ovulation indefinitely because 13/27 of the breastfeeding mothers ovulated while still lactating; ovulation occurred in 9/27 (33%) of breastfeeding mothers during the phase of lactational amenorrhea but was followed by menstruation in every case. In breastfeeding mothers the frequency of ovular cycles progressively increased with time ovulation being observed in 9/20 (45%) of the 1st cycles during lactation 20/30 (66%) of later cycles during lactation 16/23 (70%) of 1st 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 1st day of consecutive menstrual cycles being 37.0 days +or- 3.3 SE during lactation compared with 29.8 days +or- 1.0 SE after lactation and 29.5 days +or- 1.0 SE in bottlefeeding mothers. This study shows that bottlefeeding is associated with an early resumption of postpartum menstruation and ovulation. In breastfeeding mothers there is complete suppression of ovulation during the greater part of lactational amenorrhea but ovualtion will return in a proportion of mothers just before the 1st menses. After return of menstruation during lactation the frequency of ovular cycles progressively increases but does not return to normal until complete weaning has taken place. (authors)

Pulsatile gonadotrophin secretion in hyperprolactinaemic amenorrhoea and the response to bromocriptine therapy

Abstract: SUMMARY 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.

Treatment of acromegaly by trans‐sphenoidal operation, 90‐yttrium implantation and bromocriptine: results in 230 patients

Abstract: SUMMARY Two hundred and thirty patients with acromegaly were diagnosed and treated in a prospective cooperative study in twelve university clinics. Primary treatment was: trans-sphenoidal surgery (152 patients), trans-sphenoidal surgery with additional cryotherapy (eighteen patients), Yttrium-90-implantation (thirty patients), bromocriptine (thirty patients). The results of endocrine assessment before treatment and 6 months after operation, 90-Y implantation or commencement of bromocriptine therapy are reported. The best results (low GH, no or little deterioration of pituitary function, low complication rate) were achieved by trans-sphenoidal surgery, especially in patients with intrasellar tumours (basal GH < 5 ng/ml in 59·7%). Results were less good with increasing tumour size. Additional cryosurgery was accompanied by a high rate of anterior pituitary insufficiency and is no longer employed. Yttrium-90-implantation resulted in less improvement in GH levels (basal GH < 5 ng/ml in 51·7. of patients with intrasellar tumours), a high rate of pituitary insufficiency and more complications. Bromocriptine treatment was least effective in lowering GH concentrations (basal GH < 5 ng/ml in 33% of patients with intrasellar tumours). Different criteria for treatment success were compared. In the entire group, basal GH concentrations below 5 ng/ml were attained in 51·7. of all patients whose values were higher than this prior to treatment. Suppressibility of GH below 2 ng/ml during glucose loading occurred in only 34·9%. An abnormal GH response to TRH/LHRH was present in 47·2. before and in 43·4% after/during treatment. The prognostic significance of this latter finding must be evaluated by further study.

24‐hour profiles of melatonin, cortisol, insulin, c‐peptide and gip following a meal and subsequent fasting

Abstract: SUMMARY 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.

Opiate mediation of amenorrhoea in hyperprolactinaemia and in weight-loss related amenorrhoea

Abstract: SUMMARY 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.

Suppressed prolactin but normal neurophysin levels in cigarette smoking breast‐feeding women

Abstract: 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.

Cushing's syndrome in pregnancy—treatment with metyrapone

Abstract: A 23-year-old female presented with severe Cushing's syndrome in the 23rd week of pregnancy. Investigations showed plasma cortisol 770 nmol/l (08.00 h) and 850 nmol/l (23.00 h); plasma ACTH was 10 ng/l (08.00 h) and 27 ng/l (23.00 h); urinary free cortisol excretion was 2460 nmol/24 h. Dexamethasone 2 mg 6-hourly for 48 h suppressed the 08.00 h plasma cortisol only to 680 nmol/l. Abdominal C.T. scan showed a right adrenal adenoma. The patient was treated with metyrapone and a good clinical improvement ensued. Plasma cortisol was reduced to 300-500 nmol/l. Depsite ultrasonographic evidence of normal fetal growth, urinary oestriol excretion was markedly deficient. Prior to the spontaneous onset of labour, there was a marked rise in plasma cortisol despite continuous metyrapone treatment. A normal female infant was born at 37 weeks' gestation. The maternal adrenal adenoma was subsequently removed. The deficiency of oestriol synthesis during the pregnancy may be explained by metyrapone-induced inhibition of C19-hydroxylation.

Opiates control acth through a noradrenergic mechanism

Abstract: The administration of 16 mg of naloxone to six normal male subjects produced a significant rise in plasma cortisol. Pre‐treatment with the noradrenergic α1‐antagonist, thymoxamine 0.2 mg/kg, blocked this rise. It is suggested that opiate inhibition of the pituitary—adrenal axis is mediated via a noradrenergic pathway.

Opiate modulation of the pituitary‐adrenal axis: effects of stress and circadian rhythm

Abstract: SUMMARY The opiate control of the pituitary-adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met-enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversely, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin-induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined. It is suggested that there is a constant tonic inhibition of the pituitary-adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.

Fertility after childbirth: infant feeding patterns, basal PRL levels and post-partum ovulation.

Abstract: The infant feeding patterns at the time of first ovulation after childbirth were determined in a longitudinal study of twenty-seven mothers who chose to breast feed their babies. Fourteen mothers suppressed ovulation throughout lactation and thirteen ovulated while still breast feeding. Those who ovulated while breast feeding had all introduced two or more supplementary feeds/day, reduced suckling frequency to less than six times/day and reduced suckling duration to less than 60 min/day at the time of first ovulation. Basal PRL levels had fallen to below 600 microunits/l in all but one of the mothers at first ovulation. Those mothers who suppressed ovulation for more than 40 weeks post-partum (late ovulation group) were compared with those who ovulated between 30 and 40 weeks post-partum (middle group) and with those who ovulated before 30 weeks post-partum (early group). The late ovulation group breast-fed for longest, suckled most intensively, maintained night feeds for longest and introduced supplementary feeds most gradually. This study suggests suckling may be the most important factor inhibiting the return of ovulation during lactation and that policies which encourage increased suckling frequency and duration will maximize the contraceptive effects of breast feeding.

Review: pituitary prolactinomas

Abstract: A distinction is made between large and small prolactinomas. They have different presenting symptoms, sex distribution and natural history. From a series of 263 patients with obviously enlarged pituitary fossae on lateral skull x‐ray, seventy‐four were identified as having chromophobe adenomas and thirty‐four of these are believed to have prolactinomas (46%). It is pointed out that an enlarged pituitary fossa is not necessarily due to a pituitary tumour. Levels of prolactin are given for patients with craniopharyngiomas, hypothalamic disorders, Cushing's syndrome, Nelson's syndrome and acromegaly. It is emphasized that a modestly elevated prolactin level with an enlarged pituitary fossa does not mean that the patient has a prolactinoma, the hyperprolactinaemia may be due to interference with the hypothalamic prolactin inhibiting mechanism. The special problems of acromegaly are discussed.

Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly.

Abstract: SUMMARY To determine whether the improvement in clinical status of patients with active acromegaly correlates with a reduction of circulating somatomedin-C, serum immunoreactive somatomedin-C was measured in twenty-seven patients before and during bromocriptine therapy. The patients were assessed using a clinical and metabolic score which included both subjective criteria of improved sweating and facial features, and objective criteria of a reduction in ring circumference and the area under the glucose tolerance curve. Using this, together with the change in GH levels before and during bromocriptine therapy, the patients could be divided into three groups. In one group, there was no clinical improvement, a less than 30% decline in somatomedin-C, and in four of six patients no significant decline in GH. In both the other groups there was clinical improvement and a greater than 30% decrease in somatomedin-C. In one of these two groups, however GH did not decline, while in the other it was reduced significantly. The results suggest that during bromocriptine treatment of acromegaly, serum somatomedin-C concentrations correlate better with clinical status than does serum GH. Since some patients have no significant fall in GH but show both clinical improvement and a reduction in somatomedin-C, it seems likely that in some patients bromocriptine may improve acromegaly by a mechanism other than a simple decrease in total immunoreactive GH secretion.

Salivary cortisol assays for assessing pituitary‐adrenal reserve

Abstract: SUMMARY Cortisol concentrations were determined in matched samples of plasma and saliva from patients and healthy volunteers throughout the course of standard tests of pituitary and adrenal reserve. During insulin tolerance tests the percentage incremental changes in cortisol concentrations in saliva were strictly comparable with those in plasma and showed less inter-subject variance. The clinical decision taken with regard to the integrity of the pituitary-adrenal axis was the same whether plasma or salivary cortisol was measured. In the short tetracosactrin test changes in salivary cortisol reflected those in plasma and patients with loss of adrenal responsiveness would have been diagnosed as such using either measurement. In normal subjects, the circadian rhythm in salivary cortisol concentrations exactly paralleled that in plasma. Absence of the circadian rhythm in cases of hypercortisolism was seen as well in saliva as in plasma. Assays for salivary cortisol therefore provide information which is as clinically useful as that of plasma determinations. Since salivary cortisol concentrations were shown to reflect the free, biologically active fraction in plasma, salivary assay may, in selected cases, provide results of greater diagnostic significance than plasma total concentrations.

Salivary testosterone: relationship to unbound plasma testosterone in normal and hyperandrogenic women.

Abstract: A sensitive radioimmunoassay (RIA) was used to measure salivary testosterone levels in normal women, in patients with polycystic ovaries (PCO), and in women with hirsutism. There was a highly significant correlation (r = 0.79, P less than 0.001) between the concentration of testosterone in saliva [12.3 +/- 7.8 (SD) pg/ml] and the concentration of unbound testosterone in plasma (5.2 +/- 3.1 pg/ml) in matched samples collected from 56 women including normals, patients with clinical signs of hyperandrogenism, and women treated with a combination of cyproterone acetate (CA) and ethinyl oestradiol (EE). The unbound plasma testosterone was measured in the dialysate directly using a sensitive RIA. Salivary and plasma testosterone levels in patients with PCO (20.6 +/- 8.5 and 626 +/- 187 pg/ml respectively, n = 14) and in those with hirsutism (13.9 +/- 5.6 and 421 +/- 170 pg/ml, n = 30) were significantly higher (P less than 0.001) than levels in normal women (7.7 +/- 2.6 and 196 +/- 68 pg/ml, n = 36). Treatment for 3 months with CA and EE resulted in a decrease (mean 68%) in salivary testosterone levels in all patients studied (n = 15), but the suppression of plasma testosterone (mean 34%) was not observed in all cases. It is concluded that measurement of salivary testosterone gives a useful indication of levels of biologically available androgen in hyperandrogenic women, before and during CA/EE therapy.

Pituitary-ovarian function before, during and after the menopause: a longitudinal study.

Abstract: 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 greater than 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.

Corticosteroid‐induced osteopenia and vitamin d metabolism. effect of vitamin d2, calcium phosphate and sodium fluoride administration

Abstract: Thirty-one patients scheduled for long-term (24 weeks) treatment with prednisone in comparatively high doses were randomly allocated to two further treatment groups. Group A received prednisone plus 'triple-treatment' (vitamin D2 45000 iu twice weekly, sodium fluoride 50 mg and calcium phosphate 4.5 g daily), group B received only prednisone. The study was undertaken in order to evaluate the effect of prednisone- and triple-treatment upon bone mineral content (BMC) and vitamin D metabolism. The groups were comparable with regard to age, sex and prednisone dose. BMC fell rapidly and similarly in both groups, demonstrating that the triple-treatment has no preventive effect on corticosteroid induced osteopenia. Serum concentrations of 25OHD2, 25OHD3 and 1,25(OH)2D were unchanged in group B (without triple-treatment), whereas in group A 25OHD2 increased enormously, 25OHD3 was suppressed possibly by substrate competition for hydroxylation in the liver and 1,25(OH)2D was halved. The suppression of 1,25(OH)2D may be an effect of raised 25OHD2 alone, or in combination with corticosteroid excess.

Development of adrenocortical failure in non-Addisonian patients with antibodies to adrenal cortex. A clinical follow-up study.

Abstract: SUMMARY Out of 1036 sera tested for the presence of antibodies to adrenal cortex using the indirect immunofluorescence (IFL) method, fifteen out of 323 patients with Graves' thyrotoxicosis, 6/105 Hashimoto's thyroiditis, 3/29 myxoedema, 2/49 asymptomatic autoimmune thyroiditis, 1/12 subacute thyroiditis, and 4/130 with myasthenia gravis were positive. Thirty antibody-positive non-addisonian patients were tested for subclinical adrenocortical failure and followed up over a period of 1–3–5 years. Three women with Graves' disease had biochemical signs of early Addison's disease at the first Synacthen test. Two young women with controlled Graves' thyrotoxicosis developed a diminished adrenocortical reserve within 2 and 3 years, respectively; one of them developed anovulatory cycles which did not respond to clomiphene treatment. Both patients had high titres of complement-fixing adrenal antibodies before the adrenal failure could be recognized by functional tests. One elderly female patient in whom a euthyroid goitre with adrenal and thyroid antibodies was detected in 1977, developed Graves' thyrotoxicosis in 1980. These observations indicate that antibodies to adrenal cortex have a high clinical significance and may allow the early diagnosis of Addison's disease even in the absence of specific clinical symptoms.

Fertility after childbirth: adequacy of post‐partum luteal phases

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

Liver damage and sex hormones in chronic male alcoholics

Abstract: 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.

The behavioural effects of testosterone undecanoate in adult men with klinefelter's syndrome: a controlled study

Abstract: 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.

Effect of radioiodine on stimulatory activity of graves’immunoglobulins

Abstract: The effects of 131I therapy on the activity of thyroid stimulating antibody (TSAb) and thyrotrophin binding inhibiting immunoglobulin (TBII) in nineteen patients with Graves' disease have been studied. Prior to 131I administration TSAb was detected in 84%, and TBII in 68% of patients. Following 131I administration TSAb and TBII were detectable in 100% of patients. The elevation 3 months after treatment of the means of both the TSAb and TBII indices for the group of nineteen patients was highly significant compared with pre treatment values. All the patients went into remission during the course of the study and the TSAb index declined in all patients, becoming undetectable in eleven; TBII also declined in most patients but remained detectable in thirteen. The study furthermore afforded the opportunity for a direct comparison of binding with stimulatory activity. These results show that after 131I therapy for Graves' hyperthyroidism there is a transient increase in TSAb as well as TBII, followed by a decline, and that the measurement of binding and stimulatory activities are in good general agreement.

Serum levels of 25‐hydroxyvitamin d, 24,25‐dihydroxyvitamin d and parathyroid hormone in patients with femoral neck fracture in southern finland

Abstract: Serum concentrations of 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D] and immunoreactive parathyroid hormone (PTH) were determined in elderly patients with fracture of the femoral neck and in age-matched controls during summer, winter and early spring in southern Finland The expected seasonal variation in 25-OHD values was observed in both patients and controls, though the patient group had significantly lower values during winter (P less than 002) and spring (P less than 001) The 24,25(OH)2D:25-OHD ratio remained constant in both patients and controls throughout the study A significant negative correlation between PTH and 25-OHD values was found in the patient group Thus, vitamin D deficiency may contribute to the high incidence of femoral neck fractures in elderly people, and the increased PTH activity, observed in many patients with these fractures, is secondary to vitamin D deficiency

Serum lipids, postheparin plasma lipase activities and glucose tolerance in patients with prolactinoma.

Abstract: SUMMARY Serum total cholesterol and triglyceride levels were determined in forty-seven women with prolactinoma and in eighty-four age- and weight-matched control women. Oral glucose tolerance tests (OGTT) were performed and postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were determined in twelve patients before and after transsphenoidal removal of the prolactinoma. The mean levels of serum cholesterol and triglyceride were significantly higher in patients than in controls. The 90% cut-off line of controls for serum cholesterol was exceeded by 36% and that for serum triglyceride by 23% of the patients. The triglyceride levels were raised only in patients with GH-deficiency whereas patients with normal GH secretion had normal triglyceride. Plasma LPL activity was significantly reduced whereas plasma HL activity was in the upper range of normal. After the removal of prolactinoma the serum prolactin levels decreased in all patients and seven started to menstruate. The oral glucose tolerance was improved and the plasma insulin response decreased. Serum lipid levels and the lipase activities, however, did not change. Conclusion: prolactinoma is associated with metabolic abnormalities characterized by hyperlipidaemia, low plasma LPL activity and insulin resistance.