bluuebunny/crossref_metadata_2025 huggingface dataset:
LEVELS OF THE OXYTOCIN‐ASSOCIATED AND VASOPRESSIN‐ASSOCIATED NEUROPHYSINS IN PLASMA AND THEIR RESPONSES IN ESSENTIAL HYPERTENSION
Authors: AMICO JANET A. , CORDER C. N. , McDONALD R. H. , ROBINSON A. G.
Published: March 2008

A group of 89 individuals with essential hypertension was evaluated with several measurements including the neurophysin believed to be the human oxytocin neurophysin (OT‐Np), and the human vasopressin neurophysin (VP‐Np). The neurophysins are proteins synthesized within cells of the supraoptic and paraventricular nuclei in conjunction with their respective hormones oxytocin and vasopressin as part of a common precursor molecule and so may reflect the simultaneous presence in plasma of their associated hormones. A poor but statistically significant correlation was noted between levels of OT‐Np and renin activity in plasma (PRA) either supine (r= 0·248) or erect (r= 0·255). Levels of OT‐Np averaged 1·75 ng/ml and were inversely correlated with creatinine (r= ‐ 0·252), supine blood pressure (r= ‐ 0·450), plasma volume (r= ‐ 0·327), and 24‐hour urine sodium (r= ‐ 0·313). Levels of Ot‐Np could be suppressed by infusion of physiologic saline. Levels of OT‐Np were lower in the volume expanded state and were positively correlated with the quantity of sodium excreted into a 24‐hour urine collected after the infusion (r= 0·426) and inversely correlated with the supine systolic (r= ‐ 0·379) and supine diastolic (r= ‐ 0·455) blood pressures recorded after the infusion of saline. Oestrogen, a stimulus to the secretion of OT‐Np, did not account for the elevation of OT‐Np observed in the study, since mean levels of oestradiol (E2) in a subset of the patients with elevated OT‐Np (E2= 36 pg/ml) were not different from levels in subjects with lower values of OT‐Np (E2= 45 pg/ml). Levels of VP‐Np averaged 0·85 ng/ml and correlated positively with PRA (r= 0·353) and 24‐hour urine excretion of dopamine (r= 0·44), and inversely with age (r= ‐ 0·263), blood pressure, and 24‐hour urine excretion of sodium (r= ‐ 0·226). Erect posture caused an elevation of VP‐Np. Therefore, levels of OT‐Np and VP‐Np respond to certain physiological stimuli and levels of OT‐Np are elevated in a subgroup of subjects with essential hypertension.
THYROTOXIC MYOPATHY ASSOCIATED WITH SUBACUTE THYROIDITIS
Authors: TAJIMA K. , MASHITA K. , YAMANE T. , YOSHIKAWA H. , KAWAMURA S. , KANG J. , KAJIYAMA Y. , MORIWAKI K. , TARUI S.
Published: March 2008

We report a case of subacute thyroiditis complicated by thyrotoxic myopathy. Previously thyrotoxic myopathy has been described as being associated with GRAVES' disease. The patient in this study was a 35‐year‐old man who developed proximal dominant muscular weakness and atrophy during the course of subacute thyroiditis. His myopathic symptoms regressed as his serum thyroxine and triiodothyronine levels returned to normal, however it took a relatively long period of time for them to do so. This suggests that marked myopathy may develop even in cases of subacute thyroiditis if the thyrotoxic state persists for a long period of time.
ANDROGEN LEVELS DURING CYPROTERONE ACETATE AND ETHINYL OESTRADIOL TREATMENT OF HIRSUTISM
Authors: RUBENS R.
Published: March 2008

Androgen levels were measured before and during 12 months of treatment with cyproterone acetate (50 mg 5th to 16th day of cycle) and ethinyl oestradiol (50 μg 5th to 26th day of cycle) in 26 patients suffering from dysfunctional hirsutism. Patients were included in whom androgen levels after a dexamethasone suppression test fell above the range found in normal non‐hirsute women on dexamethasone. Eighty percent of patients showed a substantial improvement of their Ferriman and Gallwey score after 12 months of treatment. During the treatment the mean level of testosterone was 64%, androstenedione 55%, testosterone oestradiol binding globulin 365%, apparent free testosterone 30%, dihydrotestosterone 74%, 5‐androstanediol 43%, dehydroepiandrosterone 44%, 5‐androstenediol 67% and dehydroepiandrosterone sulphate 74% of basal levels. From the results it is concluded that this treatment is effective both clinically and biochemically in reducing hyperandrogenism.
FAMILIAL ACROMEGALY
Authors: JONES M. K. , EVANS P. J. , JONES I. R. , THOMAS J. P.
Published: March 2008

An uncle and nephew with acromegaly are described. Two other families with acromegaly have been reported by others and three other possible cases are reviewed. Our patients are unlikely to form part of the multiple endocrine neoplasia (MEN) type 1 syndrome because of the absence of other endocrine disease at an advanced age. A family history of acromegaly should be considered in those presenting with the disease.
A RECEPTOR ASSAY FOR THE MEASUREMENT OF TSH RECEPTOR ANTIBODIES IN UNEXTRACTED SERUM
Authors: SOUTHGATE KAY , CREAGH FIONUALA , TEECE MICHELLE , KINGSWOOD C. , SMITH B. REES
Published: March 2008

A receptor assay for TSH receptor antibodies is described in which unextracted serum, detergent solubilised TSH receptors and 125I‐labelled TSH are used. The assay was rapid and reproducible with coefficients of inter‐assay variation of 12·3%, 2·1 and 2·6% at mean inhibition of TSH binding values of 11, 53, and 79 respectively. Assay sensitivity could be increased by reducing the volume of receptors used but some increase in the scatter of values obtained with individual normal sera was also observed. Comparison of human and porcine TSH receptor preparations indicated that porcine tissue gave greater sensitivity. Analysis of different groups of patients and normal subjects (n= 21) showed the absence of detectable TSH receptor antibody activity in 16 patients with rheumatoid arthritis, 10 with multinodular goitre and 12 with Hashimoto's disease. However the antibody was readily detectable in 28 out of 28 GRAVES' patients (treated and untreated) who were hyperthyroid at the time of assay.
EFFECT OF ANDROGENS ON PLASMA SOMATOMEDIN‐C/INSULIN‐LIKE GROWTH FACTOR I RESPONSES TO GROWTH HORMONE
Authors: CRAFT W. H. , UNDERWOOD L. E.
Published: March 2008

In search of the mechanism for the relatively high plasma somatomedin‐C (Sm‐C) concentrations in pubertal boys and girls, we have measured the plasma Sm‐C responses to exogenous growth hormone (GH) in prepubertal hypopituitary boys before and after testosterone administration. Sm‐C responses were determined in 5 hypopituitary boys (9–14 years of age) who were given two successive injections of GH (0·1 U/kg) 48 h apart. Eight days later, after administering 200 mg testosterone IM, their Sm‐C responses to the same GH challenge were reassessed. There were no significant differences between the pre‐testosterone Sm‐C response to GH and the post‐testosterone response, despite evidence for reductions in 24 h urinary nitrogen excretion and serum urea nitrogen concentrations in response to testosterone. The results provide no evidence that androgen augments the effect of GH to raise plasma Sm‐C during puberty, or that androgen has a direct stimulatory effect on Sm‐C production. By inference and from published reports, it appears more likely that a sex hormone‐stimulated increase in GH secretion is responsible for the increased Sm‐C observed during puberty.
INFUSION OF GRADED CONCENTRATIONS OF SOMATOSTATIN IN MAN: PHARMACOKINETICS AND DIFFERENTIAL INHIBITORY EFFECTS ON PITUITARY AND ISLET HORMONES
Authors: SKAMENE A. , PATEL Y. C.
Published: March 2008

The resent study was undertaken (1) to determine the plasma levels of somatostatin‐like immunoreactivity (SLI) during constant infusion of graded concentrations of synthetic somatostatin‐14 (S‐14); (2) to determine the half‐life (t1/2) and metabolic clearance rate (MCR) of SLI; (3) to correlate the plasma SLI levels with the degree of inhibition of pituitary and islet hormone secretion and (4) to establish whether the plasma SLI levels capable of inhibiting pituitary and islet hormone secretion fall into the physiological range. Four normal subjects on separate occasions were each infused with saline or S‐14 (25, 50, and 75 μg/h) at a constant rate for 2 1/2 h. Thirty min following the infusions, TRH (200 μg) and arginine (0·5 g/kg) were given i.v. Blood samples were drawn every 15 min for measurement of GH, TSH, insulin, glucagon and SLI (by RIA of acid‐ethanol extracted plasma) and at rapid intervals for 10 min after stopping the infusions for measurement of SLI disappearance. During S‐14 infusions, plasma SLI rose rapidly, reached a plateau from 15–150 min and declined rapidly on cessation of the infusions with a mean t1/2 of 2·72 ± 0·45 min. Mean plateau SLI levels were: 149 ± 3 pg/ml (25 μg/h), 465 ± 35 pg/ml (50 μg/h), and 1244 ± 71 pg/ml (75 μg/h). SLI was cleared rapidly but the MCR exhibited a dose‐dependent decrease from 3225 ± 699 ml/min for the 25 μg infusion to 1249 ± 241 ml/min for the 75 μg/h infusion (P < 0·05). The 25 μg/h infusion dose produced near‐maximal suppression of GH secretion and inhibited insulin secretion but not TSH or glucagon secretion. The intermediate dose significantly inhibited GH, TSH, and insulin but not glucagon whereas the 75 μg/h infusion suppressed all four hormones. In six normal subjects endogenous plasma SLI rose from a basal value of 32·5 ± 4·9 pg/ml to 75·5 ± 9·0 pg/ml following ingestion of a mixed meal. This level was 50% of that resulting from
POSTPARTUM HYPOGONADOTROPHINISM: EVIDENCE FOR INCREASED OPIOID INHIBITION
Authors: ISHIZUKA B. , QUIGLEY M. E. , YEN S. S. C.
Published: March 2008

To investigate a proposed role for endogenous opioids in the inhibition of LH: RH‐gonadotrophin release in the postpartum hypogonadotrophic state, LH and FSH responses to naloxone infusion (1·6 mg/h for 2 h) and to a pulse of LHRH (10 μg) were measured in five non breast‐feeding women. Sequential studies were made at four intervals during the first 25 d postpartum. LH and FSH responses to naloxone were absent on Day 10 postpartum, but significant increments were observed in all studies performed between Days 13–25 postpartum. The relative increments of FSH and LH during naloxone varied as the puerperium progressed; a 3‐fold greater release of FSH than LH was found on Day 13 to 15 while the reverse was observed on Day 25. The intermediate days (17–20) yield an equal response. There was a positive linear correlation between the LH and FSH responses to naloxone infusion and to LHRH. These data suggest that the hypogonadotrophinism of the puerperium is due at least in part to increased opioid inhibition of LHRH secretion.
THE FEMINISATION OF GONADOTROPHIN RESPONSES IN INTACT MALE TRANSSEXUALS
Authors: GOH H. H. , RATNAM S. S. , LONDON D. R.
Published: March 2008

In castrated animals and hypogonadal men other workers have shown an LH surge following oestrogen administration similar to that found in the normal female. However, there is no evidence that this can be achieved in intact males. We have therefore studied male transsexual patients before and after chronic oestrogen therapy given for at least three months to feminise the body habitus before undergoing plastic surgery. Subjects were assessed for the acute effects of oestradiol valerate on sex steroid hormone levels and gonadotrophin responses to gonadotrophin releasing hormone. The results showed that longterm treatment could transform the normal male pattern of a suppressive eifect of oestrogen on gonadotrophin release to one where the oestrogen increased LH levels and amplified the effect of LHRH on gonadotrophin release. This pattern is similar to that found in normal women and indicates that longterm oestrogen treatment to males can feminise gonadotrophin responses.
FACTORS IN THE CONTROL OF PLASMA RENIN ACTIVITY AND CONCENTRATION IN TYPE 1 (INSULIN‐DEPENDENT) DIABETES
Authors: DRURY P. L. , BODANSKY H. J. , ODDIE C. J. , EDWARDS C. R. W.
Published: March 2008

Possible factors involved in the control of plasma renin activity (PRA) and concentration (PRC) have been analysed in 49 patients with long‐standing Type 1 diabetes and in 40 healthy controls matched for age and sex. Eighteen of the diabetic subjects were clinically free of all microvascular and macrovascular complications of their disease (Group A); 31 had proliferative retinopathy (Group B). Both lying and standing PRA and PRC were similar in Group A and healthy controls. Mean PRA was 50–115% higher in Group B diabetics than in controls (P<0·001 supine and erect) and 50–70% higher than in Group A diabetics (P<0·05 supine and erect); PRC also was 60% higher in Group B than in Group A (P<0·05 supine and erect). Control subjects showed significant falls in both PRA and PRC with increasing age, while Groups A and B showed significant falls in PRA or PRC with age. Group A showed a significant inverse correlation between systolic blood pressure and supine PRC (r= ‐0·57), but this was not significant in the controls and was completely absent in Group B. With correction for the effect of age there were significant relationships of PRA and PRC with sodium excretion in the controls and in Group A, but not in Group B. PRA and PRC are thus normal in uncomplicated long‐standing Type 1 diabetes, but regulation of renin secretion appears to be impaired in patients with microvascular disease. Renin secretion inappropriate to their blood pressure and sodium status may contribute to maintenance of their relative hypertension.; Correspondence: Dr P. L. Drury, Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE.
ABNORMAL DIETARY REGULATION OF ERYTHROCYTE INSULIN RECEPTOR AFFINITY IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: WARD G. M. , NAYLOR B. A. , SARGENT R. M. , TURNER R. C.
Published: March 2008

Decreased insulin binding to receptors is associated with the insulin resistance of obese and non‐obese non‐insulin‐dependent diabetics. ‘Down Regulation’ by elevated insulin levels has been suggested as the cause, but factors influencing receptor affinity have not been examined. To investigate the control of receptors in diabetes, 10 non‐insulin‐dependent diabetics and 10 normal subjects were studied after 6 d on low and 6 d on high calorie diets of fixed composition (700 and 2800 Kcal/70 kg of ideal body weight). The binding of insulin by erythrocytes of non‐diabetics, as predicted, increased on the low and decreased on the high calorie diets, due to altered affinity. In contrast, the binding in the diabetics did not change significantly, and the responses to the low and high calorie diets were less than in the normal subjects (P < 0·05 and P < 0·001 respectively). Indeed, the insulin binding in all 5 non‐obese diabetics changed in the opposite direction (P < 0·01) to the non‐diabetics, whereas the obese diabetics showed a mixed response. The changes in receptor binding in the diabetics was completely unrelated to the diurnal plasma insulin levels during 24 h studies. We conclude that the dietary regulation of erythrocyte insulin receptor affinity in non‐insulin‐dependent diabetes is abnormal, and insulin receptor affinity is regulated by factors other than insulin. The relation of this abnormality to the insulin resistance needs further investigation.
SPECIFIC SUPPRESSOR T CELL FUNCTION IN A PATIENT WITH GRAVES' DISEASE AND HER HEALTHY IDENTICAL TWIN
Authors: BALÁZS CŠ. , STENSZKY VALERIA , KOZMA L. , FARID NADIR R.
Published: March 2008

Immunoregulatory defects have been suggested in autoimmune disorders including GRAVES' disease. The finding that Concanavalin A‐induced suppressor T cell function was sub‐optimal in GRAVES' disease has been disputed; a restricted defect in TSH‐receptor antigen‐specific suppressor cells has instead been proposed by Okita et al. (1980). To explore this further, we studied both specific and non‐specific suppressor cell function in a pair of HLA identical twins, one of whom had GRAVES' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/106 cells) the patient's mononuclear cells (MNCs) incorporated more {3H}‐thymidine (7365 cpm/106 cells) in response to thyroid membrane antigen (TMA). Removal of glass‐adherent cells before addition of antigen increased {3H}‐uptake by cells from the healthy twin to 1808 cpm but reduced those from the GRAVES' twin to 3411 cpm. The influence of MNCs cultured with Con A or TMA for 24 h upon {3H}‐thymidine uptake by 2 × 106 indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non‐specific and specific suppressor cell function respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H‐thymidine uptake 3250 vs 7365 cpm/106). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/106 cells). We conclude that (I) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) the increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of {3H}incorporation upon their removal; (3) in the patient, the specific suppressor cell defect is more severe than the non‐specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory defect in Graves' disease.
MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING
Authors: MOMOTANI NAOKO , ITO KUNIHIKO , HAMADA NOBORU , BAN YOSHIO , NISHIKAWA YOSHIHIKO , MIMURA TAKASHI
Published: March 2008

Six hundred and forty‐three neonates from mothers with GRAVES' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6·0% (three of 50), 0·3% (one of 350), 1·7% (two of 117) and 0·0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P < 0·01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.
SALIVARY CORTISOL LEVELS IN TRUE AND APPARENT HYPERCORTISOLISM
Authors: EVANS P. J. , PETERS J. R. , DYAS J. , WALKER R. F. , RIAD‐FAHMY D. , HALL R.
Published: March 2008

Total plasma cortisol measurements may be misleading when there are variations in the plasma cortisol‐binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol‐binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic‐pituitary‐adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary‐dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half‐life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary‐dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion. The correlation between plasma and salivary cortisol measurements during the dexamethasone infusion was r=0·989 (P < 0·001) for normals and r= 0·982 (P < 0·001) for Cushing's patients. Measurements of plasma and salivary cortisol were compared in pregnancy and during low dose oestrogen therapy; both these conditions are known to be associated with elevated cortisol binding globulin concentrations. A significant difference was demonstrated between the 0900 h plasma cortisol levels of normal subjects and those both in the third trimester of pregnancy of the oestrogen containing contraceptive pill. No difference was observed in the 0900 h salivary cortisol between control and pregnant or oestrogen treated groups.
EFFECT OF METOCLOPRAMIDE ON ALDOSTERONE AND REGULATORY FACTORS IN MAN
Authors: GILCHRIST N. L. , ESPINER E. A. , NICHOLLS M. G. , DONALD R. A.
Published: March 2008

To determine the role of known secretagogues in the aldosterone response to dopamine blocking agents, plasma levels of ACTH, angiotensin II, potassium and plasma catecholamines were measured in five normal male subjects before and after intravenous injection of saline or 10 mg metoclopramide. There were no consistent changes in hormone levels after saline injection. After metoclopramide, plasma aldosterone increased three‐fold to peak values at 20 min post‐injection. A significant increase in aldosterone was observed within 10 min during which period there was no significant change in plasma ACTH, plasma renin activity All or K. Plasma levels of cortisol, noradrenaline, adrenaline and dopamine showed no significant changes after injection of metoclopramide which induced a ten‐fold rise in plasma prolactin. These results provide direct evidence that factors other than the plasma concentration of ACTH, All and K—or fluctuations in plasma catecholamines—are likely to be responsible for the acute increase in plasma aldosterone after metoclopramide injection in normal man.
CHOLINERGIC REGULATION OF PANCREATIC POLYPEPTIDE SECRETION IN CHRONIC RENAL FAILURE
Authors: LAMERS C. B. H. W. , VAN LEUSEN R. , DE JONG A. J. L. , VAN LEER E. , DIEMEL J. M. , PEETOOM J. J. , JANSEN J. B. J. M.
Published: March 2008

Secretion of pancreatic polypeptide (PP) is regulated mainly by cholinergic mechanisms and we have studied this in patients with chronic renal failure (CRF). Basal serum PP concentrations in 25 patients with CRF (401 ± 80; 116–2100 pmol/1; mean ± SEM and range) were significantly higher than in 65 normal subjects (33 ± 2; 21–120 pmol/1, P<0·001). Ingestion of a standard test meal induced significantly larger increases in serum PP in 11 patients with CRF (304 ± 45; 155–640 pmol/1) than in 11 normal subjects (140 ± 33; 51–440 pmol/1, P < 0·005). Insulin‐hypoglycaemia (0·1 U/kg i.v.) provoked similar increases in serum PP in five patients with CRF (404 ± 79; 170–665 pmol/1) as in five normal subjects (449 ± 92; 180–706 pmol/1). Administration of atropine (1 mg i.v.) did not normalize the elevated basal serum PP concentrations in five patients with CRF. On the other hand, administration of the same dose of atropine 60 min after ingestion of food decreased postprandial serum PP levels to basal values within one hour both in five patients with CRF and in six normal subjects. Sephadex G‐50 column chromatography of basal, postprandial and post‐atro‐pine sera from three patients with CRF revealed at least three different molecular forms. The PP peak coeluting with the 4200 molecular weight human PP standard comprised more than half of total PP immunoreactivity and was the only peak to be influenced by feeding or atropine. We conclude that in patients with CRF, PP secretion stimulated by cholinergic mechanisms is normal. In such patients post‐prandially released PP is dependent mainly upon cholinergic mechanisms, whereas the elevated basal serum PP concentration is not under cholinergic control.
PRELIMINARY EXPERIENCES WITH A BIOASSAY FOR ADRENOCORTICOTROPHIN (ACTH) IN UNEXTRACTED HUMAN PLASMA USING DISPERSED GUINEA‐PIG ADRENAL CELLS
Authors: LAMBERT A. , FROST J. , ROBERTSON W. R.
Published: March 2008

A simple, accurate and precise dispersed cell bioassay suitable for the assay of ACTH levels >50 ng/1 in unextracted human plasma is described. Isolated adrenal cells were prepared by tryptic digestion of the guinea‐pig adrenal gland and cortisol production by these cells was controlled specifically by ACTH. The cortisol response to 2 ng/1 of human pituitary ACTH (1–39) was always significantly (P < 0·05, n= 17) different from the control. ACTH concentrations between 1 and 20 ng/1 gave a 14 ± 3 fold (n= 17) increment in cortisol response. Dilutions of test plasmas were parallel with standard ACTH (1–39) when the plasma concentrations were maintained throughout at 4% (1 in 25 dilution) by the addition of dexamethasone‐suppressed plasma (‘ACTH free’). Using a 25 fold plasma dilution, the limit of detection of ACTH in unextracted plasma was 50 ng/1. Recovery of ACTH (1–39) spiked into dexamethasone suppressed plasma at concentrations of 250 and 100 ng/1 was 97·10% (n=17) and 114 ± 15% (n= 17) respectively. The within assay coefficient of variation (CV) of both quality control and patients' samples never exceeded 9% while between assay variation was 13%. The sample throughput was 30 plasma samples/week/technician.
PROINSULIN IN HUMAN SERUM: PROBLEMS IN MEASUREMENT AND INTERPRETATION
Authors: GRAY I. P. , SIDDLE K. , DOCHERTY K. , FRANK B. H. , HALES C. N.
Published: March 2008

The immunoreactivity of an extracted pancreatic human proinsulin standard in an indirect immunoradiometric assay was found to be at least one hundred times higher than that of biosynthetic human proinsulin. Limited tryptic digestion of the biosynthetic proinsulin increased its immunoreactivity in the assay and this was attributed to the production of partially cleaved proinsulin molecules which still retained the C‐peptide moeity. This inference was confirmed by the finding that pure samples of 65/A1 and 32/33 split proinsulins reacted in the assay very similarly to the pancreatic proinsulin standard. The implications of these results are that the immunoassays of proinsulin using antisera to C‐peptide may recognise the intact proinsulin molecule very poorly, if at all, and that the ‘proinsulin’ measured by such assays of human serum may be largely if not entirely intermediates of proinsulin cleavage.
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA: ASSOCIATION WITH NEONATAL PRIMARY HYPERPARATHYROIDISM, AND POSSIBLE LINKAGE WITH HLA HAPLOTYPE
Authors: SOPWITH A. M. , BURNS CLAIRE , GRANT D. B. , TAYLOR G. W. , WOLF EVA , BESSER G. M.
Published: March 2008

A kindred is described, six members of which fulfilled criteria for the syndrome of familial hypocalciuric hypercalcaemia (FHH). The majority of these individuals were asymptomatic: their hypercalcaemia was revealed by biochemical screening after parathyroid surgery had failed to diminish the elevated serum calcium concentration of the index case. In contrast to those members of the family diagnosed as adults, the daughter subsequently born to the index case included in her expression of FHH clinical features of severe neonatal primary hyperparathyroidism. Four hyperplastic parathyroid glands were excised, and following surgical intervention the baby improved clinically and accelerated the healing of her skeletal lesions. Her case suggests that an association does exist between FHH and neonatal primary hyperparathyroidism. Of the ten individuals at risk, inheritance of hypocalciuric hypercalcaemia was paralleled in eight cases by inheritance of the HLA haplotype All BW55 CW3 DR4. Such possible linkage has not previously been reported.
THE EFFECT OF OESTROGEN (MESTRANOL) ON THE THYROTROPHIN RESPONSE TO THYROTROPHIN RELEASING HORMONE IN POSTMENOPAUSAL OOPHORECTOMISED WOMEN
Authors: ABDALLA H. I. , BEASTALL G. H. , HART D. M.
Published: March 2008

The thyrotrophin (TSH) responses to thyrotrophin releasing hormone (TRH) in 16 oophorectomised postmenopausal women on long term treatment with mestranol 24 μg daily were compared to those in 16 oophorectomised postmenopausal women on placebo treatment. No significant difference between the groups was found in either basal TSH levels or the TSH response to TRH. It is therefore unlikely that the difference in TSH response to TRH between men and women of reproductive age is due to a direct stimulatory effect of oestrogen in women.
ANTITHYROID TREATMENT OF MATERNAL HYPERTHYROIDISM DURING LACTATION
Authors: LAMBERG B.‐A. , IKONEN E. , ÖSTERLUND K. , TERAMO K. , PEKONEN F. , PELTOLA J. , VÄLIMÄKI M.
Published: March 2008

Eleven pregnant women were treated for hyperthyroidism with carbimazole (CZ) and one with propylthiouracil (PTU). Based upon a previous study it was decided that lactation should be permitted if the dose required after delivery did not exceed 15 mg of CZ or 150 mg of PTU. In the patients studied here the daily dose of CZ varied from 5 to 15 mg and that of PTU was 125 mg. TSH was measured in cord blood and in the blood of the newborn infants usually after 2 and 3 weeks of lactation. Serum T4 was measured serially in the infants' blood from day 4 up to 21 day of age, at least. In all instances the TSH concentration in cord blood remained below 45 mU/1 the level used in screening for neonatal hypothyroidism. Serum TSH and T4 were all within the appropriate reference limits during the 3 weeks of study with only one exception. In the infant whose mother was treated with PTU the serum T4 measured 5 d after birth was slightly below the lower limit but later returned to normal. Since serum TSH and T4 did not deviate from the reference range in newborn infants during lactation, we conclude that breast‐feeding can be permitted if the daily dose of CZ does not exceed 15 mg (or 150 mg of PTU) and if facilities are available for measuring neonatal serum TSH and T4.
THE ROLE OF ENDOGENOUS OPIOIDS IN THE CHLORPROPAMIDE ALCOHOL FLUSH
Authors: JOHNSTON C. , WILES P. G. , MEDBAK S. , BOWCOCK S. , COOKE E. D. , PYKE D. A. , REES LESLEY H.
Published: March 2008

The response of plasma immunoreactive met‐enkephalin (IR‐met‐enkephalin) to ethanol (8 g by mouth) after chlorpropamide (250 mg daily for 14 d) was studied in three groups of non‐insulin dependent diabetics (a) six diabetics who showed chlorpropamide alcohol flush (CPAF) and in whom the reaction could be blocked by indomethacin, (b) five diabetics who showed CPAF but in whom the flush could not be blocked by indomethacin and (c) five diabetics who did not show CPAF. A rise in plasma IR‐met‐enkephalin was observed in all three groups. When the two groups of flushers were re‐tested with the addition of an infusion of naloxone a rise in plasma IR‐met‐enkephalin was still demonstrated in both groups regardless of whether the flush was blocked by naloxone. Naloxone blocked the flush only in those six subjects whose flush could be blocked by indomethacin. In five subjects, all flushers, CPAF was tested using intravenous and oral ethanol in doses producing similar plasma ethanol levels. A facial flush was induced by both intravenous and oral ethanol. In three flushers, plasma IR‐met‐enkephalin levels were measured during CPAF testing with both intravenous and oral ethanol. None showed a rise in plasma IR‐met‐enkephalin after intravenous ethanol, despite the appearance of a facial flush, whereas all showed a rise after oral ethanol. We therefore conclude that CPAF is unlikely to be caused by a rise in plasma IR‐met‐enkephalin.
APPARENT MINERALOCORTICOID EXCESS AND DEFICIENT 11β‐OXIDATION OF CORTISOL IN A YOUNG FEMALE
Authors: HARINCK H. I. J. , VAN BRUMMELEN P. , VAN SETERS A. P. , MOOLENAAR A. J.
Published: March 2008

A 19‐year‐old female, known to have had hypertension and hypokalemic alkalosis since the age of 9 months, was found to have suppressed renin, negligible plasma and urinary aldosterone and low plasma levels of other known sodium‐retaining steroids. Despite the normal plasma cortisol the urinary excretion of 17‐oxosteroids and 17‐oxogenic steroids was low as was the cortisol secretion rate, suggesting a diminished metabolic clearance of cortisol. This was confirmed by the demonstration of a prolonged t1/2 of 14C‐cortisol. The abnormally high urinary excretion ratios of cortisol to cortisone, tetrahydracortisol to tetrahydrocortisone and 11‐hydroxy‐aetiocholanolone to 11‐oxy‐aetio‐cholanolone indicate that the diminished cortisol breakdown is the result of deficient 11β‐oxidation. Moreover, the urinary excretion of free cortisol was elevated, probably due to diminished tubular reabsorption of cortisol. Hypokalemic alkalosis did not respond to spironolactone, but was partly corrected by amiloride. No response to dexamethasone was observed, but dexamethasone combined with aminogluthetimide normalized blood pressure and serum K. These findings support the involvement of a sodium‐retaining, kaliuretic steroid in this rare syndrome.
INHIBITORY EFFECT OF CIMETIDINE ON L‐DOPA‐STIMULATED GROWTH HORMONE RELEASE IN NORMAL MAN
Authors: ZANOBONI A. , GALMOZZI G. , MARINONI S. , ZANOBONI‐MUCIACCIA WANDA
Published: March 2008

Some evidence suggests the existence of a histaminergic influence on GH secretion in animals and man. We used cimetidine, a specific H2‐receptor antagonist, to study the possible interference of H2‐receptor blockade on plasma GH release by L‐dopa and on PRL inhibition by L‐dopa in normal man. Seven healthy normal male volunteers aged 23–36 years received a single oral dose of L‐dopa (500 mg) or an i.v. bolus of cimetidine (300 mg) or both (L‐dopa 30 min before cimetidine). Blood samples were taken at various times over 2 h and plasma GH and PRL levels measured. Cimetidine alone did not alter basal plasma GH values; L‐dopa elicited the well‐known GH releasing effect with peak values at 75 min (15.65 ± 2.8 ng/ml); cimetidine injected 30 min after L‐dopa ingestion significantly blunted the GH response to L‐dopa and peak values (4.7 ± 1.6 ng/ml) were delayed to 105 min. Cimetidine provoked a rapid rise in plasma PRL with the peak value of 15 ± 3 ng/ml at 15 min, followed by a return to near basal values in 90–120 min. L‐Dopa completely inhibited the PRL response to cimetidine. We conclude that there is an inhibitory influence of the H2‐receptor antagonist cimetidine on GH release by L‐dopa. This, together with the action of cimetidine on PRL secretion (with or without L‐dopa), suggests a possible antidopaminergic effect of H2‐receptor blockade at the level of the central nervous system.
TOTAL DEFICIENCY OF CORTICOSTEROID‐BINDING GLOBULIN
Authors: ROITMAN A. , BRUCHIS S. , BAUMAN B. , KAUFMAN H. , LARON Z.
Published: March 2008

An obese 15‐year‐old boy of Jewish Iranian origin who is the offspring of consanguineous parents was found to have very low levels of total cortisol in the plasma. Investigation of the family revealed a complete lack of cortisol‐binding‐globulin (CBG) in the proband and a sister, evidently the first cases of total CBG deficiency to be reported. The parents and a brother were found to have half the normal levels. This study indicates that CBG deficiency, a benign condition, is compatible with a codominant or recessive autosomal trait inheritance.
INFLUENCE OF DIETARY CALCIUM ON SERUM 1,25‐DIHYDROXYVITAMIN D CONCENTRATIONS IN RENAL STONE FORMERS
Authors: D'AMOUR P. , GASCON‐BARRÉ MARIELLE , DUFRESNE L. , PERREAULT J. ‐P.
Published: March 2008

The role of 1,25‐dihydroxyvitamin D (1,25(OH)2D) in the pathogenesis of idiopathic hypercalciuria was studied in 37 renal stone formers who, during two 10‐day periods, followed first a normal and then a low calcium diet. The following samples were taken during each diet; (1) 24 h urine; (2) fasting blood and urine; (3) blood and urine following a 1 g oral calcium load. Patients were divided according to serum calcium level, 24 h urinary calcium excretion on the first diet and fasting calcium excretion on the second diet. Eight patients were found to be normocalciuric (NSF), 16 had absorptive hypercalciuria (AH), five renal hypercalciuria (RH) and eight primary hyperparathyroidism. In NSF and AH, a positive correlation was found between the fasting and the 24 hour urinary calcium (r = 0.787, P<0.001), while negative correlations were found between the fasting urinary calcium and the serum parathyroid hormone (r= ‐0.703, P<0.001) or the fasting urinary cyclic AMP (r= ‐0.434, P < 0.01). Patients with RH had higher serum PTH and urinary cAMP levels for a given degree of fasting calciuria mainly on the low calcium diet. Mean serum 1,25(OH)2D was similar in NSF (43.6 ± 4.5 pg/ml), AH (43.6 ± 2.3 pg/ml) and RH (40.4 ± 4.8 pg/ml) on the first diet; increases were similar in all groups after 10 d of calcium restriction. A positive correlation was found between the serum 1,25(OH)2D concentrations and the 24 h urinary calcium excretion on the first diet in NSF (r = 0.889, P<0.001) but not in AH or RH. There was no evidence of such correlation with the low calcium diet. No correlation between the calciuric response to calcium loading and the serum concentrations of 1,25(OH)2D was found. The results suggest that serum concentrations of 1,25(OH)2D may be related to urinary calcium excretion in NSF more than in AH or RH. The factors responsible for the hyperabsorption of calcium in the latter patients remain to be elucidated.
OVARIAN STEROIDOGENESIS IN AN ADRENALECTOMIZED GIRL WITH 21‐HYDROXYLASE DEFICIENCY
Authors: ZACHMANN M. , MANELLA B. , KEMPKEN B. , KNORR‐MUERSET G. , ATARES M. , PRADER A.
Published: March 2008

A girl with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency could not be controlled by conventional treatment, and was adrenalectomized at age 8.5 years (bone age 13.5 years). After surgery, puberty and menarche occurred. On replacement therapy, her progress was uneventful up to the age of 16 years, when menstruations ceased and signs of virilization reappeared. Testosterone, androstenedione, and 17‐hydroxyprogesterone in plasma, and pregnanetriol in urine were high, but DHEA in plasma, and pregnenetriol and pregnanetriolone in urine were low. Oestrogens in plasma were normal. There was no steroid response to ACTH, and marked, but somewhat slow suppression by dexamethasone. HMG induced a strong rise in oestrone and oestradiol. Ethinyloestradiol reduced not only oestradiol in plasma, but also testosterone, androstenedione, and 17‐hydroxyprogesterone. With subsequent dexamethasone treatment, menstruation restarted, and the values returned to normal. It is concluded that virilization may reoccur in patients with 21‐hydroxylase deficiency even after adrenalectomy, and that the ovaries in this patient contain some tissue, which has properties of adrenal (suppressibility by dexamethasone) and ovarian tissue (suppressibility by ethinyl oestradiol, preference for Δ4‐pathway, low steroid 11‐oxygenation) at the same time.
ACUTE DOPAMINERGIC BLOCKADE BY SULPIRIDE STIMULATES β‐ENDORPHIN SECRETION IN PREGNANT WOMEN
Authors: SAMRA A. B. ABOU , PUGEAT M. , DECHAUD H. , NACHURY L. , TOURNIAIRE J.
Published: March 2008

The pars intermedia of the pituitary gland is well developed in most animal species but rudimentary in adult human subjects. Unlike the anterior pituitary, the intermediate lobe metabolizes proopiomelanocorticotrophin (POMC) mainly to β‐endorphin and to α‐melanotrophin (α‐MSH). This activity of the pars intermedia is under an inhibitory dopaminergic control. Biochemical and immunohistochemical evidence suggests the hyperplasia of the intermediate lobe during human pregnancy. The present study demonstrates that an acute dopaminergic blockade by sulpiride dramatically increases plasma concentrations of β‐endorphin in pregnant women but not in non‐pregnant women providing functional evidence for the intermediate lobe hypothesis.
DIFFERENTIAL EFFECTS OF OVINE AND HUMAN CORTICOTROPHIN‐RELEASING FACTOR IN HUMAN SUBJECTS
Authors: HERMUS A. R. M. M. , PIETERS G. F. F. M. , PESMAN G. J. , BUYS W. C. A. M. , SMALS A. G. H. , BENRAAD T. J. , KLOPPENBORG P. W. C.
Published: March 2008

Ten healthy subjects received 200 μg of human CRF (hCRF) and 200 μg of ovine CRF (oCRF) as an intravenous bolus injection on two different occasions. After hCRF plasma ACTH levels rose significantly (P< 0.0005, by Friedman's nonparametric analysis of variance) from a basal value of 35 ± 3 pg/ml (mean ± SEM) to a peak value of 80 ± 7 pg/ml 30 min after hCRF administration. This ACTH response was followed by a rise in plasma cortisol levels (P< 0.0005, by Friedman's test) from a baseline value of 0.32 ± 0.03 /μmol/l to a peak value of 0.56 ± 0.02 /μmol/l 60 min after hCRF. Ovine CRF elicited similar rises in the plasma ACTH and cortisol levels. However, as derived from the faster rate of decline of ACTH and cortisol after hCRF than after oCRF, human CRF had a significantly shorter duration of action than ovine CRF in humans. Human CRF not only stimulated ACTH release by the human pituitary gland but also prolactin release. After hCRF administration prolactin levels rose significantly (P< 0.005, by Friedman's test) from a basal value of 179 ± 18 mU/l to a peak value of 288 ± 34 mU/l at 10 min.
CONTRASTING EFFECTS OF SUBCUTANEOUS PULSATILE GnRH THERAPY IN CONGENITAL ADRENAL HYPOPLASIA AND KALLMANN'S SYNDROME
Authors: GORDON D. , COHEN H. N. , BEASTALL G. H. , HAY I. D. , THOMSON J. A.
Published: March 2008

A patient with congenital adrenal hypoplasia (AH) and hypogonadotrophic hypogonadism was treated with pulsatile subcutaneous GnRH therapy for 16 weeks in an attempt to induce puberty. No rise in serum LH or FSH concentrations occurred despite increasing doses of GnRH (2.8 μg/pulse‐22.4 μg/pulse). In contrast a similar programme of therapy successfully initiated the biochemical changes of puberty in a patient with Kallmann's syndrome. Both patients before therapy had low basal serum LH and FSH concentrations with blunted LH and FSH responses to GnRH stimulation. After 1 week, serum LH and FSH rose into the normal adult range in the patient with Kallmann's syndrome. This study fails to confirm a previous report which suggested that intermittent low dose GnRH therapy may be of value in inducing puberty in AH. The reasons for the difference of pituitary responsiveness to GnRH in AH and Kallmann's syndrome are unclear at present.
THE INFLUENCE OF ADRENERGIC DENERVATION ON THE RESPONSE TO FEEDING OF THE GASTROENTEROPANCREATIC SYSTEM IN MAN
Authors: FRIER B. M. , CORRALL R. J. M. , ADRIAN T. E. , BLOOM S. R. , STRACHAN R. K. , HEADING R. C.
Published: March 2008

The effect of adrenergic denervation on the metabolic and hormonal responses to a standard meal was studied in six tetraplegic subjects (pre‐ganglionic sympathectomy) and compared with six normal subjects. Gastric emptying, estimated by isotope scintiscanning, was similar in both groups. Following the meal the mean blood glucose and plasma insulin rose in both groups, but were higher and remained elevated for longer in the tetraplegic subjects. There were no significant differences in the secretion of pancreatic glucagon, enteroglucagon, gastric inhibitory peptide (GIF) and neurotensin between the two groups. The mean basal and post‐prandial levels of pancreatic polypeptide and motilin were significantly higher in the tetraplegic group. This study confirms the presence of mild glucose intolerance in tetraplegic subjects which is not explicable on the basis of abnormal insulin or pancreatic glucagon secretion or abnormal gastric emptying. In addition the results provide evidence for a sympathetic inhibitory influence on the secretion of pancreatic polypeptide and motilin in man, which is probably adrenergically‐mediated.
HYPERINSULINAEMIA AND INSULIN RESISTANCE OF CIRRHOSIS: THE IMPORTANCE OF INSULIN HYPERSECRETION
Authors: PROIETTO J. , DUDLEY F. J. , AITKEN P. , ALFORD F. P.
Published: March 2008

The mechanism for the hyperinsulinaemia in cirrhosis was investigated using two different approaches. In the first study, the metabolic clearance rate of insulin was measured at steady state in 13 cirrhotic and 13 weight‐matched control subjects. With comparable insulin infusion rates (1.00 ± 0.19 versus 1.07 ± 0.15 mU/kg/min), steady‐state plasma insulin concentrations (104 ± 25 versus 87 ± 12 μU/ml; P>0.5) and MCRIRI (13.6 ± 1.6 versus 15.4 ± 2.0 ml/kg/min; P>0.5) were similar. In the second study, fasting and oral glucose stimulated C‐peptide/insulin ratios were compared in 16 cirrhotic and 18 weight matched control subjects. Although fasting glucose levels were significantly higher in the cirrhotic groups, all values were in the normal range (5.5 ± 0.3 versus 4.8 ± 0.1 mmol/l, P < 0.02). However, fasting insulin (0.171 ± 0.02 versus 0.068 ± 0.004 nmol/l) and C‐peptide (1.02 ± 0.13 versus 0.42 ± 0.02 nmol/l) were strikingly higher (P< 0.001) in cirrhotic subjects. On the other hand, fasting C‐peptide/insulin ratios were not statistically different in the two groups (6.18 ± 0.52 versus 6.77 ± 0.46; P>0.3). This suggests that beta cell hypersecretion was the principal cause of the fasting hyperinsulinaemia, rather than decreased insulin hepatic extraction. Following the glucose load in 13 of the control and seven of the cirrhotic group, the C‐peptide/insulin ratio fell in both groups but was significantly lower in the cirrhotic compared to control subjects at 30, 60 and 120 min, consistent with possible impairment of hepatic insulin extraction. We conclude that, in cirrhosis, fasting hyperinsulinaemia is due to beta cell hypersecretion, whereas at higher insulin secretion rates following a glucose load, reduced hepatic insulin extraction may also contribute to the hyperinsulinaemia.
STUDIES ON THE MECHANISMS OF SOMATOSTATIN RELEASE AFTER INSULIN INDUCED HYPOGLYCAEMIA IN MAN
Authors: WEBB SUSAN , LEVY I. , WASS J. A. H. , LLORENS A. , PENMAN ERICA , CASAMITJANA ROSER , WU PING , GAYA JOAN , MARTINEZ M. J. , RIVERA FRANCISCA
Published: March 2008

Insulin‐induced hypoglycaemia, which stimulates gastric acid secretion, is associated with an increase in circulating somatostatin levels in man. In order to assess the mechanisms involved in this rise, six normal volunteers connected to a Biostator for continuous glucose monitoring were studied, on three separate occasions. On each occasion after basal blood sampling, 0.15 i.u. /kg body weight of insulin was administered i.v. and further samples were obtained intermittently over 150 min. On one occasion, dextrose was infused by the Biostator to prevent hypoglycaemia, while on the other two, a constant infusion of either normal saline or the specific H2 antagonist cimetidine was administered. Insulin plus dextrose caused no significant changes in circulating somatostatin levels, whereas insulin plus saline was associated with a marked, sustained and significant rise in all subjects; insulin plus cimetidine also produced a rise but it was delayed; the area under the curve was significantly (P<0.05) greater with insulin plus saline than with insulin plus cimetidine. These results show that in man insulin itself does not stimulate somatostatin secretion directly, but indirectly via hypoglycaemia. Further, the inhibition of gastric acid secretion with cimetidine reduces somatostatin release during insulin‐induced hypoglycaemia. This suggests that gastric acid may mediate somatostatin secretion associated with insulin‐induced hypoglycaemia.