bluuebunny/crossref_metadata_2025 huggingface dataset:
FERTILITY AFTER CHILDBIRTH: CHANGES IN SERUM GONADOTROPHIN LEVELS IN BOTTLE AND BREAST FEEDING WOMEN
Authors: GLASIER ANNA , McNEILLY A. S. , HOWIE P. W.
Published: March 2008

Changes in basal serum gonadotrophin levels during the resumption of ovarian activity post partum have been studied longitudinally in breast and bottle feeding mothers. On the basis of urinary steroid levels, ovarian activity was classified as showing complete suppression, follicular activity only, deficient luteal phases or normal menstrual cycles. Complete suppression of ovarian activity during lactation was associated with normal levels of FSH but low levels of LH. The resumption of follicular development was not accompanied by any increase in levels of either LH or FSH when compared with the phase of complete suppression and this pattern persisted during menstrual cycles characterized by deficient luteal phase progesterone secretion. Basal LH levels did not rise to normal levels during lactation until the resumption of normal ovulatory cycles. FSH secretion remained at a level comparable with the follicular phase of normal ovulatory cycles throughout the post partum period.

In mothers who did not breast feed, LH levels rose more rapidly than in breast feeding mothers and had returned to within normal limits by three weeks post partum. At 4 weeks post partum FSH levels were lower in bottle feeding mothers than in breast feeders probably in response to the early rise in oestrogen levels among bottle feeders.

These results suggest that decreased LH but not FSH secretion may be important in maintaining infertility associated with breast feeding. The absence of any change in LH or FSH at the onset of follicular development suggests that an alteration in the sensitivity of the ovary to gonadotrophins or in the pattern of gonadotrophin secretion may be involved in the observed patterns of post partum ovarian activity during lactation.
INHIBITION OF 3‐BETA‐HYDROXY STEROID DEHYDROGENASE ACTIVITY IN FIRST TRIMESTER HUMAN PREGNANCY WITH TRILOSTANE AND WIN 32729
Authors: van der SPUY Z. M. , JONES D. L. , WRIGHT C. S. W. , PIURA B. , PAINTIN D. B. , JAMES V. H. T. , JACOBS H. S.
Published: March 2008

The effects of equivalent doses of two inhibitors of the 3‐beta‐hydroxy steroid dehydrogenase enzyme system—WIN 24540 (trilostane) and WIN 32729—on the secretion of progesterone in early human pregnancy are described. Patients and controls less than 12 weeks pregnant were given a single dose of either drug and the resultant hormonal changes monitored for 71/2 h.

A consistent fall in plasma progesterone concentrations occurred at all doses and, at the highest dose, they fell to less than 50% of pre‐treatment levels. However, whilst with trilostane the associated increase in plasma concentrations of pregnenolone was always accompanied by a rise in plasma DHA concentrations, with WIN 32729 there appeared to be no adrenal effect at the lower dosage levels.

These data demonstrate inhibition of progesterone secretion in human pregnancy using non‐hormonally active steroids. The pattern of steroid precursors indicates that while both drugs inhibit 3‐beta‐hydroxy steroid dehydrogenase activity, WIN 32729 is more selective and only interferes with adrenal steroid biosynthesis at high doses.
DIURNAL PATTERNS OF SERUM IMMUNOREACTIVE CALCITONIN IN HEALTHY MALES AND IN INSULIN DEPENDENT DIABETICS
Authors: EMMERTSEN K. , CHRISTENSEN S. ENGKJER , SCHMITZ O. , MARQVERSEN J.
Published: March 2008

Serum immunoreactive calcitonin (iCT) was measured half‐hourly for 27 h in five healthy males and four insulin dependent juvenile diabetic males during normal activity. In another group of four healthy males studied during 12 h the first meal was postponed 8 h. Duplicate measurements of an internal reference standard in all radioimmunoassay runs gave a mean value of 58 pg/ml with an intra‐assay variation of 4.7 pg/ml (SD) and an interassay variation of 10.8 pg/ml (SD). Results of serum iCT determinations in one subject were excluded as the majority of values were below the lower limit of detection (20 pg/ml).

For all three groups serum iCT levels varied little and unsystematically during day and night‐time and no diurnal peaks were observed. Food intake did not affect serum iCT levels significantly. With the present radioimmunoassay, results of serum iCT measurements can thus be interpreted without taking the sampling time or meals into account.

Expert technical assistance has been provided by Inga Bisgaard, Joan Hansen, Janet Mikkelsen, and Birgit Mortensen. This work was supported by grants from the Danish Cancer Society, the Danish Medical Research Council, and the Institute of Experimental Clinical Research, University of Aarhus.
ACUTE CHANGES IN THYROID FUNCTION TESTS FOLLOWING INGESTION OF THYROXINE
Authors: SYMONS R. G. , MURPHY L. J.
Published: March 2008

The timing of blood sample collection in relation to ingestion of thyroxine has been thought to be of no consequence in the assessment of patients receiving thyroxine medication. We have investigated changes in serum thyroid hormones after oral ingestion of thyroxine.

Therapeutic doses of thyroxine (100–300 μg) were given to five normal, euthyroid subjects and eleven patients receiving long‐term thyroxine‐replacement medication. Blood samples were collected prior to and following ingestion of thyroxine.

A significant increase in total thyroxine (T4), free thyroxine index (FTI) and free T4 (FT4) concentration was observed at all doses. No significant change was observed in 3,5,3′‐triiodothyronine, 3,3′,5′‐triiodothyronine or thyrotrophin concentrations. Although T4, FT1 and FT4 were significantly elevated 1 h after ingestion of all doses of thyroxine and remained elevated for at least 6 h, supranormal values were observed only after ingestion of the highest dose of thyroxine. The levels of T4, FT1 and FT4 in patients receiving thyroxine should be interpreted in relation to the time of thyroxine administration. Standardisation of blood collection in patients receiving thyroxine replacement would be desirable.
INSULIN HYPOGLYCAEMIA AND CHOLINERGIC BLOCKADE: RESPONSE OF PLASMA IMMUNOREACTIVE β‐ENDORPHIN
Authors: COPOLOV D. , JETHWA J. , STERN A. , CLEMENTS J. , FUNDER J. W.
Published: March 2008

Six normal subjects were studied to investigate the mechanisms involved in the release of immunoreactive β‐endorphin (ir‐βEP) in response to insulin hypoglycaemia. Insulin alone (0·2 U/kg body weight) was followed after a 30 min lag period by a ≃ 2·5 fold elevation of plasma ir‐βEP, with a return to basal levels by 90 min. Concurrent infusion of 10% dextrose at 250 ml/h for 2 h prevented the increase in plasma ir‐βEP levels, suggesting an effect of hypoglycaemia rather than a direct effect of insulin. Premedication with atropine 0·6 mg at ‐30 min was followed by hypoglycaemia equivalent to that seen with insulin alone, but no increase in plasma ir‐βEP, suggesting the involvement of cholinergic mechanisms in the neural mediation of ir‐βEP release in response to hypoglycaemia.
EFFECT OF THE COMBINATION OF DEXAMETHASONE AND SODIUM IPODATE ON SERUM THYROID HORMONES IN GRAVES' DISEASE
Authors: ARTEAGA E. , LÓPEZ J. M. , RODRÍGUEZ J. A. , MICHAUD P. , LÓPEZ G.
Published: March 2008

To investigate the effect of the combination of dexamethasone (Dex) and sodium ipodate (SI) on hyperthyroidism, we studied 24 patients with typical GRAVES' disease, divided into four groups of six persons each. Three groups (Study I) were studied acutely (24 h) to determine the effects of Dex (5 mg every 12 h intramuscularly), SI (one oral dose of 3 g) and both drugs at the same doses, upon T4, T3, and rT3 at 0900 h before therapy was started and 24 h later. The group on Dex and that on SI had a similar T3 decrement of 25·9±4·0% and 35·8±5·0%, respectively, (P < 0·05), whereas the effect of both drugs combined was greater (64·2±3·6%; P<0·01, Dex, and P<0·01, SI, respectively). The increment of rT3 was markedly greater in those patients on SI than in those on Dex (561·3±149·2% and 58·9±11%, respectively, P<0·025). A fourth group (Study II) was studied for seven days while receiving both Dex (1 mg orally three times per day) and SI (500 mg orally three times per day). Both T4 (from 18·8 ± 1·1 to 13·1 ± 1·1 μg/dl, P < 0·02) and T3 (from 593 · 41 to 136·3 ± 12·7 ng/dl, P< 0·001) decreased at day 8. The initial brisk increment of rT3 at 24 h (808 ± 149%, P< 0·005) then diminished concomitantly with the fall of its precursor, T4. The pulse rate correlated with plasma T3 concentration (r= 0·67, P< 0·001) and varied from 104·7 ± 3·9 on day 1 to 77·3 ± 3·0 beats/min (P< 0·001) on day 4 and then remained stable. These results show that Dex and SI have potent inhibitory effects at the level of peripheral conversion of T4 and on the thyroid gland itself and that the combined use of these drugs significantly increases these effects. Considering the rapid clinical improvement of thyrotoxicosis achieved with both drugs, this regimen may be valuable in the initial treatment of some patients.
THE RELATIONSHIP BETWEEN 17β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY AND OESTROGEN CONCENTRATIONS IN HUMAN BREAST TUMOURS AND IN NORMAL BREAST TISSUE
Authors: BONNEY ROSEMARY C. , REED M. J. , DAVIDSON KATHRYN , BERANEK P. A. , JAMES V. H. T.
Published: March 2008

The activity of 17β‐hydroxysteroid dehydrogenase (17βHSD) was measured in human breast tumours and in normal breast tissue from premenopausal, perimenopausal and postmenopausal women. Enzyme activity was higher in tumour tissue than in normal tissue from the same breast and under the conditions of the assay the oxidation of oestradiol was higher than the reduction of oestrone. The physiological status of the women in the study did not relate to the activity of the enzyme in either normal or tumour tissue although fibroadenomas had less activity than adenocarcinomas.

In postmenopausal women tumour tissue oestrogens were 2–3 fold higher than in normal tissue from the same breast. Furthermore, tumour tissue concentrations of oestradiol tended to be higher than those of oestrone although in normal tissue the two oestrogens were present in similar concentrations. In plasma from the same women oestrone was the predominant oestrogen.

There appears to be no direct relationship between 17βHSD activity and oestrogen concentrations but the enzyme may play a part in determining the balance between oestrone and oestradiol according to substrate and cofactor availability.
INSULIN SENSITIVITY IN HYPERTHYROIDISM: MEASUREMENT BY THE GLUCOSE CLAMP TECHNIQUE
Authors: McCULLOCH A. J. , HOME P. D. , HEINE R. , PONCHNER M. , HANNING I. , JOHNSTON D. G. , CLARK F. , ALBERTI K. G. M. M.
Published: March 2008

Sensitivity to porcine insulin has been compared in overnight fasted hyper‐ thyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C‐peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 ± 0.02 (mean ± S.E.) vs. control 0.06 ± 0.01 mmol/l,P< 0.01) and blood 3‐hydroxybutyrate (0.28 [0.03–0.79, range] vs 0.09 [0.01–0.29] mmol/l,P< 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 ± 4 vs 44 ± 1 mU/l) and insulin metabolic clearance rates were similar (1.21 ± 0.10 vs 1.25 ± 0.03 l/min). Serum C‐peptide levels also decreased by similar amounts (40 ± 8 vs 47 ± 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 ± 50 vs 330 ± 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3‐Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin‐stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.
IDENTIFICATION OF SUBSETS OF PATIENTS WITH GRAVES’DISEASE BY CLUSTER ANALYSIS
Authors: STENSZKY VALERIA , BALÁZS CS. , KOZMA L. , ROCHLITZ SZ. , BEAR J. C. , FARID NADIR R.
Published: March 2008

We have applied cluster analysis methods to forty‐nine laboratory and clinical characteristics (including 26 HLA‐A, B antigens) observed in 196 Graves’disease patients. Three subgroups could be identified: group I (seventy‐nine patients) had small goitres, low indices of autoimmunity and a tendency to remission with medical treatment; group IIa (twenty‐nine patients) had clinical and laboratory features of‘Hashitoxicosis'; Group IIb (eighty‐four patients) had a high incidence of ophthalmopathy, familial aggregation, marked evidence of autoaggression and a tendency to relapsing hyperthyroidism. The prevalence of HLA‐B8 was 8.9% in group I, 20.7% in group IIa and 86.9% in group IIb. This study demonstrates that Graves’disease can be subdivided using cluster analysis into clinically relevant subgroups which are further distinguished by their correlation with HLA‐B8. Possible immunological bases for these observed patterns are discussed.
SKIN THICKNESS IN PATIENTS WITH ACROMEGALY AND CUSHING'S SYNDROME AND RESPONSE TO TREATMENT
Authors: FERGUSON J. K. , DONALD R. A. , WESTON T. S. , ESPINER E. A.
Published: March 2008

Radiological assessment of skin thickness (ST) was assessed in 22 patients with acromegaly and 17 patients with Cushing's syndrome. The age ranges of the patients studied and the 55 individuals in the control group were comparable. The skin thickness in males was significantly greater than in females (P < 0.01). Mean skin thickness in patients with acromegaly and Cushing's syndrome was significantly greater and less respectively than the mean skin thickness of the normal controls (P < 0.02). Following successful treatment of acromegaly (growth hormone < 5μg/l) there was a significant reduction in skin thickness (P < 0.02 males: P < 0.01 females). The skin thickness declined at approximately 0.3 mm/year for the first two years and more slowly thereafter. A highly significant correlation was observed between the logarithm of the pre and post treatment plasma GH concentrations and ST values. With one exception, all patients with growth hormone (GH) levels > 5μg/l had ST values above the normal range. At an average of 4.5 years after successful treatment of Cushings syndrome the average increase in ST was 0.23 mm (P < 0.01).

It is concluded that the measurement of skin thickness is a useful screening test for both acromegaly and Cushing's syndrome and provides an objective assessment of the clinical response to treatment.
STEROIDOGENIC RESPONSE TO A SINGLE INJECTION OF hCG IN PRE‐ AND EARLY PUBERTAL CRYPTORCHID BOYS
Authors: TAPANAINEN J. , MARTIKAINEN H. , DUNKEL L. , PERHEENTUPA J. , VIHKO R.
Published: March 2008

The temporal response patterns of the concentrations of serum testosterone, oestradiol, 17‐hydroxyprogesterone, pregnenolone, progesterone, androstenedione and 5α‐dihydrotestosterone to a single i.m. dose of hCG (5000IU/1.7 m2) were investigated in prepubertal and early pubertal cryptorchid boys, and compared with the response patterns obtained earlier in adult men. The rapid reponse (at approximately 2–4 h) of serum testosterone was lacking in all boys, whereas the slow response at 2–5 days was constant. The relative response (the maximum stimulated concentration vs. the basal level) of serum testosterone was 70‐fold in prepubertal boys and 6‐fold at early puberty, compared with 2.4‐fold in adult men. Serum oestradiol and 17‐hydroxyprogesterone concentrations did not increase in the prepubertal boys, but did increase at early puberty, revealing a pattern similar to thac observed in adult men. Hence, the prepubertal endocrine testis appears to be very responsive to hCG stimulation, and this responsiveness is rapidly lost with advancing puberty. The absolute increases, however, were smallest in prepubertal boys, perhaps reflecting the small potential Leydig cell mass.

The responses of serum oestradiol and 17‐hydroxyprogesterone to hCG appeared later during the boys’development than the response of serum testosterone. The relative testosterone response was maximal in the absence of an oestradiol response. It is suggested that testicular oestradiol production in response to LH/hCG appears in the course of puberty and results in intratesticular short‐loop feed‐back inhibition of androgen production. This is reflected by the appearance of a 17‐hydroxyprogesterone response and by a decrease in relative testosterone response.
ADRENAL ABNORMALITIES IN IDIOPATHIC HIRSUTISM
Authors: MOORE AIDEEN , MAGEE FERGAL , CUNNINGHAM SEAN , CULLITON MARIE , McKENNA T. JOSEPH
Published: March 2008

The possibility that abnormal adrenal androgen production may be present in patients with idiopathic hirsutism was examined. Plasma testosterone, dihydrotestosterone and androstenedione levels were elevated in hirsute patients. In response to exogenous α1–24 ACTH the increments in plasma androstenedione, dehydroepiandrosterone (DHA) and cortisol were significantly greater in hirsute patients than in normal subjects. The testosterone response was exaggerated following endogenous stimulation induced by metyrapone. Treatment with dexamethasone, 0.5 mg each night for 3 months, corrected both the androgen excess and the exaggerated androgen responses but not the excessive cortisol response to stimulation. These observations indicate adrenal abnormalities in idiopathic hirsutism. The dissociation of cortisol and adrenal androgen responsiveness following dexamethasone suggests that the abnormalities observed may be due to excessive adrenal androgen production stimulated by a dexamethasone‐suppressible factor other than ACTH. Excess adrenal androgen production may be the primary disorder leading to the development of idiopathic hirsutism.
CYSTIC FIBROSIS AND NORMAL FIBROBLASTS HAVE IDENTICAL GLUCOCORTICOID RECEPTOR PROFILES AND INDUCED PROTEIN RESPONSES
Authors: KHALID B. A. K. , GYORKI S. , WARNE G. L. , FUNDER J. W.
Published: March 2008

The possibility of differences in glucocorticoid sensitivity between normal and cystic fibrosis fibroblasts was studied in cultured cells derived from forearm skin biopsies. Both normal and cystic fibrosis cells bound tritiated dexamethasone with high affinity (Kd 37°C ± 10 nmol/l) to a limited class of sites (concentration ± 50,000/cell); no difference between cystic fibrosis and normal cells was seen in the nuclear transfer of receptor‐bound tritiated dexamethasone. After 4 h exposure to dexamethasone and analysis of 35S‐methionine labelled proteins by 2‐dimensional gel electrophoresis, both normal and cystic fibrosis cells showed increased abundance of protein kappa (molecular weight ∼ 41,000; pKi∼6.5) over non‐steroid exposed gels. After 16 h exposure, in both cystic fibrosis and normal cells exposed to dexamethasone a decrease in protein omega (mol. wt ∼ 42,000; pKi∼ 5.4) was seen compared with control. We interpret these data as evidence against a difference in glucocorticoid receptor or effector mechanisms between cystic fibrosis and normal fibroblasts.
INCREASED PLASMA PANCREATIC POLYPEPTIDE IN CHRONIC ALCOHOL ABUSE
Authors: FINK R. S. , ADRIAN T. E. , MARGOT D. H. , BLOOM S. R.
Published: March 2008

Post‐prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP — mean ± SE mean) was significantly greater in alcoholics (control, 28 ± 5 pmol/l; alcoholics, post‐withdrawal day 1, 62 ± 14 pmol/1, P < 0.05; and post‐withdrawal day 14, 89 ± 17 pmol/l, P < 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 ± 63 units; alcoholics, day 1, 1310 ± 231 units, P < 0.005; day 14, 1066 ± 66, P < 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.
REPRODUCTIVE HORMONE CHANGES DURING WEIGHT GAIN IN MALE ANORECTICS
Authors: WHEELER M. J. , CRISP A. H. , HSU L. K. G. , CHEN C. N.
Published: March 2008

Plasma LH, FSH, testosterone and sex‐hormone‐binding globulin have been measured in a total of ten male anorectics. There was no significant correlation between body weight and FSH levels or body weight and SHBG levels. Both LH and testosterone concentrations were significantly correlated with body weight. They were well below the adult normal range at low body weight and rose with weight gain although in many cases neither hormone reached normal levels at target weight.

The plasma LH and FSH response to 50 μg LHRH was measured in five male anorectics on twelve occasions, and compared with the responses of twelve normal adult males. The anorectic patients showed a FSH response which was normal on eleven occasions and slightly raised on one occasion. The LH response was below normal at weights below 40 kg, exaggerated between 45 kg and 50 kg and within normal limits at other weight ranges. These results are compared with previous findings in female anorectics.
SERUM FREE THYROXINE CONCENTRATION AND FREE THYROID HORMONE INDICES IN NORMAL PREGNANCY
Authors: HOPTON M. R. , ASHWELL K. , And I. V. SCOTT , HARROP J. S.
Published: March 2008

Serum free thyroxine (FT4) concentrations were shown to be significantly reduced at 36–38 weeks normal pregnancy, both as measured FT4 by the Amerlex method (P < 0.001), and as calculated FT4 (P < 0.001) using accepted molecular weight and affinity constant data for the binding proteins. Serum FT4 concentrations as determined by the Immophase method were normal at 36–38 weeks normal pregnancy. All methods gave normal serum FT4 concentrations in subjects taking the oral contraceptive pill. FT4I and FT3I, derived using the MAA T3 uptake‐value, were higher than normal at 36–38 weeks pregnancy (P < 0.001), whereas T4/TBG and T3/TBG were both reduced (P < 0.001).

The observation that serum FT4 concentrations may fall in late pregnancy, as demonstrated both by the Amerlex radioimmunoassay technique and by calculation, suggests that circulating FT4 may not be the sole determinant of thyroid status at this time. From a practical viewpoint, it is important to note that currently available direct and indirect methods of assessing serum FT4 concentrations produce different patterns of change in pregnancy.
EXPERIENCE WITH TRILOSTANE IN THE TREATMENT OF CUSHING'S SYNDROME
Authors: DEWIS P. , ANDERSON D. C. , BU'LOCK DENISE E. , EARNSHAW ROSEMARY , KELLY W. F.
Published: March 2008

Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3β‐hydroxysteroid dehydrogenase Δ4,Δ5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.
THE ENDOCRINE EVALUATION OF THREE CHILDREN WITH VASOMOTOR FLUSHES FOLLOWING
Authors: SURGERY HYPOTHALAMIC , WITT MARY F. , BLETHEN SANDRA L.
Published: March 2008

Although vasomotor instability or hot flushes are a well‐known occurrence in women with natural or artificially‐induced menopause, they have not previously been described in children. We report three children in different stages of puberty who developed vasomotor instability following surgery involving the hypothalamic‐pituitary region. One, a 16 7/12 year old female with Tanner III breast development, had low oestradiol levels both pre‐and post‐operatively, but developed vasomotor symptoms only in the post‐operative period. The second, a 124/12 year old boy, was sexually mature and had normal male levels of testosterone and total oestrogen when he developed hot flushes post‐operatively. The third case, a boy, was prepubertal at the time of craniopharyngioma resection.

Our results support the conclusion that neither oestrogen deficiency nor gonadotrophin excess are absolute requirements for the development of hot flushes. It is possible that either pressure‐related factors or actual manipulation of the hypothalamic‐pituitary region result in biochemical changes which result in the development of post‐operative vasomotor instability in these children.
THYROID HORMONES IN NON‐INSULIN‐DEPENDENT DIABETES BEFORE AND AFTER DIETARY TREATMENT
Authors: SHEPPARD M. C. , RAMSDEN D. B.
Published: March 2008

In a group of 8 moderately obese non‐insulin‐dependent diabetics, both serum total T3 and T4 concentrations and serum free T3 and T4 concentrations were significantly lower than control values. Serum TBG levels did not differ. Five patients demonstrated an apparently successful response to dietary treatment with loss of symptoms and glycosuria and fall in post‐prandial blood glucose and HbAl. Serum concentrations of thyroid hormones and TBG, however, were not significantly altered. These abnormalities may be unrelated to hyperglycaemia and may reflect the nutritional status of the patients.
MILD HYPOTHYROIDISM AND OEDEMA: EVIDENCE FOR INCREASED CAPILLARY PERMEABILITY TO PROTEIN
Authors: WHEATLEY T. , EDWARDS O. M.
Published: March 2008

Nine female patients with normal serum total thyroxine (T4) and triiodothyronine (T3) but elevated thyroid stimulating hormone (TSH) levels were studied. Six patients had generalised oedema associated with maximal diurnal weight gains in excess of 1.4 kg. Under conditions of forced water diuresis, before and during physiological replacement of 1‐thyroxine, the supine transcapillary escape rate of albumin (TERA) was measured, while the venous colloid osmotic pressure (COP), packed cell volume (PCV) and urinary exretion of water and electrolytes were studied in both the supine and upright positions. The TERA, diurnal weight gain and orthostatic increase in COP fell significantly with treatment. In the six patients with oedema and excessive diurnal weight gains, the retention of salt and water on tilting was reduced with thyroxine treatment. In female patients we consider generalised oedema associated with excessive diurnal weight gain, to be a common and early symptom of hypothyroidism, meriting thyroxine replacement therapy.
PLASMA SOMATOSTATIN INCREASES DURING HYPOGLYCAEMIA IN INSULIN‐DEPENDENT PATIENTS WITH AND WITHOUT B‐CELL FUNCTION
Authors: MADSBAD S. , HILSTED J. , KRARUP T. , TRONIER B. , SESTOFT L.
Published: March 2008

Responses of somatostatin‐like immunoreactivity (SLI) to hypoglycaemia were investigated in seven type 1 (insulin‐dependent) patients with residual B‐cell function, eight patients without B‐cell function, and six healthy controls. A higher basal level of SLI was found in the group with B‐cell function when compared with the group without B‐cell function. The basal level in the normal subjects was in between the two diabetic groups. All the diabetics had a somatostatin response to hypoglycaemia which was independent of residual B‐cell function and no different from that of normal subjects.
INDIRECT EVIDENCE THAT THE ACTION OF CYPROTERONE ACETATE ON THE SKIN IS DUE TO A METABOLITE
Authors: LYONS F. , SHUSTER S.
Published: March 2008

Cyproterone acetate, applied as 1% solution in ethanol or isopropyl myristate, did not decrease the sebum excretion rate (SER) when applied to forehead skin of patients with acne, although SER is decreased when the drug is given systemically. The probable explanation is that cyproterone acetate owes its local action to a metabolite formed systemically. The present study shows this is unlikely to be the 17β‐hydroxy cyproterone acetate.
ADRENAL PROGESTERONE, 17α‐HYDROXYPROGESTERONE AND CORTISOL RESPONSES TO SYNACTHEN IN NORMAL WOMEN AND WOMEN WITH VARIOUS GYNAECOLOGICAL DISORDERS
Authors: CONWAY D. I. , ANDERSON D. C. , GORDON M. T. , BU'LOCK D. E. , HILLIER V. F.
Published: March 2008

In apparently normal subjects there is marked heterogeneity in the adrenal's capacity to produce the progestogens progesterone (Po) and 17α‐hydroxyprogesterone (17Po). We have now screened for the possibility that adrenal progestogens might be an aetiological factor in some patients with hitherto unexplained gynaecological disorders by measuring the responses to acute stimulation with ACTH after overnight dexamethasone suppression. Plasma progesterone (Po), 17α‐hydroxyprogesterone (17Po), and cortisol were assayed in 65 gynaecologically normal women and in 187 with a variety of gynaecological problems including dysfunctional uterine bleeding, unexplained primary infertility, endometriosis, polycystic ovaries, idiopathic hirsutism, and premenstrual syndrome. Responses to ACTH were compared with those in normal subjects according to predominant diagnostic category or categories. There was a wide spectrum of progestogen response to Synacthen in all groups with close agreement between the 30‐ and 60‐min increments in the serum levels for any one steroid. The test was reproducible from one cycle to the next for 17Po (a relatively weak progestogen) and cortisol but much less so for the strong progestogen Po. This variability was not due to spontaneous fluctuation in dexamethasone‐suppressed serum Po levels and remains unexplained. The 60‐min Po and 17Po increments tended to increase slightly with age. Overall, the 60‐min Po increments were a little higher amongst the patients with unexplained primary infertility than amongst controls. There were no significant differences in 17Po increments between normal women and patients, with an equal incidence of marked hyperresponse (exceeding 6 nmol/l increment) in both populations. Unexpectedly, the 18 patients complaining of severe premenstrual symptoms had significantly lower cortisol responses than other groups. We conclude that except in overt 21‐hydroxylase deficiency, adrenal progestogens are unlikely to be a major factor in causing gynaecological disorders.
THYROID FUNCTION AND IMMUNOLOGICAL ACTIVITY DURING AND AFTER MEDICAL TREATMENT OF GRAVES' DISEASE
Authors: GOSSAGE A. A. R. , CRAWLEY J. C. W. , COPPING S. , HINGE D. , HIMSWORTH R. L.
Published: March 2008

The variable clinical course of Graves' disease has been followed in 27 patients each studied for 2 years from the time of diagnosis. Thyroid hormone synthesis was blocked with large doses of antithyroid drugs for the first 12 months while euthyroidism was maintained with triiodothyronine. The latter was given alone from 12 to 18 months, and for the last 6 months the patients received no treatment. The activity of the disease was determined by repeated measurements of thyroid uptake of pertechnetate and by assay of thyrotrophin receptor antibodies (TSH binding inhibitory immunoglobulins).

Retrospectively there were no features on presentation which singly or in combination indicated the clinical outcome: 16 patients remained in remission (Group 1) whilst in 11 hyperthyroidism had recurred before the end of the study (Group 2). Both measures of disease activity (thyroid uptake and antibody levels) fell during the first 12 months in patients of both groups. Recurrence of Graves' disease could be predicted in some but not all patients of Group 2 at 12 months by higher thyroid uptakes and levels of thyrotrophin receptor antibodies. There was, however, evidence of abnormal thyroid function, from which we infer continuing activity of the disease, 12 to 18 months after diagnosis in all patients of Group 1, even though these patients had normal TRH tests during the last phase of the study.

The difference in the course of Graves' disease 12 to 24 months after diagnosis between those patients who remained in remission and those who did not was relative: in no patient was completely normal physiological control of thyroid function re‐established. Clinical remission from hyperthyroidism at this time is a level of disease activity at which the normal physiological output of thyroid hormones is not exceeded.
CONSISTENCY AND VARIABILITY IN THE CHARACTER OF THYROTROPHIN RECEPTOR ANTIBODIES IN GRAVEs' DISEASE
Authors: GOSSAGE A. A. R. , CRAWLEY J. C. W. , COPPING S. , HINGE D. , HIMSWORTH R. L.
Published: March 2008

At diagnosis there was no correlation between the uptake of pertechnetate by the thyroid and thyrotrophin receptor antibodies (TRAb) measured as TSH binding inhibitory immunoglobulins in a series of 27 patients with Graves' disease. TRAb were detectable initially in 19 patients, in 11 of these there was a significant positive correlation (P > 0·05) between serial measurements of pertechnetate uptake and TRAb made during 2 years following diagnosis. In five patients pertechnetate uptake fell with time whilst TRAb levels were maintained or fluctuated. In the remaining three of the 19 patients both measurements were low and did not change during treatment.

We conclude that TRAb in any individual patient are a mixture of immunoglobulins of variable effectiveness as thyroid stimulators. In a majority of patients the composition of this mixture remains constant during the course of the illness and the clinical state reflects the levels of TRAb in the blood. In a minority, however, the character of these antibodies may alter with time or there is a change in the responsiveness of the thyroid gland. The general lack of correlation between measurements of thyroid stimulating activity and TSH binding inhibitory immunoglobulins in groups of patients is due to differences between patients in the composition of TRAb.
TRACKING OF INDIUM‐111‐OXINE LABELLED LYMPHOCYTES IN AUTOIMMUNE THYROID DISEASE
Authors: POZZILLI P. , POZZILLI C. , PANTANO P. , NEGRI M. , ANDREANI D. , CUDWORTH A. G.
Published: March 2008

Peripheral lymphocytes (∼108) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 μCi of indium‐111‐oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging.

Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell‐mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.
A MIXED LONGITUDINAL STUDY OF ADRENAL STEROID EXCRETION IN CHILDHOOD AND THE MECHANISM OF ADRENARCHE
Authors: KELNAR C. J. H. , BROOK C. G. D.
Published: March 2008

Twenty four‐hour urine samples have been collected 6 monthly for 18 months from 127 normal boys aged between 7·5 and 17 years. Urinary steroid metabolites have been measured by gas‐liquid chromatography and ratios of steroid metabolites used to draw conclusions about likely enzymic activities at each step in the adrenal biosynthetic pathway.

DHA excretion rose throughout the study, especially between 7·5 and 11 years. Metabolites of cortisol and corticosterone did not increase when related to surface area. During adrenarche there were changes consistent with a decrease in 3β‐hydroxysteroid dehydrogenase activity, a slight rise in 17α hydroxylase activity, a marked rise in 17,20 lyase activity, and a fall in 11β hydroxylase activity.

These data are compatible with the hypothesis that a small reduction in the ability to synthesize cortisol requires a marginal increase in the secretion of ACTH and/or other CRF‐induced peptides to maintain cortisol production rate. ACTH itself or a dexamethasone‐suppressible CRF‐induced peptide would in such a case control the growth of the zona reticularis at adrenarche, which thus appears to be primarily an adrenal event.
THE EFFECT OF MINOR INCREMENTS IN PLASMA THYROXINE ON HEART RATE AND URINARY SODIUM EXCRETION
Authors: BELL G. M. , SAWERS J. S. A. , FORFAR J. C. , DOIG A. , TOFT A. D.
Published: March 2008

We studied day/night (D:N) patterns of urinary sodium excretion and the 24 hour ambulatory electrocardiogram in seven normal subjects before and during the administration of T4. Thyroxine increased thyroid hormone levels within the normal range and inhibited the plasma TSH response to TRH. This was associated with a significant decrease in D:N sodium excretion (P < 0·01) and D:N urine flow (P < 0·01), a significant increase in mean nocturnal heart rate (P < 0·01), and a lesser increment in mean daytime heart rate (P < 0·05).

These responses to small changes in thyroid hormone levels suggest that the anterior pituitary is not alone in recognising minor thyroid hormone excess. The clinical implication is that some patients with a normal T3 and T4 but an impaired TSH response to TRH might benefit from antithyroid treatment.
LH PULSE FREQUENCY IN RELATION TO POSITIVE OESTROGEN‐GONADOTROPHIN FEEDBACK IN AMENORRHOEA
Authors: EL SHEIKH M. A. A. , MOLLOY B. G. , OAKEY R. E. , CHAPMAN C. , HANCOCK K. W. , GLASS M. R.
Published: March 2008

The relationship between the pattern of pulsatile LH release and the response to oestrogen provocation was studied in twenty amenorrhoeic or oligomenorrhoeic subjects. In 12 subjects with positive oestrogen‐gonadotrophin feedback a definite pulsatile pattern of LH release was demonstrated with a pulse frequency of 60–80 min and an increase from nadir to peak ranging between 30 and 58%. The mean basal LH concentration was significantly higher in this group (P < 0·001).

Of eight subjects who had absence of positive feedback, five showed infrequent pulses, 1–2 during the four‐hour period. These were of low amplitude and with a percentage increase of 45–70 from nadir to peak. The remaining three did not have a pulsatile pattern of LH release.

Positive feedback, as demonstrated by an oestrogen provocation test was thus found only in patients having 3 or more LH pulses in the 4 h study period; an LH pulse frequency similar to that in the early follicular phase in regularly menstruating women.
ACTH FUNCTION IN WOMEN WITH THE POLYCYSTIC OVARIAN SYNDROME
Authors: HORROCKS P. M. , LONDON D. R. , KANDEEL F. R. , BUTT W. R. , LYNCH S. S. , HOLDER G. , LOGAN‐EDWARDS R.
Published: March 2008

Serum androgen levels, including dehydroepiandrosterone sulphate (DHAS) which is thought to be solely of adrenal origin, are elevated in women with the polycystic ovarian syndrome. We have investigated the possibility that this may be due to a mild form of congenital adrenal hyperplasia by measuring basal and stimulated levels of ACTH in women with this condition and have compared them to levels in normal women. We found no difference in the diurnal rhythm of ACTH between patients and normal subjects nor any difference in stimulated levels achieved after a single‐dose oral metyrapone test. Thus there is no evidence from this study to support the idea that these patients might have congenital adrenal hyperplasia. There are two alternative hypotheses to explain the elevated DHAS levels. They may be associated with the high oestrogen levels, which interfere with the enzyme 3β‐hydroxysteroid dehydrogenase, or there may be alteration of the factors controlling adrenal androgen secretion.
24 HOUR MELATONIN SECRETORY PATTERN IN CUSHING'S SYNDROME
Authors: FEVRE‐MONTANGE M. , TOURNIAIRE J. , ESTOUR B. , BAJARD L.
Published: March 2008

The concentrations of plasma melatonin and cortisol were determined every 20 min during a 24 h period in 6 women aged 24 to 45 years with Cushing's syndrome of differing aetiologies (4 adrenal adenomas, 2 adrenal hyperplasia). Melatonin was assayed after chloroform extraction according to the method of Rollag and Niswender (1976). Abnormal melatonin secretory patterns were found in all the patients; 24 h melatonin concentration means varied from 130 to 413 pg/ml and were not significantly higher than the 24 h mean in 4 controls (215 ± 126 pg/ml). All six subjects however showed a significant increase of melatonin during the day period (302 ± 109 as compared with controls 129 ± 65 mg/ml, mean ± SD; P<0.005). No relationship could be found between abnormal melatonin levels and the sexual status of the patients (4 with amenorrhoea, 2 normally menstruating women). An alteration of melatonin secretory pattern is present in Cushing's syndrome, whatever the aetiology. It is suggested that hypercortisolism, by itself, may modify the pattern of melatonin secretion.
A HIGHLY SENSITIVE CYTOCHEMICAL BIOASSAY FOR PLASMA ANGIOTENSIN II
Authors: JONES JULIA C. , MACGREGOR G. A. , SAGNELLA G. A. , MORTON J. J. , ALAGHBAND‐ZADEH JAMSHID
Published: March 2008

A highly sensitive cytochemical bioassay has been developed for measuring angiotensin II in human plasma. The assay depends on the ability of angiotensin II to alter the reducing potency of the zona glomerulosa as measured by Prussian blue staining and microdensitometry. An inverse correlation between the intensity of the stain and the logarithm of concentration existed over the range 0.05‐5.0 fmol/l of angiotensin II. The limit of sensitivity of the assay in plasma was 50 fmol/l; the index of precision was 0.07 ± 0.04 (mean ± SD; n = 15); and the coefficient of variation of a quality control sample was 34%. The response was specific for angiotensin II; approximately 102 times more angiotensin III and approximately 106 times more ACTH was required to produce a similar effect. Angiotensin I had no significant activity. A significant inverse relationship existed between sodium intake and bioactive angiotensin II in 5 normal subjects studied on low, normal and high sodium diets. Extremely low levels of angiotensin II were detected in anephric subjects.
DIMINUTION OF PROLACTIN AND INCREASE OF THYROTROPHIN RESPONSE TO THYROTROPHIN RELEASING HORMONE OCCURRING INDEPENDENTLY OF CHANGES IN BASAL LEVEL OF THESE HORMONES DURING TREATMENT OF HYPOTHYROIDISM
Authors: VAN GROENENDAEL J. H. L. M. , FISCHER H. R. A. , HACKENG W. H. L. , SCHOPMAN W. , SILBERBUSCH J.
Published: March 2008

In order to study the effect of rising thyroid hormone levels in hypothyroidism upon prolactin responses to TRH, in relation to changes in basal prolactin concentration and to changes in TSH responses, we followed 18 patients by performing TRH tests before and after 14, 28, 42 and 56 d on gradually increasing levothyroxine dosages, plus a final test when euthyroidism was achieved.

Basal prolactin rose initially, at day 14, followed by a return on days 28, 42 and 56 to a level similar to the pretherapeutic value, while at euthyroidism prolactin had fallen below the original value. The area under the prolactin response curve on TRH stimulation was unchanged at 14 d, notwithstanding the rise of basal prolactin concentration. At 28, 42 and 56 d the responses declined progressively along with basal prolactin concentrations that remained equivalent to the pretreatment level.

The TSH response to TRH rose at 14, 28, and 42 d along with a continuous downward course of basal TSH.

Thus, substitution with L‐thyroxine inhibited the responsivity of prolactin but enhanced that of TSH to TRH. The fact that these changes occurred in opposite directions, appears to rule out a negative feed‐back effect of T4 on hypothalamic TRH secretion.

The effects on responses were shown to occur independently of those on basal secretion of prolactin and TSH.
PREVALENCE OF SALT‐LOSING AMONG CONGENITAL ADRENAL HYPERPLASIA PATIENTS
Authors: FIFE D. , RAPPAPORT ELIZABETH B.
Published: March 2008

Among clinic patients with congenital adrenal hyperplasia (CAH) the observed frequency of salt‐losing has increased significantly over the past 30 years. Comparing estimates from various clinics, older estimates of the frequency of salt‐losing are lower than estimates cited in more recent literature. Within the patient population of a single long‐established clinic, an increase in the frequency of salt‐losing can also be observed. It is likely that the increase in the frequency of salt‐losing CAH reflects improved case finding and survival of salt‐losing patients. Based on reports of recent populations of CAH patients, the frequency of salt‐losing among CAH patients is approximately 66%.
THE RENIN–ANGIOTENSIN SYSTEM AND TOTAL BODY SODIUM AND POTASSIUM IN HYPERTENSIVE WOMEN TAKING OESTROGEN–PROGESTAGEN ORAL CONTRACEPTIVES
Authors: McAREAVEY D. , CUMMING A. M. M. , BODDY K. , BROWN J. J. , FRASER R. , LECKIE B. J. , LEVER A. F. , MORTON J. J. , ROBERTSON J. I. S. , WILLIAMS E. D.
Published: March 2008

Measurements of total body sodium and potassium, and of components of the renin–angiotensin–aldosterone system, were made in a group of women who developed hypertension while taking oestrogen–progestagen oral contraceptives. The results were compared with similar measurements made in age‐matched women with essential hypertension. Total body sodium and potassium were normal in both groups. Plasma renin‐substrate was significantly elevated in the women taking oral contraceptives, while concentrations of active renin were similar and normal in both groups. Thus plasma angiotensin II was significantly elevated in the pill users; overall the product of renin and renin substrate concentrations correlated significantly with angiotensin II. The rise in plasma angiotensin II in conjunction with normal total body sodium could therefore contribute to the increase in blood pressure induced by oestrogen–progestagen oral contraceptives.
PLASMA CALCITONIN AND ACTH RESPONSES TO LYSINE VASOPRESSIN, CALCIUM AND PENTAGASTRIN IN A PATIENT WITH MEDULLARY THYROID CARCINOMA ASSOCIATED WITH CUSHING'S SYNDROME
Authors: SHIMATSU AKIRA , KATO YUZURU , TANAKA ISSEY , NAKAI YOSHIKATSU , FUKUNAGA MASAO , IMURA HIROO
Published: March 2008

In a case study of medullary thyroid carcinoma (MTC) associated with Cushing's syndrome, elevated levels of urinary 17‐hydroxycorticosteroids, plasma ACTH, cortisol, calcitonin (CT) and somatostatin (GHRIH) were documented. Lysine vasopressin administration further increased the levels of plasma ACTH, cortisol and CT, whereas the administration of calcium and pentagastrin increased only the level of plasma CT. Immunoreactive ACTH, CT and GHRIH were highly concentrated in the tumour tissues. Basal plasma ACTH levels were more progressively increased than plasma CT during the postoperative course when the patient was treated with o,p′‐DDD, since the tumour was not completely resected. These findings suggest that the secretion of ACTH and CT from MTC were regulated in a different manner.
THE EFFECTS OF PROLONGED BROMOCRIPTINE ADMINISTRATION ON PRL SECRETION GH AND GLYCAEMIC CONTROL IN STABLE INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: SCOBIE I.N. , KESSON C.M. , RATCLIFFE J.G. , MACCUISH A.C.
Published: March 2008

Plasma glucose, PRL and GH concentrations were measured at hourly intervals over a 24‐h period before and after oral bromocriptine administration in a dosage of 7±5 mg/day for 6 weeks in nine stable insulin‐dependent diabetic men. The pattern of PRL secretion was noted to be normal in stable diabetes (with a mean concentration of 205 mu/l ± 23 SEM) and was effectively suppressed by bromocriptine (to a mean concentration of 51 mu/l ± 2 SEM). This suppression of PRL secretion caused no major alteration in glycaemic control, mean plasma glucose for the group was 10±6 mmol/l ± 3± 4 SD before and 9±6 mmol/l ± 3·1 SD after bromocriptine administration. Bromocriptine produced no change in plasma glucose or GH profiles. It is concluded that PRL secretion is not a major influence on carbohydrate metabolism in stable diabetics.