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1. |
GONADOTROPHIN RELEASE IN OVARIECTOMIZED PATIENTS |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 333-338
R. RAVID,
G. JEDWAB,
E. PERSITZ,
M. P. DAVID,
N. KARNI,
S. GIL,
T. CORDOVA,
A. HARELL,
D. AYALON,
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摘要:
SUMMARYAdministration of clomiphene citrate (150 mg/day) for 5 days to twenty‐four ovariectomized patients and seven normal female patients evoked a significant release of FSH and LH in the normal control group and suppressed the gonadotrophin secretion in the castrated patients. A similar suppressive effect on gonadotrophin secretion was noted in eight ovariectomized patients treated for 10 days with low doses (50 μg/day) of ethinyl oestradiol.It is suggested that in the ovariectomized hypoestrogenic patients, clomiphene acted as an oestrogen, suppressing by a negative feedback action gonadotrophin release in a way similar to ethinyl oestradiol. In the normal control group with an adequate steroid environment, clomiphene acted (probably at the hypothalamic level) as an oestrogen antagonist and stimulated gonadotrophin secretion. In view of our findings, it seems as if the ability of anovulatory patients to respond to clomiphene treatment by increased gonadotrophin secretion depends upon the absolute concentration of the compound in the different organs and by the quantitative relation of clomiphene to the endogenous oestrogens.There is still a considerable degree of uncertainty about the exact mode of action of clomiphene (1‐[p‐β‐diethyl‐aminoethoxyphenyl]‐1,2, dipheny1‐2 chloroethylene citrate) a non‐steroidal oestrogen antagonist. However, it appears increasingly evident that this compound which possesses antioestrogenic properties acts probably in an indirect manner, by competing with oestradiol for the receptor sites at the hypothalamic centres regulating gonadotrophin secretion, thus stimulating gonadotrophin releasing hormone (LHRH) secretion, with a subsequent release of FSH and LH (Igarashiet al., 1967; Sekiet al., 1970).By contrast, in prepubertal children, a paradoxical suppression of both LH and FSH release was demonstrated following administration of clomiphene (Kelchet al., 1971). The explanation offered for this phenomenon was that the immature hypothalamic gonadostat is hypersensitive to sex steroids, and as clomiphene has intrinsic oestrogenic properties, it could account for the unexpected gonadotrophin suppression rather than stimulation in the prepubertal child. A similar effect could be obtained in prepubertal children by administration of low doses of oestrogens (Kelchet al., 1971).In order to gain additional information on the mode of action of clomiphene at the hypothalamic and pituitary levels, we studied the effect of clomiphene and of low doses of oestrogens on LH and FSH release in ovariectomized patients. These patients provide a suitable model for the investigation of the mode of action of clomiphene on a normal hypothalamic‐pituitary system in an environment free of gonadal steroi
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02019.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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2. |
THE HORMONE RESPONSE TO A SYNTHETIC ANDROGEN (MESTEROLONE) IN OLIGOSPERMIA |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 339-345
F. R. JACKAMAN,
I. D. ANSELL,
R. GHANADIAN,
P. V. A. McLOUGHLIN,
J. G. LEWIS,
G. D. CHISHOLM,
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摘要:
SUMMARYForty subfertile men with oligospermia were treated with a synthetic androgen (Mesterolone). The effect of the drug was evaluated by measuring serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and analysing the semen before and after treatment. The results demonstrated that in twenty‐three patients treated for 6‐9 months there was a significant decrease in serum testosterone (P<0.01); the means ± SEM before and after treatment were 17.05 ± 0.95 and 14.7 ± 0.95 (nmol/1 serum) respectively. There was a pronounced increase in serum LH (P<0.01), the values being 2.73 ± 0.26 and 3.61 ± 0.3 (u/l) respectively. However, no significant difference was found in serum FSH before and after treatment. The sperm concentration showed a variable response to treatment. In twenty‐one patients there was either no change or worsening in the sperm concentration, whereas in nineteen patients an improvement was observed. The analysis of variance of sperm concentration and motility for the periods before and after treatment, for all the patients, showed no significant difference in the sperm concentrationF1.145=2.82 (P= 0.1).Various drugs have been used to improve the seminal quality in oligospermic males in whom no obvious cause can be found. These drugs have included human gonadotrophins, clomiphene, corticosteroids and androgens (testosterone, methyl‐testosterone, fluoxymesterone and Mesterolone). Mesterolone (Proviron) is a synthetic steroid (17β‐hydroxy‐1α‐methyl‐5α‐androstan‐3‐one) which is thought to contribute to the androgen pool but not to be recognized by the hypothalamus/pituitary system and not to suppress endogenous androgen production through reducing pituitary gonadotrophins (Petryet al., 1968; Gerhardset al., 1968).Improvement in the quality of semen by Mesterolone has already been reported (Schellen&Beek, 1972; Somerville&Hendry, 1972; Barwinet al., 1973) but there has been no detailed study of serum gonadotrophin and testosterone levels during a clinical trial with this drug. This study was designed to investigate the effect of Mesterolone on (1) the semen analysis and (2) the serum hormone values (FSH, LH and t
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02020.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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3. |
NYCTOHEMERAL SECRETION OF GROWTH HORMONE IN NORMAL CHILDREN OF SHORT STATURE AND IN CHILDREN WITH HYPOPITUITARISM AND INTRAUTERINE GROWTH RETARDATION |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 347-359
P. M. HOWSE,
P. H. W. RAYNER,
J. W. WILLIAMS,
B. T. RUDD,
P. V. BERTRANDE,
C. R. S. THOMPSON,
L. A. JONES,
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摘要:
SUMMARYA continuous blood sampling technique has been used to monitor human growth hormone (GH) during sleep in fourteen normal short children (age range 6.5‐15.0 years), twelve hypopituitary children (2.8‐17.3 years), three children with psychosocial GH deficiency (4.0‐13.0 years), and three children with intrauterine growth retardation (9.5‐11.3 years). The mean GH level of a 5 h sleep period (22.30‐03.30 hours) was used to represent the GH response to sleep. The GH response to insulin induced hypoglycaemia (IST) was also determined. In normal short children there was a significant relationship between 5 h mean GH levels and chronological age. The curve defining this relationship was similar to the third centile linear growth velocity curve. The 5 h mean GH levels of the hypopituitary and psycho‐social GH deficiency children were more than 2 SD below the age related mean established for normal short children. The children with intrauterine growth retardation demonstrated values which were more than 2 SD above the age related mean.The evaluation of serum growth hormone (GH) during sleep, has recently been used as a test of pituitary function in growth retarded children (Eastman&Lazarus, 1973; Wiseet al., 1975). Interpretation of the response is difficult because normal GH values during sleep have not been established.We have used a continuous blood sampling technique to define the range of nocturnal GH levels for normal short children. The sleep GH response of children with hypopituitarism, psychosocial GH deficiency and intrauterine growth retardation (IUGR) has been similarly investigated and is reported with reference to the range established for normal sho
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02021.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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4. |
DECREASED SERUM THYROID HORMONE LEVELS AND INCREASED TSH RESPONSE TO TRH IN INFANTS WITH COELIAC DISEASE |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 361-367
M. VANDERSCHUEREN‐LODEWEYCKX,
E. EGGERMONT,
C. CORNETTE,
C. BECKERS,
P. MALVAUX,
R. EECKELS,
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摘要:
SUMMARYPlasma levels of thyrotrophin before and after the intravenous administration of 200 μg of thyrotrophin releasing hormone have been studied in eleven patients with active gluten‐induced enteropathy and in a group of twenty‐one normal prepubertal children. In nine out of eleven coeliac patients an exaggerated and/or sustained response of plasma thyrotrophin is observed. Basal plasma thyrotrophin level is not significantly different from the value observed in normal children. However, plasma levels recorded 20 and 60 min after injection of the releasing hormone are significantly higher than in control children (at 20 min:P<0.01; at 60 min:P<0.001). Serum levels of dialysed triiodothyronine and thyroxine and of triiodothyronine are significantly lower in coeliac patients than in normal infants (P<0.01). These data support the evidence of an endocrine dysfunction in coeliac disease. It is not clear whether it is due to malnutrition and/or to some direct action of circulating gluten‐peptides on the hypothalamus.Insulin‐induced growth hormone (GH) secretion is inadequate in most of the coeliac patients during the active phase of the disease and returns towards normal during recovery provided the diet is strictly glutenfree (Vanderschueren‐Lodeweyckxet al., 1973). These data, suggesting a dysfunction in the hypothalamo‐hypophyseal system during active coeliac disease, prompted us to study the release of thyrotrophin (TSH) induced by the administration of synthetic thyrotrophin releasing hormone (TRH) in patients with active coe
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02022.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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5. |
THYROID HORMONE LEVELS AND PROTEIN BINDING IN PATIENTS ON LONG‐TERM DIPHENYLHYDANTOIN TREATMENT |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 369-376
P. HEYMA,
R. G. LARKINS,
D. PERRY‐KEENE,
C. T. PETER,
D. ROSS,
J. G. SLOMAN,
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摘要:
SUMMARYThe effect of long‐term diphenylhydantoin (DPH) treatment on thyroid hormone concentrations and protein binding was determined in a randomized controlled trial. As has been demonstrated previously, total thyroxine (T4) concentrations were significanly depressed in patients on DPH. There was no significant effect on indirect indices of protein binding of thyroid hormones, and the free thyroxine index (FTI) was also significantly depressed. Triiodothyronine (T3) and thyrotrophin (TSH) concentrations were either unaffected, or only very slightly affected by DPH. Significant effects on the FTI were still apparent 4 weeks after discontinuing treatment. It is concluded that the depression of total T4 levels observedin vivois not due solely to diminished protein binding, but may instead be largely explained by reports suggesting enhanced degradation of T4 following DPH therapy.Since 1961 it has been known that diphenylhydantoin (DPH) has a significant effect on the levels of the circulating thyroid hormones in the plasma (Oppenheimeret al., 1961). It is known that the effect is extrathyroidal (Oppenheimeret al., 1961) and it was initially assumed to be due to an effect on protein binding. This assumption followed the demonstration that DPH decreased the binding of thyroxine (T4) to throxine binding globulin (TBG)in vitro(Oppenheimer&Tavernetti, 1962). However, more recent work (Chin&Schussler, 1968; Larsenet al., 1970; Hansenet al., 1974; Stjernholmet al., 1975) has suggested that there may be a true depression of free T4.Most previous studies have been in epileptic patients for whom the control groups were not totally comparable (Hansenet al., 1974; Chin&Schussler, 1968) or in normal subjects who underwent DPH therapy for only a short time (i.e. 1‐2 weeks, Hansenet al., 1974). Moreover, DPH dosage in earlier studies has for the most part been arbitrarily decided upon, or evaluated by clinical signs. It is known that there are extremely variable individual responses to given doses of DPH (Richens&Dunlop, 1975), resulting in variable plasma levels of DPH.This study describes the effects of long‐term DPH treatment on thyroid function and thyroid hormone protein binding. A comparable control group was also studied, and DPH concentration in the blood was continually monitored. The same patients were reexamined after discontinuation of therapy, to elucidate the duration of the e
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02023.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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6. |
AN INVESTIGATION INTO GONADAL DYSFUNCTION IN PATIENTS WITH IDIOPATHIC HAEMOCHROMATOSIS |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 377-385
W. R. BEZWODA,
T. H. BOTHWELL,
L. A. WALT,
S. KRONHEIM,
B. L. PIMSTONE†,
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摘要:
SUMMARYEndocrine studies were performed on twelve patients with proven idiopathic haemochromatosis. Basal gonadotrophin levels and/or their responses to LH releasing hormone (LHRH) were low in nine patients, all of whom showed low plasma testosterone levels and clinical evidence of hypogonadism. Those patients with normal gonadotrophin responses had higher testosterone values, suggesting that the poor testosterone secretion was primarily due to inadequate trophic stimulation. No patient showed hypothyroidism of hypothalamic‐pituitary origin, while the cortisol response to hypoglycaemia was normal in all six patients studied. GH responses were more variable and difficult to interpret, since the number of the patients studied was small and the degree of hypoglycaemia after insulin was unpredictable.While hypogonadism is extremely common in patients with long‐standing idiopathic haemochromatosis (Bricaireet al., 1971), there is some controversy as to its cause. Suggested aetiologies include functional disturbance at the hypothalamic or pituitary level (Tourniaireet al., 1974; Stocks&Powell, 1972), primary gonadal failure (Simonet al., 1972), or a combination of both (Simonet al., 1972; Walkeret al., 1976). In an attempt to evaluate this problem, we have studied plasma gonadotrophin responses to both LH releasing hormone (LHRH) and clomiphene, and the plasma testosterone basally and after human chorionic gonadotrophin (HCG) in patients with proven haemochromatotis. The results of certain other tests of anterior pituitary function are also repor
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02024.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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7. |
VASOVAGAL HYPOTENSION AND VASOPRESSIN RELEASE |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 387-393
R. C. WIGGINS,
ISIK BASAR,
J.D.H. SLATER,
MARY FORSLING,
C.M. RAMAGE,
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摘要:
SUMMARYMild vasovagal hypotension occurred in two normal male volunteers during insertion of indwelling venous cannulae. In spite of a rapid intravenous fluid load (3.6‐4.6 litres in 90 min) both subjects passed little urine for 100 min. When the experiment was repeated without vasovagal hypotension, a rapid large diuresis followed the fluid load. The prolonged oliguria after vasovagal hypotension was the result of vasopressin release. This was demonstrated by measuring vasopressin in the blood and urine and by observing the renal response to a water load. The observation in man that a mild transient hypotensive episode may reduce urine flow for 100 min has clinical significance.The control of vasopressin release is conventionally regarded as being dominated by the osmolality of the extracellular fuid; however, changes in plasma volume are also important (Johnson, Zehr&Moore, 1970; Share, 1967; Robertson&Athar, 1976). The existence of receptors in the left atrium and carotid sinus which provide the afferent limb to a neurogenic reflex mechanism for vasopressin release has been well established in animals (Henryet al., 1956; Mulcahyet al., 1973; Moran&Zimmerman, 1967), but little is known about their relevance to clinical situations in man. By chance we have been able to measure and observe the physiological effect of vasopressin released in response to a mild vasovagal hypotensive episode in two normal young me
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02025.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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8. |
THE EFFECT OF ISOPRENALINE ON PLASMA RENIN ACTIVITY IN MAN: A DOSE‐RESPONSE CURVE |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 395-399
ROY DAVIES,
J. D. H. SLATER,
M. RUDOLF,
D. M. GEDDES,
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摘要:
SUMMARYFour normal subjects on a free sodium intake received intravenous isoprenaline in doses of 2, 4, 8 and 16 μg over 2 min. Three of the subjects received a second infusion of 8 μg. The rate of renin release indexed by changes in plasma renin activity increased in all subjects at each dose level. The mean peak leveles of plasma renin were 9%, 29% and 77% above the mean control levels at doses of 2, 4 and 8 μMg respectively. The response of 16 μg was no different from that seen with 8 μg. The renin response obtained at 8 μg was highly reproducible such that the coefficient of variation for duplicate estimations of plasma renin (twelve duplicates) ranged from 1.7 to 4%.The rate of renin release from the kidney is known to be under adrenergic control (Vander, 1965; Wathenet al., 1965; Allisonet al., 1970; Uedaet al., 1973) and recent studies in animals and man have indicated that an intrarenal beta‐adrenoreceptor mediates this release (Tobertet al., 1973; Inoue, 1973; Vandongenet al., 1973; Sabtoet al., 1975). Isoprenaline is the archetypal beta‐adrenergic agonist with equal effects upon both beta1and beta2receptors (Landset al., 1967). We have previously shown that minute bolus injections of this agent provokes renin release in normal people (Davieset al., 1975). However, there appears to have been no systematic investigation of a dose‐response relationship for the release of renin provoked by isoprenaline in man. The aim of this study was to attempt to define such a relationship and, mindful of the possible application of this technique to studies of the adrenergic control of renin release in patients, we have documented the reproducibility of th
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02026.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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9. |
BOOK REVIEWS |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 401-402
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摘要:
Book Reviewed in this article:Metabolism and the Response to Znjuly. Edited by A. W. WILKINSON and SIR DAVID CUTHBERTSONTrace Methods in Hormone Research. Volume 8. By E. GURPIDE.General Endocrinology. By C. D. TURNER and J. T. BAGNARA.
ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02027.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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10. |
ANNOUNCEMENTS |
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Clinical Endocrinology,
Volume 6,
Issue 5,
1977,
Page 403-403
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ISSN:0300-0664
DOI:10.1111/j.1365-2265.1977.tb02028.x
出版商:Blackwell Publishing Ltd
年代:1977
数据来源: WILEY
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