bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTIBODIES AGAINST SERTOLI CELLS IN HUMAN INFERTILITY
Authors: WALL J. R. , STEDRONSKA JITKA , LESSOF M. H.
Published: March 2008

Antibodies reacting with a cytoplasmic component of Sertoli cells were detected in the serum of a 20‐year‐old man with hypogonadism and azospermia. The appearances on testicular biopsy were of Leydig cell hypoplasia and maturation arrest of the germinal cells, but apparently normal Sertoli cells. These findings contrasted with those seen in ninety‐three infertile men, in whom Sertoli cell antibodies were not found but in whom antibodies against the germinal cells were found in ten cases (11%), whilst spermatozoal antibodies were detected in twenty‐four cases (26%) and other antibodies (thyroid cytoplasmic, gastric parietal cell, mitochondrial ‘M’ and antinuclear antibodies) in seventeen cases (18%).

It is postulated that autoimmunity involving the germinal or Sertoli cells may be a cause of testicular disease. The only other case in which Sertoli cell antibodies have been found was that of an infertile woman with Sjögren's disease. This raises the possibility that there may be a Sertoli cell equivalent in the ovary containing a similar range of enzymes or other antigenic components and that autoimmunity involving these components may also be a cause of infertility in the female.
CIRCADIAN RHYTHM OF PLASMA CORTICOSTEROIDS IN CONGENITAL ADRENAL HYPERPLASIA
Authors: RESCHINI E. , GLUSTINA G. , D'ALBERTON A. , CROSIGNANI P. G.
Published: March 2008

Circadian rhythm and dexamethasone suppression of plasma fluorogenic corticosteroids and plasma progesterone were studied in six patients with the simple virilizing form of congenital adrenal hyperplasia. Basal levels of plasma fluorogenic steroids were normal or high in the untreated patients. A definite circadian variation was demonstrated, suggesting a similar variation in ACTH secretion. Dexamethasone administration in the form of the overnight suppression test was followed by a virtually complete disappearance of plasma fluorescence. Plasma progesterone levels were high in the morning hours and showed a circadian variation and dexamethasone suppression similar to those of fluorogenic steroids. The diagnostic and therapeutic importance of these findings is discussed.
CONTROL OF PLASMA ALDOSTERONE IN SUPINE ANEPHRIC MAN
Authors: VETTER W. , ZÁRUBA K. , ARMBRUSTER H. , BECKERHOFF R. , RECK G. , SIEGENTHALER W.
Published: March 2008

Plasma aldosterone, plasma cortisol, plasma renin activity and the serum concentrations of sodium and potassium were determined at short time‐intervals in four supine anephric patients. Two patients were studied the night before and the night following haemodialysis. In both patients increases in plasma aldosterone occurred without concomitant alterations in serum sodium and serum potassium while plasma renin activity was uniformly undetectable. However, the observed fluctuations in plasma aldosterone were markedly more pronounced the night following haemodialysis. Under the latter conditions, typical secretory episodes of aldosterone occurred. The onset of these secretory episodes was not associated with simultaneous increases in plasma cortisol, whereas before haemodialysis changes in plasma aldosterone were paralleled by those in plasma cortisol. Except for the peak values of the secretory episodes of aldosterone, plasma aldosterone was markedly higher the night before than the night following haemodialysis. These differences between pre‐ and post‐haemodialysis aldosterone values correlated well with serum potassium, which was approximately 1 mEq/1 lower the night following haemodialysis. Two patients were studied the night following haemodialysis under normal conditions and with suppression of ACTH secretion by dexamethasone. Under both conditions, a typical episodic secretion of aldosterone was observed. In both patients plasma ACTH was below the lower limit of detectability (<20 pg/ml) under dexamethasone medication. It was concluded from our experiments that: (1) the differences between pre‐ and post‐haemodialysis aldosterone values reflect a direct influence of potassium on the secretion of aldosterone; (2) the fluctuations in plasma aldosterone which were observed the night before haemodialysis were mostly probably mediated through ACTH; and (3) an unknown factor had caused episodic secretion of aldosterone the night following haemodialysis.
A CASE OF TESTICULAR FEMINIZATION WITH XYY KARYOTYPE
Authors: WESTARP CHRISTIAN VON , KILLINGER DONALD W. , VOLPÉ ROBERT
Published: March 2008

An unusual case of testicular feminization is reported, characterized by a 47 XYY karyotype in blood and gonads. Plasma testosterone varied between 509 and 557 ng/100 ml. Testosterone production was normal at 6.18 mg/day. There was very little response to human chorionic gonadotrophin stimulation. Gonadectomy revealed small testes, only one of which was shown to be metabolically active.
EVIDENCE FOR AN UNDERLYING ADRENOCORTICAL ABNORMALITY IN HIRSUTE WOMEN
Authors: FLEETWOOD J. A. , LEIGH R. J. , HALL R. , SMITH P. A.
Published: March 2008

Urinary testosterone levels were measured in twenty‐eight hirsute women and ten control subjects before and after the administration of corticotrophin. Twenty‐four patients had elevated basal urinary testosterone levels, and of these, nineteen showed an abnormal response to corticotrophin stimulation. Ten hirsute women from the latter group of nineteen, and eight control subjects, were further studied by measurement of the urinary pregnanetriol excretion before and following the concurrent administration of corticotrophin and metyrapone. An abnormal increment in pregnanetriol excretion was observed in eight out of the ten hirsute patients. It is suggested that this is evidence that an adrenal abnormality may be responsible for certain cases of idiopathic hirsutism, which may be operative at the 21‐hydroxylase level.
INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS AND INTRANASAL ADMINISTRATION OF LH/FSH‐RH: THE DURATION OF EFFECT AND OCCURRENCE OF ASYNCHRONOUS PULSATILE RELEASE OF LH AND FSH
Authors: MORTIMER C. H. , BESSER G. M. , HOOK JANET , McNEILLY A. S.
Published: March 2008

The duration of action of 100 μg of the synthetic gonadotrophin releasing hormone, the decapeptide LH/FSH‐RH, was compared in three subjects after intravenous, intramuscular and subcutaneous administration, given in random order at 7–10 day intervals. The levels of serum LH and FSH were followed over 9 hr. Each route of administration was equally effective in promoting LH and FSH release, and the magnitude of the responses and their time course were the same in each case. Two of these subjects then received 2 mg of the pure material dissolved in 0±5 or 1 ml of 0±9% NaCl by intranasal application. Although definite LH and FSH responses were seen, this route was less effective in promoting gonadotrophin release despite the higher dose used. In three further subjects blood sampling was carried out at 10 min intervals for 4 hr, following i.v., i.m. or s.c. injection of LH/FSH‐RH; pulsatile release of LH and FSH was observed in each subject but the fluctuations in LH and FSH were asynchronous. The therapeutic implications of subcutaneous and intranasal administration of the material are discussed.
CHANGES IN SERUM THYROXINE‐BINDING PROTEINS IN ENDEMIC GOITRE AND ENDEMIC CRETINISM
Authors: WELLBY M. L. , PHAROAH P. O. D. , HETZEL B. S.
Published: March 2008

Patients with endemic goitre in an iodine deficient area in the Territory of Papua and New Guinea (TPNG) have very little clinical evidence of hypothyroidism although serum thyroxine (T4) levels are usually very subnormal. The activities of T4‐binding proteins in both goitrous and non‐goitrous iodine deficient TPNG subjects were therefore investigated but no overall deficiencies were found to account for the low T4 levels. The mean serum T4‐binding pre‐albumin (TBPA) level (169 μg/100 ml as T4‐binding capacity) was less than the level seen in Australian subjects (187 μg/100 ml); however, this decrease was counteracted by the increase in T4‐binding globulin (TBG) level (27±3 μg) in iodine‐deficient TPNG compared with 19±9 μg in Australia.

Measurements of TBG and TBPA levels were also made during pregnancy in TPNG subjects, and found to increase to the same extent as in pregnancy in Australian subjects. This suggests that the pathogenesis of endemic cretinism (in TPNG) is dependent on some factor other than TBG deficiency during pregnancy.
THE TRH TEST IN THE COURSE OF TREATMENT OF HYPERTHYROIDISM
Authors: von zur MüHLEN A. , HESCH R. D. , KÖBBERLING J.
Published: March 2008

In nine patients with thyrotoxicosis (three patients with ophthalmopathy, one patient with T3 thyrotoxicosis) we followed plasma levels of triiodothyronine (T3) and thyrotoxine (T4) and the TRH induced TSH release before and under treatment with propythiouracil (PTU), carbimazole or methimazol. The patients were observed for 2‐8 months and did not receive any thyroid hormones during this time. Before treatment the TSH responses to TRH were absent in all patients. After commencement of antithyroid drug therapy the T3 and T4 plasma values decreased to normal (T3) or subnormal levels (T4) within 1‐5 weeks and the patients became euthyroid, but at that time the TRH test was still negative in all patients. Moreover, there was a lag of between 2 weeks and 4 months in five of the patient before the TRH test became positive. The duration of this lag could not be correlated with any data of the history or the clinical signs. Several possible explanations for this observation are discussed. Our results suggest that the TRH‐test is not suited for the control of the therapeutic effect of antithyroid drug therapy.
CIRCULATING LEVELS OF CORTICOTROPHIN AND CORTISOL AFTER INFUSIONS OF L‐DOPA, DOPAMINE AND NORADRENALINE, IN MAN
Authors: WILCOX C. S. , AMINOFF M. J. , MILLAR J. G. B. , KEENAN J. , KREMER M.
Published: March 2008

Intravenous infusions of noradrenaline and dopamine in normal saline, and l‐dopa in sodium lactate, were given to seven patients with Parkinsonism, and to five healthy volunteers. Infusions of saline and lactate were given, in a similar manner, to six additional healthy volunteers, who formed a control group. Dopamine and noradrenaline were each given in gradually increasing doses, for periods of 4 min, until a 30% increase in systolic blood pressure had occurred. l‐Dopa (320 mg) was given at a constant rate of infusion over 80 min. Plasma fluorogenic corticosteroids (cortisol) increased with dopamine, and decreased with noradrenaline. These changes were significantly different from the control group in the case of noradrenline only. ACTH values changed in a similar manner. l‐Dopa produced a consistent rise in both ACTH and cortisol that was significantly different from control subjects. The implications of these observations are discussed.
SERUM TRIIODOTHYRONINE 7–15 YEARS AFTER FRACTIONATED LOW DOSE RADIOIODINE THERAPY OF THYROTOXICOSIS
Authors: HERRMANN J. , SCHAPS D. , RUSCHE H. J. , BERGER M. , KRÜSKEMPER H. L. , von zur MÜHLEN A. , HACKENBERG K. , REINWEIN D.
Published: March 2008

In 189 of 334 patients, who had been treated with fractionated doses of radio‐iodine for Graves' disease 7–15 years ago, the serum concentrations of triiodothyronine have been estimated in addition to the following parameters: Protein bound 127iodine (PB127I), free thyroxine index, cholesterol‐ and TSH‐level in serum, tendon reflex time and clinical index according to Billewitz et al. (1969). In forty‐one of the 189 sera the free T4 (AFT4) and free T3 (AFT3) concentrations were measured as well. The following hormonal and clinical patterns were observed:

Euthyroidism, with all parameters within the normal range in 148 patients (= 78.4%).

Hypothyroidism with low serum T3, PBI, AFT4, AFT3 and elevated TSH in six subjects (= 3.2%).

Persistent hyperthyroidism with increased thyroid hormone concentrations and low TSH in seven cases (= 3.7%).

In twenty‐eight clinically euthyroid patients (= 14.8%) TSH was elevated with normal PBI and AFT4. Twenty of these subjects had a low normal T3 and in nine the T3 was clearly in the hypothyroid range (40 ± 12 μg/dl).

The constellation of normal T3, low T4 and elevated TSH, which has been frequently found after radioiodine therapy, has been seen in only moderate form in ten cases.
THE INACTIVATION OF THYROTROPHIN RELEASING HORMONE BY PLASMA IN THYROID DISEASE
Authors: JEFFCOATE S. L. , WHITE NICKI
Published: March 2008

The inactivation of immunoreactive TRH in vitro by human plasma has been investigated. In a preliminary study, 2.5 ng TRH was destroyed by 50 μl plasma at a mean rate of 1.7%/min in eight subjects. The per cent inactivation of the same amount of TRH at three plasma dose levels was measured after 60 min in seventy unselected patients attending a thyroid clinic. There was no significant difference in the results obtained in those subsequently shown to be euthyroid (forty‐three patients), hyperthyroid (eighteen patients) or hypothyroid (nine subjects).
CONCENTRATION OF OESTRONE AND OESTRADIOL IN FOLLICULAR FLUID AND OVARIAN VENOUS BLOOD OF WOMEN
Authors: BAIRD DAVID T. , FRASER IAN S.
Published: March 2008

The concentrations of oestrone and oestradiol as measured by a double isotope derivative method in fluid from Graafian follicles at different phases of the menstrual cycle were compared to the corresponding concentrations in ovarian and peripheral venous plasma collected simultaneously. In follicular fluid the concentration of oestradiol was much greater than that of oestrone. The concentrations of oestrogens were similar in fluid collected from small follicles at all phases of the cycle. The concentration of oestradiol in large follicles (>1 cm diameter) was much higher in the mid‐late follicular phase of the cycle (mean = 5390 ± 1330 nmol/1) than in large or small follicles at other phases of the cycle. In the mid‐late follicular phase of the cycle large follicles were invariably associated with high concentrations of oestradiol in venous plasma draining the corresponding ovary (mean 49 ± 12 nmol/1). The mean ratio of oestradiol/oestrone in fluid from large follicles in which the concentration of oestradiol was greater than 1400 nmol/1 (18.0 ± 1.0, n= 10) was significantly higher than the ratio in corresponding samples of ovarian venous plasma (10.7 ± 1.4, n= 11). These findings suggest that when the concentration of oestradiol in a Graafian follicle exceeds 3500 nmol/l it is likely to be functionally active.
SEX HORMONE LEVELS AND GONADOTROPHIN RELEASE IN THE POLYCYSTIC OVARY SYNDROME
Authors: DUIGNAN N. M. , SHAW R. W. , RUDD B. T. , HOLDER G. , WILLIAMS J. W. , BUTT W. R. , LOGAN‐EDWARDS R. , LONDON D. R.
Published: March 2008

The response to synthetic luteinizing hormone‐releasing hormone was studied in eighteen patients with the polycystic ovary syndrome. The release of follicle‐stimulating hormone was similar to that found in normal women. The mean response of luteinizing hormone was similar to that found in the luteal phase, but significantly greater (P<0.02) than that found in the early follicular phase of the normal menstrual cycle. Basal serum levels of FSH and LH, estimated in twenty‐five patients, were similar to those found in normal subjects. The sex hormone binding globulin capacity was reduced in twenty‐four of them. Basal serum testosterone levels were elevated in twelve of twenty‐two patients and the mean level was significantly greater (P<0.01) than the mean level of normal women. Basal serum androstenedione levels were elevated in nine of twenty‐two patients and the mean level was also significantly greater (P<0.02) than normal. There was a highly significant negative correlation (r=−0.86; P<0.001) between basal testosterone and LH levels. These data suggest that the pituitary gland of patients with the polycystic ovary syndrome contains adequate amounts of LH but that the ovulatory surge of LH which occurs in normal women is inhibited by testosterone acting on either the pituitary or, more probably, on the hypothalamus.
STEROIDOGENESIS IN A VIRILIZING OVARIAN TUMOUR
Authors: MASCHLER I. , WEIDENFELD J. , FLEISCHER B. , EHRENFELD E. N. , FINKELSTEIN M.
Published: March 2008

A metabolic study with tissue from a virilizing arrhenoblastoma, using as precursors [7‐3H]pregnenolone, [7‐3H]17α‐hydroxypregnenolone, [4‐14C]17α‐hydroxy‐progesterone and [4‐14C]testosterone, revealed that in spite of a deficient activity of 3β‐hydroxysteroid dehydrogenase‐5‐isomerase the overall production of test‐osterone was compensated by an increased activity of a lyase converting[4‐14C]17α‐hydroxyprogesterone to testosterone (via androstenedione) and was comparable to the production obtained by normal ovarian tissue. The masculinizing effects of the tumour in vivo were most probably caused by accumulation of testosterone due to deficiencies in enzymes catabolizing testosterone to 17‐ketosteroids and its aromatization to oestrogen. The unique property of the arrhenoblastoma to convert [4‐14C]17α‐hydroxyprogesterone to [4‐14C]11‐deoxycortisol (Reichstein's compound S) suggests an adrenal origin of the tumour which may explain its limited capacity to aromatize testosterone.
THYROTROPHIN AND PROLACTIN RESPONSIVENESS TO THYROTROPHIN RELEASING HORMONE IN CUSHING'S DISEASE
Authors: KUKU S. F. , CHILD D. F. , NADER S. , FRASER T. R.
Published: March 2008

Serum thyrotrophin response to thyrotrophin releasing hormone was impaired in all of eight subjects with untreated Cushing's disease; while all of six similar subjects tested after adequate treatment by a pituitary implant of 198 Au then showed a normal response. In all five of the untreated patients studied, the serum prolactin response to TRH was normal. Thus chronically excessive cortisol levels as seen in Cushing's disease inhibit pituitary TSH responsiveness to TRH without affecting the prolactin response to TRH

Evidently the release of TSH and of prolactin by TRH are governed by independent mechanisms.
HYPOTHALAMIC HORMONE INTERACTION IN ACROMEGALY
Authors: GOMEZ‐PAN A. , TUNBRIDGE W. M. G. , DUNS ANNE , HALL R. , BESSER G. M. , COY D. H. , SCHALLY A. V. , KASTIN A. J.
Published: March 2008

The growth hormone response to the administration of the currently available synthetic hypothalamic hormones was assessed in eleven patients with acromegaly. Eight of them showed a positive GH response to thyrotrophin releasing hormone and three showed no response. The GH response to TRH was shown to be unrelated to the thyrotrophin response to TRH. The GH response to TRH was inhibited by the administration of growth hormone release inhibiting hormone. Luteinizing hormone/follicle stimulating hormone releasing hormone (LHRH) caused a positive GH response in four patients, but this was trivial in three.

The TRH mediated GH release in acromegaly is not mediated via TSH and appears to be attributable to loss of specificity of the receptor sites on the somatotroph to the hypothalamic hormones.
GONADOTROPHIN HORMONE RELEASING TESTS IN WOMEN RECEIVING HORMONAL CONTRACEPTION
Authors: PEREZ‐LOPEZ F. R. , L'HERMITE M. , ROBYN C.
Published: March 2008

Gonadotrophin secretion by the pituitary was tested by i.v. injections of synthetic LH and FSH releasing hormone (LHRH) in five normal women between day 21 and day 25 of the luteal phase of the cycle, in twelve women receiving contraception with i.m. injection of medroxyprogesterone acetate and in eight women taking combined oral contraceptives of different varieties. Treatment with oral contraceptives led to a decrease or even to complete suppression of the response and possibly the reserve capacity of both LH and FSH secretions.

Treatment with medroxyprogesterone acetate for several years lowered basal serum LH and FSH as did oral contraceptives but had much less effect on the responses to LRH.

In long‐term steroid contraception, progestogens alone seem to exert much less deleterious effect on gonadotrophin function than when used in combination with an oestrogen.
SYSTOLIC TIME INTERVALS IN THYROID DISEASE
Authors: HILLIS W. S. , BREMNER W. F. , LAWRIE T. D. V. , THOMSON J. A.
Published: March 2008

The systolic time intervals; total electro‐mechanical systole (QS2), left ventricular ejection time (LVET), pre‐ejection period (PEP), and ratio of PEP/LVET were measured from external readings in twenty hyperthyroid and fifteen hypothyroid patients. The hyperthyroid subjects showed shortening of the PEP and reduction in the PEP/LVET. The hypothyroid group showed lengthening of the PEP, shortening of the LVET and increased PEP/LVET. These changes returned towards normal in ten patients rendered euthyroid with appropriate therapy. The value of these measurements to predict the thyroid status was examined in a mixed group of seventy‐four patients. There was close agreement between diagnosis predicted from systolic time intervals and that made independently from clinical and biochemical assessment, suggesting that the systolic time intervals may have been a useful place in the clinical assessment of thyroid patients.
IMMUNOREACTIVE ACTH AND CORTISOL PLASMA LEVELS DURING PREGNANCY. DETECTION AND PARTIAL PURIFICATION OF CORTICOTROPHIN‐LIKE PLACENTAL HORMONE: THE HUMAN CHORIONIC CORTICOTROPIN (HCC)
Authors: GENAZZANI A. R. , FRAIOLI F. , HURLIMANN J. , FIORETTI P. , FELBER J. P.
Published: March 2008

The high plasma Cortisol and ACTH levels present in pregnant women as well as the non‐parallelism of their plasma extract dilution curves in comparison with the standard curve in the ACTH radioimmunoassay, are evidence for the presence of an ACTH‐like substance during pregnancy which would interfere with the assay.

Placental extracts were obtained by acid‐acetone extraction, followed by partial purification with oxycellulose and by extraction with porous glass powder. A substance was detected which partially cross‐reacted with synthetic human ACTH in the radioimmunoassay and which showed biological activity using the assay procedure described by Lipscomb & Nelson. The data sustain the existence of an ACTH‐like placental hormone: human chorionic corticotrophin (HCC).
TREATMENT OF ACROMEGALY BY TRANSSPHENOIDAL HYPOPHYSECTOMY WITH CRYOAPPLICATION
Authors: PELKONEN RISTO , GRAHNE BERTEL
Published: March 2008

The therapeutic effect of transsphenoidal hypophysectomy with cryoapplication has been studied in twenty‐nine patients with active acromegaly. The mean follow‐up time was 15 months (3‐54 months).

A significant improvement of symptoms and signs occurred in all but three patients. The level of plasma immunoreactive growth hormone (IRGH) was reduced in all but two patients and a normal level of plasma IRGH was achieved in sixteen patients. Skin thickness, the level of serum inorganic phosphorus and the urinary excretion of hydroxyproline and calcium were significantly decreased in the great majority of the patients.

The operation was not accompanied by any visual complications, but cerebrospinal rhinorrhoea, subsiding spontaneously, developed in two and postoperative meningitis in one patient. Hypothyroidism and adrenocortical deficiency developed in eight, gonadotrophin deficiency in thirteen, and persistent diabetes insipidus in one patient.

It is concluded that transsphenoidal hypophysectomy with cryoapplication is a safe and effective method for the treatment of acromegalic patients.
HYPOGONADISM AND PARATHYROID ADENOMA IN CONGENITAL POIKILODERMA (ROTHMUND‐THOMSON SYNDROME)
Authors: WERDER E. A. , MÜRSET G. , ILLIG R. , PRADER A.
Published: March 2008

In two adult patients with congenital poikiloderma (Rothmund‐Thomson syndrome) the following endocrine abnormalities were found: Patient 1, female, with short stature had primary amenorrhoea and did not develop secondary sexual characteristics. Despite lacking an oestrogen effect on the vaginal smear and the low urinary oestrogen excretion, basal LH and FSH and their response to LH‐RH were normal. At age 36 a parathyroid adenoma was diagnosed because of increased immunoreactive plasma parathyroid hormone and persistent hypercalcaemia. After removal of the tumour the patient remained normocalcaemic. The result of growth hormone response to insulin in the intermediate range was suggestive of partial deficiency. In patient 2, male, hypergonadotropic hypogonadism with small testes and high basal LH and FSH levels as well as increased LH and FSH response to LH‐RH were found. Plasma testosterone was normal. Endocrine abnormalities in previously published cases are summarized.
FUNCTIONAL HYPOPARATHYROIDISM AND PARATHYROID HORMONE END‐ORGAN RESISTANCE IN HUMAN MAGNESIUM DEFICIENCY
Authors: RUDE ROBERT K. , OLDHAM SUSAN B. , SINGER FREDERICK R.
Published: March 2008

Hypocalcaemia is a well‐recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5.6 mg/dl and mean initial serum magnesium concentration was 0.75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (<150 pg/ml) or normal (<550 pg/ml) in all but two patients. Serial measurments made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24 h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144‐300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30‐60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end‐organ resistance to PTH in these patients.

The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the
QUANTITATION OF THE ACCELERATING EFFECT OF METYRAPONE ON CORTISOL METABOLISM
Authors: BLICHERT‐TOFT MOGENS , KEHLET HENRIK
Published: March 2008

Summary

Quantitation of the accelerating effect of metyrapone on cortisol metabolism has been made by determination of the metabolic clearance rate (MCR) of exogenous cortisol during a metyrapone load. Six adrenalectomized patients were studied. The slope of cortisol concentrations in plasma was determined after intravenous administration of 0.3 mg cortisol/kg b. w. with or without metyrapone 17.5 mg/kg b. w./h. In all six patients studied, the MCR of cortisol increased during metyrapone load from an average of 12.3 ± 5.0 (SD) 1/h to 29.6 ± 15.7 (SD) 1/h or corrected for body weight 3.0 ± 1.1 (SD) ml/kg b.w./min to 7.1 ± 2.5 (SD) ml/kg b.w./min

The discrepancy discovered in clinical practice between the relatively small rise in plasma total corticosteroid concentration and the greater increase in urinary excretion of corticosteroid metabolites during the metyrapone test may be explained by the findings in this study.
NYCTOHEMERAL VARIATION AND SUPPRESSIBILITY OF PLASMA ACTH IN VARIOUS STAGES OF CUSHING'S DISEASE
Authors: COOK DAVID M. , KENDALL JOHN W. , ALLEN JOHN P. , LAGERQUIST LYNN G.
Published: March 2008

In order to define nyctohemeral plasma ACTH secretory patterns, frequent plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary‐dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21‐hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease.

The effect of graded doses of dexamethasone, 2, 8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentration was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrast, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.
EFFECT OF THYROXINE ON THE INACTIVATION OF THYROTROPHIN‐RELEASING HORMONE BY RAT AND HUMAN PLASMA
Authors: DUPONT ANDRE , LABRIE FERNAND , LEVASSEUR LISE , DUSSAULT JEAN‐H. , SCHALLY ANDREW V.
Published: March 2008

The inactivation of synthetic [3H]thyrotrophin‐releasing hormone (TRH) by plasma was studied in rats treated with propylthiouracil (PTU) alone or with PTU and thyroxine. 48 h after the onset of treatment with thyroxine, the capacity of rat plasma to inactivate [3H]TRH was significantly increased. The percentage of deamidation of TRH to TRH‐free acid was increased 2‐fold after 4 days of administration of thyroid hormone. The inactivation of TRH by plasma from hypothyroid patients was compared to that obtained from hyperthyroid patients. Extraction of human plasma incubated with [3H]TRH, followed by thin‐layer electrophoresis, showed that transformation of [3H]TRH into TRH‐free acid was 44% higher in plasma from hyperthyroid than from hypothyroid patients (P < 0.05). These data suggest that the inactivation process of TRH by blood proteins could be an important factor in the regulation of the hypothalamo‐hypophyseal‐thyroid axis in rat and man.
CHANGES IN THE PITUITARY‐TESTICULAR SYSTEM WITH AGE
Authors: BAKER H. W. G. , BURGER H. G. , de KRETSER D. M. , HUDSON B. , O'CONNOR S. , WANG C. , MIROVICS A. , COURT J. , DUNLOP M. , RENNIE G. C.
Published: March 2008

In order to provide a comprehensive account of pituitary‐testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clinical measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.
EFFECT OF OESTRADIOL ON GONADOTROPHIN RELEASE INDUCED BY LHRH IN MEN
Authors: D'AGATA R. , GULIZIA S. , ANDÓ S. , VITALE G. , POLOSA P.
Published: March 2008

In order to study the role of the oestradiol on the feed‐back mechanism, fourteen men were subjected to LHRH test before and after treatment with oestradiol. The oestrogen was administered i.m., 3 μg/kg/24 h and 150 μg/kg/24 h, in two groups of patients. Doses of 3 and 150 μg respectively produced a reduction of LH release of 74% and 60% below control. FSH response to LHRH was almost abolished by oestrogens. Our findings show that oestrogensin men decrease the pituitary response to LHRH.
A PERSPECTIVE ON ALDOSTERONE ABNORMALITIES
Authors: BIGLIERI EDWARD G.
Published: March 2008

Not all the varied clinical disorders in which aldosterone and the mineralocorticoid hormones are involved have been reviewed. Only those disorders in which the mineralocorticoid hormones and their regulatory factors are the principal cause of the biochemical and clinical abnormalities have been examied. These are many and varied. Appreciation of the extent and magnitude of their involvement in the regulation of blood pressure, body fluids, and electrolyte composition continues to grow.

The major direct clinical impact of the mineralocorticoid hormones appears to be in two areas: hypertension and potassium homeostasis. Their part in the mosaic of hypertension is established in primary hyperaldosteronism, but they also appear to affect and modify the hypertensive process in primary or essential hypertension. The probe continues.

Hypoaldosteronism is more than the rare occurrence associated with Addison's disease. It may be the clue to the presence of nonaldosterone mineralocorticoid excess syndromes, and is obviously of critical imporatnce in an increasing number of patients with chronic renal failure of varied aetiologies.
THE EFFECT OF ELECTRIC CONVULSION THERAPY ON THE CIRCULATING CONCENTRATIONS OF PITUITARY HORMONES, CORTISOL AND CYCLIC ADENOSINE MONOPHOSPHATE
Authors: YLIKORKALA O. , KAUPPILA A. , HAAPALAHTI J. , KARPPANEN H.
Published: March 2008

In order to evaluate the effect of electroconvulsive therapy on the human pituitary‐adrenal function, serial plasma samples were assayed for FSH, LH, TSH, HGH, ACTH, cortisol and cyclic AMP before and after nine shocks in five subjects. A prominent finding was the rapid stimulation of the ACTH‐cortisol production in all subjects, while no consistent changes in FSH, LH, TSH, HGH or cyclic AMP were found.
LUTEINIZING HORMONE SECRETION IN PATIENTS PRESENTING WITH POST‐ORAL CONTRACEPTIVE AMENORRHOEA: EVIDENCE FOR A HYPOTHALAMIC FEEDBACK ABNORMALITY
Authors: MARSHALL J. C. , REED P. I. , GORDON H.
Published: March 2008

Twenty‐four patients who presented with amenorrhoea after discontinuing oral contraceptives were studies. In fourteen patients underlying conditions were present which could account for the amenorrhoea. Two patients were pregnant, two had premature ovarian failure and four polycystic ovarian disease. Pituitary tumours were present in three patients, and in another three radiological abnormalities of the pituitary fossa suggested the presence of an intrasellar tumour. Basal serum luteinizing hormone levels reliably differentiated ovarian from hypothalamic or pituitary lesions. Varied patterns of serum LH response to clomiphene were present in the patients with post‐oral contraceptive amenorrhoe or pituitary lesions. Most patients showed normal hormone response patterns, with a secondary LH occurred despite normal oestradiol responses. This suggests an abnormality of the positive feedback system for oestrogens. Subsequent stimulation with clomiphene produced normal LH responses in these patients showing that the abnormality was reversible.

These findings are consistent with the hypothesis that post‐oral contraceptive amenorrhoea is the result of continuing suppression of normal hypothalamic pituitary feedback systems after the sex steroids have been stopped. The different patterns of hormone response to clomiphene suggest varying degrees of feedback abnormality, and in some patients the positive feedback mechanism only is impaired.
CASE OF HYPERTHYROIDISM DUE TO A CHROMOPHOBE ADENOMA*
Authors: BAYLIS P. H.
Published: March 2008

A 23‐year‐old man with secondary hypogonadism was also found to be thyrotoxic. Results of thyroid function tests were in the hyperthyroid range but the serum TSH was inappropriately high. A pituitary tumour was demonstrated and following hypophysectomy he became biochemically hypothyroid. Evidence is presented and discussed that his hyperthyroidism was due to excessive TSH production by the pituitary tumour.
TOTAL THYROIDAL CONTENT OF IODINE IN THYROTOXIC PATIENTS MEASURED BY IN VIVO NEUTRON ACTIVATION ANALYSIS
Authors: ROBERTSON I. , BODDY K. , HOOPER M. J. , STEVENSON R. D. , McGHIE T. , ALEXANDER W. D. , WILSON G. M.
Published: March 2008

This paper describes an in vivo method for measurign total thyroidal iodine stores by activation analysis, its evaluation and measurements in thyrotoxic patients. There was good correlation between measurements of solutions of iodine and post‐mortem thyroids by activation analysis and chemical analysis. Measurements in thyrotoxic patients showed low levels in untreted and treated (antithyroid drugs) patients and a marked increase in patients studied whilst in clinical remission. The practical importance of this method of measurement of thyroidal iodine stores is that it is a relaible in vivo measurement obtained at a single visit and should enable the definition of the relationship of thyroidal iodine stores to pathophysiology and prognosis.
THE DEVELOPMENT OF A RADIOIMMUNOASSAY FOR THE MEASUREMENT OF HUMAN PLASMA ARGININE VASOPRESSIN
Authors: BAYLIS P. H. , HEATH D. A.
Published: March 2008

A radioimmunoassay for AVP capable of measuring human plasma AVP is described, Iodination was performed by the chloramine T method and purified by chromatography on Sephadex G‐25. Specific activity of 125I‐AVP was 1710×155 Ci/mmol. Antiserum of high affinity (Keq= 2.7×1011l/mol) has been raised in rabbits, which shows slight cross‐reactivity with LVP and negligible reactivity with oxytocin. The aqueous assay is capable of detecting 0.4 fmol of AVP/tube and it is highly reproducible.

A Florisil extraction technique is described in detail and gives recovery of 70% of synthetic AVP added to plasma over a wide physiological range. The lowest detectable concentration of plasma AVP is 0.3 pmol/l.

The method has been validated by studying changes in plasma AVP concentration following overnight dehydration (plasma AVP = 3.46×1.89 (SD) pmol/l), and water loading (plasma AVP = 1.54×0.59 pmol/l), P < 0.005, in normal subjects. A A highly significant positive correlation has been found between plasma AVP and plasma osmolality (r=+0.75). Plasma AVP concentration has also been determined in patients with DI and the syndrome of inappropriate ADH secretion. No effect was found on the level of plasma AVP in normally hydrated volunteers undergoing postural change but levels rose following strenuous exercise from basal concentrations of 1.57×0.59 pmol/l to 4.77×3.43 pmol/l, P < 0.01.
MALE PSEUDOHERMAPHRODITISM DUE TO PARTIAL END‐ORGAN INSENSITIVITY TO ANDROGENS
Authors: BARRAGRY J. M. , MAKIN H. L. J. , MORRIS D. V. , TRAFFORD D. J. H. , MASON A. STUART
Published: March 2008

A 46XY individual with incomplete male pseudohermaphroditism was studied. The phenotype was distinctive, with a masculine habitus despite a small phallus, gynaecomastia and diminished virilization. Plasma levels of testosterone, oestrogens, gonadotrophins and sex‐hormone binding globulin were elevated. It is proposed that this syndrome is a variant of Type I incomplete male pseudohermaphroditism.
THE RELATIONSHIP BETWEEN THYROID FUNCTION AND THE RENAL RESPONSE TO PARATHYROID HORMONE
Authors: ASHBY J. P. , MacPHERSON J. N. , STRONG J. A.
Published: March 2008

SUMMARY. The effect of thyroid status on renal adenosine 3′, 5′‐cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex.
THE EFFECT OF INSULIN ON LUNG METABOLISM IN THE RAT
Authors: STUBBS W. A. , MORGAN I. , LLOYD B. , ALBERTI K. G. M. M.
Published: March 2008

A new model has been established for the perfused in situ rat lung. During perfusion with glucose at 4 mmol/1, physiological concentrations of insulin (50 mu/1) caused an initial 1.5 fold increase in lactate production; the increase being sustained at 30% for the 4 h of perfusion. The observation that the lung responds to physiological concentrations of insulin could have important implications with respect to whole body carbohydrate metabolism.
CLEARANCE OF EXOGENOUS PARATHYROID HORMONE IN NORMAL AND URAEMIC MAN
Authors: PAPAPOULOS S. E. , HENDY G. N. , TOMLINSON S. , LEWIN I. G. , O'RIORDAN J. L. H.
Published: March 2008

1. The clearance of unlabelled bovine parathyroid hormone (BPTH) was studied after injection or infusion of the hormone into ten normal subjects and six patients with chronic renal failure (two of whom had been nephrectomized).

2. The build‐up and clearance of the hormone was monitored using amino‐and carboxy‐terminal region‐specific immunoradiometric assays.

3. In the normal subjects amino‐terminal BPTH was cleared rapidly. The mean plasma half‐disappearance time (t1/2)was 5.5 min and the mean metabolic clearance rate (MCR) was 10.37 ml/kg/min. Carboxy‐terminal immunoreactivity was cleared less rapidly, persisting for some hours in the circulation after termination of an infusion.

4. In patients with chronic renal failure the amino‐terminal region was also cleared more rapidly from the circulation than the carboxy‐terminal region.

5. As a group, the chronic renal failure patients (with kidneys and anephric subjects) cleared amino‐terminal BPTH more slowly than the normal group (mean t1/2= 7.95 min and mean MCR = 4.98 ml/kg/min). The value for MCR was significantly different from that of the normal group, although there was some overlap between the values for the two groups.

6. In one of the anephric subjects studied the values for the clearance of aminoterminal immunoreactivity were within the normal range, as was the MCR. This indicates that some organ other than the kidney plays an important role in the metabolism of parathyroid hormone in man.

7. There was no correlation between t1/2 and MCR for the normal, chronic renal failure or combined groups.

8. In the uraemic subjects the metabolic clearance rate was inversely related to plasma creatinine levels.
THE CHARACTERIZATION OF GROWTH HORMONE RELEASE INHIBITING HORMONE‐LIKE IMMUNOREACTIVITY IN NORMAL URINE
Authors: KRONHEIM S. , BERELOWITZ M. , PIMSTONE B. L.
Published: March 2008

SUMMARY. Using a previously described radioimmunoassay for growth hormone release inhibiting hormone (GH‐RIH), the presence of GH‐RIH‐like immunoreactivity in urine has been characterized by demonstrating mobility identical to synthetic GH‐RIH standard on two sephadex gel chromatographic systems, and parallelism of dilutions of the sephadex fractions with synthetic GH‐RIH. Furthermore, 74% of the sephadex fraction cross‐reacting in the immunoassay bound to antibody conjugated to sepharose and could be eluted by 1 M acetic acid. This immunospecific eluate showed identity with synthetic GH‐RIH on both ion exchange and thin layer chromatography. Thus GH‐RIH‐like immunoreactivity is present in normal urine; this may have potential relevance in the search for a physiological role for this peptide.
THE SPECTRUM OF THYROID DISEASE IN A COMMUNITY: THE WHICKHAM SURVEY
Authors: TUNBRIDGE W. M. G. , EVERED D. C. , HALL R. , APPLETON D. , BREWIS M. , CLARK F. , EVANS J. GRIMLEY , YOUNG E. , BIRD T. , SMITH P. A.
Published: March 2008

A survey has been conducted in Whickham, County Durham, to determine the prevalence of thyroid disorders in the community. Two thousand seven hundred and seventy‐nine people (82.4% of the available sample) were seen in the survey. The prevalence of overt hyperthyroidism was 19/1000 females rising to 27/1000 females when possible cases were included, compared with 1.6–2.3/1000 males. The prevalence of overt hyothyroidism was 14/1000 females rising to 19/1000 females when possible cases were included, compared with less than 1/1000 males. The prevalence of spontaneous overt hypothyroidism (excluding iatrogenic cases) was 10/1000 females or 15/1000 females including unconfirmed cases. Minor degrees of hypothyroidism were defined on the basis of elevated serum thyrotrophin (TSH) levels in the absence of obvious clinical features of hypothyroidism. TSH levels did not vary with age in males but increased markedly in females after the age of 45 years. The rise of TSH with age in females was virtually abolished when persons with thyroid antibodies were excluded from the sample. TSH levels above 6 mu/1 were shown to reflect a significant lowering of circulating thyroxine levels and showed a strong association with thyroid antibodies in both sexes, independent of age. Elevated TSH levels (>6mu/l) were recorded in 7.5% of females and 2.8% of males of all ages. Thyroglobulin antibodies were present in 2% of the sample. Thyroid cytoplasmic antibodies were present in 6.8% of the sample (females 10.3%, males 2.7%) and their frequency did not vary significantly with age in males but increased markedly in females over 45 years of age. 3% of the sample (females 5.1%, males 1.1%) had thyroid antibodies and elevated TSH levels and the relative risk of a high TSH level in subjects with antibodies was 20:1 for males and 13:1 for females, independent of age. Small goitres (palpable but not visible) were found in 8.6% of the sample and obvious goitres (palpable and visible) in 6.9%. Goitres were four times more common in females than in males and were most commonly found in younger rather than older females. TSH levels were slightly but not significantly lower in those with goitre than in those without goitre. There was a weak association between goitre and antibodies in females but not males.
SHORT‐TERM FLUCTUATIONS IN PLASMA CORTISOL IN CUSHING'S SYNDROME
Authors: VETTER H. , STRASS R. , BAYER J.‐M. , BECKERHOFF R. , ARMBRUSTER H. , VETTER W.
Published: March 2008

Short‐term fluctuations in plasma cortisol were determined overnight in twelve patients with Cushing's syndrome: eight patients with bilateral adrenal hyperplasia of hypothalamic‐pituitary origin, three patients with a cortisol producing adenoma and one patient with a carcinoma of the adrenal cortex. While either secretory episodes in plasma cortisol or a fixed pattern of cortisol secretion were observed both in patients with pituitary dependent and in those with pituitary independent hypercorticism, a typical night‐day variation in plasma cortisol was only found in one of the eight patients with Cushing's syndrome of hypothalamic‐pituitary origin. The patient with a cortisol producing carcinoma showed only minor fluctuations in plasma cortisol throughout the test period.

The results indicate that no discrimination can be made between patients with pituitary dependent or independent Cushing's syndrome by demonstrating an episodic or a fixed secretion of cortisol. It seems, however, that the finding of a typical night‐day variation in hormone secretion points to hypercorticism of hypothalamic‐pituitary origin.