bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TOXIC EFFECTS OF SMALL IODINE SUPPLEMENTS IN PATIENTS WITH AUTONOMOUS THYROID NODULES
Authors: LIVADAS D. P. , KOUTRAS D. A. , SOUVATZOGLOU A. , BECKERS C.
Published: March 2008

In sixteen cases of toxic adenoma of the thyroid (autonomous hot nodule with complete suppression of the surrounding normal parenchyma) potassium iodide was given in doses of 100 μg/day for one week, 200 μg/day for another and 400 jug/day for a third week. There was a progressive increase in the serum T4 level. Serum T3 also increased, although this was significant only after the first week. Serum TSH was undetectable throughout the entire period of the study. This metabolic pattern is different from the response seen in cases of nontoxic endemic goitre, where small iodine supplements induce an increase in serum T4 but a decrease in serum T3. Furthermore, the present results may explain the phenomenon of iodineinduced or iodine‐precipitated hyperthyroidism (Jod‐Basedow) when patients with autonomous thyroid are presented with a high iodine intake. In contrast to the results obtained with small iodide doses, two other cases treated with large pharmacological doses of iodide showed a decrease in both serum T4 and serum T3. It is concluded that the physician should be aware of the possibility of precipitating or aggravating thyrotoxicosis in patients with an autonomous hot nodule by increasing their intake of iodine.
SERUM FSH, LH AND PROLACTIN IN NORMAL MALES AND PATIENTS WITH PROSTATIC DISEASES
Authors: HAMMOND G. L. , KONTTURI M. , MÄÄTTÄLÄ P. , PUUKKA M. , VIHKO R.
Published: March 2008

Serum FSH, LH and prolactin were measured in fifty‐eight normal males between 30 and 80 years of age. At the same time, similar estimations were performed on samples taken from 232 patients with benign prostatic hypertrophy (BPH) and twenty‐six patients with prostatic carcinoma. The three groups were compared with respect to age, and it was observed that significant rises related to age occurred in the serum levels of FSH, LH and prolactin in normal men after the sixth decade. The patient groups did not differ significantly from each other, or from the normal age‐matched population in respect to prolactin and FSH levels. Serum LH in both the carcinoma and BPH patient groups, however, differed significantly from the controls, and remained at the level associated with younger normal males. It is suggested that testosterone metabolites from the prostate exert a negative feedback on pituitary LH secretion.
AMILORIDE IN THE TREATMENT OF PRIMARY HYPERALDOSTERONISM AND ESSENTIAL HYPERTENSION
Authors: KREMER D. , BODDY K. , BROWN J. J. , DAVIES D. L. , FRASER R. , LEVER A. F. , MORTON J. J. , ROBERTSON J. I. S.
Published: March 2008

Amiloride (40 mg/day) was given to nineteen patients with primary hyperaldosteronism. There were significant falls in systolic and diastolic blood pressure, in total exchangeable sodium, and in serum sodium and bicarbonate; while total exchangeable potassium, total body potassium, serum potassium, chloride and urea, and plasma renin, angiotensin II and aldosterone all increased significantly. Amiloride was effective in reducing blood pressure in patients with and without adrenocortical adenoma. No carry‐over effect was seen on withdrawing amiloride. Similar changes were associated with amiloride treatment in five patients with essential hypertension; hyperkalaemia was not observed. Only negligible side‐effects were encountered in the entire series of twenty‐four patients.
THE THYROIDAL PRODUCTION OF REVERSE TRIIODOTHYRONINE IN AUTONOMOUS ADENOMA
Authors: REINWEIN D. , DURRER H. , EMRICH D. , MEINHOLD H. , WENZEL K. W.
Published: March 2008

SUMMARY. The ratios of reverse triiodothyronine (rT3) to triiodothyronine (T3) concentrations were similar (0.89±0.09) in twenty‐three autonomous thyroid nodules (fourteen decompensated, nine compensated) and paranodular tissues (0.82±0.08), whereas the serum ratio was significantly lower (0.098±0.014). This is compatible with the hypothesis that thyroidal rT3 and T3 production from mono‐ and di‐iodotyrosine may be a random process in contrast to non‐random extrathyroidal rT3 and T3 formation.
CIRCADIAN RHYTHM OF PLASMA CORTICOSTEROIDS IN HEROIN DEPENDENT SUBJECTS
Authors: GHODSE A. HAMID , REED J. L.
Published: March 2008

SUMMARY. The circadian rhythm of corticosteroid secretion was investigated in six heroin dependent subjects by measuring plasma corticosteroids at 09.00 hours and 24.00 hours. All results were within the normal range and it seems unlikely that chronic heroin dependence affects the hypothalamic control of corticosteroid secretion.
THE ROLE OF DOPAMINERGIC DEPLETION IN THE PATHOGENESIS OF CUSHING'S DISEASE AND THE POSSIBLE CONSEQUENCES FOR MEDICAL THERAPY
Authors: LAMBERTS S. W. J. , TIMMERMANS H. A. T. , DE JONG F. H. , BIRKENHÄGER J. C.
Published: March 2008

In four patients suffering from pituitary dependent Cushing's syndrome plasma ACTH and cortisol were lowered after a single dose of 2.5 mg bromocriptine, but ACTH and cortisol responses to hypoglycaemia remained absent after bromocriptine administration. In contrast, in three of these patients a growth hormone response which had previously been absent appeared to return 3 h after bromocriptine. While untreated, basal prolactin levels were at the upper limit of normal and a subnormal response was seen after hypoglycaemia. With bromocriptine therapy, basal prolactin levels were depressed and no reaction to hypoglycaemia was seen. In three patients 400 μg TRH did not elicit an increase of TSH and growth hormone while a normal increase of prolactin was induced. In one patient a dose of 2.5 mg bromocriptine caused an attack of nausea and hypotension possibly complicated by relative adrenocortical insufficiency. Four patients were studied during treatment with a daily dose of 5–20 mg bromocriptine for 1–20 weeks. In one patient, pituitary‐adrenocortical function escaped three times from the effect of bromocriptine treatment. One patient showed an increase of urinary 17‐OHCS during treatment lasting 7 days. Two other patients responded well to bromocriptine therapy, In one patient the treatment had to be stopped after 7 days because of complaints of extreme muscle weakness, while urinary 17‐OHCS had become low‐normal; in another patient Cortisol Secretion Rate was normalized throughout bromocriptine treatment lasting 20 weeks.

Our results suggest that a hypothalamic dopaminergic depletion plays a role in the abnormal ACTH and growth hormone secretion in pituitary dependent Cushing's syndrome. The place of bromocriptine in the management of Cushing's disease remains uncertain.
THE BEHAVIOUR OF THYROID HORMONES IN AN INFANT WITH UNTREATED NEONATAL THYROTOXICOSIS
Authors: WILKIN T. J. , KENYON EILEEN , ISLES T. E.
Published: March 2008

The clinical course from birth and serial measurements of serum T3, T4 and TSH in an infant with untreated neonatal thyrotoxicosis are reported. The thyroid hormone levels fell exponentially with time at rates very much slower than those previously reported for the maternally‐transmitted thyroid stimulating antibody generally thought to cause the disorder. Steady physiological levels of thyroid hormones were achieved after 110 days (serum T3 = 3.4 nmol/1, T4 = 118 nmol/1). TSH first rose to a measurable level after about 90 days.
EFFECT OF PIMOZIDE ON LEVODOPA‐INDUCED GROWTH HORMONE RELEASE IN MAN
Authors: MASALA A. , DELITALA G. , ALAGNA S. , DEVILLA L.
Published: March 2008

SUMMARY. Serum growth hormone (GH) behaviour after levodopa administration was measured in twelve healthy subjects both in basal conditions and after a 4 day course of pimozide (4 mg daily), a specific blocker of dopamine (DA) receptors. In addition, fasting plasma GH was measured on the first, second and third day of treatment. No significant difference was found between GH response to levodopa in basal conditions and after pimozide; moreover, fasting GH was uninfluenced by pimozide.
TIME‐COURSE OF PHYSIOLOGICAL HYPERPROLACTINAEMIA DURING TWO YEARS LACTATION
Authors: DELVOYE PIERRE , DELOGNE‐DESNOECK JOSIANE , UWAYITU‐NYAMPETA  , ROBYN CLAUDE
Published: March 2008

SUMMARY. In Central Africa, mothers on nursing for 2 years are hyperprolactinaemic during the first 15–18 post‐partum months; serum prolactin levels are some three times higher than in non‐pregnant and non‐lactating women.
EVIDENCE FOR A DOPAMINERGIC ACTIVITY OF METHYSERGIDE IN HUMANS
Authors: OPPIZZI G. , VERDE G. , DE STEFANO L. , COZZI R. , BOTALLA L. , LIUZZI A. , CHIODINI P. G.
Published: March 2008

The acute administration of 2 mg of methysergide significantly reduced plasma prolactin levels in nine normal subjects and in seven hyperprolactinaemic patients. The prolactin lowering effect of this drug was abolished by sulpiride. Moreover methysergide lowered plasma GH levels in four out of nine acromegalic patients, who were also responsive to a dopaminergic drug such as bromocriptine. Although methysergide did not significantly blunt the TRH‐induced prolactin release, our data suggest that this drug may affect GH and prolactin release through a dopaminergic mechanism of action. This effect should be taken into account when methysergide is employed as antiserotoninergic drug in neuroendocrinological studies.
LOW SERUM l‐T3 LEVELS IN THE ELDERLY SICK: PROTEIN BINDING, THYROID AND PITUITARY RESPONSIVENESS, AND REVERSE T3 CONCENTRATIONS
Authors: BURROWS A. W. , COOPER E. , SHAKESPEAR R. A. , AICKIN C. M. , FRASER S. , HESCH R.‐D. , BURKE C. W.
Published: March 2008

Thyroid function was studied in thirty‐five euthyroid geriatric inpatients to define the relative importance of T4 to T3 conversion or pituitary‐thyroid dysfunction as a cause of low serum T3 concentrations. A previously reported finding of low serum total T3 levels was confirmed, and was associated with a fall in mean unbound T3 to 5.23 pmol/l (6.70 in younger normal subjects) and a rise in unbound T4 to 52.7 pmol/l (36.4 in normals). However, the protein binding of T3 and T4 was weaker in the patients (e.g. per cent unbound T4 increased 1.4 times) despite a mean increase in serum immunoreactive TBG concentration of 30%. Mean serum reverse T3 concentration (rT3) was nearly doubled in the patients (0.42 nmol/l compared with 0.24 in normals) but the correlation between high rT3 and low T3 was not close, and in a fifth of patients low T3 was not associated with high rT3. The T3 response to TSH injection was greater in patients with low T3 levels, and the T4 response smaller. The overall effect of TSH injection was to restore the previously increased T4 to T3 ratio of the patients to normal. The TSH response to TRH was absent in about a third of patients, and delayed in about another quarter, especially, although not exclusively so, in patients with low serum T3. The data suggest that several factors are concerned in the pathogenesis of low serum T3 concentrations in the elderly in hospital. Among these may be a shift in T4 deiodination from T3 to rT3, and hypothalamo‐pituitary TSH dysfunction. But it appears that other undefined factors may be responsible (such as nutrition or steroid levels); the pathogenesis is probably not the same in all patients.
MALE PSEUDOHERMAPHRODITISM WITH GYNAECOMASTIA DUE TO TESTICULAR 17‐KETOSTEROID REDUCTASE DEFICIENCY
Authors: AKESODE F. ADEMOLA , MEYER WALTER J. , MIGEON CLAUDE J.
Published: March 2008

A 28‐year‐old male pseudohermaphrodite with gynaecomastia was raised as a female until the age of 17 years, at which time he developed masculine features (deepening of the voice, development of facial hair, male distribution of body hair and male body habitus) and assumed a male gender role. He had a small phallus with perineal urethra, absence of labioscrotal fusion, presence of vaginal pouch and undescended testes. The testicular biopsy showed hyalinization of the tubular basement membrane, lack of spermatogenesis and hyperplastic Leydig cells. Baseline peripheral plasma studies showed androstenedione concentrations ten times normal, low testosterone, elevated oestrone and elevated gonadotrophins. The in vitro incubation of testicular tissue showed no significant conversion of androstenedione to testosterone. However, two types of peripheral tissues, skin fibroblasts and erythrocytes, had a normal conversion, as did the body overall as measured by the technique of androstenedione constant infusion. These studies demonstrate that the 17‐keto‐steroid reductase deficiency of the patient was limited to the testes.
THYROID FUNCTION AND THYROID REGULATION IN EUTHYROID MEN WITH CHRONIC LIVER DISEASE: EVIDENCE OF MULTIPLE ABNORMALITIES
Authors: GREEN J. R. B. , SNITCHER E. J. , MOWAT N. A. G. , EKINS R. P. , REES LESLEY H. , DAWSON A. M.
Published: March 2008

Total and free serum thyroxine (T4) and triiodothyronine (T3), basal serum thyrotrophin (TSH) and the serum TSH response to a standard intravenous dose of thyrotrophin releasing hormone (TRH) have been measured in fifteen men with liver cirrhosis and in eight alcoholic men with fatty liver change. All the patients studied were clinically euthyroid. In cirrhotics, total T4 and free T4 (FT4) concentrations were normal as were free T3 (FT3) concentrations but total T3 concentrations were significantly reduced and basal TSH concentrations were significantly higher than normal. Alcoholics with fatty liver change had normal basal TSH concentrations and normal total and free thyroid hormone concentrations apart from reduced FT4. Correlation of thyroid function tests with liver function (serum albumin concentration) showed significant positive correlations for serum albumin with both total T3 and FT3 and significant negative correlations with both FT4 and basal TSH. Nine of fifteen cirrhotics had an abnormal serum TSH response to TRH, the commonest abnormal pattern being a delayed response (seven patients). Three of eight alcoholics with fatty liver change also had an abnormal TSH response to TRH. These findings not only show complex disturbances in hypothalamic‐pituitary‐thyroid relationships in chronic liver disease but also provide indirect evidence of reduced extra‐thyroidal conversion of T4 to T3.
LIPID PROFILES AND CARDIOVASCULAR DISEASE IN THE WHICKHAM AREA WITH PARTICULAR REFERENCE TO THYROID FAILURE
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

The age and sex distribution of ischaemic heart disease (IHD), other vascular disorders and serum lipid concentrations and the possible association between these factors and thyroid failure have been examined in a community survey. A past history of IHD occurred in 7.5% of males and 4.8% of females.‘Chest pain on effort’was found in 7.4% of males and 7.8% of females and‘possible infarction’in 5.4% of males and 3.8% of females. Major ECG changes were found in 4.7% of both sexes and minor changes in 6.5% of males and 11% of females. Intermittent claudication was present in 4.8% and cerebrovascular accidents had occurred in 2% of the sample. Diastolic blood pressures greater than 100mmHg were found in 13% of all males and 11% of all females. Cholesterol concentrations were normally distributed. Mean cholesterol rose by approximately 0.25 mmol/1/decade in both sexes to reach a maximum in the 55–64 years age group and declined slightly thereafter. Trigly‐ceride values were skewed to the right and increased by 0.2 mmol/1/decade in males up to the 45–54 years age group and by 0.1 mmol/1/decade in females to a peak in the 65–74 years age group — and declined after these ages. Electrophoresis revealed Type IIa patterns in 3% of males and 9% of females, IIb in 1% of both sexes and Type IV in 13% of males and 3% of females. There was no association in males between IHD and thyroid antibodies or minor degrees of thyroid failure. There was a weak association between minor ECG changes and minor degrees of hypothyroidism (but not thyroid antibodies) in females which was independent of other variables. The significance of this observation depends upon the interpretation of the ECG abnormalities and will only be established by longitudinal studies. No association was noted between lipid concentrations and thyroid antibodies or minor degrees of hypothyroidism.
THE HYPOGLYCAEMIC ACTION OF SOMATOSTATIN IN THE ANAESTHETIZED DOG
Authors: BLAUTH C. I. A. , SÖNKSEN P. H. , TOMPKINS C. V. , BLOOM S. R.
Published: March 2008

The hypoglycaemic action of somatostatin was investigated in fasted anaesthetized dogs. An isotopic turnover technique with radioactive D‐[2‐3H] glucose tracer was used to measure the rats of hepatic production and peripheral utilization of glucose before, during, and after a 60 min infusion of 150 μg somatostatin. Plasma concentrations of insulin, glucagon, growth hormone, cortisol and free fatty acids were also measured.

Somatostatin infusion caused a fall of plasma glucose demonstrable within 10 min. After 60 min plasma glucose had fallen to 75% of the pre‐infusion concentration. Simultaneously the specific activity of the D‐[2‐3H] glucose increased and calculation of the rates of production and utilization of glucose over 10 min intervals indicated that the mean hepatic production rate of glucose fell to 59% of the pre‐infusion rate while the rate of peripheral utilization of glucose fell to 83% of the pre‐infusion rate. These results show that the hypoglycaemic action of intravenous somatostatin depends exclusively upon the inhibition of hepatic glucose production. This effect may have been partly due to a fall of plasma glucagon concentration and occurred despite a fall of plasma insulin to less than 1 mu 1‐1.
FAMILIAL GOITRE WITH PARTIAL IODINE ORGANIFICATION DEFECT, LACK OF THYROGLOBULIN, AND HIGH LEVELS OF THYROID PEROXIDASE
Authors: NIEPOMNISZCZE HUGO , MEDEIROS‐NETO GERALDO A. , REFETOFF SAMUEL , DEGROOT LESLIE J. , FANG VICTOR S.
Published: March 2008

From a sibship of three sisters having congenital goitre and normal hearing, two had impairment of organification of iodide. S1 (4 years old) had goitre since birth, euthyroidism, and a negative perchlorate test. S2 (15 years old) and S3 (13 years old) were hypothyroid, and had radioiodide discharge after potassium perchlorate administration of 19.8% and 26.1%, respectively. Thyroid tissue was obtained at thyroidectomy. Peroxidase activity, in the thyroidal subcellular particles, was found to be qualitatively normal, but quantitatively increased. In the triiodide assay, the activity was: S1 6912 u, S2 2590 u, and S3 3844 u (normal values 900‐1700 u). In the tyrosine‐iodinase assay, the activities, expressed as nmoles of iodide incorporation per gram of tissue, were S1 1046, S2 471, and S3 547 (normal values 220‐410). The activity of the thyroidal NADPH‐cytochrome c reductase, an enzyme possible involved in hydrogen peroxide generation, was: S1 0.084, S2 0.047, and S3 0.055 (normal values 0.018 μEq/min/mg). No thyroglobulin was detected by analytical ultracentrifugation, polyacrylamide gel electrophoresis, or double immunodiffusion in agar of the supernatant fractions. In patient S3, whose gland was labelled in vivo with 125I, 60% of the total radioactivity of the gland (pooled nodular and paranodular specimens) was in a particulate iodoprotein that was solubilized by trypsin, deoxycholate or digitonin. In the soluble fraction there were two iodoproteins: iodoalbumin, and a second iodoprotein similar to the solubilized particulate iodoprotein.

It is postulated that absence of the normal thyroidal receptor protein might be in some cases a cause of iodine organification defect.
A LONG‐TERM FOLLOW UP OF PATIENTS WITH AUTOIMMUNE THYROID DISEASE
Authors: KHANGURE M. S. , DINGLE P. R. , STEPHENSON J. , BIRD T. , HALL R. , EVERED D. C.
Published: March 2008

A survey in a general practice in the North‐East of England in 1963 detected thyroglobulin antibodies in 16.2% of women and 4.3% of men. High titres of antibodies were found in 4.6% of women and 1.6% of men. Forty‐six subjects with thyroglobulin antibodies (from an original total of fifty‐two) were studied in 1972 and forty of these were studied further in 1975. These subjects were compared with a group of age‐ and sex‐matched controls from the original survey. Three of the subjects had developed overt hypothyroidism by 1975 and a raised serum thyroid‐stimulating hormone (TSH) concentration was found more frequently in euthyroid subjects previously found to be antibody positive. There was a striking difference in the antibody studies in that only 26% of the previously antibody positive subjects had thyroglobulin antibodies in 1972 and 30% in 1975. A raised serum TSH concentration was found to correlate with cytoplasmic antibodies and particularly with the combination of cytoplasmic and thyroglobulin antibodies.
PLASMA AND PITUITARY THYROTROPHIN (TSH) IN SEVERE AND PROLONGED HYPOTHYROIDISM, AS STUDIED IN THE RAT
Authors: CACICEDO L. , GARCIA M. D. , DE ESCOBAR G. MORREALE
Published: March 2008

Thyroidectomized rats, kept on a low iodine diet, were killed at 60, 80 and 270 days after thyroidectomy and plasma and pituitary TSH levels measured. Pituitary TSH content was lower in the thyroidectomized rats than in the controls at 60 and 80 days, starting to increase between 60 and 80 days, and reaching higher values than those of the controls by 270 days. Plasma TSH was higher in the thyroidectomized rats than in the controls at all the times studied, but declined markedly between 60 days (17.53 ± 1.98 μg/ml) and 270 days (3.63 ± 0.49 μg/ml). This decrease in plasma TSH levels was accompanied by a decrease in plasma PBI: from 0.69 ± 0.08 μg/dl at 60 days to 0.06 ± 0.01 μg/dl at 270 days. The daily injection of 1.75 μg T4/100 g body weight for 12 days in either thyroidectomized rats or normal intact rats resulted in a decline of plasma TSH levels in both groups. Pituitary TSH content increased in the thyroidectomized rats and decreased in the controls after T4 treatment. Present results agree with previous observations indicating that severe and chronic thyroid hormone deficiency is not accompanied by a progressive increase in circulating TSH levels, though an elevation is always found even in mild or subclinical forms or primary hypothyroidism. They show that in the rat this cannot be accounted for by an impairment of TSH synthesis, as previously suggessted: an impairment of TSH secretion appears more probable.
DIURNAL VARIATIONS IN PLASMA PROLACTIN, GROWTH HORMONE, CORTISOL AND BLOOD GLUCOSE IN LABILE DIABETES MELLITUS
Authors: DREJER JENS , HENDRIKSEN CARSTEN , NIELSEN LILL MOLL , BINDER CHRISTIAN , HAGEN CLAUS , KEHLET HENRIK
Published: March 2008

In labile diabetes mellitus without ketoacidosis we have studied plasma prolactin levels and a possible causal connection between fluctuation in blood glucose concentration and plasma prolactin, growth hormone and cortisol levels. The hormone concentrations in plasma and blood glucose concentration were determined at 20 min intervals for a 24 h period in six male patients with insulin treated diabetes mellitus. Prolactin varied within the normal range but without any significant rise in relation to sleep in five out of the six patients. Growth hormone levels were low with superimposed secretory peaks. Plasma cortisol showed a normal diurnal rhythm. Blood glucose fluctuated as expected, but the variations and especially the falls in blood glucose to non‐hypoglycaemic levels were not followed by increases in plasma hormone concentrations. No relationship could be demonstrated between the changes in the plasma concentration of prolactin, growth hormone and cortisol.
HIGH LEVEL OF A NERVE GROWTH FACTOR IN THE SERUM OF A PATIENT WITH MEDULLARY CARCINOMA OF THE THYROID GLAND
Authors: BIGAZZI MARIO , REVOLTELLA ROBERTO , Aand SILVIO CASCIANO , VIGNETI ELIANA
Published: March 2008

The serum of a patient with a familial medullary thyroid carcinoma showed levels of a factor, active in the nerve growth factor (NGF) bioassay and cross‐reacting immunologically with mouse NGF, 20‐1000 times higher than sera from normal controls or from patients with unrelated tumours. Variations of the level of this factor in the serum closely correlated with the progression of the disease. One of the patient's sons, apparently clinically normal, also showed high levels of this factor in the serum, raising the possibility that abnormality in the production of this factor could be present at an early stage of the disease.
EFFECTS OF A FEMINIZING TESTICULAR LEYDIG CELL TUMOUR ON NONTUMOROUS TESTICULAR TISSUE: AN ULTRASTRUCTURAL STUDY
Authors: SOHVAL ARTHUR R. , CHURG JACOB , SUZUKI YASUNOSUKE , KATZ NORMAN , GABRILOVE J. LESTER
Published: March 2008

The ultrastructural effects of a Leydig cell tumour of the testis on nontumorous testicular tissue have not yet been reported. Described here are the electron microscopic findings in the nonneoplastic testicular tissue of a patient with a feminizing testicular Leydig cell neoplasm. Serial studies were carried out over a period of 3 1/2 years prior to removal of the tumour.

The overall general picture was characterized by progressive degeneration of Leydig cells, cells of the germinal series and Sertoli cells. Concomitantly, there was increasing thickening and fibrosis of the tubular walls. Cytoplasmic focal accumulations of glycogen, increasing with the duration of the disease, were conspicuous in many spermatogonia. All of these alterations are nonspecific and are attributable to adverse endocrine effects introduced by the oestrogen‐secreting tumour. They were present bilaterally and were more prominent on the tumour‐bearing side.

Attention is drawn to the role of artifacts, fixation technique and degenerative processes in the production and appearance of certain ultrastructural findings, such as ‘light’ and ‘dark’ cells, myelin figures, membranous whorls and focal glycogen accumulations.
RADIOIMMUNOASSAY OF FREE THYROID HORMONE CONCENTRATIONS IN THE INVESTIGATION OF THYROID DISEASE
Authors: YEO P. P. B. , LEWIS M. , EVERED D. C.
Published: March 2008

Direct radioimmunoassay of free triiodothyronine (fT3) and free thyroxine (fT4) in serum dialysate has been performed in fifty‐two normals, twenty‐one hyperthyroid, and twenty‐one hypothyroid patients. In health, there is an almost equimolar concentration of fT3 and fT4. In hyperthyroidism, the free thyroid hormone concentrations were clearly discriminated from the normals. In a proportion of the symptomatic hypothyroids studied, the free hormone values fell within the normal range, challenging the concept that free thyroid hormone concentrations are the sole determinants of thyroid status. In the population studied, there were statistically significant correlations between fT3 and fT4, as well as the free hormones with their respective total hormone levels. It is concluded that fT3 and fT4 estimations are unlikely to play a major role in the routine investigation of thyroid disease.
FASTING HYPERGLYCAEMIA AND RELATIVELY UNIMPAIRED MEAL RESPONSES IN MILD DIABETES
Authors: TURNER R. C. , MANN J. I. , SIMPSON R. D. , HARRIS E. , MAXWELL R.
Published: March 2008

Plasma glucose, insulin and triglyceride changes in response to a standard breakfast and an oral glucose tolerance test have been studied in normal, obese and diabetic subjects. Mild diabetics with an abnormal oral glucose tolerance test may have normal or near‐normal incremental glucose responses to a standard breakfast. A raised fasting plasma glucose is the predominant day‐to‐day glucose abnormality of mild diabetes. Diabetics have decreased insulin responses to oral glucose compared with the meal, and the deficient insulin response to glucose probably accounts for both the raised fasting plasma glucose levels and the abnormal oral GTT. The initial insulin response to a meal is normal in mild diabetics, and is probably stimulated by secretogogues other than glucose. The oral glucose tolerance test is apposite for the diagnosis of diabetes in view of the impaired insulin response to glucose, but accurate measurement of the basal plasma glucose may be of equal value. The diabetic and obese subjects had normal triglyceride levels, and there was no detectable impairment of disposal of the exogenous triglyceride following the breakfast.
PENILE SIZE AND GROWTH IN CHILDREN AND ADOLESCENTS WITH ISOLATED GONADOTROPHIN DEFIENCY (IGnD)
Authors: LARON ZVI , KAUSHANSKI ARIE , JOSEFSBERG ZEEV
Published: March 2008

Penile length and circumference were measured in twenty boys with isolated gonadotrophin deficiency, before and during the administration of androgen therapy. Their age ranged between 3 and 20 years. Considering as normal, measurements above the tenth centile, in all the patients but four the penile length was below normal, and in two it was borderline. Penis circumference was normal in two, borderline in four and subnormal in sixteen. Regular administration of androgen therapy increased penile length in eleven out of fourteen patients with achievement of normal length in four.

It is concluded that congenital lack of LH and testicular androgen activation causes small sized penises, even in the prepubertal period. Gonadotrophin deficiency should be looked for in patients with measurements below the tenth centile. Early diagnosis and institution of androgen therapy between 11 and 12 years is likely to increase penile size and prevent the psychological side effects of undersized genitals and delayed puberty.
THE COMBINED EFFECT OF GROWTH HORMONE AND METHANDROSTENOLONE ON THE LINEAR GROWTH OF PATIENTS WITH MULTIPLE PITUITARY HORMONE DEFICIENCIES
Authors: PERTZELAN A. , BLUM I. , GRUNEBAUM M. , LARON Z.
Published: March 2008

Six patients with multiple pituitary hormone deficiencies (MPHD) were initially treated with separate courses of methandrostenolone and growth hormone and later with the two drugs combined. During the basal period the mean growth velocity was 2.8 cm/year. Methandrostenolone alone, 0.02‐0.05 mg/kg/day given to four of the patients led to an acceleration of the growth velocity to a mean of 5.0 cm/year, while growth hormone 6 mg/week alone accelerated the growth rate to a mean of 6.0 cm/year. Combined therapy led to a striking increase in the mean growth rate to 9.3 cm/year. The shortcoming of the combined growth hormone‐androgen therapy was the fast acceleration in skeletal maturation even after short‐term administration.
GONADAL FUNCTION IN BLOOM'S SYNDROME
Authors: KAULI R. , PRAGER‐LEWIN R. , KAUFMAN H. , LARON Z.
Published: March 2008

Five patients with Bloom's syndrome aged from 2 8/12 to 27 years, all of whom had hypogonadism, were subjected to an i.v. LHRH test and two of them to an i.m. HCG test. There was increased responsiveness of plasma LH and FSH, indicating that the hypogonadism is primary in nature and of early development. The tubular element of the testis seems to be mainly affected, as indicated by the particularly high FSH response to LHRH stimulation, a history of sterility in the two adult patients and documented azoospermia in one of them. The Leydig cells seem to be less affected and secrete sufficient androgens to enable puberty within acceptable normal limits. Hypogonadism seems to be a major characteristic of Bloom's syndrome.
NORMAL PLASMA CALCITONIN: CIRCADIAN VARIATION AND RESPONSE TO STIMULI
Authors: HILLYARD CARMEL J. , COOKE T. J. C. , COOMBES R. C. , EVANS IMOGEN M. A. , MACINTYRE I.
Published: March 2008

A simple, reproducible extraction method has been developed, which is capable of measuring calcitonin in normal individuals. Normal calcitonin levels show a circadian variation, with a peak around midday and respond to known stimuli for calcitonin release.
EVALUATION OF 3 HOUR METYRAPONE TEST IN CHILDREN AND ADOLESCENTS
Authors: LEISTI SEPPO
Published: March 2008

An evaluation of a new 3 h metyrapone test is presented. The test consists of one oral dose of metyrapone given at 08.00‐09.00 hours, and determination of plasma deoxycortisol from a single capillary blood sample taken 3 h later. The test has been assessed in children and adolescents in conjunction with a 5 day metyrapone test, insulin test, vasopressin test, and ACTH test in forty‐five reference subjects, in thirty‐six hypopituitary subjects with normal or deficient ACTH secretion, in three subjects with primary adrenocortical disease and in ten subjects prior to and after pharmacological prednisone medication.

During the first hour after metyrapone the plasma cortisol level decresed to almost the low level maintained for the rest of the 3 h period. The plasma deoxycortisol concentration was basally < 35 nmol/1 and increased continously during the 3 h period to the mean level of 299 (95% confidence interval 133‐669) nmol/1 in the reference subjects. The new test proved to be as accurate as the insulin test in detecting ACTH deficiency.

No significant rise was observed in the plasma somatotrophin (GH) level in those children who had a normal GH response to insulin hypoglycaemia.
GONADOTROPHIN RELEASE IN OVARIECTOMIZED PATIENTS
Authors: RAVID R. , JEDWAB G. , PERSITZ E. , DAVID M. P. , KARNI N. , GIL S. , CORDOVA T. , HARELL A. , AYALON D.
Published: March 2008

Administration 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 (Igarashi et al., 1967; Seki et al., 1970).

By contrast, in prepubertal children, a paradoxical suppression of both LH and FSH release was demonstrated following administration of clomiphene (Kelch et 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 (Kelch et 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 steroid (Tepperman, 1973).
DECREASED SERUM THYROID HORMONE LEVELS AND INCREASED TSH RESPONSE TO TRH IN INFANTS WITH COELIAC DISEASE
Authors: VANDERSCHUEREN‐LODEWEYCKX M. , EGGERMONT E. , CORNETTE C. , BECKERS C. , MALVAUX P. , EECKELS R.
Published: March 2008

Plasma 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‐Lodeweyckx et 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 coeliac disease.
THYROID HORMONE LEVELS AND PROTEIN BINDING IN PATIENTS ON LONG‐TERM DIPHENYLHYDANTOIN TREATMENT
Authors: HEYMA P. , LARKINS R. G. , PERRY‐KEENE D. , PETER C. T. , ROSS D. , SLOMAN J. G.
Published: March 2008

The 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 observed in vivo is 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 (Oppenheimer et al., 1961). It is known that the effect is extrathyroidal (Oppenheimer et 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; Larsen et al., 1970; Hansen et al., 1974; Stjernholm et 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 (Hansen et al., 1974; Chin & Schussler, 1968) or in normal subjects who underwent DPH therapy for only a short time (i.e. 1‐2 weeks, Hansen et 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 effect.
AN INVESTIGATION INTO GONADAL DYSFUNCTION IN PATIENTS WITH IDIOPATHIC HAEMOCHROMATOSIS
Authors: BEZWODA W. R. , BOTHWELL T. H. , VAN DER WALT L. A. , KRONHEIM S. , PIMSTONE† B. L.
Published: March 2008

Endocrine 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 (Bricaire et al., 1971), there is some controversy as to its cause. Suggested aetiologies include functional disturbance at the hypothalamic or pituitary level (Tourniaire et al., 1974; Stocks & Powell, 1972), primary gonadal failure (Simon et al., 1972), or a combination of both (Simon et al., 1972; Walker et 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 reported.
VASOVAGAL HYPOTENSION AND VASOPRESSIN RELEASE
Authors: WIGGINS R. C. , BASAR ISIK , SLATER J.D.H. , FORSLING MARY , RAMAGE C.M.
Published: March 2008

Mild 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 (Henry et al., 1956; Mulcahy et 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 men.
THE EFFECT OF ISOPRENALINE ON PLASMA RENIN ACTIVITY IN MAN: A DOSE‐RESPONSE CURVE
Authors: DAVIES ROY , SLATER J. D. H. , RUDOLF M. , GEDDES D. M.
Published: March 2008

Four 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; Wathen et al., 1965; Allison et al., 1970; Ueda et al., 1973) and recent studies in animals and man have indicated that an intrarenal beta‐adrenoreceptor mediates this release (Tobert et al., 1973; Inoue, 1973; Vandongen et al., 1973; Sabto et al., 1975). Isoprenaline is the archetypal beta‐adrenergic agonist with equal effects upon both beta1 and beta2 receptors (Lands et al., 1967). We have previously shown that minute bolus injections of this agent provokes renin release in normal people (Davies et 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 this response.
COMPARISON OF THE PHARMACOKINETICS IN MAN OF TWO SYNTHETIC ACTH ANALOGES: a1–24 AND SUBSTITUTED β1–18 ACTH.
Authors: JEFFCOATE W.J. , PHENEKOS C. , RATCLIFFE J. G. , WILLIAMS SALLY , REES LESLEY , BESSER G.M.
Published: March 2008

The synthetic substituted corticotrophin analogue, a1–18 ACTH, was given intravenously or subcutaneously to thirteen human volunteers in whom endogenous secretion of ACTH had been suppressed with dexamethasone. Plasma levels of a1–18 ACTH over the succeeding 12–24 h were determined by radioimmunoassay and bioassy, together with the fluorometric corticosteroid responses. The plasma disappearance rate of a1–18 ACTH was compared with that of the corticotrophin fragment, a1–24 ACTH (tetracosactrin, Synacthen), in both unmodified and depot forms.

Plasma levels of a1–18 ACTH were higher and were detectable for longer after intravenous rather than subcutaneous administration. The higher levels were associated with greater and more prologed corticosteroid responses. In addition, the corticosteroid response to the intravenous injection of 1 mg of a1–18 was greater and more prolonged than the response to the intravenous injection of the same dose of a1–24 ACTH. The plasma levels of immunoreactive a1–24 ACTH were not detectable for more than 4 h after this dose. After the intramuscular administration of 1 mg of the depot preparation, however, detectable plasma levels persisted for 12 h. It is concluded that the brief corticotrophic activity of unmodified a1–24 ACTH is due mainly to its rapid clearance from the circulation.

There was no significant dissociation between the disappearance rates of immuno‐ and bio‐active a1–18 ACTH. This contrasted with a1–24 ACTH whose bioactivity disappeared from plasma significantly faster than immunoreactivity. This difference probably reflects the greater stability of a1‐18 ACTH In the circulation and this in turn accounts, in part at least, for its prolonged corticotrophic activity.

In a separate study the peptides were given intranasally through special applicators to eleven dexamethasone suppressed volunteers. The plasma levels of a1–18 ACTH after a 1 mg dose were lower than when given by other routes but the corteroid response was unaltered. The corticosteroid response to a 1 mg dose of intranasal a1–24 ACTH was brief and similar to that which followed an intavenous or subcutaneous injection; it was not significantly prolonged if 5 mg was given. It is concluded that intranasal a1–24 ACTH is unlikely to be of value but itranasal a1–18ACTH may be therapeutically useful.