bluuebunny/crossref_metadata_2025 huggingface dataset:
A RADIOIMMUNOASSAY FOR 3,5‐DIIODOTHYRONINE*
Authors: MEINHOLD H. , SCHÜRNBRAND P.
Published: March 2008

A radioimmunoassay for the measurement of 3,5‐diiodothyronine (3,5‐T2) using a 3H‐labelled derivative of 3,5‐T2 as tracer has been developed. The cross‐reactivity of the antiserum was relatively high for T3 (3.1%) and low for T4 (< 0.0015%). 3,5‐T2 serum concentrations measured after fractional enrichment of 3,5‐T2 were near or below the detection limit of 0.1 nmol/l in ten normal subjects and 0.38 nmol/l in five hyperthyroid patients. 3,5‐T2 was also detected in thyroid tissue. The serum half‐time of 3,5‐T2 estimated after injection of 2 mg 3,5‐T2 in three normal volunteers was 4.5 h.
SERUM STEROIDS IN NORMAL MALES AND PATIENTS WITH PROSTATIC DISEASES
Authors: HAMMOND G. L. , KONTTURI M. , VIHKO P. , VIHKO R.
Published: March 2008

The subjects investigated comprised 57 normal males between 30 and 80 years of age; 40 patients between 50 and 80 years of age suffering from benign prostatic hypertrophy (BPH), and 11 untreated prostatic carcinoma (Ca) patients aged between 57 and 79 years. Serum concentrations of oestradiol, pregnenolone, progesterone, 17α‐hydroxyprogesterone, androstenedione, testosterone, 5α‐dihydrotestosterone and androsterone were determined from a single serum sample (1.6 ml). Oestradiol was determined by an automated non‐chromatographic radioimmunoassay, while other steroids were determined by radioimmunoassays, after solvent extraction and chromatographic purification on Lipidex‐5000(tm) microcolumns. When patient groups were compared with the 25 normal males between 50 and 80 years of age, several conclusions could be drawn. Serum concentrations of 5α‐dihydrotestosterone (P < 0.01) and 17α‐hydroxyprogesterone (P < 0.001) were both significantly higher in the BPH patients when compared with the normal males. This trend was also apparent in the serum concentrations of progesterone and testosterone in the older BPH patients. Although the mean concentrations of 5α‐dihydrotestosterone and 17α‐hydroxyprogesterone were slightly higher in carcinoma patients than normal males, these differences were not statistically significant. No differences were seen in the concentrations of pregnenolone, androstenedione, androsterone and oestradiol between normal subjects and patients with BPH or prostatic Ca.
ANDROGEN AND CORTISOL RESPONSES TO ACTH STIMULATION IN WOMEN WITH HYPERPROLACTINAEMIA
Authors: KANDEEL F. R. , RUDD B. T. , BUTT W. R. , DWARDS R. LOGANE , LONDON D. R.
Published: March 2008

Basal serum concentrations of androgens (testosterone and dihydrotestosterone) and dehydroepiandrosterone sulphate (DHAS) were measured in 7 normal and in 14 anovulatory women with raised serum prolactin. No patient had detectable skull x‐ray abnormalities. The mean DHAS, but not the androgens, were significantly higher in the women with hyperprolactinaemia (p < 0.01) and in 7 of the 14 the values were above the normal range which is 2.9–11.2 μmol/l. The 7 normal subjects and 9 of the women with hyperprolactinaemia were given ACTH (0.5 mg twice daily for four days). Cortisol and androgen concentrations in response to ACTH were not significantly different in the two groups, but the levels of DHAS (p < 0.001) were significantly higher over the four days in patients with hyperprolactinaemia. The concentrations of DHAS in these women were significantly higher by two days and continued to rise on day four of the test, but the concentration of androgens was greatest at two days as in the normal group.

Treatment with bromocriptine to suppress plasma prolactin concentrations also lowered DHAS within 2–4 weeks, (p < 0.01) and the suppression was maintained for three months. Androgens initially increased significantly (p < 0.05) but by three months decreased again to the initial values.

Taken together these results suggest that in the hyperprolactinaemic state biosynthesis by the Δ5 pathway to DHAS is favoured and there is partial inhibition of 3β‐ol‐dehydrogenase isomerase resulting in impaired conversion of Δ5 to Δ4 steroids.
A POSSIBLE ACTH SECRETING TUMOUR OF THE PITUITARY DEVELOPING IN A CONVENTIONALLY TREATED CASE OF ADDISON'S DISEASE
Authors: HIMSWORTH R. L. , LEWIS J. G. , REES LESLEY H.
Published: March 2008

A patient with Addison's disease, treated with conventional corticosteroid therapy, developed endocrine and radiological features suggestive of an ACTH secreting pituitary tumour. The negative feedback control of ACTH secretion by the inhibitory effect of hydrocortisone was shown to be preserved although attenuated. Retiming and alteration of corticosteroid therapy reinforced this feedback control, without the need for supraphysiological amounts of steroid, and resulted in the regression of the endocrine disorder.
ECTOPIC INSULIN AND OCCAM'S RAZOR:* REAPPRAISAL OF THE RIDDLE OF TUMOUR HYPOGLYCAEMIA
Authors: SKRABANEK PETR , POWELL DAVID
Published: March 2008

The concept of ectopic insulin production is challenged on the basis of a review of 120 cases from the literature on extrapancreatic tumours associated with hypoglycaemia in which insulin or insulin‐like activity were measured. No case met two or more of five criteria of ectopic hormone production. The evidence indicates that hypoglycaemia of extrapancreatic tumours cannot be attributed to insulin. In those rare cases in which plasma insulin was reported as high, pancreatic beta‐cells could not be excluded as the source of insulin. Interestingly, many of these dubious cases had carcinoid histology. The review also points out a close association between some spindle‐cell tumours and carcinoid tumours which may be relevant to discussion on the disputed origin of some “mesothelial” tumours.

Nonsuppressible insulin‐like activity (NSILA) consists of a number of factors mimicking insulin activity which compete with insulin or proinsulin for membrane receptors and may crossreact in bioassays, immunoassays, and receptor assays. The question of whether one or several of these substances may be responsible for extrapancreatic hypoglycaemia remains to be elucidated.
TISSUE GROWTH HORMONE RELEASE INHIBITING HORMONE‐LIKE IMMUNOREACTIVITY IN EXPERIMENTAL HYPOTHYROIDISM AND HYPOPITUITARISM
Authors: BERELOWITZ M. , PIMSTONE B. , SHAPIRO B. , KRONHEIM S. , DE WIT D.
Published: March 2008

Hypothyroidism in rats was associated with an increase in immunoreactive GH‐RIH in brain, pancreas and gut, although release from the latter may be diminished as portal GH‐RIH‐like immunoreactivity was lower than control values. Hypophysectomy resulted in a depletion of immunoreactive GH‐RIH in the septum and preoptic area of the brain and gastric antrum, but an increase in pancreas; portal venous GH‐RIH‐like immunoreactivity was not different from control concentrations, possibly reflecting both elevated and lowered immunoreactive GH‐RIH in different regions of tissue subserved by the portal vein. Inferior vena caval GH‐RIH‐like immunoreactivity was always lower than in the portal vein and was not influenced by tissue pertubations in hypothyroidism and hypopituitarism which made regional blood sampling of great important in evaluating tissue changes.
EFFECTS OF ORAL TESTOSTERONE UNDECANOATE IN HYPOGONADAL MALE PATIENTS*
Authors: FRANCHIMONT P. , KICOVIC P. M. , MATTEI A. , ROULIER R.
Published: March 2008

Effects on plasma T, DHT, A, FSH, LH and PRL concentrations and the pituitary responsiveness to the LHRH/TRH stimulation, as well as on libido and sexual, mental and physical activities were studied in ten hypogonadal male patients undergoing therapy with oral testosterone undecanoate (TU) for 9 weeks. The daily dose of TU needed for satisfactory clinical effect was 120 mg (6 cases) and 240 mg (4 cases).

There was a significant rise in circulation androgen concentrations in all patients. Mean plasma T, DHT and A increased at 9 weeks from 1.20, 0.12 and 0.36 ng/ml to 4.34 (P < 0.0004), 0.39 (P < 0.0004) and 1.24 ng/ml (P < 0.005), respectively. In hypergonadotrophic patients (N = 6) plasma FSH and LH fell progressively (P < 0.05), while in hypogonadotrophic patients (N = 4) a marked rise in plasma FSH (P < 0.05) was found, while LH tended to rise as well. Base‐line plasma PRL remained unchanged. In three out of four patients with poor PRL response to TRH, normal responses were established after TU therapy.

Increase in libido and sexual activity was reported by nine patients. An increase in mental and physical activity was found in seven and two patients, respectively. Tolerance was excellent. It was concluded that oral TU is an effective form of substitution therapy in male hypogonadal patients.
ON THE EFFECT OF THYROTROPIN AND IMMUNOGLOBULINS RELATED TO GRAVES' DISEASE ON THYROTROPIN SYNTHESIS AND SECRETION
Authors: DANDONA P. , EL KABIR D. J.
Published: March 2008

The effect of exogenous thyroxine (T4), thyrotropin (TSH), long acting thyroid stimulator (LATS), immunoglobulin G fractions from (a) thyrotoxic sera without LATS and (b) sera from patients with ophthalmic Graves' disease, upon serum TSH concentration and pituitary TSH content has been investigated in the guinea‐pig. Pituitary TSH content was significantly lower in animals injected with T4 (1.80 mU), TSH (2.80 mU) and LATS (3.20 mU) than that in the controls (6.40 mU). Thyroidectomy caused a significant elevation in serum TSH concentration (22.30 mU/dl vs 6.67 in sham operated controls) but no significant alteration in pituitary TSH content (4.40 mU vs 3.80 mU in sham operated controls). TSH injections in thyroidectomised animals induced a significant increase in serum TSH concentration (31.60 mU/dl) and the pituitary TSH content (6.50 mU). Two out of four IgG samples from patients with ophthalmic Graves' disease caused a fall in serum TSH concentration (12.90 and 14.40 mU/dl) with a concomitant rise in pituitary TSH content (9.00 and 9.30 mU) in thyroidectomized animals. It is concluded (1) that exogenous TSH induces an enhanced TSH synthesis and release in thyroidectomised guinea‐pigs which suggests the presence of a positive ‘short loop’ feedback for TSH and (2) that IgG fractions from some sera of ophthalmic Graves' disease may have the ability to inhibit TSH release from the pituitary. This inhibitory effect, hitherto not described, may be responsible for the diminished TRH induced TSH release in some patients with euthyroid Graves' disease.
THYROID IODINE CONCENTRATION AND TOTAL THYROID IODINE IN NORMAL SUBJECTS AND IN ENDEMIC GOITRE SUBJECTS
Authors: HELLSTERN PETER , KELLER HANS ERICH , WEINHEIMER BALTHASAR , WESCH HORST
Published: March 2008

Thyroid iodine concentration and total thyroid iodine were determined by an automated technique by means of the eerie arsenious acid reaction in 42 males and 13 females. The thyroids were taken from autopsy material in a region with a low dietary intake. The accuracy of the method to estimate iodine was checked by neutron activation analysis. There was an excellent correlation between the iodine contents of thyroid specimens, when measured by chemical or by activation analysis. The mean iodine concentration was 1.86 mg/g dry weight and was found to be lower than in non‐goitrous regions. In goitres, the mean iodine concentration was significantly lower, and the mean total thyroid iodine was significantly higher, when compared with the data of thyroids of normal weight. There was no significant difference in iodine concentration and total iodine between males and females. The thyroid iodine concentration did not depend upon age in adults. The data were log normally distributed. It was established that mean iodine concentrations under 2 mg/g dry weight or 0.45 mg/g fresh weight are to be regarded as an important index of iodine deficiency.
A SENSITIVE BIOASSAY OF PARATHYROID HORMONE IN PLASMA
Authors: CHAMBERS D. J. , DUNHAM JANE , ZANELLI JOAN M. , PARSONS J. A. , BITENSKY LUCILLE , CHAYEN J.
Published: March 2008

Understanding of calcium metabolism in health and disease has been retarded by the lack of an adequately sensitive bioassay of parathyroid hormone. The problem of dissociation of bioactivity and immunoactivity, well recognized for other polypeptide hormones, is exaggerated in the case of parathyroid hormone by the disproportionately long half‐time in the circulation of the immunoreactive fragments. A new method of assaying the biological activity of parathyroid hormone in plasma has been developed, based on the cytochemical methods which have yielded highly sensitive bioassays of other polypeptide hormones. It depends on the stimulation of glucose 6‐phosphate dehydrogenase activity in the distal convoluted tubules of segments of guinea‐pig kidney maintained in vitro, and measured by microdensitometry. The limit of sensitivity of the assay is 5 fg/ml (bPTH); the index of precision is 0.09 ± 0.04 (mean ± SEM; n= 11).
THE EFFECT OF SHORT‐ AND LONG‐TERM CORTICOSTEROID TREATMENT ON SLEEP‐ASSOCIATED GROWTH HORMONE SECRETION
Authors: MOTSON R. W. , GLASS D. N. , SMITH D. A. , DALY J. R.
Published: March 2008

Eight healthy medical students and four renal transplant patients had blood sampled two or three times hourly throughout EEG monitored nocturnal sleep. This was carried out on the healthy subjects for a total of 12 nights without medication (control nights asleep), a total of 12 nights following 40 mg of flucortolone the previous morning, and a total of 6 nights with similar blood sampling when sleep was prevented (control nights awake). Four renal transplant patients who were receiving long‐term therapy with prednisolone were similarly studied (total of 7 nights asleep). Circulating corticosteroid and growth hormone (GH) levels were determined. A peak of GH was seen during the first 2 h of sleep on the control nights when slow‐wave sleep predominated. The GH peak was absent on the control nights awake. The pattern of plasma corticosteroid levels was identical during control nights asleep and awake. Both single‐dose and chronic corticosteroid administration inhibited the GH peak associated with slow‐wave sleep. Chronic corticosteroid therapy, but not single‐dose administration in the morning, suppressed the circadian rise of plasma corticosteroids which normally occurs late in sleep.
‘LOW T3 SYNDROME’ IN PATIENTS CHRONICALLY TREATED WITH AN IODINE‐CONTAINING DRUG, AMIODARONE
Authors: JONCKHEER M. H. , BLOCKX P. , BROECKAERT I. , CORNETTE C. , BECKERS C.
Published: March 2008

Cardiac patients treated with the iodinecontaining drug ‘amiodarone’ undergo a significant iodine overload whch can last for months after the drug has been withdrawn. Some patients develop hyperthyroidism and others hypothyroidism. In the hyper‐ or hypothyroid patients, the indices of thyroid function are modified as usually observed in these situations. In the patients remaining euthyroid while taking amiodarone or after its withdrawal, but still under its influence as shown by the iodine overload, a ‘low‐T3 syndrome’ is observed, this state being characterized by a high total T4, a low free T4, a normal T3 resin uptake, a low total T3, a normal free T3, a high r‐T3 and a relative TSH‐unresponsiveness to TRH.
THE EFFECT OF PROPRANOLOL ON THYROID HORMONES AND OXYGEN CONSUMPTION IN THYROTOXICOSIS
Authors: SAUNDERS J. , HALL SUSAN E. H. , CROWTHER A. , SÖNKSEN P. H.
Published: March 2008

The possibility that propranolol may exert its beneficial actions in thyrotoxicosis by an effect on thyroid hormone concentrations has been investigated by measuring these and oxygen consumption in a group of thyrotoxic patients before and after treatment with propranolol. Following treatment a significant fall in plasma T3 concentration and oxygen consumption occurred and a direct correlation was found between these two variables. Propranolol may, therefore, exert some of its beneficial effects in thyrotoxicosis by an action on T3 metabolism.
BROMOCRIPTINE TREATMENT OF MALES WITH PITUITARY TUMOURS, HYPERPROLACTINAEMIA, AND HYPOGONADISM
Authors: NAGULESPAREN M. , ANG V. , JENKINS J. S.
Published: March 2008

Plasma prolactin concentrations were measured in thirty‐four males with pituitary tumours and twenty‐two patients (65%) were found to have hyperprolactinaemia. Plasma testosterone concentrations were subnormal in twenty‐nine patients. Ten patients with hyperprolactinaemia were treated with bromocnptine; prolactin was restored to normal values in eight patients but testosterone secretion remained deficient. Two patients were resistant to bromocriptine. Some improvement in libido and potency was obtained after restoration of normal prolactin concentrations in four cases in spite of persistently low testosterone secretion. For maximal improvement in sexual function treatmentwithbothbromocdptineand testosterone was required.
INFLUENCE OF LOWER BODY NEGATIVE PRESSURE UPON ARGININE VASOPRESSIN RELEASE
Authors: BAYLIS P. H. , STOCKLEY R. A. , HEATH D. A.
Published: March 2008

Lower body negative pressure (9‐12 kPa) was applied to ten normal subjects. Large increases in plasma arginine vasopression concentration occurred only in subjects that experienced syncopal symptoms and developed hypotension. Blood samples obtained from the superior vena cava at 1/2 min intervals during application of negative pressure showed that maximal plasma vasopressin concentrations occurred with hypotension. Chromatography of the presyncopal plasma on Sephadex G‐25 gave a large peak which eluted in the position of synthetic arginine vasopressin.
CORRELATIONS BETWEEN PROLACTIN AND PROGESTERONE, OESTRADIOL‐1 7‐β AND OESTRIOL DURING EARLY HUMAN PREGNANCY
Authors: And J. HERTZ. A. N. ANDERSEN , LARSEN J. F.
Published: March 2008

The correlations between serum prolactin and progesterone, oestradiol‐17‐β and oestriol were determineed in 125 pregnant females between the sixth and fourteenth week of pregnancy. No significant correlations were found between prolactin and progesterone. Correlations between prolactin and oestradiol‐17‐β and oestriol were mostly positive, but only significant during the twelfth week of pregnancy.
THYROXINE, TRIIODOTHYRONINE AND THYROTROPHIN LEVELS IN MENINGOCOCCAL MENINGITIS, TYPHOID FEVER AND OTHER FEBRILE CONDITIONS
Authors: MAHARAJAN G. , ETTA K. M. , SINGH AJIT , AHUJA I. S. , AHUJA G. K.
Published: March 2008

Thyroid status was estimated serially by measuring triiodothyronine (T3), thyroxine (T4) and thyrotrophin (hTSH) in 20 patients suffering from meningococcal meningitis, typhoid fever and other acute febrile illnesses.

Significantly low T3 and only slightly increased T4 were observed in all the patients. hTSH was normal in all of these. A significant reciprocal relationship was found between the degree of fever and fall in T3 concentrations.

T3 tended to rise in patients who recovered but in those who deteriorated or died, T3 remained persistently low.
INCREASED THYROTROPHIN SECRETION INDUCED BY SULPIRIDE IN MAN
Authors: MASSARA F. , CAMANNI F. , BELFORTE L. , VERGANO V. , MOLINATTI G. M.
Published: March 2008

100 mg i.m. sulpiride (a dopamine‐receptor‐blocking drug) led to a significant rise in plasma TSH in normal women, in female patients with galactorrhoea, and, to a much more marked degree, in male and female patients with primary hypothyroidism. In the hypothyroid patients, there was a significant positive correlation between basal TSH and its maximum increment after sulpiride. The drug proved to be an even more potent stimulator of PRL, at least in subjects with normal blood PRL. Normal males, on the other hand, displayed no significant changes in TSH after sulpiride. Continuous administration (150 mg/day per os for 15 days) also resulted in enhancement of TSH in normal women. These results suggest that TSH release is controlled by a dopaminergic mechanism in man. The more accentuated TSH response in hypothyroid patients may perhaps be attributable to the absence of negative‐feedback on the part of thyroid hormones.
HORMONAL RESPONSES DURING TREATMENT OF ACUTE DIABETIC KETOACIDOSIS WITH CONSTANT INSULIN INFUSIONS
Authors: SCOTT R. S. , ESPINER E. A. , DONALD R. A. , LIVESEY J. H.
Published: March 2008

Changes in glucagon, growth hormone (GH), cortisol, renin and aldosterone accompanying the metabolic disturbances and dehydration of severe diabetic ketoacidosis were studied over a 24 h period in eight patients treated with a constant intravenous insulin infusion. Mean steady state plasma‐free insulin levels achieved were 28.6–49 mu/l in patients receiving 2 u/h but a satisfactory rate of fall of glucose was not always obtained until the infusion dose was increased to 4 u/h or more. The total insulin dose administered was positively correlated with the level of plasma glucagon and cortisol on admission. During insulin infusion, both glucagon and cortisol fell but the rate of fall was not related to dose or plasma level of free insulin achieved. In six of eight patients studied increments in plasma GH above admission levels were observed during insulin treatment. Admission values of both plasma renin activity and plasma aldosterone were raised. The renin levels were highest in newly diagnosed diabetics, and two patients with long‐established diabetes showed only small increments despite profound dehydration. Plasma renin activity, but not plasma aldosterone correlated with the fluid and sodium retention over the initial 24 h treatment period, but not with potassium requirements. The urinary excretion rates of the small molecular weight proteins GH and insulin, were considerably elevated over the treatment and convalescent periods.
THE EFFECTS OF DOPAMINE, BROMOCRIPTINE, LERGOTRILE AND METOCLOPRAMIDE ON PROLACTIN RELEASE FROM CONTINUOUSLY PERFUSED COLUMNS OF ISOLATED RAT PITUITARY CELLS
Authors: YEO T. , THORNER M. O. , JONES ANN , LOWRY P. J. , BESSER G. M.
Published: March 2008

The control of secretion of prolactin was studied using continuous perfusion of a column of isolated rat pituitary cells supported by Bio‐Gel polyacrylamide beads. Prolactin secretion was inhibited repeatedly by dopamine and rapidly recovered in its absence. Maximum inhibition was achieved at 5 ± 107 M dopamine. Bromocriptine and lergotrile directly inhibited prolactin release from the pituitary cells. Bromocriptine had a longterm action in inhibiting secretion. The dopamine receptor blocking agent, metoclopramide, overcame the inhibitory effect of dopamine but had no effect on prolactin secretion in its absence.
THYROTROPIN, FREE AND TOTAL TRIIODOTHYRONINE, AND THYROXINE IN SERUM DURING SURGERY
Authors: KEHLET H. , KLAUBER P. V. , WEEKE J.
Published: March 2008

Changes in free and total thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) in serum were measured before, during, and for nine days after uncomplicated abdominal surgery in eight patients. The results showed a pronounced fall in total as well as in free T3 levels, amounting to 50% in both variables on the first postoperative day, and returning towards preoperative levels on the seventh and ninth day. Apart from an increase during surgery, free T4 levels were constant in the whole period despite a slight postoperative decrease in Total T4. The TSH level fell about 80% within the first 24 postoperative h, but returned to the preoperative level thereafter. These results suggest a suppression of both T3 and TSH production during the pre‐ and early postoperative period.
CLINICAL EVALUATION OF A RADIOIMMUNOASSAY FOR β‐MSH‐RELATED PEPTIDES (LIPOTROPHINS) IN HUMAN PLASMA
Authors: GRAY C. E. , RATCLIFFE J. G.
Published: March 2008

A radioimmunoassay for β‐MSH related peptides (‘β‐MSH’) which measures βh‐ and γh‐lipotrophin (LPH) and β‐MSH, was used to assess LPH status and the stability of ‘β‐MSH’ in blood and plasma.‘β‐MSH’ concentrations correlated well with ACTH levels in paired snap‐frozen plasma samples from normal subjects, from patients with pathologically elevated hormone levels (except those with chronic renal failure), and during acute stimulation and suppression tests (r= 0.913, P > 0.001). The mean ratio of ‘β‐MSH’ and ACTH levels in most situations was approximately unity. In chronic renal failure,‘β‐MSH’ concentrations were significantly higher than ACTH (mean ratio 4.1). Lesser degrees of dissociation of hormone levels were also found in patients with the ectopic ACTH syndrome (mean ratio 2.8). Basal ‘β‐MSH’ levels were uniformly elevated in patients with Cushing's disease after bilateral adrenalectomy, Nelson's syndrome, ectopic ACTH syndrome, and Addison's disease and overlapped the normal range in patients with untreated Cushing's disease. There was complete separation of ‘β‐MSH’ levels in ACTH‐dependent and ACTH‐independent (adrenal tumour) causes of Cushing's syndrome. Endogenous ‘β‐MSH’ immunoactivity was more stable than ACTH in blood and plasma. There was no significant decrease of ‘β‐MSH’ immunoactivity in samples kept at ambient temperature for 24 h or after four cycles of freezing and thawing plasma.‘β‐MSH’ levels also did not change significantly in unhaemolysed blood samples transported at ambient temperature by first class mail. It is concluded that the ‘β‐MSH’ assay provides at least as good discrimination as the ACTH assay in situations in which the latter is diagnostically valuable. Determination of the ratio of ‘β‐MSH’ to ACTH levels may help to distinguish between untreated Cushing's disease and the ectopic ACTH syndrome. The stability of ‘β‐MSH’ immunoactivity allows unhaemolysed blood and plasma samples to be transported at ambient temperature without loss of diagnostic value.
SELECTIVE VENOUS SAMPLING IN THE DIAGNOSIS AND LOCALIZATION OF PHAEOCHROMOCYTOMA
Authors: JONES D. HUW , ALLISON D. J. , HAMILTON CARLENE A. , REID JOHN L.
Published: March 2008

Plasma noradrenaline levels were measured at several sites in the systemic venous system by selective catheterisation in ten hypertensive patients in whom phaeo‐chromocytoma was suspected on clinical or biochemical grounds. Four patients had localized noradrenaline elevation and the diagnosis of phaeochromocytoma was confirmed at operation. The remaining six patients demonstrated no localized elevation of noradrenaline and there has been no evidence of a tumour on follow up. The technique allows the diagnosis and accurate localization of phaeochromocytoma and is useful in excluding the tumour in patients with essential hypertension.
PITUITARY‐GONADAL DYSFUNCTION IN LOW‐OUTPUT CARDIAC FAILURE
Authors: TAPPLER BRIAN , KATZ MAURICE
Published: March 2008

Diminished cardiac output and digoxin therapy appear to have opposing effects on testosterone, oestradiol and luteinizing hormone concentrations. Depression of the levels of these hormones was significantly correlated with a decrease in cardiac index and elevation was noted by digoxin therapy of long duration. The effect of cardiac output is most marked on testosterone and that of digoxin on oestradiol.
EFFECT OF THE ANGIOTENSIN II ANTAGONIST SARALASIN ON PLASMA ALDOSTERONE CONCENTRATION AND ON BLOOD PRESSURE BEFORE AND DURING SODIUM DEPLETION IN NORMAL SUBJECTS
Authors: AGABITI‐ROSEI E. , BROWN J. J. , BROWN W. C. B. , ERASER R. , TRUST P. M. , LEVER A. F. , MORTON J. J. , ROBERTSON J. I. S.
Published: March 2008

The effect of the angiotensin II antagonist saralasin on plasma aldosterone, plasma angiotensin II and blood pressure was studied in six normal supine subjects both before and during sodium depletion. Before sodium depletion, infusion of saralasin produced no consistent changes; during sodium depletion, infusion of the angiotensin antagonist caused a fall in plasma aldosterone and an increase in plasma angiotensin II in each subject. It is concluded that angiotensin II plays a major part in stimulating aldosterone secretion during sodium depletion in man.
FUNCTIONAL SIGNIFICANCE OF ANTIBODY FORMATION AFTER LONG‐TERM SALMON CALCITONIN THERAPY
Authors: HOSKING D. J. , DENTON L. B. , CADGE B. , MARTIN T. J.
Published: March 2008

Twenty patients with Paget's disease were challenged with porcine (PCT) and salmon (SCT) calcitonin before and after 6 months SCT therapy. Acute hypocalcaemia was clearly related to the prevailing rate of bone turnover but responses to PCT showed that treatment had not disturbed this relationship. Although antibodies to SCT developed in eight patients during the period of treatment the acute hypocalcaemic response to SCT was not diminished in relation to bone turnover. It is suggested that antibodies which develop during the course of SCT therapy do not necessarily exert a functionally effective neutralizing action.
THE RELATIONSHIP BETWEEN THE ‘IDIOPATHIC OEDEMA SYNDROME’ AND SUBCLINICAL HYPOTHYROIDISM
Authors: AL‐KHADER A. A. , ABER G. M.
Published: March 2008

Thyroid function has been studied in eleven patients with the ‘idiopathic oedema syndrome’. Six patients have been shown to have subclinical hypothyroidism associated with the presence of thyroid antibodies. All responded to treatment with sodium thyroxine. Five patients had normal thyroid function, absence of thyroid antibodies and failed to respond to treatment with sodium thyroxine.
THYROID STIMULATING ANTIBODIES AND METASTATIC THYROID CARCINOMA
Authors: SNOW M.H. , DAVIES T. , SMITH B. REES , ROSS W. M. , EVANS R. G. B. , TENG C. S. , HALL REGINALD
Published: March 2008

A patient with previously treated follicular carcinoma of the thyroid developed Graves' disease with a high titre of thyroid‐stimulating antibodies (TSAb). He developed functioning pulmonary metastases leading to hyperthyroidism. Levels of TSAb paralleled the functional status of the metastases suggesting that hyperfunction of the neoplastic tissue was caused by TSAb.
PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONE
Authors: TAMAGNA ELLEN I. , CARLSON HAROLD E. , HERSHMAN JEROME M. , REED ALLAN W.
Published: March 2008

A 32‐year‐old Caucasian male, clinically euthyroid, with paranoid schizophrenia and granulocytopenia, had elevated total and free serum T4 and T3; serum TSH was normal (2.7 ± 0.7 μU/ml). There was no goitre present, no evidence of Graves' disease, and no evidence of pituitary tumour. He had a normal response to methyl‐TRH, with a TSH increment of 14.6 μU/ml, T3 increment of 212 ng/dl, and T4 increment of 4.7 μg/dl; baseline prolactin was normal with a normal response to methyl‐TRH. T3 therapy (100 μg/day) decreased the thyroidal radioactive iodine uptake to less than half the baseline value and decreased the TSH increment in response to methyl‐TRH to 4.1 μU/ml. Iodine therapy caused an increase in his base‐line TSH with an increase in the TSH response to TSH. The metabolic clearance rates (MCR) and production rates (PR) of T3 and T4 were increased. Baseline serum levels of glycoprotein hormone α‐subunit were normal and showed a slight increase in response to methyl‐TRH, similar to normal subjects. This patient has evidence of partial pituitary and peripheral resistance to thyroid hormone; his only evidence for hyperthyroidism is the elevated MCR and PR of T3 and T4.
A PASSIVE HAEMAGGLUTINATION (TRC) INHIBITOR IN THYROTOXIC SERUM
Authors: WILKIN T. J. , BECK J. SWANSON , HAYES P. C. , POTTS R. C. , YOUNG R. J.
Published: March 2008

The tanned red cell haemagglutination test system is widely used in the screening of thyroid and other auto‐immune diseases. We report a phenomenon which casts some doubt on the reliability of the technique.

Anti‐thyroglobulin antibody (anti‐Tg) was measured by passive haemagglutination (TRC) and a double‐antibody precipitation technique (DAT) in serum samples taken serially from thirty‐three patients undergoing an 18‐month course of treatment with carbimazole and T3 for thyrotoxicosis. Anti‐Tg was undetectable by both techniques throughout treatment in 21% of the patients, and there was good concordance between results of TRC and DAT in most of the remainder. However, in four (29%) of the 14 Tg antibody‐positive patients, the TRC titre intermittently and abruptly fell to undetectable levels for long periods while the DAT remained unchanged. The hypothesis that a haemagglutination inhibitor was the cause of this phenomenon was tested by mixing increasing dilutions of a TRC‐negative/DAT‐positive serum with similar dilutions of a TRC‐positive/DAT‐positive serum removed from the same patient at another time, and also with dilutions of a known strongly positive TRC control serum. In both cases, the undiluted TRC‐negative/DAT‐positive serum completely inhibited agglutination by the TRC‐positive serum at all dilutions. The inhibition was immunologically non‐specific since the samples which inhibited the anti‐Tg system also inhibited agglutination in the anti‐thyroid microsomal antibody and anti‐DNA systems. It is suggested that some serum specimens from thyrotoxic patients inhibit the second‐order reaction of haemagglutination, but not the first‐order reaction of antigen binding. The practical significance is the demonstration of false negative haemagglutination results in patients known to have high levels of Tg antibody.
SCREENING FOR NEONATAL HYPOTHYROIDISM BY THYROXINE AND THYROTROPHIN RADIOIMMUNOASSAYS USING DRIED BLOOD SAMPLES ON FILTER PAPER
Authors: BECKERS C. , CORNETTE C. , FRANCOIS B. , BOUCKAERT A.
Published: March 2008

A routine and automatized methodology for thyroxine (T4) and thyrotrophin (TSH) radioimmunoassay (RIA) using dried blood samples on filter paper is described. T4‐RIA was performed on one single dot (5 mm diameter equivalent to 4 μl of serum) while two dots were necessary for TSH‐RIA. Reference filter papers were introduced in each assay for quality control. In a preliminary study on 4,155 neonates, samples generally obtained between the 5th–7th day gave a mean ‘dot‐T4′ of 97.95 ± 36.04 nmol/l and a mean ‘dot‐TSH’ of 10.19 mU/l ±8.25, corresponding to 2.47 mU/l of serum. Within an 18‐month period (November 1976‐April 1978), a total of 16.522 neonates have been screened allowing detection of three cases of congenital hypothyroidism (incidence 1: 5507), two cases of congenitally low TBG and thirty‐three cases of transient hypothyroidism.
L‐THYROXINE TREATMENT OF DIFFUSE NON‐TOXIC GOITRE EVALUATED BY ULTRASONIC DETERMINATION OF THYROID VOLUME
Authors: HANSEN J. MØLHOLM , KAMPMANN J. , MADSEN S. NISTRUP , SKOVSTED L. , SOLGAARD S. , GRYTTER C. , GRQNTVEDT T. , RASMUSSEN S. NORBY
Published: March 2008

The effect of a daily dose of 150 μg 1‐thyroxine for one year was studied in forty‐five patients with diffuse non‐toxic goitre. Thyroid volume was evaluated by ultrasonic scanning. A decrease in the median value of the thyroid volume of about 20% was found after 3 months of therapy and no further change in the median value was observed in the following 9 months of treatment. About 50% of the patients showed a response to therapy and about 30% obtained normal size of the thyroid gland. Median value of the thyroid volume returned to pretreatment value 3 months after thyroxine therapy was stopped.

A considerable increase in serum T4 and free T4 index was noted after 3 months of therapy and these elevated values persisted unaltered during the following 9 months of treatment. Serum T3 was studied before and after 3 months of thyroxine therapy in eleven of the patients. A small and insignificant increase in serum T3 and free T3 index was observed.
DOPAMINE IS A PHYSIOLOGICAL REGULATOR OF THYROTROPHIN (TSH) SECRETION IN NORMAL MAN
Authors: SCANLON M. F. , WEIGHTMAN D. R. , SHALE D. J. , MORA B. , HEATH M. , SNOW M. H. , LEWIS M. , HALL R.
Published: March 2008

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3‐hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the control of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.
SERUM THYROGLOBULIN IN THE DIAGNOSIS AND MANAGEMENT OF THYROID CARCINOMA
Authors: SHLOSSBERG A. H. , JACOBSON J. C. , IBBERTSON H. K.
Published: March 2008

Serum thyroglobulin (Tg) was measured by radioimmunoassay in sixty‐two control subjects, 173 euthyroid patients with nodular goitre and eighty‐one patients with previously treated differentiated thyroid carcinoma. Tg was elevated in 65% of nodular goitres and failed to fall with thyroxine treatment in ten/fifteen patients treated. A diagnosis of differentiated carcinoma was confirmed in fourteen/sixty‐four of these patients and Tg was elevated in twelve. Of sixty‐five treated thyroid carcinoma patients without evidence of residual tumour, serum Tg was undetectable in thirty‐nine, normal in twenty‐four and elevated in two. There was evidence of residual tissue in the thyroid in seventeen of the patients with detectable Tg. Of the sixteen patients with residual tumour or metastases Tg was elevated in fifteen. There was a positive correlation between goitre size and Tg levels in multinodular goitre, and thyroid carcinomas of large bulk were associated with higher Tg levels. Serum Tg was normal in medullary carcinoma and in two patients with thyroid metastases from extra‐thyroidal malignancies. High Tg levels in patients with residual metastases from thyroid carcinoma following thyroid ablation indicates Tg production by tumour tissue. Measurement of serum Tg of limited value in the differential diagnosis of nodular thyroid disease. It is particularly useful following surgery and 131I therapy for differentiated thyroid carcinoma. In these patients it gives confirmation of thyroid ablation and may provide evidence of residual tumour tissue when other tests are negative.
PLASMA LEVELS OF NORETHINDRONE AFTER SINGLE ORAL DOSE ADMINISTRATION OF NORETHINDRONE AND LYNESTRENOL
Authors: ODLIND V. , WEINER E. , VICTOR A. , JOHANSSON E. D. B.
Published: March 2008

Single oral doses of 0.3 mg, 0.5 mg and 5 mg Norethindrone (NET) and 0.5 mg and 5 mg Lynestrenol (lyn) were given to five women. Lynestrenol is probably metabolized through NET and exerts its main biological activity as NET. Plasma concentrations of NET were determined by a radioimmunoassay at different intervals after administration of the tablets. Peak concentrations of NET were found within two hours after intake of each tablet. The plasma half life of NET after NET and lyn administration for the period 8–24 h was 8–11 h. No significant difference was found between the half life of NET after the NET tablets and after the lyn tablets. When 5 mg NET was given the plasma half life of NET for the period 24–72 h was around 10 h and this was significantly shorter than the half‐life of NET after 5 mg lyn, which was 161/2 h. The systemic availability of the drugs was estimated by calculating and comparing the areas under the plasma concentration versus time curve (AUC). 0–24 h. The AUC 0.24 after 0.3 mg NET was almost identical to the AUC 0–24 after 0.5 mg lyn. The AUC 0–24 after 0.5 mg NET was significantly larger than after 0.5 mg lyn. No difference was found between the AUC 0–24 after 5 mg lyn and 5 mg NET. This study supports the concept of a conversion from lyn to NET. It also shows that there were only minor pharrnacokinetic differences between the drugs when all samples were measured as NET.
ACROMEGALY DUE TO PRODUCTION OF A GROWTH HORMONE RELEASING FACTOR BY A BRONCHIAL CARCINOID TUMOUR
Authors: SHALET S. M. , BEARDWELL C. G. , MacFARLANE I. A. , ELLISON M. L. , NORMAN C. M. , REES L. H. , HUGHES M.
Published: March 2008

We have studied growth hormone production in a patient with a bronchial carcinoid and acromegaly. The absence of growth hormone from the carcinoid tumour was demonstrated by extraction, cell culture and immunoperoxidase techniques. Using a linked perfusion culture system, effluent from the bronchial carcinoid tumour culture stimulated a rapid release of growth hormone from a rat pituitary mono‐layer. This is the first time evidence of growth hormone releasing activity by a bronchial carcinoid has been demonstrated in a patient with the clinical and biochemical manifestations of excess growth hormone production.
INHIBITION OF CIMETIDINE‐INDUCED HYPERPROLACTINAEMIA BY PRETREATMENT WITH LEVODOPA OR BROMOCRIPTINE
Authors: ROLANDI ERMANNO , MASTURZO PAOLA , BARRECA TOMMASO
Published: March 2008

A single i.v. administration of cimetidine, an histamine receptor antagonist, produced a significant increase in serum prolactin (PRL) levels in fifteen normal men. This effect was suppressed by pretreatment with levodopa or bromo‐criptine.
SEMINAL PLASMA LEVELS OF TESTOSTERONE AND 5α–DIHYDROTESTOSTERONE IN AZOOSPERMIC PATIENTS
Authors: PAZZAGLI M. , GIUSTI G. , FORTI G. , FIORELLI G. , MENCHINI‐FABRIS F. , SCARSELLI G. F. , GUAZZELLI R. , CONTI C. , BORRELLI D. , CICCHI P. , SERIO M.
Published: March 2008

Testosterone (T) and 5α‐dihydrotestosterone (DHT) have been measured in seminal plasma of sixteen azoospermic patients with tubular damage (germinal cell arrest or Sertoli cell only syndrome) and five patients affected by azoospermia of obstructive origin. In both groups T values were not significantly different from controls, while DHT was significantly lower in patients affected by azoospermia of obstructive origin.
EXPERIENCE WITH HUMAN GROWTH HORMONE IN GREAT BRITAIN: THE REPORT OF THE MRC WORKING PARTY
Authors: MILNER R. D. G. , RUSSELL‐FRASER T. , BROOK C. G. D. , COTES P. M. , FARQUHAR J. W. , PARKIN J. M. , PREECE M. A. , SNODGRASS G. J. A. I. , MASON A. STUART , TANNER J. M. , VINCE F. P.
Published: March 2008

The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by path‐ologists in the National Health Service, is just enought to meet demand, but research conducted on behalf of the Working Party suggests that hCH deficiency is more common than has been thought and that the prevalence may be as high as one in 10000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply.

Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti‐hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of the shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977.
RADIATION‐INDUCED HYPERPROLACTINAEMIA IN A TREATED ACROMEGALIC
Authors: SHALET S. M. , MacFARLANE I. A. , BEARDWELL C. G.
Published: March 2008

A 31‐year‐old acromegalic was normoprolactinaemic after partial removal of her pituitary tumour. The post‐operative external pituitary irradiation lowered the mean growth hormone (GH) level from 75 mU/1 to less than 1 mU/1 within 2 years. However, at the same time hyperprolactinaemia developed. These changes in the GH and prolactin levels were confirmed 3 and 4 years after irradiation. The cause of the hyperprolactinaemia was radiation‐induced hypothalamic damage. Therefore it is suggested that similar damage may occur in patients receiving external pituitary irradiation for‘prolactinomas’and that this mechanism may contribute to the persistent hyperprolactinaemia observed in such patients.
PLASMA UNCONJUGATED OESTRIOL AND UNCONJUGATED OESTRADIOL‐17β IN LATE PREGNANCY: INDIVIDUAL FLUCTUATION OF CONCENTRATIONS FROM DAY TO DAY AND EVERY 10 MINUTES
Authors: HULL M. G. R. , MONRO P. P. , MORGAN R. J. M. , MURRAY M. A. F.
Published: March 2008

Plasma unconjugated oestriol (E3) and unconjugated oestradiol‐17β (E2) were determined by radioimmunoassay. In ten normal women in their last month of pregnancy the individual fluctuation of E3 concentrations (mean of the coefficients of variation, CV) from day to day (over 5 days) was 15.6% (range 6.4–26.2%). The individual fluctuation of E2 determined in eight of these women was 16.9 (10.4–25.5) %. In six of the same women who had blood samples collected every 10 min (for 3 h) the individual fluctuation of E3 concentrations was 13.8 (7.0–25.1) %, and of E2 was 16.1 (11.3–26.0) %. The degree of fluctuation of E3 in individuals was in proportion to the mean concentration, unlike E2, suggesting that in clinical practice individual changes in E3 values would be as easy to interpret at low levels as at high levels. The finding that concentrations of plasma unconjugated E3 fluctuate in individuals no more than for E2 or than reported for total E3, and less than reported for 24‐h urinary oestrogens, lends practical support to the theoretical preference for the assay of plasma unconjugated E3 to assess feto‐placental function.
THE DIAGNOSTIC VALUE OF PHARMACODYNAMIC TESTS IN THE HYPERPROLACTINAEMIC SYNDROME
Authors: AYALON D. , PERSITZ E. , RAVID R. , JEDWAB G. , AVIDAN S. , CORDOVA T. , HARELL A.
Published: March 2008

Patterns of prolactin (PRL) secretion were studied in a group of 18 hyperprolactinaemic patients with galactorrhoea and menstrual disorders and in a control group of thrty‐two women in the early puerperium (24 h after a normal delivery) following provocative (TRH and Chlorpromazine) and suppressive (L‐Dopa and bromocriptine) stimuli. Five out of the eighteen hyperprolactinaemic patients tested had radiological evidence of a pituitary tumour, and two were treated surgically. The early puerperium patients with elevated basal PRL levels (100–700 ng/ml) demonstrated a significant PRL response to the various treatments. On the other hand, in the hyperprolactinaemic group, an impaired PRL response to TRH, Chlorpromazine and L‐Dopa was noted in patients with basal PRL levels higher than 30 ng/ml, whereas bromocriptine suppressed effectively PRL levels in all the hyperprolactinaemic patients tested irrespective of their basal PRL concentrations. The ratio between the fall in PRL concentrations (as percent of the baseline) after L‐Dopa administration (Δ%L) versus the PRL decrement after bromocriptine treatment (Δ%B) was calculated. In the early puerperium group with normal pituitary prolactin secreting cells this ratio was equal to 0.8. In the hyperprolactinaemic group, the five patients with radiological evidence of a pituitary tumour had significantly lower ratios ranging from 0.2 to 0.57. These data suggest that in terms of prolactin release, prolactin producing tumour cells are intrinsically refractory to hypothalamic dopaminergic signals. The calculation of individual Δ%L/Δ%B ratios may serve, therefore, as a valuable indicator for early detection of autonomous pituitary prolactin secreting cells and for evaluation of the extent of the pituitary lesion.