bluuebunny/crossref_metadata_2025 huggingface dataset:
‘BIG ACTH’ AND CALCITONIN IN AN ECTOPIC HORMONE SECRETING TUMOUR OF THE LIVER
Authors: HIMSWORTH R. L. , BLOOMFIELD GLENYS A. , COOMBES R. C. , ELLISON MORAG , GILKES J. J. H. , LOWRY P. J. , SETCHELL K. D. R. , SLAVIN G. , REES LESLEY H.
Published: March 2008

A young man presented with rapidly developing Cushing's syndrome which was due to the ectopic secretion of ACTH and β‐MSH‐like material from hepatic tumour deposits, possibly originating from biliary radicals. This association of the ectopic ACTH syndrome has not previously been described. During the 22 month course of the illness the plasma immunoreactive ACTH and ‘β‐MSH’ concentrations rose by logarithmic progression. The plasma calcitonin concentration was also raised but did not change during the last 12 months. At any stage of the illness the plasma concentration of the ecotopically produced hormones was stable except that after hydrocortisone there were inconstant variations.

During the course of the illness the ectopic ACTH became biologically less potent. This ineffectual ACTH was present in the plasma, in the tumour, and in the medium in which the tumour was cultured, in a large molecular weight form. This ‘big ACTH’ differed from the normal ACTH found in the patient's pituitary and from authentic ACTH in its immunochemical character: the C‐terminal antigenic determinant (33–39 region of ACTH) was masked in the large molecular weight form but was uncovered after extraction in neutral buffer and this ‘big ACTH’ was more readily extracted from the tumour at pH 7.0. The tumour tissue also contained immunoreactive β‐MSH‐like material and immunoreactive calcitonin which resembled calcitonin M chromatographically.
SYNCHRONOUS NYCTOHEMERAL RHYTHMS IN HUMAN BLOOD MELATONIN AND IN HUMAN POST‐MORTEM PINEAL ENZYME
Authors: SMITH J. A. , PADWICK D. , MEE T. J. X. , MINNEMAN K. P. , BIRD E. D.
Published: March 2008

Serum melatonin was measured by radioimmunoassay at 4‐hourly intervals for 24 h in five normal men, and shown to exhibit nyctohemeral variations. The highest concentrations of serum melatonin occurred at 02.00 hours and the lowest concentrations at 14.00 hours. The synthetic enzymes for melatonin, serotonin‐N‐acetyl transferase (SNAT) and hydroxyindole‐O‐methyltransferase (HIOMT) were measured in post‐mortem pineal organs from thirty‐six men and women, and the activity of both enzymes was directly related to the time of death of the subject, resulting in a similar nyctohemeral curve as that observed with serum melatonin. The SNAT and HIOMT enzymes were stable when measured in pineal organs held under the usual post‐mortem conditions.

These observations indicate a nyctohemeral rhythm in human pineal function and suggests that any clinical interpretation of pineal dysfunction in disease states should take into consideration this normal rhythm.
THE PRESENCE OF IMMUNOREACTIVE GROWTH HORMONE RELEASE‐INHIBITING HORMONE IN NORMAL CEREBROSPINAL FLUID
Authors: KRONHEIM S. , BERELOWITZ M. , PIMSTONE B. L.
Published: March 2008

Immunoreactive GHRIH is present in normal CSF at a level of 55±28 pg/ml. Immunoreactivity shows mobility identical to synthetic GHRIH standard on sephadex and thin layer chromatography, and can be removed by antibody conjugated to sepharose.
EFFECT OF PSYCHOSOCIAL STIMULI AND LIMBIC LESIONS ON PROLACTIN AT REST AND FOLLOWING STRESS
Authors: BROWN GREGORY M. , SEGGIE JO , FELDMANN JOSEPH
Published: March 2008

Many of the factors altering corticosterone in the rat have similar effects on prolactin. Resting prolactin, like corticosterone, is higher in animals housed singly than in those multiply housed. Unlike corticosterone, gentling did not lower prolactin. An exquisite sensitivity to environmental stimuli which results in rapid elevations in prolactin levels has been indentified in the rat which is considerably greater than that for corticosterone. Like corticosterone, the pattern of prolactin stress responses varies according to time of day. This differential sensitivity may well account for the diurnal variation in prolactin reported by some investigators. The limbic system has an important influence on prolactin. Lesions of the septal region do not modify resting levels but alter the pattern of prolactin stress responses in ways which are only partly similar to the effects of such lesions on corticosterone.

In rhesus monkeys, individual variation in resting prolactin levels was observed, similar to that seen in the human. Levels are stable over periods of up to 50 days and are characteristic of the individual animal. In response to the stress of electric shock or shaping to a bar press response, prolactin elevation occurs only in animals with high resting levels, suggesting that a common mechanism is responsible for controlling both resting levels and magnitude of stress responses.
INCREASES IN SERUM CONCENTRATIONS OF FOLLICLE‐STIMULATING HORMONE (FSH) DURING THYROTROPHIN‐RELEASING HORMONE (TRH) INFUSIONS IN NORMAL MEN
Authors: BREMNER W. J. , DE KRETSER D. M. , BURGER H. G.
Published: March 2008

Increases in serum FSH values to approximately 50% above basal concentrations were found during TRH infusions of 2.0 μg/min into normal men (n= 10). These increases could not be explained by cros‐reactivity of thyrotrophin (TSH) in the FSH assay. No significant change was found in serum concentrations of FSH during saline infusions (n = 4) nor in LH concentrations during either TRH or saline infusions. Many previous studies using single injections of TRH have failed to demonstrate changes in serum FSH concentrations. It is possible that prolonged infusions of TRH, as used in this study, are more likely to lead to non‐specificity of the effects of this tripeptide on pituitary hormone secretion.
STUDY OF THE EFFECTS OF BROMOCRIPTINE ON SEXUAL IMPOTENCE
Authors: AMBROSI B. , BARA ROSSELLA , TRAVAGLINI P. , WEBER GIOVANNA , PECCOZ P. BECK , RONDENA M. , ELLI R. , FAGLIA G.
Published: March 2008

Serum testosterone, prolactin, LH, FSH and plasma 17β‐oestradiol levels were determined in forty‐seven male patients with sexual impotence. Low testosterone values and slightly elevated prolactin levels were observed in 19% and in 17% of cases, respectively. Since sexual function in the male seems to be controlled by both dopaminergic stimulatory and serotoninergic inhibitory mechanisms, bromocriptine was given orally to seventeen patients. As the preliminary results appeared encouraging, a double blind study was undertaken in the other thirty patients. No appreciable difference in hormonal pattern was noticed between bromocriptine and placebo treatment. As far as sexual function was concerned, good results were obtained in 52% of cases treated with bromocriptine and in 44% of patients given placebo.
POSITIVE FEEDBACK OF OESTROGEN ON LH SECRETION IN WOMEN ON NEUROLEPTIC DRUGS
Authors: WEISS GERSON , SCHMIDT CECELIA , KLEINBERG D. L. , GANGULY MANIK
Published: March 2008

The effect of a‐adrenergic and dopaminersc blockade on the ability of pituitary‐hypothalamic axis to produce an LH surge in response to oestrogen, was studied in eleven women treated with the neuroleptic agents haloperidol, fluphenazine or chlorpromazine. Seven women on no medication were controls. 6.6 mg of oestradiol benzoate (OB) was injected i.m. after control serum was obtained and daily serum samples were obtained for four additional days. Sera were assayed for total oestrogens, LH, FSH and prolactin.

Six of seven women in the control group and eight of eleven women treated with neuroleptic agents had LH surges to OB challenge. The mean prolactin of the treated women was 33.1 ± 3.6(SEM) ng/ml and the mean prolactin of the controls was 14.9 ± 1.5(SEM) ng/ml, P < 0.005. Elevated levels of circulating prolactin did not prevent an LH surge to OB challenge.

These results indicate that even in subjects with catecholamine blockade, an LH surge can be induced. This contrasts to results obtained in rats and suggests that the control mechanism of LH surge production differs in rodents and humans.
PROLACTIN SECRETION IN GIRLS WITH ISOLATED GONADOTROPHIN DEFICIENCY
Authors: PERTZELAN A. , ASSA S. , KERET R. , LARON Z.
Published: March 2008

Plasma prolactin, basal levels and the response to an i.v. injection of TRH (100 μ/m2) was determined in five girls with isolated gonadotrophin deficiency of hypothalamic origin before and after at least 3 months cyclic replacement therapy with conjugated oestrogens(1.25 rng/day). The basal plasma prolactin levels were similar during both tests, however, during oestrogen therapy the mean peak response to TRH almost doubled and the sum of all the values obtained (basal, +15, +30 and +60 min) was significantly higher. It is of note that even upon prolonged oestrogen deprivation the releasable prolactin response to TRH was adequate.
HISTOPATHOLOGY OF RENAL OSTEODYSTROPHY WITH PARTICULAR REFERENCE TO THE EFFECTS OF lα‐HYDROXYVITAMIN D3 IN PATIENTS TREATED BY LONG‐TERM HAEMODIALYSIS
Authors: ELLIS H. A. , PIERIDES A. M. , FEEST T. G. , WARD M. K. , KERR D. N. S.
Published: March 2008

(1)The bone histology of 233 non‐dialysed and 276 haemodialysed patients with chronic renal failure is reviewed. In non‐dialysed patients osteitis fibrosa occurred in 83.7% and osteomalacia in 23.6% of patients. Osteomalacia was not found in the absence of osteitis fibrosa. In haemodialysed patients there was a more variable bone histology, sometimes resembling non‐dialysed bone disease, but in general with a greater incidence of osteomalacia, especially with increasing time on dialysis. In some patients there was a predominance of osteomalacia accompanied by no or only mild osteitis fibrosa and the serum alkaline phosphatase was normal. (2) The results of treating twenty‐six haemodialysed patients with lα‐hydroxy vitamin D3 (lα‐OHD3) are described. Patients with osteomalacia and minimal or no osteitis fibrosa and a normal serum alkaline phosphatase (Group I) in general failed to respond and it is suggested that 1,25‐dihydroxyvitamin D3 deficiency is not the sole factor responsible for the osteomalacia in these patients. In contrast, lα‐OHD3 therapy was effective in improving osteitis fibrosa and osteomalacia in some patients with moderate to severe degrees of osteitis fibrosa and osteomalacia (Group IIa) and in improving osteitis fibrosa where this occurred alone (Group IIb).
HYPERPARATHYROIDISM IN CHRONIC RENAL FAILURE
Authors: PAPAPOULOS S. E. , BROWNJOHN A. M. , JUNOR B. J. R. , MARSH F. P. , GOODWIN F. J. , HATELY W. , LEWIN I. G. , TOMLINSON S. , HENDY G. N. , O'RIORDAN J. L. H.
Published: March 2008

The high circulating concentrations of immunoassayable parathyroid hormone observed in chronic renal failure are due to a number of factors. These include altered metabolism of the hormone and also end‐organ unresponsiveness which may, indirectly, cause increased secretion of parathyroid hormone. The response of the overactive parathyroid glands to changes in plasma calcium and magnesium is variable and caution is needed in evaluating the suppressibility of parathyroid hormone secretion in acute studies. lα‐Hydroxylated derivatives of vitamin D can effectively suppress parathyroid gland overactivity. This effect may not necessarily be mediated through hypercalcaemia and vitamin D metabolites may act directly on the parathyroid glands.
BONE DISEASE AND H YPERP AR ATH YROI DISM IN CHRONIC RENAL FAILURE: THE EFFECT OF lα‐HYDROXYVITAMIN D3
Authors: PEACOCK M. , AARON J. E. , WALKER G. S. , DAVISON A. M.
Published: March 2008

Plasma biochemistry, iliac crest bone biopsy and calcium and phosphate absorption were performed in ninety patients with chronic renal failure, forty‐one of whom were on maintenance haemodialysis. The studies were repeated in a number of these patients after at least 6 months treatment with 1α‐hydroxyvitamin D3 (lα‐OHD3).

Before lα‐OHD3 treatment all patients had some abnormality in bone histology; there was an increase in the osteoid volume, the osteoid and resorbing surfaces and a decrease in the calcification fronts. There was no differences between those on and those not on haemodialysis, although the amount of osteoid increased with the length of dialysis. Plasma parathyroid hormone (PTH) was increased in all patients in the presence of hypo‐normo‐ or hypercalcaemia, but the plasma calcium was higher in the haemodialysed patients. Malabsorption of calcium and phosphorus was present but it was significantly worse in the non‐dialysed patients. Hyperphosphataemia was more marked in the non‐dialysed patients and plasma alkaline phosphatase was raised in a number of patients. Plasma PTH correlated positively with plasma alkaline phosphatase and plasma calcium but was unrelated to any of the bone histology parameters.

Treatment with lα‐OHD3 corrected the malabsorption of calcium and phosphorus and cured the proximal myopathy. There was a rise in plasma calcium and phosphate, but the rise in phosphate could be prevented with aluminium hydroxide in most patients. Only in 56% of patients was a rise in plasma calcium associated with a suppression of PTH, which did not fall into the normal range. In twenty‐six patients repeat biopsies on lα‐OHD3 showed improvement in histology.

It is concluded that lα‐OHD3 corrects the malabsorption and improves the bone histology and the myopathy of renal failure. Tertiary or autonomous hyperparathyroidism occurred in 44% of patients.
THE EFFECT OF lα‐HYDROXYVITAMIN D3 IN PATIENTS WITH CHRONIC RENAL FAILURE, WITH PARTICULAR EMPHASIS ON THE RENAL HANDLING OF PHOSPHATE
Authors: MADSEN SØREN , ØLGAARD KLAUS
Published: March 2008

The present study was undertaken to elucidate the clinical, skeletal, intestinal and especially the renal effect of lα‐hydroxyvitamin D3 (lα‐OHD3), a synthetic vitamin D analogue. Seventeen patients in the uraemic state were investigated before and after long‐term treatment (mean 12.6 months) with lα‐OHD3. Serum total calcium, serum ionized calcium (Ca2+), phosphorus, alkaline phosphatases, magnesium, parathyroid hormone (iPTH), 241Am‐photonabsorptiometry, 99mtechnetium‐polyphosphate scintigraphy, intestinal 47Calciurn‐absorption and X‐ray survey of the skeleton were measured. In the uraemic patients (dialysed as well as non‐dialysed), a total or partial normalization of the bone‐related parameters was found, including relief of bone pain.

In order to evaluate the effect of lα‐OHD3 on the renal handling of phosphate, ten non‐parathyroidectomized (non‐PTX) and five totally parathyroidectornized (PTX) patients were studied. Both groups were investigated before and after administration of lα‐OHD3. The PTX patients were vitamin D depleted and hypocal‐caemic before the study. During P‐infusion, the maximal tubular reabsorption of phosphate (TmP), [51Cr]‐EDTA clearance (GFR), parathyroid hormone (iPTH) and Ca2+ were measured. The TmP/GFR‐ratio was used as an index of the renal handling of phosphate. It was demonstrated (1)that lα‐OHD3 exhibits no antiphos‐phaturic effect in man in the absence of PTH, and (2) that the lα‐OHD3 induced changes in the renal handhg of phosphate are mediated by suppression of iPTH.
PHOSPHATE AND lα‐HYDROXYVITAMIN D3 THERAPY IN HAEMODIALYSIS PATIENTS
Authors: DAVISON A. M. , PEACOCK M. , WALKER G. S. , MARSHALL D. H. , Mclaughlin M. S. F. , ROBINSON P. J. A.
Published: March 2008

Thirty‐nine adult patients on maintenance haemodialysis were treated with lα‐hydroxyvitamin D3 for 8 months. Twenty patients (Group I) were treated without concurrent aluminium hydroxide therapy, and nineteen patients (Group II) were given aluminium hydroxide to achieve a pre‐dialysis plasma phosphate of 1.60mmol/l or less.

There was malabsorption of calcium and phosphorus in both groups. The radio‐calcium absorption in Group II did not increase after reduction of plasma phosphate with aluminium hydroxide. In Group I higher doses of lα‐hydroxyvitamin D3 were required as compared to Group II to increase calcium absorption to normal without causing hypercalcaemia above 3 mmol/l.

The plasma calcium increased from a mean value of 2.65 mmol/l to 2.90 mmol/l after lα‐hydroxyvitamin D3 therapy in Group I, while in Group II it rose from 2.66 mmol/l to 2.69 mmol/l after phosphate reduction and then to 2.87 mmol/l on lα‐hydroxyvitamin D3. The plasma calcium in Group I and II was not significantly different after 8 months therapy. The plasma phosphate in Group II showed no significant change during the 8 months.

There was considerable increase in corneal calcification, pruritus and soft tissue calcification in Group I on lα‐hydroxyvitamin D3 whde in Group II there was little increase. The difference in these parameters of metastatic calcification was attributed to the higher plasma phosphate in Group I.

Resolution of sub‐periosteal erosions occurred in seven of eleven patients in Group I and only four of nine in Group II. Periosteal new bone formation developed in six patients in Group I and none in Group II.
TREATMENT OF SENILE OSTEOPOROSIS WITH 1α‐HYDROXYVITAMIN D3
Authors: SØRENSEN O. H. , ANDERSEN R. B. , CHRISTENSEN M. S. , FRIIS T. , HJORTH L. , JØRGENSEN F. S. , LUND B. , MELSEN F. , MOSEKILDE L.
Published: March 2008

About 30% of patients with clinical osteoporosis had histological signs of osteo‐malacia, in spite of normal serum 25‐hydroxyvitamin D3 (25‐OHD3). The excess osteoid disappeared during treatment with lα‐hydroxyvitamin D, (1α‐OHD3). These patients might have reduced ability to convert 25‐OHD3 to 1,25‐dihydroxy‐vitamin D3 (1,25–(0H)2D3). The intestinal calcium absorption increased during treatment with lα‐OHD3, but this was accompanied by a rise in urinary calcium excretion. Photon absorptiometry of the forearm indicated increased bone mineral content during treatment with a daily dose of 2 μg lα‐OHD3 and a supplement of 1 g of calcium. This therapeutic combination, however, caused frequent episodes of hypercalcaemia, so further studies are necessary to evaluate an appropriate dose of lα‐OHD3 with or without a calcium supplement.
TREATMENT OF PATIENTS WITH SENILE, POST‐MENOPAUSAL AND CORTICOSTEROID‐INDUCED OSTEOPOROSIS WITH lα‐HYDROXYVITAMIN D3 AND CALCIUM: SHORT‐ AND LONG‐TERM EFFECTS
Authors: LINDHOLM T. S. , SEVASTIKOGLOU J. A. , LINDGREN U.
Published: March 2008

The immediate effect of lα‐hydroxyvitamin D3 (1α‐OHD3) and calcium on blood and urine chemistry and intestinal calcium absorption rate was studied in seventeen patients, six with sede, five with post‐menopausal, and six with corticosteroid‐induced osteoporosis. In all groups, there was a significant increase in calcium absorption rate and uripary calcium excretion. In patients with post‐menopausal and corticosteroid‐induced osteoporosis, the serum calcium level was significantly increased even further. In patients with corticosteroid‐induced osteoporosis, the excretion of urinary phosphate increased significantly. In the other groups, it also increased, although non‐significantly.

The effect of long‐term treatment with 1α‐OHD3 and calcium supplements was followed in five patients with senile and five with post‐menopausal osteoporosis. Six patients were fully relieved from lumbar pain, and, in nine, physical activity was greatly improved. Despite the treatment, compression of lumbar vertebrae increased in three patients. In both groups, urinary calcium excretion increased significantly. Six patients had occasional hypercalcaemia, although their serum calcium and phosphate were generally normal. The uripary phosphate excretion decreased, although non‐significantly. The bone mineral content rose in five patients and decreased in another five, although non‐significantly. The trabecular bone area determined by repeated bone biopsies in four treated patients significantly increased.
1α‐HYDROXYVITAMIN D3 IN THE LONG‐TERM MANAGEMENT OF H YPOP A R ATH Y ROIDISM AND PSEUDOHYPOPARATHYROIDISM
Authors: LEWIN I. G. , PAPAPOULOS S. E. , O'RIORDAN J. L. H.
Published: March 2008

Normocalcaemia was restored and maintained in eleven hypoparathyroid and two pseudohypoparathyroid patients treated for up to 36 months with 1α‐hydroxy‐vitamin D3. It was found to be a potent compound, maintenance doses rangmg from 4μg weekly to 2μg daily. Supplementary oral calcium was used in acutely and profoundly hypocalcaemic patients but was given to only two patients as part of long‐term therapy. Hypercalcaemic episodes occurring during treatment were of short duration and could be controlled by withdrawal of medication alone.
LONG‐TERM THERAPY WITH 1 α‐HYDROXYVITAMIN D3 IN CHILDREN WITH‘PSEUDO‐DEFICIENCY’RICKETS
Authors: BALSAN S. , GARABEDIAN M. , COURTECUISSE V. , GUERIS J. , DOMMERGUES J. P. , CREIGNOU L. , LE DENUFF M. J. , RIVRON J.
Published: March 2008

This investigation confirms that lα‐hydroxywtamin D3 (lα‐OHD3) is a potent drug for the treatment of patients with pseudo‐deficiency rickets (Balsan et al., 1975a; Reade et al., 1975; Prader et al., 1976). lα‐OHD3 corrects their intestinal malabsorption of calcium and phosphorus, normalizes their serum calcium and phosphate concentrations and promotes healing of skeletal lesions. This study also shows differences in the needs for la–OHD3 of children with PDR. Three factors appear to be of importance: familial sensitivity, severity of chronic secondary hyperparathyroidism, and periods of increased growth velocity. Tolerance to long–term 1a–OHD3 therapy, at doses varying from 0.5 to 1 pgjd is excellent. Surveillance of patients should include regular measurements of 24 h urinary excretion of calcium, since hypercalciuria is the first signal of overdosage.
SERUM LIPIDS IN TREATED DIABETIC CHILDREN AND THEIR FAMILIES
Authors: MANN J. I. , HUGHSON W. G. , HOLMAN R. R. , HONOUR A. J. , THOROGOOD M. , SMITH A. , BAUM J. D.
Published: March 2008

Fasting lipid concentrations have been measured in fifty treated juvenile diabetics, their siblings and parents to determine which types of hyperlipoproteinaemia co‐exist with juvenile diabetes and whether the abnormalities relate to diabetic control, or represent familial disorders. Lipid concentrations amongst the parents did not differ from adult controls. Triglyceride concentrations were significantly higher in those diabetic children with fasting blood glucose concentrations >10 mmol/l than those with concentrations <10 mmol/l. The latter group had similar trigly‐ceride levels to non‐diabetic siblings. Cholesterol concentrations were not related to fasting blood glucose and were similar in diabetic and sibling controls. Hyperlipoproteinaemia (types IIa, IIb and IV) was present in ten of the diabetic patients. Six of the nine diabetic patients with raised cholesterol had at least one parent with cholesterol in the highest quintile for the control population, whereas only six of the forty‐one with lower levels had parents in this category. A similar trend for cholesterol was apparent amongst the non‐diabetic siblings. However, no association was apparent between the triglyceride levels of diabetics (or their siblings) and parents. Thus although hyperlipidaemia associated with juvenile diabetes appears to be largely due to inadequate control, raised cholesterol concentrations frequently occur.
DIAGNOSTIC PROCEDURES IN DISORDERS OF CALCIUM METABOLISM
Authors: NORDIN B. E. C.
Published: March 2008

The investigation of a patient with a suspected disorder of calcium metabolism is most rapidly and efficiently performed by observing a standard procedure, the initial stages of which are simple and mandatory, the later stages more complex and determined by the initial results and the depth of investigation required. Needless to say, the investigations are preceded by history taking and routine physical examination.

The following account is a summary of available procedures, most of which have been described elsewhere in greater detail (Nordin et al., 1976a).
THE SULPIRIDE TEST IN PANHYPOPITUITARISM
Authors: BATRINOS M. L. , PAVLOU SP. N. , PITOULIS SP. A. , SFIKAKI A. P. , ALEXANDRIDES TH. K. , PIADITIS G. P.
Published: March 2008

The results obtained with a new test of prolactin (PRL) release in six panhypo‐pituitary patients as compared to fourteen normal subjects (eight females and six males) are presented. The test consists of the i.m. administration of 100 mg of sulphide and the measurement of plasma PRL by a double antibody radio‐immunoassay techniques at −15, 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Mean baseline PRL values were not significantly different in the three groups. After sulpiride a 800–4200% increment of prolactin over control values was noted in the females and 1200–3500% increment in the males. The peak values were obtained at 15 or 30 min (6030·670 mu/l ± SEM in the females and 5550·870 mu/l in the males). The mean values were not significantly different in the two sexes until the sixtieth minute but were significantly higher (P > 0.05) in the female thereafter. In the hypopituitary patients a complete failure of response was noted. These results show that the sulpiride test possesses a considerable potential as a screening procedure in the diagnosis of pituitary insufficiency.
ASSESSMENT OF PROLACTIN RELEASE IN PITUITARY DWARFISM WITH THE SULPIRIDE TEST
Authors: BATRINOS M. L. , PAVLOU SP. N. , PITOULIS SP. A. , SFIKAKI A. P. , ANOUSAKIS CH. , ALEXANDRIDES TH. K. , PIADITIS G. P.
Published: March 2008

We report here the results obtained with a new test of prolactin (PRL) release in six normal pre‐pubertal boys, eleven children with short stature of non‐pituitary origin and in thirteen pituitary dwarfs. The test consists of the administration of 100 mg of sulphide i.m. and the measurement of PRL in serum samples up to 120 min after injection. Baseline PRL concentrations were not clearly different in the three groups. After sulpiride a marked increase (3–10 times over control values) in PRL was noted in all normal and short children without pituitary disease. A complete failure of response was observed in ten of the thirteen pituitary dwarfs. It is concluded that sulpiride has considerable potential in the differential diagnosis of children with stunted growth.
ENDOCRINE STUDIES IN MALE PSEUDOHERMAPHRODITISM IN CHILDHOOD AND ADOLESCENCE
Authors: SAVAGE M. O. , CHAUSSAIN J. L. , EVAIN D. , ROGER M. , CANLORBE P. , JOB J. C.
Published: March 2008

The clinical and endocrine features of fifty cases of male pseudohermaphroditism and XY karyotype aged from 6 months to 20 years have been studied. Thirty‐two subjects were pre‐pubertal and eighteen, of whom ten developed gynaecomastia, were pubertal. A definite aetiology was established in 12%. 4% had deficient testosterone biosynthesis and 8% mixed gonadal dysgenesis. In the remaining 88% an aetiology of androgen unresponsiveness at the target areas is suggested. Hormonal investigations in these subjects showed that before puberty basal plasma testosterone and oestradiol were slightly but significantly elevated, whereas testosterone response to stimulation with human chorionic gonadotrophin was significantly diminished. In the pubertal subjects basal plasma testosterone, oestradiol, serum binding capacity of testosterone‐oestradiol binding globulin and basal plasma LH were significantly elevated. These hormonal features in pubertal or post‐pubertal male pseudo‐hermaphrodites appear to be characteristic of androgen unresponsiveness. The presence in addition of elevated basal plasma testosterone and oestradiol in the pre‐pubertal subjects suggest that some of these findings may be present from early childhood.
PLASMA STEROID AND GONADOTROPHIN PROFILES IN OVULATORY BUT INFERTILE WOMEN
Authors: LENTON ELIZABETH A. , ADAMS MALCOLM , COOKE IAN D.
Published: March 2008

A group of twelve patients with a history of infertility lasting at least 2 years despite evidence of regular ovulatory cycles, were selected from an Infertility Clinic after thorough investigation had revealed no other obvious cause for their infertility. Daily plasma gonadotrophin and steroid concentrations were measured in twenty cycles from these women and the results compared with the hormonal profiles obtained from a group of eleven control ‘normal’ women. No significant differences were found in the concentrations of LH, FSH or oestradiol although plasma progesterone concentrations were significantly lower in the infertile women, particularly during the first half of the luteal phase. In the absence of any other demonstrable defect, it was assumed that the decreased progesterone secretion was directly or indirectly implicated in the pathogenesis of their infertility, and a number of therapeutic regimes (progesterone supplementation of the luteal phase or additional stimulation by either anti‐oestrogens or exogenous gonadotrophins) were assessed for their efficacy in correcting this defect. Although plasma progesterone concentrations after most of these regimes were significantly increased, none of the patients in this series conceived.
EVIDENCE FOR THYROIDAL SECRETION OF 3,3′,5′‐TRIIODOTHYRONINE IN MAN AND ITS CONTROL BY TSH
Authors: HOOPER M. J. , RATCLIFFE J. G. , RATCLIFFE W. A. , MARSHALL J. , YOUNG R. E. , NGAEI G. , CLARK D. H.
Published: March 2008

Thyroidal secretion of 3,3′,5′‐triiodothyronine (reverse T3, rT3) and its control by TSH was assessed by measuring (1) arterio‐venous hormone gradients in patients undergoing surgery, (2) changes of hormone concentrations after induction of anaesthesia, and (3) changes induced by TRH administration. In ten patients in whom thyroid activity was under TSH control (parathyroidectomy and non‐toxic goitre) increased thyroid vein/carotid artery ratios (TV/CA) for rT3 (mean TV/CA ratio 2.53) were found when compared to six patients with non‐toxic goitre on suppressive doses of T4 (mean TV/CA ratio, 1.27) (P > 0.05). The mean calculated operative secretion rate of rT3 was 12.5 μg/day but only 2.4 μg/day in patients receiving T4. In thirteen patients undergoing elective surgery induction of anaesthesia significantly increased rT3 levels. In nine euthyroid adults intravenous TRH (200 μg) increased peripheral venous rT3 levels between 3 h (P > 0.005) and 8 h (P > 0.05) after the injection. It is concluded that significant amounts of rT3 are secreted by the thyroid gland at operation and this is, in part, under TSH control.
TESTICULAR FUNCTION FOLLOWING IRRADIATION OF THE HUMAN PREPUBERTAL TESTIS
Authors: SHALET S. M. , BEARDWELL C. G. , JACOBS H. S. , PEARSON D.
Published: March 2008

Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo‐ or azoospermia (0 to 5.6 million/ml), seven of whom had an elevated serum follicle‐stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration.

A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range for prepubertal boys in all eight. The mean gonadotrophin levels were not significantly different from the mean levels of normal prepubertal males. Thus irradiation‐induced damage to the germinal epithelium in prepubertal boys produces raised FSH levels after puberty but not before it.

We conclude, therefore, that inhibin has a minor role in the control of the prepubertal hypothalamic‐pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation.
CHANGES IN PITUITARY GONADOTROPINS DURING THE AMENORRHOEA‐GALACTORRHOEA SYNDROME DUE TO SULPIRIDE
Authors: BUVAT J. , THOMAS K. , RACADOT A. , BLACKER C. , BUVAT‐HERBAUT M. , FERIN F. , LINQUETTE M.
Published: March 2008

Sulpiride, a dopamine receptor blocker which raises prolactin, was given to six women with idiopathic amenorrhoea for 10 days and to eleven women with regular cycles for 3 to 6 months. The latter group developed galactorrhoea and amenorrhoea during treatment. Basal LH and FSH concentrations showed no significant changes. At 3 months but not at 10 days (amenorrhoea group) or 6 months (regular menses group) the area‐under‐the‐curve of LH response to LHRH was increased. FSH responses to LHRH was not altered. The significance of these results to the hyper‐prolactinaemia‐amenorrhoea syndromes are discussed.
NON‐TOXIC GOITRE: DIAGNOSTIC ROLE OF ASPIRATION CYTOLOGY, ANTIBODIES AND SERUM THYROTROPHIN
Authors: GUTTERIDGE D. H. , ORELL S. R.
Published: March 2008

Fifty cases of bilateral non‐toxic goitre, largely unselected, have been studied using fine needle aspiration cytology (without local anaesthesia); four techniques of thyroid antibody tests; serum thyroid biochemistry (including radioimmunoassay of TSH) and clinical evaluation. Autoimmune thyroiditis was found cytologically in 64%; simple colloid goitre in 24%; subacute thyroiditis of de Quervain in 10%. Aspiration cytology was the most sensitive means of detecting autoimmune thyroiditis and subacute thyroiditis. Two antibodies directed against the intra‐cellular cyto‐plasmic antigen‐the complement fixation test and an immunofluorescent antibody were of lesser value in detecting autoimmune thyroiditis (80% positivity) though equal to each other. Serum TSH was of some value‐being elevated in 63% of cases of autoimmune thyroiditis and in no cases of simple colloid goitre. Two major cytological subtypes of autoimmune thyroiditis have been described‐with significant differences in duration of goitre, mode of presentation, frequency of hypo‐thyroidism, and response to thyroxine therapy. The high frequency of autoimmune thyroiditis in this series suggests that endemic goitre is unlikely in Western Australia.
THE EFFECT OF SERUM IONIZED CALCIUM ELEVATION ON SOMATOSTATIN INHIBITION OF GLUCOSE‐INDUCED INSULIN RELEASE IN HUMANS
Authors: WAJCHENBERG B. L. , CESAR F. P. , LEME C. E. , SILVA H. B. , LERARIO A. C. , COY D. H. , SCHALLY A. V.
Published: March 2008

The effect of somatostatin on the insulin response to an acute intravenous glucose load was studied in five normal subjects before and after induction of hypercalcaemia. In the normocalcaemic state, the insulin response to glucose was depressed by somatostatin. In the hypercalcaemic state, insulin responses to glucose in the presence of somatostatin, were partially restored and appeared to be related to the level of increment of serum ionized calcium. It is concluded that, in the human being, hypercalcaemia and somatostatin have opposite actions on glucose‐stimulated insulin secretion.
INCREASED SERUM OESTRONE AND OESTRADIOL FOLLOWING SPIRONOLACTONE ADMINISTRATION IN HYPERTENSIVE MEN
Authors: MIYATAKE AKIHIKO , NOMA KEIZO , NAKAO KIYOHIDE , MORIMOTO YASUHIKO , YAMAMURA YUICHI
Published: March 2008

The present study was undertaken to evaluate long‐term effects of spironolactone on basal serum oestrone, oestradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. Patients were divided into two groups: a conventional‐dosage group, consisting of six males with essential hypertension who took 75 to 150 mg of spironolactone daily for 12 weeks, and a high‐dosage group, consisting of two males with idiopathic hyperaldosteronism who took 300 mg of spironolactone daily for more than 40 weeks.

In the conventional‐dosage group, serum oestrone concentrations significantly increased (P > 0.01) at 12 weeks, serum oestradiol concentrations gradually increased throughout the study period, however, the increments were not statistically significant (P > 0.2). Basal serum testosterone, LH and prolactin concentrations were not significantly changed throughout the study period. Enhancement of serum prolactin response to TRH was not found in any of the patients in the conventional‐dosage group.

In the high‐dosage group, serum oestrone maintained high levels from the beginning of this study, and serum oestradiol concentrations increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations did not show any definite change throughout the study period.

Thus, long‐term spironolactone treatment increased the serum levels of oestrone and oestradiol in hypertensive men followed by the development of gynaecomastia. The elevations in circulating oestrogens could well explain the oestrogenic side‐effects of spironolactone treatment.
PROLACTIN AND LUTEAL INSUFFICIENCY
Authors: SARRIS S. , SWYER G. I. M. , MCGARRIGLE H. H. G. , LAWRENCE D. M. , LITTLE V. , LACHELIN G. C. L.
Published: March 2008

The relationship between mid‐luteal plasma levels of progesterone and prolactin was studied in 75 women with regular menstrual cycles. Eighteen women had normal prolactin (mean 260 ± 51.7 mU/l) and normal progesterone levels (mean 67 ± 21.3 nmol/l). Thirty‐nine women had elevated prolactin levels (mean 850 ± 503 mU/l); progesterone levels were normal in all cases (mean 61 ± 22.3nmol/l). Eighteen women had evidence of luteal deficiency (mean progesterone 15.3 ± 7.7 nmol/l); prolactin levels were normal in all cases (mean 243 106 mU/l). There was no correlation between plasma prolactin and progesterone levels.
FURTHER STUDIES ON THE EFFECTS OF DIHYDROTESTOSTERONE ON GONADOTROPHIN RELEASE INDUCED BY LH‐RH IN MEN
Authors: ANDÒ S. , POLOSA P. , D'AGATA R.
Published: March 2008

In order to determine the effect of dihydrotestosterone on the feed‐back mechanism of the hypothalamo‐pituitary testis axis, seven men were subjected to LH‐RH tests before and after treatment with dihydrotestosterone.

Our results clearly show that DHT at least in pharmacological doses, inhibits directly basal LH‐RH and gonadotrophin secretion, without affecting the pulsatile gonadotrophin release or impairing the pituitary response to LH‐RH. The physiological significance of these observations remains however to be proven.
ACROMEGALY: INSENSITIVITY OF THE PANCREATIC ALPHA CELL TO HYPERGLYCAEMIA*
Authors: SEINO YUTAKA , TAMINATO TOMOHIKO , GOTO YASUO , INOUE YOSHIMICHI , KADOWAKI SEIZO , MORI KOZABURO , IMURA HIROO
Published: March 2008

Plasma glucagon levels were determined after 50 g of oral glucose loading in eleven acromegalics and fourteen normal subjects. Basal plasma glucagon levels were significantly elevated in patients with acromegaly, as compared with those in normal subjects. Oral glucose loading caused a decrease in plasma glucagon in normal subjects but not in acromegalics. Since this non‐suppressibility of plasma glucagon by orally administered glucose was observed even in acromegalics without diabetes, it is concluded that insensitivity of the pancreatic alpha cell to hyper‐glycaemia exists in patients with acromegaly as well as in diabetics.
INAPPROPRIATE TRIIODOTHYRONINE (T3) AND THYROXINE (T4) RADIOIMMUNOASSAY LEVELS SECONDARY TO CIRCULATING THYROID HORMONE AUTOANTIBODIES
Authors: GINSBERG JODY , SEGAL D. , EHRLICH R. M. , WALFISH P. G.
Published: March 2008

A 16‐year‐old boy with chronic lymphocytic thyroiditis was noted to have a low free thyroxine (T4) level, low triiodothyronine resin uptake (T3U), and high serum thyrotropin (TSH) values. Unexpectedly, markedly elevated T3 radioimmunoassay (RIA) and T4 (RIA) values, using a double antibody technique were obtained when performed directly on unextracted serum samples. Extremely low T4 (RIA) values were noted when polyethylene glycol (PEG) was used to separate bound from free hormone. The presence of circulating T3‐ and T4‐binding immunoglobulins was suspected and confirmed with the following special studies. With undiluted serum in a T3 (RIA) system, using dextran‐coated charcoal separation, 82% binding of 125I‐labelled T3 occurred in the absence of specific first antibody, with 55% binding retained at 1: 7 dilution with T3‐free serum. Comparable results were obtained in the T4 (RIA) system using polyethylene glycol separation. Following ethanol extraction, low T4 (RIA) and low normal T3 (RIA) values were obtained, using a double antibody technique. There was ten‐fold greater binding by the patient's serum to rabbit anti‐human IgG in both the T3 and T4 radioassay systems as compared to controls. No preferential binding to rabbit anti‐human IgM was noted. Scatchard plot analyses for the antibodies against T3 and T4 showed high affinity constants for these hormones. With adequate l‐thyroxine therapy, an appropriate decline in serum TSH to normal was achieved. It is concluded that where RIA determinations of T3 and T4 are inconsistent with other laboratory and clinical indices, the presence of autoantibodies to thyroid hormones should be suspected and appropriate tests undertaken.
BOOK REVIEW
Authors: TRUSWELL A. S.
Published: March 2008

Book Review in this Article

Nutritional Imbalances in Infant and Adult Disease. Ed. by M. S. Seelig
24 HOUR PROFILE OF 18‐HYDROXY‐11‐DEOXYCORTICOSTERONE IN NORMAL SUPINE MAN: RELATIONSHIP WITH CORTISOL AND ALDOSTERONE
Authors: SULON J. , SPARANO F. , SCIARRA F. , GIAQUINTO G. , GENARD P.
Published: March 2008

Daily profiles of plasma 18‐hydroxy‐11‐deoxycorticosterone (18‐OH‐DOC) were studied in four normal supine men on a normal sodium intake. Blood was taken every hour from 01.00 to 24.00 hours. Plasma cortisol (F) and aldosterone (A) were determined hourly for comparative studies. 18‐OH‐DOC fluctuated considerably during the 24 h period of investigation, the highest values being found during the early morning hours in synchrony with F. The episodic secretions of 18‐OH‐DOC were also significantly correlated with those of A, which in turn paralleled those of F. We conclude that ACTH, plays a definite role in the regulation of 18‐OH‐DOC in normal supine men on a normal sodium diet.
EVALUATION OF THE RESULTS OF TRANS‐SPHENOIDAL SURGERY IN ACROMEGALY BY ASSESSMENT OF THE GROWTH HORMONE RESPONSE TO THYROTROPHIN‐RELEASING HORMONE
Authors: FAGLIA G. , PARACCHI A. , FERRARI C. , BECK‐PECCOZ P.
Published: March 2008

Eighteen acromegalic patients GH‐responsive to TRH were reinvestigated following trans‐sphenoidal surgery and radiotherapy. Basal serum GH decreased below 10 μg/l in thirteen cases; nine of them became GH‐unresponsive to TRH 1 month after operation, and another one following conventional pituitary irradiation. Four of these ten patients also showed a normal GH response to l‐Dopa after treatment, and five responded normally to insulin‐induced hypoglycaemia; two patients had a normal GH secretory pattern after both these stimuli.

No recurrences were observed over a follow‐up period of 15–80 months among the ten patients who became GH‐unresponsive to TRH following operation, while one of the three subjects still responsive to TRH in spite of normalized basal serum GH concentration relapsed 10 months after surgery. Three patients with normalized TRH test following operation were repeatedly reinvestigated over a 3–6 years period and always found unresponsive.

The present study shows that the ‘paradoxical’ GH responses to TRH and l‐Dopa frequently disappear after surgery, that complete normalization of GH secretory pattern may rarely be attained, and that the disappearance of GH response to TRH probably indicates satisfactory treatment of acromegaly. These data suggest that the ‘paradoxical’ GH responses frequently found in acromegaly are dependent on the adenoma per se and not on hypothalamic dysfunction.
HYPERTHYROIDISM INDUCED BY SECONDARY CARCINOMA IN THE THYROID
Authors: EDMONDS C. J. , THOMPSON B. D.
Published: March 2008

A young women presenting with hyperthyroidism proved to have diffuse infiltration of the thyroid with carcinoma probably from a primary breast adenocarcinoma. The gland was diffusely infiltrated with tumour although the thyroid follicles were intact. Blood thyroid hormone levels were raised but thyroid uptake of iodine was undetectable. It is suggested that the tumour released a locally active agent which stimulated hormone release but not iodine uptake, the latter being very low due to suppression of TSH.
BOOK REVIEW
Authors: REES LESLEY H.
Published: March 2008

Book Review in this Article

Melanocyte Stimulating Hormone: Control, Chemistry and Effects. Frontiers of Hormone Research. Ed. by F. J. TILDERS, D. F. SWAAB and TJ. B. VAN WIMERSA GREIDANUS. S. Karger
GLUCAGON RESPONSE TO ARGININE IN GROWTH HORMONE DEFICIENT CHILDREN BEFORE AND AFTER TREATMENT WITH GROWTH HORMONE AND IN CHILDREN WITH NON‐ENDOCRINE SHORT STATURE
Authors: LEVITSKY LYNNE L. , UEHARA JANE A. , MARCHICHOW JO ANN , DUMBOVIC NIVES
Published: March 2008

In order to assess the role of growth hormone in the modulation of alpha cell function, the plasma pancreatic glucagon response to intravenous arginine (0.5 g/kg) was determined in thirty‐two children with non‐endocrine short stature and in eighteen growth hormone deficient children. 60 min after arginine infusion, the growth hormone deficient children had significantly higher (P<0.05) plasma glucagon values than the children with non‐endocrine short stature. Following short‐term growth hormone therapy (2 iu qd or bid for 5 days) in eleven of these growth hormone deficient children, plasma pancreatic glucagon response to arginine was diminished, and there was a significantly (P<0.02) more rapid return to basal values than in the untreated group. The same trends persisted after long‐term growth hormone therapy (2 iu three times per week for 12–30 months) in ten children but were not statistically significant.

We conclude that growth hormone may play a role in modulating plasma pancreatic glucagon response. The persistent glucagon response to arginine noted in growth hormone deficient children might reflect a greater gluconeogenic stress imposed upon these children during fasting or decreased catabolism of glucagon in the growth hormone deficient state.
BROMOCRIPTINE: LACK OF EFFECT ON THE ANGIOTENSIN II AND ALDOSTERONE RESPONSES TO SODIUM DEPRIVATION
Authors: SEMPLE PETER F. , MASON PETER A.
Published: March 2008

Five normal subjects took a low sodium diet for four days on two occasions, one with and one without added bromocriptine 2.5 mg three times a day by mouth. Daily measurements of urinary electrolytes and the concentrations of plasma renin (PRC), angiotensin II (AII), aldosterone, 18‐hydroxycorticosterone, cortisol, electrolytes and prolactin were made in both phases of the study. Deprivation of sodium without bromocriptine resulted in progressive and highly significant increases in the plasma concentration of aldosterone from 230 ± 50 to 418 ± 44 (SEM) pmol/l, 18‐hydroxycorticosterone from 627 ± 138 to 1420 ± 478 pmol/l, PRC from 108 ± 38 to 166 ± 14 μU/ml and AII from 16 ± 3 to 29 ± 4 pmol/l. Similar changes were found during bromocriptine administration despite suppression of prolactin secretion. Sodium deprivation together with bromocriptine resulted in increases in the plasma concentrations of aldosterone from 230 ± 47 to 416 ± 72 pmol/l, 18‐hydroxycorticosterone from 630 ± 99 to 1629 ± 552 pmol/l, PRC from 105 ± 12 μU/ml and AII from 14 ± 3 to 26 ± 5 pmol/l. Plasma cortisol did not change either in response to sodium deprivation or bromocriptine. Mean cumulative negative sodium balance was 101 ± 14 mmol on bromocriptine and 118 ± 14 mmol in the control period. We conclude that prolactin is not necessary for the steroidogenic response to sodium deprivation in man.
THYROID FUNCTION IN EARLY SUB‐ACUTE THYROIDITIS
Authors: GÓROWSKI TADEUSZ , KANIEWSKI MAREK , GABRYELEWICZ MARIA
Published: March 2008

A 53‐year‐old woman with an early form of de Quervain's disease involving both thyroid lobes was found to have her thyroid uptake of iodine suppressed, although the serum thyroid hormone concentrations were normal while the administration of TRH resulted in significant increase in the serum TSH concentrations. After administration of TSH the thyroid reserve was found to below. The diagnosis of sub‐acute thyroiditis was confirmed on biopsy. The above data seem to indicate that the suppression of the thyroid uptake in the early stage of de Quervain's disease may be directly caused by the inflammatory condition of the gland, rather than, as is usually the case, by the excess of thyroid hormones and, consequently, by the suppression of pituitary TSH secretion.