bluuebunny/crossref_metadata_2025 huggingface dataset:
SINGLE DOSE DEXAMETHASONE SUPPRESSION TEST IN CHILDREN: DOSE RELATIONSHIP TO BODY SIZE
Authors: HINDMARSH P. C. , BROOK C. G. D.
Published: March 2008

We have performed an overnight single dose dexamethasone suppression test in 15 children at different dosages to determine the minimum dose required to suppress the 0800 h serum cortisol level. With a dexamethasone dose of 0·1 mg/m2 two of seven children showed suppression. When the dose was increased to 0·3 mg/m2 all of six patients showed suppression as did three given dexamethasone 0·5 mg/m2. We recommend that doses of dexamethasone should be calculated in terms of body surface area when assessing the hypothalamo‐pituitary axis in children and that a dose of 0·3 mg/m2 should be used for suppression tests.
THE HALF‐LIFE OF ENDOGENOUS INSULIN AND C‐PEPTIDE IN MAN ASSESSED BY SOMATOSTATIN SUPPRESSION
Authors: MATTHEWS D. R. , RUDENSKI A. S. , BURNETT M. A. , DARLING P. , TURNER R. C.
Published: March 2008

The in‐vivo half‐lives of insulin and C‐peptide have been assessed in normal man by a method which examines the decline of endogenously produced insulin and C‐peptide after somatostatin suppression of secretion. Venous blood samples were taken each minute from seven normal subjects: i. v. glucose (0·1 g/kg ideal body weight) was given over 1 min to stimulate secretion, followed by a bolus of 250 fig of somatostatin‐14 and an infusion of a further 250 jug somatostatin‐14 over the subsequent 30 min. Plasma samples were analysed for C‐peptide, glucose and insulin. The initial mono‐exponential half‐lives over 8 min were 3·9 · 0·3 and 10·2 · 0·7 min respectively (mean · SEM), with subsequent slower declines. Log transformed insulin and C‐peptide yielded biphasic declinations which were assessed by a two‐pool model. The rate constant of clearance of insulin implied avid uptake, while the kinetics of C‐peptide clearance were slower, and irreversible loss might be explained by glomerular filtration alone. The somatostatin suppression method of measuring hormone kinetics could be used for newly described hormones which are not available for in‐vivo studies.
IMPAIRED GROWTH HORMONE RESPONSE TO GROWTH HORMONE RELEASING FACTOR AND INSULIN‐HYPOGLYCAEMIA IN OBESITY
Authors: KOPELMAN P. G. , NOONAN K. , GOULTON R. , FORREST A. J.
Published: March 2008

We have previously reported an impaired growth hormone (GH) response and abnormal prolactin release to insulin‐hypoglycaemia in obesity. We suggested that obese women with an absent prolactin response to hypoglycaemia (‘non‐responders’) have a disorder of hypothalamic function. We have now investigated the GH response to i. v. growth hormone releasing factor, GHRF (1–29)NH2, in 14 obese women and nine age‐matched normal‐weight women. We found a significantly reduced GH response to GHRF in the obese women as compared with controls (mean peak · SEM: obese 8·9 · 2 mu/l, controls 28 · 2 mu/l; P >0·01). When the obese women were divided on the basis of their prolactin response to insulin‐hypoglycaemia (seven ‘non‐responders’, mean weight 102 · 5 kg; seven responders, mean weight 108·8 kg) a similar GH response to GHRF was found between the two groups but the GH response to hypoglycaemia was significantly less in the ‘non‐responder’ women (mean peak ‘non‐responders’ 10·5 · 3 mu/l, responders 27·4 mu/l; P < 0·05). We conclude that obesity may be characterized by an impaired GH response to both i. v. GHRF and insulin‐hypoglycaemia, which suggests altered hypothalamic‐pitui‐tary function. The finding that the GH response to hypoglycaemia is significantly less in the obese prolactin ‘non‐responder’ women supports the hypothesis for a hypothalamic disorder.
HLA ANTIGENS AND FAMILIAL BENIGN HYPERCALCAEMIA
Authors: PATERSON C. R. , LEHENY W. , O'SULLIVAN A. F.
Published: March 2008

We have determined the blood groups and HLA haplotypes in 15 members in four generations of a large kindred with familial benign hypercalcaemia (familial hypocalciuric hypercalcaemia). No linkage was seen between the disorder and ABO or Rh blood groups or the HLA antigens.
THE ROLE OF PLASMA OSMOLALITY, ANGIOTENSIN II AND DOPAMINE IN VASOPRESSIN RELEASE IN MAN
Authors: MORTON J. J. , CONNELL J. M. C. , HUGHES M. J. , INGLIS G. C. , WALLACE E. C. H.
Published: March 2008

A sensitive and specific radioimmunoassay for arginine vasopressin was used to compare the relative importance of changes in plasma osmolality, angiotensin II and dopamine in the regulation of vasopressin secretion in man. One hour after water loading plasma vasopressin fell from 0·40 to 0·06 pmol/1, while 8 h and 24 h fluid restriction resulted in a rise of vasopressin from 0·29 to 0·54 and 1·37 pmol/1 respectively. In contrast neither dietary sodium deprivation, when plasma angiotensin II increased 5‐fold, nor dopamine infusion, at a rate which increased circulating dopamine levels up to 244‐fold, had any effect on basal plasma vasopressin values. These results confirm that, under physiological conditions, osmoregulation is the major mechanism controlling vasopressin release and suggests that circulating angiotensin II and dopamine have no significant part to play.
THE EFFECT OF SPIRONOLACTONE ON HIRSUTISM AND FEMALE ANDROGEN METABOLISM
Authors: DORRINGTON‐WARD P. , MCCARTNEY A. C. E. , HOLLAND S. , SCULLY J. , CARTER G. , ALAGHBAND‐ZADEH J. , WISE P.
Published: March 2008

An objective evaluation of the anti‐androgen effects of spironolactone was performed in a consecutive series of 12 hirsute patients receiving a daily dose of 150 mg; nine completed the study. Using a computer assisted image analyser, hair diameter on two weekly shavings decreased significantly over a 12 month period in three of the patients, although growth rate and mean diameter did not change in the group as a whole. Plasma testosterone fell significantly to a mean of 53% of basal levels. The mean free testosterone (derived) fell significantly to 64% of basal by the sixth month (P= > 0·005) and remained significantly depressed for the remainder of the study. There was subjective benefit in hair growth and greasiness and a significant reduction in the semi‐objective Ferriman‐Gallwey index in nine of 10 subjects assessed for at least 9 months. We conclude that although spironolactone was not consistently successful, it may represent effective therapy for a sub group of patients with hirsutism.
THYROID STIMULATION BY (FAB)2 AND FAB FRAGMENTS OF TSH RECEPTOR ANTIBODY
Authors: CREAGH F. M. , PARKES A. B. , TUNN E. , GINSBERG J. , HASHIM F. , SMITH B. REES
Published: March 2008

The TSH receptor binding and thyroid stimulating properties of (Fab)2 and Fab fragments of Graves’ IgG have been investigated. (Fab)2 fragments were prepared by pepsin digestion of IgG and Fab fragments by reduction of (Fab)2 or papain digestion of IgG. (Fab)2 and Fab were effective in inhibiting TSH binding to its receptor with all five patients’ sera studied and both preparations stimulated cyclic AMP release from isolated thyroid cells. However Fab fragments were less active thyroid stimulators than their parent (Fab)2 in all five cases. These studies indicate that antibody divalency is not essential for thyroid stimulation by TSH receptor antibodies.
RESTORATION OF DEXAMETHASONE SUPPRESSION BY INCOMPLETE ADENOMECTOMY IN CUSHING'S DISEASE
Authors: JEFFCOATE W. J. , DAUNCEY S. , SELBY C.
Published: March 2008

Two cases of pituitary‐dependent Cushing's disease are described. Selective transphenoidal adenomectomy was attempted in each, but proved incomplete. Although both patients had persistent Cushing's disease after the operation, both were shown to have been rendered fully dexamethasone suppressible. The pathophysiological basis of partial suppressibility is discussed, as are the criteria for the diagnosis of cure in Cushing's disease treated by selective adenomectomy.
GLUCOCORTICOID DEFICIENCY WITH ACHALASIA OF THE CARDIA AND LACK OF LACRIMATION
Authors: POMBO M. , DEVESA J. , TABORDA A. , IGLESIAS M. , GARCIA‐MORENO F. , GAUDIERO G. J. , MARTINÓN J. M. , CASTRO‐GAGO M. , PEÑA J.
Published: March 2008

Four recent reports describe a multisystem disorder in which ACTH insensitivity is associated with achalasia and alacrima. We report studies on a male patient with this rare triad. The patient had alacrima from birth; isolated glucocorticoid deficiency had been diagnosed at 3·5 years of age and achalasia at age 6. The possibility that this syndrome could be due to a parasympathetic degeneration has already been proposed; the cause of the glucocorticoid deficiency, however, remains unclear. Parasympathetic function in other areas was investigated to determine whether there might be a more generalized abnormality. Specific cardiac tests of parasympathetic function showed that parasympathetic input to the heart was affected in the patient, while the same tests in an Addisonian child were normal. We show, then, a hitherto undetected parasympathetic abnormality in a patient with this syndrome, suggesting a generalized disturbance of this system. On this basis we may hypothesize that the glucocorticoid failure may be a consequence of the loss of parasympathetic input to the adrenal gland, although this remains to be demonstrated experimentally.
ASSOCIATION OF HLA ANTIGENS WITH THYROTOXIC GRAVES’ DISEASE AND PERIODIC PARALYSIS IN HONG KONG CHINESE
Authors: HAWKINS B. R. , MA J. T. C. , LAM K. S. L. , WANG C. C. L. , YEUNG R. T. T.
Published: March 2008

The HLA‐A and ‐B antigen distribution in 132 Hong Kong Chinese patients with Graves’ disease, including 24 with thyrotoxic periodic paralysis, was compared with that in 110 controls. The HLA‐DR antigen distribution in 68 patients was compared with that in 47 controls. The prevalence of Bw46 was significantly increased in patients with Graves’ disease and with periodic paralysis. The prevalence of DRw9 was also slightly increased but not at a statistically significant level. The high prevalence of Bw46 related to patients with early age at onset whereas patients with later age at onset had a significantly increased prevalence of HLA B5. It is suggested that Graves’ disease in Chinese is due to two HLA‐associated mechanisms in which early‐onset disease is associated with Bw46 and late‐onset disease with B5.
MULTIPLE INTRACRANIAL METASTASES FROM A PROLACTIN SECRETING PITUITARY TUMOUR
Authors: GASSER R. W. , FINKENSTEDT G. , SKRABAL F. , TWERDY K. , GRUNERT V. , MAYR U. , FROMMHOLD H. , ZUR NEDDEN D. , FEICHTINGER J. , HOFSTAEDTER F.
Published: March 2008

A 28 year old man presented with partial hypopituitarism and signs of a pituitary tumour. A chromophobe adenoma was partially removed by right frontal craniotomy. Seven years later complete hypopituitarism and hyperprolactinaemia were documented, at which time there was no evidence of tumour recurrence on CT scan. The patient was treated with bromocriptine but the pituitary tumour redeveloped a year later. Nine years after the original operation the first metastasis was demonstrated together with very high prolactin levels. The intracranial metastasis, and the pituitary tumour were removed at a second craniotomy following which the prolactin concentration fell. Further metastases developed subsequently and the patient died 12 years after the initial diagnosis. At autopsy multiple metastases were found in the brain, tumour cells were present in the subarachnoid space and in cerebral veins. The pituitary tumour and secondaries were shown by immunocytochemistry to contain prolactin but not ACTH or growth hormone. This appears to be the third well documented case of a metastasizing, prolactin secreting pituitary tumour.
THE ABSENCE OF ANY EFFECT OF METHIMAZOLE ON IN VITRO CELL‐MEDIATED CYTOTOXICITY
Authors: WEETMAN A. P. , GUNN CATHERINE , HALL R. , McGREGOR A. M.
Published: March 2008

Two recent studies have reported that antithyroid drugs inhibit killer (K) and natural killer (NK) cell function in vitro, which could be relevant to the changes in these cell populations during treatment of GRAVES' disease. In contrast to these reports we have found no in vitro effect of pharmacologically relevant concentrations of methimazole (MMI) (100 μmol/l) on (i) NK cell function using K562 cells or MOLT‐4 cells as targets, (ii) K cell function using antibody‐dependent cytotoxicity assays with L929 cells or thyroid‐antigen‐coated chick red cells, or (iii) monocyte‐dependent cytotoxin‐mediated killing of L929 cells. Enhanced cytotoxicity was found with 1 mmol/l MMI in some of these assays but this was not consistent since it occurred only in certain individual cultures. Since we have shown previously that 100 μmol/l MMI inhibits oxygen radical generation, the present results add to the evidence that these radicals are not directly involved in cell‐mediated cytotoxicity and do not support the concept that antithyroid drugs have a significant effect on antibody‐dependent cell‐mediated cytotoxicity in GRAVES' disease.
BIOACTIVE FORMS OF SERUM LACTOGENS: EFFECTS OF TREATMENT OF PROLACTINOMA PATIENTS WITH BROMOCRIPTINE
Authors: RENNIE P. S. , PRIOR J. C. , BRUCHOVSKY N. , GOUT P. W.
Published: March 2008

An in vitro bioassay for lactogenic hormones, based on the specific mitogenic effects of lactogens on cultured Nb2 node rat lymphoma cells, was used to measure the levels of lactogens in whole serum and in fractionated serum samples from three patients with prolactin (PRL) secreting pituitary adenomas. Under basal conditions, after pituitary stimulation, and following treatment with bromocriptine which greatly decreased the serum PRL levels, the bioassay (BA) results closely paralleled fluctuations in the sum of radioimmunoassay (RIA) estimates of serum PRL and growth hormone concentrations. The extreme sensitivity (10 pg/ml) of the BA facilitated measurement of PRL in fractions obtained after Sephadex G‐100 chromatography of only 0·1 to 0·3 ml of sera from both untreated and bromocriptine‐treated prolactinoma patients. In both types of samples, similar heterogenous patterns of bioactive PRL were observed, although most of the recovered activity appeared to be due to monomeric PRL. BA and RIA of fractions obtained after DEAE cellulose chromatography of sera from untreated prolactinoma patients revealed two PRL peaks, the first one containing 75% of the activity. Therapy with bromocriptine led to a reduction in the total serum PRL activity and, in particular, in the activity of the second peak.
ALTERATION IN THE NOCTURNAL PULSATILE RELEASE OF GH DURING THE INDUCTION OF PUBERTY USING LOW DOSE PULSATILE LHRH: A CASE REPORT
Authors: STANHOPE R. , PRINGLE P. J. , BROOK C. G. D.
Published: March 2008

A 16.4 year old girl with idiopathic hypogonadotrophic hypogonadism had successful induction of puberty by administration of low dose LHRH by pulsatile subcutaneous infusion at night. Peak serum GH was increased with therapy but more importantly, pulsatile secretion of GH which was minimal before treatment, was restored after one week of LHRH treatment.
PARATHYROID HORMONE‐LIKE BIOACTIVITY IN A PATIENT WITH SEVERE OSTEITIS FIBROSA CYSTICA DUE TO MALIGNANCY: RENOTROPIC ACTIONS OF A TUMOUR EXTRACT AS ASSESSED BY CYTOCHEMICAL BIOASSAY
Authors: LOVERIDGE N. , KENT G. N. , HEATH D. A. , JONES E. L.
Published: March 2008

A patient is described with malignancy, hypercalcaemia and radiological evidence of severe parathyroid bone disease but undetectable concentrations of circulating immunoreactive PTH. Autopsy showed the tumour to be a metastatic bronchial carcinoid with no evidence of primary parathyroid disease. Extracts of the tumour had no PTH immunoreactivity but had high concentrations of a substance with identical activity to PTH in a cytochemical bioassay. The biological activity of the extract was not inhibited by PTH antibodies but was inhibited by an antagonist to PTH bioactivity.
PITUITARY CUSHING'S DISEASE ARISING FROM A PREVIOUSLY NON‐FUNCTIONAL CORTICOTROPHIC CHROMOPHOBE ADENOMA
Authors: VAUGHAN N. J. A. , LAROCHE C. M. , GOODMAN I. , DAVIES M. J. , JENKINS J. S.
Published: March 2008

Severe pituitary Cushing's disease of sudden onset after 18 years of unsuccessful treatment for a previously non‐functioning chromophobe adenoma is described in a middle‐aged woman. Initial presentation with symptoms of optic nerve compression had been preceded by two years of amenorrhoea. Transfrontal resection of a chromophobe adenoma followed by radiotherapy, performed both at this time and again after a recurrence eight years later, failed to eradicate the tumour. Ten more years elapsed before she rapidly developed florid features of Cushing's syndrome. Plasma ACTH levels were markedly elevated and were only partially reduced by further transfrontal surgery, complete removal of the tumour proving impossible. Subsequent bilateral adrenalcctomy was performed to control her hypercortisolism and a course of cytotoxic chemotherapy was administered in an attempt to treat the tumour recurrence. Immunocyto‐chemical staining of tumour obtained at surgery demonstrated ACTH immunoreactivity both before and after the development of Cushing's disease. Although silent corticotrophic adenomas of the human pituitary, including chromophobic tumours, have been previously described, this is the first report of such a tumour becoming functional, sufficient to cause clinically evident Cushing's disease.
T‐CELL SENSITIZATION TO AUTOLOGOUS THYROID CELLS AND NORMAL NON‐SPECIFIC SUPPRESSOR T‐CELL FUNCTION IN GRAVES' DISEASE
Authors: DAVIES T. F. , BERMAS B. , PLATZER M. , ROMAN S. H.
Published: March 2008

We have employed a syngeneic system utilizing thyroid cell monolayers initiated following thyroid surgery co‐cultured with autologous T cells to demonstrate T cell autosensitization in patients with GRAVES' disease. Antigen‐induced blasto‐genesis was monitored using 24 h [3H]thymidine uptake. Control experiments with 5 d cultured normal human thyroid cells from tissue around benign adenomata showed no evidence of syngeneic T cell autosensitization. Human thyroid cells alone were unable to incorporate [3H]thymidine in the presence of bTSH. In three of four experiments with GRAVES' thyroid cells there was significant induction of autologous T cell blastogenesis with a mean stimulation index of 220%. In parallel experiments we explored the non‐specific helper and suppressor T cell function of these and similar patients with GRAVES' disease. In normal controls (n= 6) increasing numbers of T cells added to a constant number of B cells (consisting of a T cell depleted peripheral mononuclear cell preparation) showed a marked helper effect measured as increasing IgG secretion. As the ratio of T:B cells increased above 4:1 there was a suppression of IgG secretion. One of two hyperthyroid GRAVES' patients was observed to have deficient T cell function as demonstrated by lack of IgG suppression. The remaining five patients (all but one of whom were euthyroid at the time of testing) had results similar to the controls indicating normal suppressor T cell function in this disease. Such data showed that patients with GRAVES' disease possessed circulating T cells which exhibited autosensitization to syngeneic thyroid cell surface antigens, a phenomenon not demonstrable in control individuals. Furthermore, this specific T cell autosensitization did not interfere with non‐specific T cell function as judged by its influence on IgG secretion.
COMPARATIVE STUDY OF NURSING MOTHERS IN AFRICA (ZAIRE) AND IN EUROPE (SWEDEN): BREASTFEEDING BEHAVIOUR, NUTRITIONAL STATUS, LACTATIONAL HYPERPROLACTINAEMIA AND STATUS OF THE MENSTRUAL CYCLE
Authors: HENNART P. , HOFVANDER Y. , VIS H. , ROBYN C.
Published: March 2008

A total of 1036 nursing mothers were investigated for their nursing behaviour, status of nutrition and menstrual cycle, serum prolactin and progesterone; 61 in Sweden, 457 in an urban area of Zaïre (Bukavu, Kivu) and 518 in a rural area of the same region (Kabare, Kivu). Lactational hyperprolactinaemia is influenced by the frequency but not by the duration of suckling. The return of luteinization of follicles, but not that of menstrual bleeding, was inversely related to the degree of lactational hyperprolactinaemia. Significant luteinization took place in only some 10% of the mothers during the first three months of lactation in Sweden and within the first year in Zaïre. In these mothers with luteinized follicles the average progesterone was only slightly above 1·0 ng/ml indicating poor luteinization. Lactational hyperprolactinaemia, the return of menstruation and luteinization during lactation were not related to the nutritional status as evaluated by the body weight indices and serum albumin. However, suckling and hyperprolactinaemia do not appear to be the only factors involved in the control of fertility during lactation. When serum prolactin levels were equally low, i.e. below 500 μU/ml, twice the number of lactating mothers with signs of luteinization were found in the urban than in the rural population of Zaïre.
THE EFFECT OF A NEW ERGOLINE DERIVATIVE, CU 32‐085, IN THE TREATMENT OF ACROMEGALY. A CONTROLLED STUDY
Authors: ESKILDSEN P. C. , HOMMEL E. , BUCHHAVE J.
Published: March 2008

The effect of a new dopamine agonist, CU 32‐085 (8α‐amino‐ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0·5 mg CU 32‐085) trial and a long‐term crossover trial with 3 month periods (placebo/CU 32‐085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH‐ and LHRH‐tests) before and after each 3 month period. Nine patients completed this long‐term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long‐term treatment, was significantly inhibited by CU 32‐085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long‐term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long‐term treatment, which forced two to interrupt the trial. We conclude that CU 32‐085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.
FOLLOW‐UP OF PROLACTIN LEVELS IN LONG‐TERM OESTROGEN‐TREATED MALE‐TO‐FEMALE TRANSSEXUALS WITH REGARD TO PROLACTINOMA INDUCTION
Authors: GOOREN L. J. G. , HARMSEN‐LOUMAN W. , VAN KESSEL H.
Published: March 2008

As in laboratory animals, long‐term oestrogen treatment in the human male might induce prolactinomas. We here report on PRL levels in 142 male‐to‐female transsexuals, treated with 100 mg cyproterone acetate and 100 μg ethinyloestradiol per day for 6–108 months (median 52). PRL levels varied markedly between individuals. No relation with age and length of treatment period was found. In 42 subjects in whom PRL levels were followed serially, a slight fall was measured after 12–15 months of treatment. Galactorrhoea, present in 10 of 142 subjects, was unrelated to PRL levels. In 34 subjects in whom PRL levels were measured during treatment and 3 weeks after withdrawal, PRL levels fell significantly. Dopamine in doses of 0·1 μg/kg/min and 1·0 μg/kg/min was administered to six subjects with PRL levels > 1000 mU/l and six subjects with PRL levels < 500 mU/l. No difference in the percentage decrease of PRL levels was found between these two groups. However, administration of monoiodotyrosine, an inhibitor of central dopamine synthesis, to these two groups, induced a significantly smaller release of PRL (expressed as percentage change) in subjects with PRL > 1000 mU/l than in those with PRL < 500 mU/l possibly indicating a loss of control of central dopaminergic regulation. These findings suggest that the risk of inducing prolactinomas through cross‐gender hormone treatment is likely to be small.
ENDOCRINE EFFECTS OF LOW DOSE AMINOGLUTETHIMIDE AS AN AROMATASE INHIBITOR IN THE TREATMENT OF BREAST CANCER
Authors: STUART‐HARRIS R. , DOWSETT M. , D'SOUZA A. , DONALDSON A. , HARRIS A. L. , JEFFCOATE S. L. , SMITH I. E.
Published: March 2008

The endocrine effects of low dose (62·5 mg, twice a day) aminoglutethimide (AG), without hydrocortisone (HC), escalating at monthly intervals to a conventional dose of AG (500 mg twice a day) combined with HC, were studied in 33 postmenopausal breast cancer patients. Pretreatment serum concentrations of oestrone (E1) and oestradiol (E2) were significantly suppressed by 62·5 mg of AG twice a day. Although further suppression of E1 appeared to occur with 125 mg of AG twice a day, this was not statistically significant. For E1 and E2, higher doses of AG or combined AG and HC failed to cause further significant suppression compared with that obtained at 125 mg of AG twice a day. Significant rises in serum androstenedione were found with all doses of AG alone, although pretreatment concentrations of androstenedione were not significantly altered by combined AG and HC treatment. Mean pretreatment concentrations of dehydroepiandrosterone sulphate (DHA‐S) were significantly suppressed by 62·5 mg of AG twice a day and further marked suppression occurred on combined AG and HC therapy. Serum cortisol, aldosterone and plasma ACTH concentrations showed no significant alterations throughout treatment. Aminoglutethimide is as effective at 125 mg twice a day without HC in its suppression of oestrogen levels as at 500 mg twice a day with HC, and its use in this form warrants clinical evaluation.
THE ASSAY FOR THYROID STIMULATING IMMUNOGLOBULINS USING CULTURED HUMAN THYROID CELLS
Authors: GRANT S. J. B. , LUTTRELL B. M. , HALES I. B.
Published: March 2008

Recent reports have shown that thyroid‐stimulating immunoglobulins (TSI) may be detected by measuring cyclic AMP increases in cultures of isolated thyroid cells in response to added patient immunoglobulins (Ig). We have compared the frequency that TSI may be detected in the Ig fraction of 114 sera from 112 patients with a variety of thyroid disorders, to the presence of thyrotrophin binding inhibitor Ig (TBII). Whereas the sera of 46 out of 48 (95·6%) patients with untreated thyrotoxic Graves' disease had detectable TSI, only 26 out of 48 (54·2%) had detectable TBII. We did not find any significant correlation between TSI and TBII for these patients but there was a significant correlation between TSI and both serum T3 (r=+0·55, P < 0·01) and T4 (r=+0·50, P < 0·01). Twelve patients were studied at the time of relapse of thyrotoxicosis due to Graves' disease. All sera contained detectable TSI whereas only one contained detectable TBII. Of the sera from 20 patients in remission after antithyroid drug therapy three were positive for TSI. One of these samples as well as two others had detectable TBII. The two samples with TBII in the absence of TSI came from patients who had developed hypothyroidism. TSI were detected in the serum of one out of nine patients with Hashimoto's thyroiditis but not in the sera of 20 other patients with a variety of non‐autoimmune thyroid disorders including five patients with thyrotoxicosis not due to Graves' disease. However TSI was found in the sera of three out of five patients with exophthalmos and no history of hyperthyroidism. In conclusion using this technique, TSI can be detected in the majority of sera from thyrotoxic Graves' disease patients. It offers information more relevant to the study and management of thyrotoxicosis than is provided by the more widely used TBII assay.
FREE THYROID HORMONE LEVELS AND TSH RESPONSE TO TRH IN PATIENTS WITH AUTONOMOUS THYROID ADENOMATA AND NORMAL T3 AND T4
Authors: LERRO S. , LOSA M. , TRISORIO M. T. , LIUZZI A.
Published: March 2008

Free thyroid hormone levels together with basal and TRH stimulated TSH levels, have been determined in 50 patients with autonomous thyroid adenomata, who had normal serum total T3 and T4 values. Similar measurements were made in 33 healthy subjects. FT3 and FT4 plasma levels were significantly higher (P < 0·01 and P < 0·05 respectively), and basal and TRH stimulated TSH were significantly lower (P < 0·05 and P < 0·001 respectively) in the patients than in the controls. The TSH response to TRH was decreased in spite of normal free thyroid hormones in 25 patients and in a further ten both the ΔTSH after TRH and the free fractions were normal. Eighteen patients were studied over periods from 4‐37 months by repeating thyroid hormone levels and TRH tests. In six of them a change of these parameters toward toxicity was observed. The data obtained in the longitudinal study indicate that the values of free thyroid hormones and the result of the TRH test obtained by a single determination may represent different steps in the evolution of autonomous thyroid adenomata rather than a distinct pathophysiological condition.
AN ANALYSIS OF THYROTROPHIN RECEPTOR BINDING AND THYROID STIMULATING ACTIVITIES IN A SERIES OF Graves' SERA
Authors: CREAGH FIONUALA , TEECE MICHELLE , WILLIAMS SUSAN , DIDCOTE SUZANNE , PERKINS W. , HASHIM F. , SMITH B. REES
Published: March 2008

Improved receptor and bioassays have been used to compare TSH receptor binding and thyroid stimulating activities in unextracted sera from 110 patients with Graves' disease. The two parameters showed a significant correlation (r= 0·65; P < 0·001) although there were some clear discrepancies. Dose‐response studies in 17 sera showed that both receptor binding and thyroid stimulating responses always increased with increasing doses of serum. In patients who were in relapse or remission following antithyroid drug treatment, the results of both bio‐ and receptor assays correlated well with disease activity with only one clear discrepancy which could have been attributable to the coexistence of autoimmune stimulation and destruction of the thyroid.
INCREASED FREQUENCY OF GOITRE IN EPILEPTIC PATIENTS ON LONG‐TERM PHENYTOIN OR CARBAMAZEPINE TREATMENT
Authors: HEGEDÜS L. , HANSEN J. M. , LÜHDORF K. , PERRILD H. , FELDT‐RASMUSSEN ULLA , KAMPMANN J. P.
Published: March 2008

Thyroid function, the clinical occurrence of goitre and ultrasonically determined thyroid gland volume were investigated in 23 patients with phenytoin‐ and 28 patients with carbamazepine‐treated convulsive disorders and compared with matched healthy controls. In the phenytoin treated group median thyroid volume was 26 ml (range 14–57 ml) compared to 17 ml (range 8–41 ml) in the controls (P < 0·01). Ten patients and four controls had a goitre (NS). Median serum T4 and FT4I levels were reduced, serum TSH level increased and serum T3, T3RU, FT3I and thyroglobulin levels unaltered compared with the controls. In the carbamazepine treated group median thyroid volume was 25 ml (range 13‐66 ml) compared to 16 ml (range 9‐44 ml) in the controls (P < 0·01). Thirteen patients and three controls had a goitre (P < 0·02). Median serum T4, FT4I and FT3I levels were reduced, serum thyroglobulin increased and serum T3, T3RU and TSH levels unaltered compared with the controls. The increase in thyroid size is probably a compensatory mechanism due to the low free thyroid hormones in serum caused by an increased hepatic degradation of thyroid hormones by phenytoin and carbamazepine.
IDENTIFICATION AND CHARACTERIZATION OF THE HUMAN HEPATIC ANDROGEN RECEPTOR
Authors: BANNISTER P. , SHERIDAN P. , LOSOWSKY M. S.
Published: March 2008

Human liver contains components in both cytosol and nucleosol which bind the synthetic testosterone derivative, mibolerone, with a high affinity, moderate capacity and a high specificity for androgens. Gel filtration chromatography shows two binding components, a high molecular weight component (mol wt. 250 000) present in cytosol alone and a low molecular weight component (mol wt. 75 000) present in cytosol and nucleosol. Human liver contains the classical androgen receptor.
CATECHOLAMINE, VASOACTIVE INTESTINAL PEPTIDE AND THYROTROPHIN‐DEPENDENT cAMP LEVELS DISPLAY A DIFFERENT SENSITIVITY TO IODOTHYRONINES IN BOTH NORMAL AND PATHOLOGICAL HUMAN THYROID CELLS IN CULTURE
Authors: BRANDI MARIA LUISA , ZONEFRATI R. , ROTELLA C. M. , TOCCAFONDI R.
Published: March 2008

As the interactions of iodothyronines on adrenergic and vipergic receptors are not clear, the effect of exogenous T3 and T4 on catecholamine‐ and VIP‐induced cAMP accumulation in human normal thyroid cells after eight days of primary culture has been investigated. To evaluate the effect of endogenous iodothyronines, the response of the adenylate cyclase system to isoprenaline, adrenaline, VIP, and TSH was studied during a 10 d period. T3 and T4 were unable to modify the catecholamine‐ and VIP‐induced cAMP accumulation in human normal thyroid cells after 6–8 days of culture, while the response to TSH was significantly inhibited. In cells cultured from thyrotoxic tissue, the response of the adenylate cyclase system to catecholamines and VIP, during a 10 d primary culture, showed a behaviour similar to controls. TSH responsiveness was negligible up to the fourth day of culture, while in normal cells a response to all the agonists was present from the beginning. In view of the lack of effect of iodothyronines on catecholamine‐ and VIP‐induced cAMP accumulation, and of the superimposable behaviour of the response to catecholamines and VIP in normal and hyperthyroid cells during the first days of culture, we can conclude that iodothyronines do not directly modify the response of the adenylate cyclase system to adrenergic and vipergic stimulation in human thyroid follicular cells. The lack of responsiveness to TSH of cells obtained from hyperthyroid tissue during the first 4 d of culture, associated with normal responsiveness to catecholamines and VIP, points to a possible involvement of biogenic amines and neuropeptides in sustaining such hyperthyroid states.
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA II. INTESTINAL CALCIUM ABSORPTION AND VITAMIN D METABOLISM
Authors: KRISTIANSEN J. H. , RØDBRO P. , CHRISTIANSEN C. , MORTENSEN J. BRØCHNER , CARL J.
Published: March 2008

We compared intestinal calcium absorption, measured by a single isotope technique, and serum concentrations of vitamin D metabolites in ten patients with familial hypocalciuric hypercalcaemia (FHH) and ten age‐ and sex‐matched healthy controls. Our results showed no significant differences in intestinal calcium absorption or in serum concentrations of vitamin D metabolites. There was a significant correlation between serum concentrations of PTH, measured with one of our assays, and 1,25(OH)2D. We conclude that neither increased intestinal calcium absorption nor altered vitamin D metabolism plays a part in the hypercalcaemia of FHH.
SPONTANEOUS GONADOTROPHIN PULSATILITY AND OVARIAN MORPHOLOGY IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY TREATED WITH CYPROTERONE ACETATE
Authors: STANHOPE R. , PRINGLE P. J. , ADAMS J. , JEFFCOATE S. L. , BROOK C. G. D.
Published: March 2008

We have studied four girls with central precocious puberty treated with cyproterone acetate for a mean of 3·6 years (range 1·5–6·3 years). Pelvic ultrasound assessment demonstrated suppression of the ovarian morphology of central precocious puberty despite the presence of spontaneous pulsatile gonadotrophin secretion at night. We suggest that the previously reported effects on gonadotrophin secretion induced by cyproterone acetate therapy, administered in recommended doses, are minor and that the predominant effect of cyproterone acetate in the treatment of girls with central precocious puberty is direct inhibition of ovarian steroidogenesis.
FACTORS AFFECTING THE SECRETION OF 18‐HYDROXYCORTISOL, A NOVEL STEROID OF RELEVANCE TO CONN'S SYNDROME
Authors: CORRIE J. E. T. , EDWARDS C. R. W. , JONES D. B. , PADFIELD P. L. , BUDD P. S.
Published: March 2008

A recently developed radioimmunoassay for direct measurement of 18‐hydroxycortisol (18‐OH‐F) in plasma and urine has been used to study the physiology of this newly described steroid in normal subjects. Plasma levels of 18‐OH‐F show a circadian variation similar to that of cortisol and are increased and suppressed by administration of ACTH and dexamethasone respectively. A clear increase was observed in response to sodium restriction but despite this, angiotensin II infusion failed to cause a rise in 18‐OH‐F levels and a possible explanation is discussed. The results are interpreted in terms of a proposed biosynthetic pathway involving 18‐hydroxylation of cortisol during a second passage through the adrenal gland.
GONADOTROPHIN CONTROL OF FOLLICULAR DEVELOPMENT
Authors: ABDULWAHID N. A. , ADAMS J. , VAN DER SPUY Z. M. , JACOBS H. S
Published: March 2008

In order to investigate the endocrine requirements for induction of follicle maturation, ovulation and luteal function we have measured plasma LH and FSH concentrations in 109 cycles induced by treatment with LHRH in 25 women with amenorrhoea of diverse aetiology. The major clinical and endocrine subgroupings were polycystic ovarian disease (PCO), Kallmann's syndrome, weight related amenorrhoea and hyperprolactinaemia. By analysis of variance of the LH and FSH concentrations obtained three times per week in the follicular phase in 77 ovulatory cycles (including 24 conception cycles), we found that in women with PCO the mean LH concentration was 19·5 IU/1. In hyperprolactinaemia and secondary amenorrhoea of non‐specific aetiology the mean LH concentration was 11·6 IU/1 and in patients with hypogonadotrophic hypogonadism and weight‐related amenorrhoea it was 7·2 IU/1. These mean LH concentrations were significantly different from each other (P < 0·001). We speculate that the high LH concentrations in the follicular phase may impair the final stages of oocyte maturation and so contribute to the infertility of these patients. FSH concentrations in the follicular phase were lower in patients with hypogonadotrophic hypogonadism and weight‐related amenorrhoea than in other groups. Although the differences were statistically significant (P < 0·001) the difference was small (mean FSH in hypogonadotrophic hypogonadism and weight‐related amenorrhoea 4·3 IU/1 vs 6·3 IU/1 in the others) and of uncertain biological significance. During the luteal phase, no differences between any of the groups in LH and FSH concentrations were found.
GLUCAGON‐STIMULATED PLASMA C‐PEPTIDE AND INSULIN LEVELS IN ACTIVE AND NON‐ACTIVE ACROMEGALICS
Authors: ROELFSEMA F. , FRÖLICH M. , GEELHOED‐DUYVESTIJN P. H. L. M. , KRUSEMAN A. C. NIEUWENHUIJZEN , LOOIJ B. J.
Published: March 2008

The glucagon‐stimulated insulin and C‐peptide release in patients with active acromegaly, cured acromegalic patients and healthy controls were studied. There was an elevation of the fasting insulin levels in active acromegalics and the fasting C‐peptide levels in both patient groups. After i.v. injection of glucagon the insulin and C‐peptide levels increased. The highest levels were recorded in active acromegalics, but cured patients also had higher levels than the control group. The insulin/C‐peptide ratio was increased in active acromegalics in comparison with that found for inactive acromegalics and normal controls. In addition, the plasma half‐lives (T1/2) of endogenous insulin and C‐peptide were measured. It was found that the T1/2 for insulin was increased in active acromegalics only. From this study we conclude that even when the treatment of acromegaly is effective insulin and C‐peptide secretion do not normalize due, probably, to increased synthesis and release upon stimulation of the pancreatic β‐cells. In active acromegaly the removal of insulin is probably also reduced.
CONCOMITANT SECRETION OF SCHWANGERSCHAFTSPROTEIN 1 AND HUMAN CHORIONIC GONADOTROPHIN FOLLOWING CONCEPTION
Authors: AHMED A.‐G. , KLOPPER A.
Published: March 2008

Daily measurements of serum oestradiol, progesterone, Schwangerschaftspro‐tein 1 (SP1) and hCG were made in 13 menstrual cycles during which conception occurred. The assays were continued until 21 d after ovulation. SP1 was detected in maternal blood 8–14 d after ovulation and hCG 9–13 d after ovulation. We conclude that these two proteins are secreted simultaneously but independently by the syncytiotrophoblast.
PATHOGENESIS OF HYPERCALCAEMIA OF MALIGNANCY
Authors: MUNDY G. R.
Published: March 2008

The hypercalcaemia of malignancy is multi‐factorial, even within individual tumours. In most cases, hypercalcaemia is due to a combination of increased bone resorption associated with uecreased renal capacity to excrete the increased extracellular fluid calcium. In solid tumours such as carcinoma of the lung, tumour‐derived growth factors are probably primarily responsible for the increased bone resorption, and a separate family of factors which interact with some parathyroid hormone (PTH) receptors cause increased renal tubular calcium reabsorption. PTH production by non‐parathyroid tumours rarely if ever occurs. In contrast, haematological malignancies such as myeloma and T‐cell lymphomas produce locally acting bone resorbing lymphokines in excessive amounts. Some T‐cell lymphomas in addition have the capacity to metabolize 25‐hydroxyvitamin D to 1,25‐dihydroxyvitamin D. In myeloma, impaired glomerular filtration frequently contributes to the pathogenesis of hypercalcaemia by impairing renal compensatory mechanisms for maintaining normal serum calcium concentrations in the presence of increased bone resorption.
INTERACTION BETWEEN GROWTH HORMONE RELEASING FACTOR (GRF) AND SOMATOSTATIN ANALOGUE (SMS 201–995) IN NORMAL SUBJECTS
Authors: LOSA M. , MÜLLER O. A. , SOBIESZCZYK S. , VON WERDER K.
Published: March 2008

Continuous infusion or pulsatile administration of growth hormone releasing factor leads to decreasing GH levels and GH responses in normal subjects. We have given 50 μg GRF 1–44 i. v. four times in 2‐hourly intervals to five normal subjects. After 1 week the same protocol was repeated after s. c. administration of 50 μg of the synthetic octapeptide somatostatin (SMS 201–995). The GH response to the same GRF doses was higher after the initial GRF pulse and blunted to the following GRF pulses (pulse I: 37·0±11·2 ng/ml; Pulse II: 5·3 ± 1·2 ng/ml; pulse III: 5·9 ± 2·5 ng/ml; pulse IV: 5·9 ± 3·2 ng/ml; mean ± SE). When SMS 201–995 was given 60 min before pulsatile GRF administration, the GH secretion pattern was reversed (pulse I: 2·4 ± 0·7 ng/ml; pulse II: 2·0 ± 0·9 ng/ml; pulse III: 4·4 ± 2·1 ng/ml; pulse IV: 11·4 ± 3·6 ng/ml). Radioimmunoas‐sayable GRF levels were not different before and after administration of SMS 201–995. The half time of disappearance was 8·6 ± 0·4 min before and 8·0 ± 0·5 min after SMS 201–995. Basal thyrotrophin and insulin levels, which remained constant over the 8 h period with GRF only, decreased significantly after SMS 201–995 administration. These findings are compatible with a limited releasable GH pool which is exhausted by chronic GRF stimulation but can be conserved by prior administration of the somatostatin analogue. Thus, when somatostatin bioactivity tapers off, there is recovery of GRF‐stimulated GH secretion.
DRAMATIC AND RAPID SHRINKAGE OF A MASSIVE INVASIVE PROLACTINOMA WITH BROMOCRIPTINE: A CASE REPORT
Authors: CLAYTON R. N. , WEBB J. , HEATH D. A. , DUNN P. J. S. , ROLFE E. B. , HOCKLEY A. D.
Published: March 2008

Shrinkage of a massive, highly invasive, longstanding (probably 40 years) prolactin‐secreting pituitary tumour is described in which tumour volume was reduced by 40% 8 d after beginning bromocriptine treatment. After 4 months of treatment the tumour was only 11% of the pretreatment volume and by 8 months it was further reduced in size being confined to the pituitary fossa, which was partially empty. Reduction in tumour volume was accompanied by a gradual reduction in serum prolactin concentrations to normal values at 4 months. Between 4 and 18 months serum prolactin has remained normal on 5 mg of bromocriptine daily. Visual function improved within 48 h of starting bromocriptine and was almost normal by 6 d. CSF rhinorrhoea developed as the tumour shrank and was successfully managed with the relatively minor procedure of a diversionary lumbo‐peritoneal shunt. Bromocriptine should be considered as the initial treatment of choice for massive invasive prolactinomas because of the significant risk of morbidity from neurosurgical treatment.
COMPARISON OF THE CLINICAL ACTIVITY OF MESULERGINE AND PERGOLIDE IN THE TREATMENT OF HYPERPROLACTINAEMIA
Authors: GROSSMAN A. , BOULOUX P‐M. G. , LONERAGAN R. , REES LESLEY H. , WASS J. A. H. , BESSER G. M.
Published: March 2008

The clinical activity of the new ergoline, mesulergine, was compared to pergolide in the treatment of hyperprolactinaemia. Mesulergine was given to 22 women and five men with hyperprolactinaemia. Serum prolactin was substantially lowered in 10 women; two subsequently conceived and completed normal pregnancies. Twelve women stopped treatment due to side‐effects, usually nausea and vomiting, or inadequate responses. The side‐effects were generally similar to those on bromocriptine; in one patient they were better and in four worse than on bromocriptine. The male patients were more tolerant of mesulergine, and substantial falls in serum prolactin were seen with evidence of tumour shrinkage. Twenty‐seven women with hyperprolactinaemia received pergolide; serum prolactin was lowered or normalized in 16. Side‐effects necessitating cessation of treatment were similar to those seen with bromocriptine. Nevertheless, four women tolerated pergolide better than bromocriptine and two women adequately treated with mesulergine had previously been intolerant of pergolide. We conclude that both pergolide and mesulergine may be useful and effective drugs in the treatment of hyperprolactinaemia as alternatives to bromocriptine.
COMPUTED TOMOGRAPHY OF THE PITUITARY FOSSA IN PRIMARY HYPOTHYROIDISM. EFFECT OF THYROXINE TREATMENT
Authors: KATEVUO K. , VÄLIMÄKI M. , KETONEN LEENA , LAMBERG B.‐A. , PELKONEN R.
Published: March 2008

Computed tomography of the pituitary fossa was performed in 12 patients with primary hypothyroidism before and after thyroxine treatment. In three, herniation of the diaphragma sellae precluded accurate measurement of the density of the hypophysis. Eight of the remaining patients showed abnormally increased density of the pituitary gland after intravenous injection of contrast substance which was significantly correlated with the serum TSH‐level (r= 0·913, P<0·001). After thyroxine treatment the intrasellar density decreased substantially in all but one. We suggest that the observed contrast enhancement reflects increased pituitary circulation associated with the augmented function of TSH‐producing cells in response to thyroid hormone deficiency.
EFFECT OF NIVAZOL ON ACTH SECRETION BY HUMAN PITUITARY CORTICOTROPHIC TUMOURS IN CELL CULTURE
Authors: ADAMS E. F. , ASHBY M. J. , BURRIN J. , YEO T. H. , DRUCKER R. , STRINGER K. , MASHITER K.
Published: March 2008

The effects of nivazol, a novel steroid which lacks glucocorticoid activity, on ACTH secretion by cell cultures of human pituitary corticotrophic tumours has been investigated. Nivazol (0·002‐20 μmol/1) inhibited ACTH secretion by 50–80%, after 4 and 24 h of incubation. (Trilostane (0·3–30 μmol/1) did not affect basal or stimulated ACTH secretion.) The potency of nivazol was comparable with that of hydrocortisone, and less than dexamethasone. The stimulatory effects of oCRF and AVP were reduced or completely blocked by nivazol in a similar manner to that previously described for hydrocortisone. It is concluded that nivazol may be of benefit in the direct treatment of Cushing's disease, particularly since it lacks glucocorticoid activity.