bluuebunny/crossref_metadata_2025_split huggingface dataset:
T LYMPHOCYTE SENSITIZATION AND SUPPRESSOR T LYMPHOCYTE DEFECT IN PATIENTS LONG AFTER TREATMENT FOR GRAVES’DISEASE
Authors: HOW JACQUES , TOPLISS DUNCAN J. , STRAKOSCH CHRISTOPHER , LEWIS MARK , ROW VAS V. , VOLPÉ ROBERT 
Published: March 2008

SUMMARYCirculating thyroid autoantibodies, T lymphocyte sensitization and suppressor T lymphocyte function were examined in thirty‐nine patients who had been treated for a mean of 10±2 years previously for hyperthyroid Graves’disease. Nineteen had been treated with radioactive iodine (131I), two with subtotal thyroidectomy, and eighteen were in long‐term remission after previous propylthiouracil (PTU) therapy. Sensitization of T lymphocytes to human thyroid antigen was studied by means of a modified migration inhibition factor test, using T lymphocyte enriched preparations, and antigen‐specific suppressor T lymphocyte function was assessed by the ability of T lymphocytes to suppress the production of migration inhibition factor by sensitized T lymphocytes of patients with active Graves’disease in response to human thyroid antigen. Despite effective correction of the hyperthyroid state in all patients, T lymphocyte sensitization to human thyroid antigen was still demonstrable in twelve of nineteen patients treated with 131I (63%), in nine of eighteen patients in remission after PTU treatment (50%) and in one of two patients after thyroidectomy. All those showing such sensitization also manifested a suppressor T lymphocyte defect. In three of the patients (all after 131I therapy) showing no such sensitization, there was nevertheless evidence of a suppressor T lymphocyte defect. On the other hand, thirteen patients (nine in the post‐PTU group, four in the post‐131I group) showed evidence of complete immunological remission. There was no correlation between the abnormal immunological findings and the number of years after treatment of the hyperthyroidism.The present study indicates that T lymphocyte sensitization and the underlying defect in suppressor T lymphocyte function are persistent in the majority of patients with Graves’disease years after 131I destructive therapy, and occur independently of the hyperthyroid state. These findings are consistent with the concept that an inherited defect in suppressor T lymphocyte function plays a primary role in the pathogenesis of Graves’disease. In addition, long‐term remissions following non‐ablative antithyroid drug therapy appear to be of two types, namely, those in which immunoregulation has been restored, and those with remission in spite of a continuingly active immunological process.
THYROID STATUS IN VARIOUS DEGREES OF PROTEIN–CALORIE MALNUTRITION IN CHILDREN
Authors: ONUORA C. , MAHARAJAN G. , SINGH AJIT , ETTA K. M. 
Published: March 2008

SUMMARYThe thyroid functional parameters of 102 children with protein–calorie malnutrition (PCM) classified as undernourished, marasmic, kwashiorkor and marasmic–kwashiorkor were studied by measuring the serum T4, T3, T3 percentage uptake (T3%UT), free thyroxine index (FTI), and (in a few subjects) TSH. Total plasma proteins, albumin and globulin were also estimated. T4 was increased markedly in the undernourished children and significantly decreased in kwashiorkor and marasmic–kwashiorkor groups. There was a consistent and significant fall in T3 levels of all PCM children. From normal values, the fall in T3 levels was progressive in the order of undernourished, marasmic, kwashiorkor and the marasmic–kwashiorkor states. The T3%UT was increased above normal in the marasmic, kwashiorkor and marasmic–kwashiorkor conditions. The FTI decreased somewhat in marasmus and kwashiorkor groups and was very low in marasmic–kwashiorkor. Total protein and albumin levels were above normal in the undernourished but became markedly depressed in the marasmic–kwashiorkor children. The changes in the levels of both T4 and T3 in our observations are well correlated with the levels of plasma proteins in the undernourished, marasmic and kwashiorkor states but not in the marasmic–kwashiorkor group.
EFFECT OF METOCLOPRAMIDE ON THE SECRETION OF ALDOSTERONE AND OTHER ADRENOCORTICAL STEROIDS
Authors: NAGAHAMA S. , FUJIMAKI M. , KAWABE H. , NAKAMURA R. , SAITO I. , SARUTA T. 
Published: March 2008

SUMMARYThe aim of this study was to determine the effect of metoclopramide, a dopamine antagonist, on the secretion of aldosterone and other adrenocortical steroids in normal subjects. An i.v. bolus injection of 10 mg of metoclopramide significantly increased the plasma PRL, plasma aldosterone and 18‐hydroxy‐corticosterone, but the plasma renin activity, plasma deoxycorticosterone, corticosterone and cortisol remained unchanged. The changes in plasma aldosterone induced by metoclopramide were significantly correlated with the basal levels of plasma aldosterone and renin activity. These results suggest that the response of plasma aldosterone to metoclopramide in normal subjects is influenced by the basal activity of renin–angiotensin–aldosterone system and the late step of aldosterone synthesis is stimulated by metoclopramide.
CALCITONIN AND POSTMENOPAUSAL OSTEOPOROSIS
Authors: LEGGATE J. , FARISH ELIZABETH , FLETCHER C. D. , McINTOSH W. , HART D. M. , SOMMERVILLE J. M. 
Published: March 2008

SUMMARYFasting serum calcitonin levels were measured in 54 postmenopausal women who had for 10 years been taking part in a double blind trial to assess the effect of the synthetic oestrogen, mestranol, on postmenopausal bone loss. There were no differences in calcitonin levels between mestranol treated and placebo groups, Fifteen of the women were challenged with a calcium infusion to measure the secretory reserve of calcitonin. Oestrogen treatment did not increase the calcitonin response to calcium infusion. The three patients who exhibited the greatest responses were placebo treated. Bone density was measured by γ‐ray absorptiometry over the ten year period and the annual rate of change of bone density calculated. No correlation could be found between basal calcitonin level or calcitonin reserve and change in bone density. Our results indicate that postmenopausal osteoporosis is not caused by a deficiency of calcitonin and that the action of oestrogen therapy to prevent bone loss does not involve calcitonin.
THE EFFECT OF KETANSERIN, A SPECIFIC SEROTONIN ANTAGONIST ON THE PRL, GH, ACTH AND CORTISOL RESPONSES TO HYPOGLYCAEMIA IN NORMAL SUBJECTS
Authors: PRESCOTT R. W. G. , KENDALL‐TAYLOR P. , WEIGHTMAN D. R. , WATSON M. J. , RATCLIFFE W. A. 
Published: March 2008

SUMMARYThe role of serotonin in the prolactin, growth hormone, ACTH and cortisol responses to hypoglycaemia has been investigated in normal subjects using a selective serotonin (5HT2) receptor antagonist, ketanserin. Circulating concentrations of these hormones were measured after administration of insulin (0·1 units/kg body weight iv) to eight normal male subjects with and without simultaneous iv ketanserin (10 mg). Plasma glucose fell to less than 2·0 mmol/l in all subjects and was unaffected by ketanserin. Ketanserin induced a 50% decrease in the serum prolactin response to hypoglycaemia, 45 and 60 min after administration of insulin (increase in serum prolactin at 60 min: 1145 ± 295 mU/l without ketanserin; 558 ± 176 mU/l with ketanserin, P < 0·05). The peak ACTH response was reduced by 30% (95·3 ± 33·6 ng/l without ketanserin; 60·0 ± 22·9 ng/l with ketanserin, P < 0‐05) but the plasma cortisol response was not significantly altered. The serum growth hormone response was unaffected by serotonin blockade. These findings suggest that serotonin, probably acting through 5HT2 receptors, is involved in the stimulation of prolactin and ACTH release but not in the release of growth hormone, during insulin induced hypoglycaemia.
CIRCANNUAL RHYTHMS OF PLASMA GROWTH HORMONE, THYROTROPIN AND THYROID HORMONES IN PREPUBERTY
Authors: BELLASTELLA A. , CRISCUOLO T. , PERRONE A. MANGO L. , SINISI A. A. , FAGGIANO M. 
Published: March 2008

SUMMARYTo clarify the occurrence of circannual GH, TSH, T4 and T3 rhythms in prepuberty we have been studying, for a four year period, 150 healthy subjects, aged 6–10, by cross‐sectional design. Plasma samples were taken at 0800 h and all hormones were measured by RIA. The occurrence of any circannual rhythm was statistically investigated by the cosinor method. A significant rhythm was validated (P= 0.02) only in TSH secretion, with annual crest time in December; GH, T4, T3 did not show a circannual rhythm. Our results seem to strengthen the hypothesis that the thyroid hormones, at least before puberty, do not play an important role in the regulation of circannual TSH periodicity.
MALIGNANT FOLLICLES OF A DIFFERENTIATED THYROID CARCINOMA RELEASING IODINATED THYROGLOBULIN INTO THE LYMPHATIC VESSELS
Authors: And F. GEBEL , STUDER H. 
Published: March 2008

SUMMARYSerial sections across a follicular thyroid carcinoma taken from a 71‐year‐old woman with hyperthyroidism and grossly elevated serum thyroglobulin were examined by PAS staining and autoradiographic techniques. PAS positive material, presumably thyroglobulin, was found in the interstitial network between follicles. Some of this material was autoradiographically positive for 125I within 17 h after tracer application. Direct connections between the lumina of tumour follicles and the lymphatic vessels surrounding them were identified. These channels can explain the release of iodinated thyroglobulin by some differentiated carcinomas.
THYROID STIMULATING ANTIBODIES: AN AID TO THE STRATEGY OF TREATMENT OF GRAVES' DISEASE?
Authors: MADEC A. M. , LAURENT M. C. , LORCY Y. , GUERRIER A. M. LE , ROSTAGNAT‐STEFANUTTI A. , ORGIAZZI J. , ALLANNIC H. 
Published: March 2008

SUMMARYIn 1976 we initiated a prospective study to specify the usefulness of thyroid stimulating antibody (TSAb) determinations in predicting the outcome of post‐antithyroid drug treatment for Graves' disease. This study was carried out on 55 patients, who were either treated for six (n= 16) or 18 months (n= 39) and followed up for an additional two‐year period. TSAb was determined on whole serum in 29 patients before and at the end of treatment, and in 26 patients at the end of treatment only. These determinations were carried out using a sensitive and reproducible microassay based on cAMP accumulation in human thyroid cell cultures. Before treatment, TSAb ranging from 170 to 1529% was present in 28/29 patients and reached significantly low levels at the end of treatment whatever its duration. TSAb was undetectable in 24/55 patients at the end of treatment. 8/16 'short‐treated’ and 18/39‘long‐treated’ patients remained in remission. As expected, initial TSAb levels had no predictive value. End‐treatment TSAb values, when low (±350%) or negative did not correlate with later evolution: in these 39 patients, relapse rate was 41%. In contrast, 13/16 patients with end‐treatment TSAb ± 350% relapsed. Relapses tended to occur earlier in patients with the highest TSAb levels. TSAb determined again during follow‐up was negative in each of the 18 patients in remission, and positive in 8/10 patients at the time of relapse, whatever its level at the end of the drug course. This study confirms that only high end‐treatment TSAb levels are predictive of relapse. In the other cases, TSAb had no prognostic value. Overall, it was shown that TSAb levels appear to reflect only partially, the activity of the underlying disturbances of Graves' disease.
LACK OF THIRST, OSMORECEPTOR DYSFUNCTION, EARLY PUBERTY AND ABNORMALLY AGGRESSIVE BEHAVIOUR IN TWO BOYS
Authors: DUNGER D. B. , LIGHTMAN S. , WILLIAMS M. , PREECE M. A. , GRANT D. B. 
Published: March 2008

SUMMARYTwo unrelated boys (C.C. 13 years; J. W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were < 1 litre and the maximal urinary osmolality was 1232 in C.C. and 950 in J.W. Plasma renin activity was elevated (> 2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0±85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour.
IMMUNOPRECIPITATION OF TSH‐TSH RECEPTOR COMPLEXES
Authors: PARKES A. B. , KAJITA Y. , BUCKLAND P. R. , HOWELLS R. D. , RICKARDS CAROLE R. , CREAGH FIONUALA M. , SMITH B. REES 
Published: March 2008

SUMMARYThe ability of Graves' sera to interact with the TSH receptor crosslinked to a 125I‐labelled photoactive derivative of TSH has been investigated. Crosslinked complexes were prepared using non‐purified detergent solubilized human thyroid and guinea pig fat TSH receptors. Affinity purified porcine TSH receptor preparations were also used. After crosslinking, the crosslinked TSH‐TSH receptor complexes were separated from aggregates and free TSH on Sephacryl S‐300, incubated with test sera followed by immunoprecipitation using anti‐IgG or Protein A. Using non‐purified human TSH receptors crosslinked to TSH, a mean ± SD of 12±· 4·9% of the crosslinked complex was immunoprecipitated with Graves' sera (n= 7) compared with 10·3 · 2·6% with Hashimoto sera (n= 6; P > 0±4) and 3·8 · 1·0% with normal sera (n= 6; P < 0·004). These values were markedly reduced when TSH receptor preparations free of other thyroid autoantigens (guinea pig fat TSH receptors) were used. Under these conditions immunoprecipitation with Graves' sera (n= 24) was 1·6 · 1·3% compared with 0·8 · 0·6% for Hashimoto sera (n= 13) and 0·8 · 0·4% for normal sera (n= 2; P= 0·003). In addition complexes formed between TSH and affinity purified porcine TSH receptors gave low immunoprecipitation values for Graves' (1·44 · 0·73%; n= 20) and Hashimoto sera (1·7 · 0·94; n= 11) which were not significantly different (P= 0·4). Overall, therefore, the effects of Graves' and Hashimoto sera were similar and the amounts of material immunoprecipitated were markedly reduced when TSH receptor preparations containing reduced amounts of other autoantigens were used. Consequently the Graves' sera did not appear to interact specifically with crosslinked TSH‐TSH receptor complexes. However the Graves' sera studied did contain TSH receptor antibodies which could inhibit the binding of labelled TSH to TSH receptors in the preparations used and our results suggest that the binding of TSH and these antibodies to the receptor is mutually exclusive.
CONGENITAL 11β‐HYDROXYSTEROID DEHYDROGENASE DEFICIENCY ASSOCIATED WITH JUVENILE HYPERTENSION: CORTICOSTEROID METABOLITE PROFILES OF FOUR PATIENTS AND THEIR FAMILIES
Authors: SHACKLETON C. H. L. , RODRIGUEZ J. , ARTEAGA E. , LOPEZ J. M. , WINTER J. S. D. 
Published: March 2008

SUMMARYFour children with 11bT‐hydroxysteroid dehydrogenase deficiency are described. All patients had severe hypertension, hypokalaemia, and low plasma aldosterone and renin activities. Two of the patients were siblings and two were unrelated. The most noticeable biochemical feature of these individuals was the extremely low excretion of cortisol metabolites containing an 11‐carbonyl group compared to the excretion of the 11β‐hydroxyl containing metabolites. Although this condition is readily diagnosed in affected individuals by urinary steroid analysis, carriers of the defect do not differ from normal in their urinary steroids. Both parents of the affected siblings had normal 11‐oxo‐steroid/11bT‐hydroxysteroid ratios under baseline conditions and the lesions could not be revealed by ACTH administration.
ACTH AND CORTISOL RESPONSES TO OVINE CORTICOTROPHIN‐RELEASING FACTOR IN PATIENTS WITH PRIMARY AND SECONDARY ADRENAL FAILURE
Authors: HERMUS A. R. M. M. , PIETERS G. F. F. M. , PESMAN G. J. , SMALS A. G. H. , BENRAAD T. J. , KLOPPENBORG P. W. C. 
Published: March 2008

SUMMARYThe ACTH and cortisol responses to an intravenous bolus injection of 100 μg ovine CRF were studied in 19 patients with adrenal failure. In all eight patients with primary adrenal failure, plasma ACTH levels increased from a mean basal level of 1494·431 (SEM) pg/ml to a peak value of 2601±220 pg/ml at 10 min. In comparison with healthy subjects absolute ACTH increments after ovine CRF were significantly augmented in the patients with Addison's disease (P* > 0.001), and the absolute ACTH responses after ovine CRF were positively correlated with the basal plasma ACTH levels. The 11 patients with secondary adrenal insufficiency could be subdivided into two groups: (A) those having little or no ACTH and cortisol response to ovine CRF (five patients) and (B) those having prolonged and pronounced ACTH responses with a biphasic pattern and a delayed second peak (six patients), followed in all patients by a marked cortisol increase. These data demonstrate that the CRF‐test can discriminate between hypothalamic and pituitary causes of secondary adrenal failure.
THE TREATMENT OF HIRSUTISM WITH A COMBINATION OF DESOGESTREL AND ETHINYL OESTRADIOL
Authors: DEWIS P. , PETSOS P. , NEWMAN M. , ANDERSON D. C. 
Published: March 2008

SUMMARYSome available oral contraceptive agents are unsuitable for the treatment of hirsutism since, although they suppress endogenous gonadotrophins and so ovarian androgen production, they contain a progestogen which is itself androgenic. The combination of 30 μg ethinyl oestradiol (EE2) and 150 μg desogestrel (Marvelon) does not suffer from this drawback. We have therefore assessed its value in 15 hirsute women treated for one year. Mean±SE androgen‐dependent hair growth, assessed photographically fell from 0·31 ± 0·01 to 0·23 ± 0·01 mm/d at 1 year (P< 0·001). Ten of the fifteen patients reported definite subjective improvement. Treatment was associated with a marked rise in SHBG concentration identical to that seen with 30 μg EE2 alone. By four months there were significant falls in serum levels of androstenedione and LH throughout the cycle, but not for testosterone, dihydrotestosterone or 5α‐androstane 3α, β17 ‐diol. Calculated free testosterone levels were significantly suppressed. All the biochemical changes were maintained after seven months of treatment. We conclude that this preparation is a suitable oral contraceptive for the treatment of hirsute women.
HORMONAL CHANGES IN POSTMENOPAUSAL WOMEN WITH BREAST CANCER TREATED WITH TRILOSTANE AND DEXAMETHASONE
Authors: BEARDWELL C. G. , HINDLEY A. C. , WILKINSON P. M. , ST JOHN JUDY , BU'LOCK DENISE 
Published: March 2008

SUMMARYPostmenopausal women with metastatic breast cancer were treated with trilostane, initially 240 mg daily increasing after 3 days to 480 mg daily and after a further three days to 960 mg daily. After 3 days at this dose dexamethasone 1 mg daily was added and this combination was continued until disease progression occurred. Partial remission was seen in 26% and stabilization of previously progressive disease in a further 13% of the first twenty‐three patients studied. During therapy with trilostane alone significant increases in DHEAS, androstene‐dione, 17‐hydroxypregnenolone, progesterone, testosterone and oestradiol were seen. A significant fall in oestrone concentration occurred at the same time. After dexamethasone was added the elevated steroid concentrations fell back to the baseline while oestrone remained depressed below this and testosterone was also significantly lowered. No change was seen in cortisol or ACTH concentration while patients were on trilostane alone but cortisol levels were undetectable after dexamethasone was added though, in most patients, ACTH remained detectable. There was no change in the ratio of Δ5: Δ4 steroids at any stage of therapy but a highly significant increase in the androstenedione: oestrone ratio was seen. We conclude that in long‐term use in vivo it is difficult to demonstrate that trilostane inhibits 3β‐hydroxysteroid dehydrogenase but it may produce inhibition of aromatase.
RELATIONSHIPS BETWEEN THE CIRCADIAN RHYTHMS OF TSH, PROLACTIN AND CORTISOL IN SURGICALLY TREATED MICROPROLACTINOMA PATIENTS
Authors: SALVADOR J. , WILSON D. W. , HARRIS P. E. , PETERS J. R. , EDWARDS C. , FOORD S. M. , DIEGUEZ C. , HALL R. , SCANLON M. F. 
Published: March 2008

SUMMARYPharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post‐operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (<420 mU/l) in all patients by surgery (pre‐op: 930–2752 mU/1, post‐op: 33–376 mU/1) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the Cortisol antibody with 11‐deoxycortisol was taken into account during the calculation of results. All subjects showed a normal Cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (± SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 ± 0.26, 1.29 ± 0.48; 0.46 ± 0.26, 0.23 ± 0.13 and −49°± 9.8°; −62°± 2.7° respectively. Based on paired t‐testing of these data there was a small but significant reduction in the amplitude (P<0.05) and acrophase (P<0.05) of the TSH rhythm during metyrapone administration but no alteration in the circadian pattern of change. The normal circadian change in PRL levels which we observed in these patients was not altered by metyrapone treatment. It appears therefore that variation in endogenous cortisol is not the sole factor involved in the determination of the circadian TSH rhythm and that it does not influence circadian PRL changes in this group of subjects.
FAILURE OF PROPHYLACTIC SURGERY TO AVERT MASSIVE PITUITARY EXPANSION IN PREGNANCY
Authors: BELCHETZ P. E. , CARTY A. , CLEARKIN L. G. , DAVIS J. C. , JEFFREYS R. V. , RAE P. G. 
Published: March 2008

SUMMARYMacroprolactinomas have a well‐recognized potential for marked expansion during pregnancy. Measures advocated to minimize this risk include prior treatment with dopamine agonists, radiotherapy and pituitary surgery. We describe a patient who underwent transsphenoidal surgery with the removal of an histologically proven prolactin‐secreting adenoma with the intention of rendering subsequent pregnancy safe. The patient remained hyperprolactinaemic and received prolonged therapy with metergoline and bromocriptine which suppressed prolactin to normal and she conceived after induction of ovulation with human menopausal gonadotrophin and human chorionic gonadotrophin. At 3 months gestation she developed headaches, vomiting, reduced visual acuity and bitemporal hemianopia caused by massive pituitary expansion. Reintroduction of bromocriptine rapidly abolished features of tumour expansion and after delivery of a full‐term normal female infant, repeat CT scan documented tumour shrinkage.