bluuebunny/crossref_metadata_2025_split huggingface dataset:
ON THE STABILITY IN VITRO OF BIOACTIVE HUMAN ADRENOCORTICOTROPHIN IN BLOOD AND PLASMA
Authors: LAMBERT A. , FROST J. , RATCLIFFE W. A. , ROBERTSON W. R. 
Published: March 2008

SUMMARYThe disappearance in vitro of ACTH from whole human blood and plasma held at 22°C has been monitored using a dispersed adrenal cell bioassay and an unextracted radioimmunoassay. In three normal subjects after a metyrapone test and two patients with Addison's disease, endogenous bioactive ACTH levels were unchanged for at least 1 h in blood and 2 h in plasma. Moreover < 50% of the bioactive plasma ACTH was still present in the plasma samples from the patients with Addison's disease after 24 h incubation at ambient temperatures. Human pituitary ACTH (1–39), spiked into plasma from dexamethasone suppressed subjects to give a concentration of 250 ng/1, was stable by bioassay for at least 2 h. No loss of biological activity was observed on subjecting plasma from a patient with Addison's disease or spiked plasma to two cycles of thawing at 37°C and freezing at — 70°C or thawing at 20°C and freezing at — 20°C. Some loss of bioactivity (20%) occurred on subjecting the patient's, but not ACTH‐spiked plasma to four cycles of thawing at 20°C/freezing at — 20°C. We conclude that bioactive ACTH (endogenous or exogenous) may be more stable in vitro in human blood and plasma than has been previously thought. If our studies can be confirmed in a larger series then it may be that conditions for handling blood specimens for ACTH assays could be reappraised.
THE GEOGRAPHICAL DISTRIBUTION OF THYROTOXICOSIS IN ENGLAND ACCORDING TO THE PRESENCE OR ABSENCE OF TSH‐RECEPTOR ANTIBODIES
Authors: PHILLIPS D. I. W. , BARKER D. J. P. , SMITH B. REES , DIDCOTE S. , MORGAN D. 
Published: March 2008

SUMMARYIn a prospective study of the incidence of thyrotoxicosis sera from 216 thyrotoxic patients in seven English towns were assayed for TSH‐receptor antibodies. The incidence of antibody negative thyrotoxicosis correlated closely with the previous prevalence of endemic goitre in the towns (r= 0·9) indicating a high current incidence of toxic nodular goitre in previously goitrous towns. Antibody positive thyrotoxicosis, an indicator of Graves’ disease, showed no correlation with goitre although there was statistically significant geographical variation in incidence. The percentage of all thyrotoxic patients who were antibody positive varied between towns, from 35% to 92%.
PITUITARY ACTH DEPENDENT CUSHING'S SYNDROME DUE TO ECTOPIC PRODUCTION OF A BOMBESIN‐LIKE PEPTIDE BY A MEDULLARY CARCINOMA OF THE THYROID
Authors: HOWLETT T. A. , PRICE JANET , HALE ANN C. , DONIACH I. , REES LESLEY H. , WASS J. A. H. , BESSER G. M. 
Published: March 2008

SUMMARYA 41‐year‐old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin‐like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin‐like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin‐like peptide, causing excessive pituitary ACTH secretion.
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA I: RENAL HANDLING OF CALCIUM, MAGNESIUM AND PHOSPHATE
Authors: KRISTIANSEN J. H. , MORTENSEN J. BROCHNER , PEDERSEN K. O. 
Published: March 2008

SUMMARYTen hypercalcaemic members from three generations of a family with familial hypocalciuric hypercalcaemia (FHH) were compared with age and sex matched healthy subjects. Two of the former had undergone unsuccessful subtotal parathyroidectomy. Our results showed that the hypercalcaemia was mainly attributable to an increased capacity for tubular reabsorption of calcium, but in part also to an increased release of calcium from bone. The relative hypermagnesaemia had a similar dual origin. The serum phosphate concentration was low and this could be accounted for in full by a decrease in renal tubular reabsorption of phosphate, as assessed by the renal threshold phosphate concentration (TmPO4/GFR). The results of PHT measurements with two radioimmuneassays were equivocal. Most patients had normal serum PTH values, but with one assay mean serum PTH was significantly higher in the hypercalcaemic group. We conclude that the abnormalities of the divalent cation and phosphate metabolism cannot be accounted for in full by increased circulating PTH activity, and are predominantly due to an intrinsic renal abnormality.
CLINICAL SIGNIFICANCE OF UNCONJUGATED 3α,5β‐TETRAHYDROALDOSTERONE AND 5β‐DIHYDROALDOSTERONE MEASURED BY RADIOIMMUNOASSAY
Authors: LEWICKA SABINA , VECSEI P. 
Published: March 2008

SUMMARYRadioimmunoassays of two unconjugated reduced metabolites of aldosterone were developed. Excretion rates of unconjugated 5β‐dihydroaldosterone (5β‐DHAld) and 3α,5β‐tetrahydroaldosterone (3α,5β‐THAld) were measured in 192 hypertensive patients and 16 normal subjects and results were compared with urinary tetrahydroaldosterone‐glucuronide(TH‐Aldo‐glu), aldosterone‐18‐glucuronide (Aldo‐18‐glu) and ‘free’ aldosterone. Generally, values of unconjugated reduced metabolites correlated with one another but in some cases were exceptionally elevated indicating alteration of urinary bacterial flora or impairment of the enzymatic system regulating the conjugation reaction. We suggest that in those cases of hypertension and suspected primary aldosteronism when aldosterone‐18‐glucuronide and tetrahydroaldosterone glucuronide values remain within normal range, determination of the free metabolite fraction may be diagnostically helpful.
PLASMA CONCENTRATIONS OF SEX HORMONES IN POSTMENOPAUSAL WOMEN IN NON‐ALCOHOLIC CIRRHOSIS
Authors: BANNISTER P. , SHERIDAN P. , LOSOWSKY M. S. 
Published: March 2008

SUMMARYSex hormone and sex hormone binding globulin (SHBG) levels were measured in the plasma of postmenopausal women with non‐alcoholic liver cirrhosis (n= 24) and compared with levels in matched controls (n= 21). Plasma oestradiol was elevated: 80 vs 30 pmol/l, P < 0·005 (median values). Plasma SHBG was elevated, 15 vs 10 mg/dl, P < 0·001. Plasma dehydroepiandrosterone sulphate levels were low, 0·35 vs 2·0 μmol/l, P < 0·0005, as were plasma androstenedione levels, 2·5 vs 4·5 nmol/l, P < 0·05. There was no significant difference in plasma testosterone. These data suggest that liver disease per se alters sex hormone and sex hormone binding globulin levels in postmenopausal women.
EFFECT OF PINEALECTOMY ON SERUM MELATONIN, LUTEINIZING HORMONE AND PROLACTIN: A CASE REPORT
Authors: CHIK C. L. , TALALLA A. , BROWN G. M. 
Published: March 2008

SUMMARYA patient, aged 47 is described in whom changes in hormonal profiles were observed following surgical excision of the pineal. She presented with a clinical syndrome of increased intracranial pressure and postmenopausal symptoms. Computerized tomographic scans showed obstructive hydrocephalus from a cystic lesion in the pineal region. Surgical removal of the cystic mass revealed a benign ependymal cyst and normal pineal tissue. After the operation, she had no nocturnal increase in serum melatonin. The morning basal LH was further elevated and night‐time PRL showed little fluctuation from the basal levels.
ABNORMAL ANDROGEN AND OESTROGEN METABOLISM IN MEN WITH STEROID SULPHATASE DEFICIENCY AND RECESSIVE X‐LINKED ICHTHYOSIS
Authors: LYKKESFELDT G. , BENNETT P. , LYKKESFELDT A. E. , MICIC S. , MØLLER S. , SVENSTRUP B. 
Published: March 2008

SUMMARYSerum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase‐deficient men with recessive X‐linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P< 0·0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction:P< 0·025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P< 0·0005 andP= 0·055, respectively), while their LH level was higher than normal (P< 0·0005). The serum levels of SHBG, total and free testoster‐one, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.
DIAGNOSTIC VALUE OF A SINGLE SERUM THYROGLOBULIN DETERMINATION ON AND OFF THYROID SUPPRESSIVE THERAPY IN THE FOLLOW‐UP OF PATIENTS WITH DIFFERENTIATED THYROID CANCER
Authors: PACINI F. , LARI R. , MAZZEO S. , GRASSO L. , TADDEI D. , PINCHERA A. 
Published: March 2008

SUMMARYTo assess the significance of a single serum thyroglobulin (Tg) determination on and off thyroid suppressive therapy, serum Tg measurements have been performed in 349 serum samples from 82 patients with differentiated thyroid cancer. All samples were collected after total thyroidectomy with or without subsequent ablation of residual thyroid tissue by radioiodine. One hundred and fifty‐three samples were obtained while the patients were on thyroid suppressive therapy and 196 after withdrawal of medication. The results of serum Tg assays were analysed in relation to the presence or absence of residual or metastatic thyroid tissue, as assessed by clinical and laboratory evaluation, including 131I whole body scan. In patients with thyroid residue but no metastases, undetectable serum Tg (false negative results) occurred in 45% of cases off therapy and in 92·9% of cases during therapy. In the presence of metastases no undetectable serum Tg result was found in patients off therapy, while four (6·9%) out of 58 samples from patients with bone and/or lung metastases and seven (31·8%) out of 22 samples from patients with lymph node metastases alone were undetectable (falsely negative) during suppressive therapy. Serum Tg was undetectable in sera from patients with no evidence of thyroid residue or metastatic disease in all but one (1·7%) of 59 samples on and three (5·4%) of 56 samples off suppressive therapy. These Tg results were confirmed to be truly rather than falsely positive, since evidence of metastatic disease was obtained by whole body scan after the administration of therapeutic doses of 131I. These data indicate that the finding of detectable serum Tg during suppressive therapy is a reliable indicator of metastatic disease, while a negative result does not exclude the presence of metastases especially in the case of lymph node involvement. In this regard assays performed off therapy have greater diagnostic value.
FAMILIAL MALE PSEUDOHERMAPHRODITISM WITH GYNAECOMASTIA DUE TO 17β‐HYDROXYSTEROID DEHYDROGENASE DEFICIENCY. A REPORT OF 3 CASES
Authors: BALDUCCI R. , TOSCANO V. , WRIGHT F. , BOZZOLAN F. , DI PIERO G. , MARODER M. , PANEI P. , SCIARRA F. , BOSCHERINI B. 
Published: March 2008

SUMMARYThree sisters with male pseudohermaphroditism due to 17β‐hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4‐5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma and rostenedione to testosterone ratio was 20–25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17β‐hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.
SHORT‐ AND LONG‐TERM EVALUATION OF NORMAL AND ABNORMAL HUMAN THYROID CELLS IN MONOLAYER CULTURE
Authors: DAVIES T. F. , PLATZER M. , SCHWARTZ A. E. , FRIEDMAN E. W. 
Published: March 2008

SUMMARYWe have investigated the TSH responsiveness of normal and abnormal human thyroid cells cultured in the short term with high serum concentrations and for up to 6 months in a low serum, chemically‐defined, medium. Cells from normal human thyroid tissue (n= 9), multinodular goitre (n= 6), benign follicular adenomata (n= 6), and differentiated thyroid carcinoma (n= 3) formed confluent monolayers which were sensitive to bovine TSH (bTSH) in concentrations greater than 25 μU/ml when assessed by the intracellular response of cyclic AMP at 7 d of culture. Such sensitivity was less than that observed with a continuously proliferating thyroid cell line (FRTL‐5) derived from Fisher rat thyroid and which responded to concentrations of bTSH as low as 5–10 μU/ml. Human cells derived from iodine/antithyroid drug treated Graves' thyroid tissue (n= 6) were less sensitive than normal cells requiring up to 500 μU/ml bTSH to increase intracellular cyclic AMP and poorly differentiated thyroid cancer cells (n= 3) failed to respond to bTSH. Long‐term human thyroid cultures of normal and follicular adenoma cells in the chemically‐defined medium used for the FRTL‐5 cells had absent fibroblast growth and continued in monolayer form without significant follicle formation. These cells remained highly sensitive to bTSH stimulation when tested after 4, 13, and 26 weeks of continuous culture. All such cell preparations failed to proliferate under conditions which favoured the rapid growth of the rat thyroid cells. These data demonstrated that while thyroid cell culture conditions described in the literature do not permit proliferation of human thyroid cells, they do allow an assessment of their functional state in vitro which may lead to a further understanding of thyroid cell pathophysiology.
ANDROGENS, BEHAVIOUR AND NOCTURNAL ERECTION IN HYPOGONADAL MEN: THE EFFECTS OF VARYING THE REPLACEMENT DOSE
Authors: O'CARROLL R. , SHAPIRO C. , BANCROFT J. 
Published: March 2008

SUMMARYThe behavioural effects of varying the replacement dose of the oral androgen testosterone undecanoate (TU, Restandol) were investigated in eight hypogonadal men. Each man was withdrawn from his previous androgen replacement regimen and after a period of no treatment was administered four doses of TU (40, 80, 120 and 160 mg/d) in four successive one‐month treatment periods using a double‐blind design. Throughout the study each man recorded his sexual interest, behaviour and mood state using a daily diary form. In addition, four hypogonadal subjects had sleep erections and sleep quality assessed in the laboratory during a state of androgen withdrawal and again after a minimum of 5 months of androgen treatment. A dose response relationship was demonstrated for frequency of sexual thoughts, arousal accompanying sexual thoughts and well‐being. Sleep erections improved significantly during testosterone administration. In men, sexual interest and sleep erections are androgen‐dependent.
LONG‐TERM RESULTS OF TRANSSPHENOIDAL PITUITARY MICROSURGERY IN 60 ACROMEGALIC PATIENTS
Authors: ROELFSEMA F. , VAN DULKEN H. , FRÖLICH M. 
Published: March 2008

SUMMARYSixty patients with clinically and biochemically active acromegaly were treated by transsphenoidal surgery. All patients underwent a full assessment of pituitary function both preoperatively and postoperatively; these studies were repeated 6 months after surgery and every year, when possible. The mean follow‐up period was 3.3 years (range 0.5‐7 years). The GH level normalized in 62% of patients after surgery. A paradoxical reaction of GH to TRH was present in 35 patients before surgery and had normalized in 17 after surgery. Large tumours were associated with higher GH levels than smaller tumours. A prognostic factor in terms of normalization of both the GH level and an eventual paradoxical reaction to TRH or a glucose challenge was a low preoperative GH level. Three out of seven patients with either a positive postoperative TRH test but a normal GH level, or a slightly elevated GH level suffered a biochemical and clinical recurrence and two of them underwent reoperation. In contrast, when the TRH test had normalized (always in association with normal GH levels) no recurrence was found. The impact of surgery on the other pituitary functions was generally slight and the numbers of patients with preoperative and postoperative impairment were about equal. Postsurgical radiation therapy was administered to patients with an elevated GH level, a non‐normalized TRH test irrespective of whether the GH level had normalized, or local invasion of the tumour. In 11 out of 17 patients with elevated GH levels after surgery, normalization was achieved by radiation therapy after a mean period of 2.7 years. The incidence of pituitary failure after irradiation appeared to be high; gonadal function in men and the GH reserve function were especially vulnerable. From this study we conclude that in many cases the adenoma can be removed effectively, without compromising the other pituitary functions. However, a substantial number of the patients require additional radiation therapy, leading to an inevitable loss of other pituitary functions.
AUTOIMMUNITY AND THE PATHOGENESIS OF LOCALIZED THYROID AUTONOMY (PLUMMER'S DISEASE)
Authors: WIENER J. D. , VAN DER GAAG R. D. 
Published: March 2008

SUMMARYThe pathogenesis of Plummer's disease (localized thyroid autonomy) is incompletely known. It has been shown that a normal thyroid follicle can harbour cells with widely different properties, and hyperactive follicles may arise from cells with both high replicating and hormonogenic potencies under the influence of chronic mild stimulation. We now find thyroid growth‐stimulating immunoglobulins (TGI) to be present in low or intermediate titre in the serum of 7 of 9 patients with Plummer's disease. Haemagglutinating antibodies against thyroid microsomal antigen were present in low titre in two of these as well as in three of 21 other patients with this disorder. Two of the patients had a suppressible goitre in addition to the autonomous nodule. One of these is described in more detail. The possibility is discussed that autoimmunity may play a pathogenic role in Plummer's disease. TGI, in relatively low litres as found here, could exert the chronic mild stimulation supposed to be the prime event in the generation of hyperactive follicles. Whether autonomy is intrinsically present in these follicles or triggered by stimulation, remains to be established. Hyperthyroidism supervenes only when the mass of autonomous cells surpasses a certain limit. It appears that these patients with Plummer's disease should be included in the multidimensional spectrum of autoimmune thyroid disease.
A PROGNOSTIC SCORE FOR Graves' DISEASE
Authors: PREUS M. , FRECKER M. F. , STENSZKY V. , BALAŠS CĈC. , FARID N. R. 
Published: March 2008

SUMMARYWe have reanalysed the clinical and laboratory data on 196 individuals with Graves' disease. The consensus of two clustering techniques and a new method of allocating patients to a cluster resulted in two groups of patients, those with a severe and others with a mild disease. The severe disorder is characterized by a high frequency of HLA‐B8 and‐Al, a low complement level, high titres of circulating immune complex and anti‐thyroglobulin antibody, a high lymphocyte transformation index and serum T3 level, a low level of active E‐rosettes, large goitres and a high value for the Crooks test. The mild disorder shows a higher frequency of HLA‐B12 and an abnormally low absolute lymphocyte number. A weight was calculated for each character according to the relative frequency in the two clusters. A total score could then be calculated for each patient based on their clinical and laboratory findings. There were two distinct distributions of scores corresponding to the two subgroups. This suggests different aetiological factors which may be more easily studied in these more homogeneous groups. Prognostic predictions can be made using the score. The risk of recurrence and the frequency and severity of ophthalmopathy increases dramatically as the score increases. The use of the score in making therapeutic decisions needs to be tested.
AUGMENTATION OF THE RESPONSE TO CRF IN MAN: RELATIVE CONTRIBUTIONS OF ENDOGENOUS ANGIOTENSIN AND VASOPRESSIN
Authors: MILSOM STELLA R. , CONAGLEN J. V. , DONALD R. A. , ESPINER E. A. , NICHOLLS M. G. , LIVESEY J. H. 
Published: March 2008

SUMMARYThe plasma ACTH response to corticotrophin releasing factor (CRF) was studied in seven normal individuals. Five subjects were restudied following 4 d of salt restriction which resulted in raised endogenous plasma angiotensin II secretion. In a third experiment six subjects were given CRF following pre‐infusion of hypertonic saline which significantly increased endogenous plasma vasopressin (AVP) levels. We were unable to demonstrate that high endogenous plasma AII levels were associated with a significant change in the plasma ACTH or cortisol responses to CRF. However there was an almost three‐fold increase in the ACTH response when endogenous plasma AVP was elevated by hypertonic saline. It is concluded that AVP is likely to be of physiological importance in potentiating the ACTH response to CRF and that AVP and CRF together may provide a better test of pituitary ACTH secretion than either peptide alone.
AMIODARONE AND THYROID HORMONE ACTION JAYNE A.
Authors: FRANKLYN JAYNE A. , DAVIS J. R. , GAMMAGE M. D. , LITTLER W. A. , RAMSDEN D. B. , SHEPPARD M. C. 
Published: March 2008

SUMMARYIn clinically euthyroid subjects on long‐term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.
STIMULATION BY FOOD OF PERIPHERAL PLASMA IMMUNOREACTIVE GROWTH HORMONE RELEASING FACTOR
Authors: SOPWITH A. M. , PENNY ELIZABETH S. , BESSER G. M. , REES LESLEY H. 
Published: March 2008

SUMMARYA highly specific radioimmunoassay has been used to study changes in peripheral human plasma growth hormone releasing factor (GRF) following the ingestion of food. From a mean basal plasma concentration of 11.8 pg/ml (range <7–15.4 pg/ml) in six normal individuals following overnight fast, the circulating concentration of GRF‐like immunoreactivity increased to a mean maximum of 36.7 pg/ml (range 20.2–77.0 pg/ml) sampled 120 min after a mixed breakfast. This increase in GRF was accompanied by suppression rather than stimulation of circulating growth hormone. The predominant source of peripheral circulating GRF‐like immunoreactivity may therefore by extrahy‐pothalamic and responds to an oral food stimulus.