bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of TSH receptor antibodies on protein kinase C in the thyroid
Authors: Ginsberg Jody , Murray Patricia G. 
Published: March 2008

SummaryOBJECTIVE There is increasing evidence that TSH activates a non‐cyclic‐AMP‐dependent pathway in the thyroid resulting in protein kinase C activation. We have previously demonstrated that TSH activates protein kinase C by causing translocation of protein kinase C from an inactive cytosolic site to its active membrane‐bound form in porcine thyroid cells. In addition, TSH can modify the protein kinase C translocation induced by the phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate. We tested six TSH receptor antibodies for their ability to activate protein kinase C in vitro.DESIGN Porcine thyroid cells were incubated with either TSH receptor antibody or immunoglobulin from pooled normal sera. Subsequently, cytosol and membrane compartments were separated and protein kinase C assessed in each compartment.PATIENTS The sera utilized in this study were obtained from patients with confirmed Graves' disease as defined by clinical evidence of thyrotoxicosis, increased free thyroxine index and suppressed TSH and increased radioactive iodine uptakes.MEASUREMENTS Protein kinase C was measured in the cytosol and membrane compartments of the porcine thyroid cells using an enzyme assay.RESULTS Compared to immunoglobulin from pooled normal sera, none of the six TSH receptor antibodies affected either cytosolic or membrane‐bound protein kinase C in porcine thyroid cells. The tumour‐promoting phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate, caused protein kinase C translocation. However, the presence of TSH receptor antibody did not modify the phorbol‐induced protein kinase C transiocation.CONCLUSION These results indicate that unlike TSH, TSH receptor antibodies neither cause translocation of protein kinase C nor modify phorbol‐mediated protein kinase C translocation In porcine thyrold cells.
Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency
Authors: Rosen Thord , Bosaeus Ingvar , TöIli Jukka , Lindstedt Göran , Bengtsson Bengt‐Åke 
Published: March 2008

SummaryOBJECTIVE Growth hormone deficiency in adults with hypopituitarism has previously received little attention. Recent data, however, suggest that GH deflciency might be essential for the long‐term prognosis of these patients. Earlier studies have documented that GH regulates body composition; in this, body composition in adult patients with hypopituitarism including GH deficiency was studied. DESIGN A follow‐up study of patients with hypopituitarism on routine replacement therapy with l‐thyroxine, cortisone acetate and sex steroids.PATIENTS One hundred and six patients (69 males, mean age 52.5 years and 37 females, mean age 53.4 years) diagnosed as having growth hormone deficiency on the basis of low IGF‐I concentration or a maximum GH‐response less than 5 mU/I after an insulin/glucagon tolerance test.MEASUREMENTS Body composition was estimated from body weight, total body water and total body potassium and the results were compared with values predicted from height, weight, age and sex, using data from a large number of healthy subjects.RESULTS The total body water was slgnificantly lower than that predicted from the observed body weight (P >0.001), as was the extracellular water (P >0.001) and the extracellular/intracellular water quotient (P >0.001). On average, the body cell mass was similar to the predicted value, but the observed/predicted body cell mass ratio correlated positively with age at follow‐up. The body cell mass was lower than predicted in subjects below the age of 50 years (P >0.01). The body fat was higher than predicted (P >0.001); the increase was also noted in lean subjects.The observed body weight in male subjects was 7.5 kg higher (P >0.001) than that predicted from healthy subjects of the same body height, a difference explained by an average increase of 6 6 kg in the body fat (P >0.001) and 1.6 kg in the body cell mass, with a simultaneous reduction of 0.7 kg in the extracellular water (NS). Male patients suffering from untreated androgen deficiency had lower body cell mass than those on androgen treatment. Female subjects weighed 3.6 kg (NS) more on average than healthy women, a difference explained by an increase in the body fat of 6.0 kg (P >0.001) with a simultaneous decrease of 2.4 kg in the extracellular water (P >0.001). The body cell mass was similar to that seen in the controls. CONCLUSIONS Adult patients with growth hormone deficiency have an increased body weight compared to normals of the same age, sex and height, due to an increment of the body fat with a simultaneous reduction in the total body water.
Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successfuI treatment
Authors: Trainer P. J. , Lawrie H. S. , Verhelst J. , Howlett T. A. , Lowe D. G. , Grossman A. B. , Savage M. O. , Afshar F. , Besser G. M. 
Published: March 2008

SummaryOBJECTIVE We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH‐secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post‐operative period.DESIGN A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi‐hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990. PATIENTS Forty‐eight consecutive patients (33 women, mean age 43, range 7–69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re‐evaluated; the patients were followed for a median time of 40 months after operation (range 15–70).MEASUREMENTS Post‐operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured.RESULTS After initial surgery, post‐operative serum cortisol was undetectable (>50 nmol/l) in 20 out of 48 patients (42%) and >300 nmol/l in 32 out of 48 patients (67%). Re‐exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels >300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post‐operative cortisol was > 50 nmol/l.Post‐operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients.CONCLUSIONS Cushing's disease has not recurred in any patient with an undetectable serum cortlsol (>50 nmol/l) post‐operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post‐operative serum cortisol undetectable.
Identification of a novel mutation in the gene encoding the β‐triiodothyronine receptor in a patient with apparent selective pituitary resistance to thyroid hormone
Authors: Mixson A. J. , Renault J. C. , Ransom S. , Bodenner D. L. , Weintraub B. D. 
Published: March 2008

SummaryOBJECTIVE We investigated whether the first patient (L‐F3) reported as having selective pituitary resistance had a mutation in the hTRβ gene. We compared the clinical parameters of this case with those of patients with generalized resistance to thyroid hormone.DESIGN The patient, L‐F3, was part of a study at the NIH to identify mutations by sequencing the hTRβ gene in kindreds with thyroid hormone resistance. The clinical data of L‐F3 as well as patients with generalized resistance to thyroid hormone were compared and analysed retrospectively.MEASUREMENT We amplified by the polymerase chain reaction and then sequenced exons 5 to 10 of the hTRβ gene in L‐F3 and a normal control. Upon finding the mutation in L‐F3, we measured the affinity constant of this mutated hTRβ receptor. Criteria developed previously were used to assess tissue responsiveness to thyroid hormone of L‐F3.RESULTS We identified a C to T transition at base 1297 in codon 333 of the hTRβ gene in the first patient (L‐F3) reported as having apparent selective pituitary resistance. This base substitution resulted in more than a fourfold decrease in T3‐binding affinity for the hTRβ 1 receptor. The mutation of L‐F3 occurred in the dimerization domain of exon 9, a region where the majority of mutations of kindreds with generalized thyroid hormone resistance have been found. Furthermore, the nucleotide substitution at base 1297 found in the apparent selective pituitary resistant case, L‐F3, was the same as in an unrelated patient (K‐T3) with generalized resistance to thyroid hormone. As a result, we compared the clinical parameters of both patients and found that they had similar patterns of resistance in several tissues. Besides the bone resistance present in both kindreds, the apparent selective pituitary resistance case also had liver and neuromuscular resistance.CONCLUSIONS These findings suggest that apparent selective pituitary resistance and generalized resistance to thyroid hormone are not qualitatively different syndromes. Nevertheless, identification of selective pituitary resistance is a useful clinical distinction since such patients with clinical and biochemical features of hyperthyroidism appear to benefit from reduction in serum thyroid hormone concentrations. In contrast, patients with more conventional forms of thyroid hormone resistance require no treatment or may benefit from increased concentrations of thyroid hormone.
Blood pressure and the renin‐angiotensin‐aldosterone system in children receiving recombinant human growth hormone
Authors: Barton J. S. , Hindmarsh P. C. , Preece M. A. , Brook C. G. D. 
Published: March 2008

SummaryOBJECTIVE We investigated the effect of growth hormone (GH) treatment on salt and water metabolism and the renin‐angiotensin‐aldosterone system in children with short stature.DESIGN Randomized, controlled study.PATIENTS Twenty‐nine short, pre‐pubertal children referred to two specialist growth clinics for further assessment.MEASUREMENTS Serial measurements of blood pressure, body weight, plasma renin activity (PRA), aldosterone, electrolytes, insulin and insulin‐like growth factor I (IGF‐I) have been made following the initiation of GH treatment.RESULTS A small and transient increase in systolic blood pressure was observed during the first week of GH treatment. The increase in blood pressure over baseline was −1.1 mmHg in controls compared to +11.5 and +3.0 mmHg in children receiving standard (20 units/m2/week) and high dose (40 units/m2/week) GH respectively (P= 0.004). Over the same time interval body weight also tended to increase with GH compared with controls. These changes were greater in those children receiving the lower dose of GH and were not significantly related to age or prior GH status.PRA did not change with GH treatment. Although plasma aldosterone concentration tended to increase with GH, maximal values did not differ from controls and all remained within our normal range. Plasma IgF‐I levels were increased by a similar amount in both treatment groups (1.5 and 1.12 U/ml compared to 0 44 U/ml in controls at 4 months). No difference in plasma insulin concentration was noted after 7 days of GH.CONCLUSIONS In contrast to adult subjects, treatment with high dose GH in childhood is not associated with activation of the renin‐angiotensin‐aldosterone system. Clinical signs consistent with transient salt and water retention are observed with GH therapy, however, suggesting either a direct effect of GH or of IGF‐I on renal tubular function. Blood pressure, plasma renin activity and plasma aldosterone levels were not increased after more prolonged GH therapy. These data suggest that high dose GH therapy in childhood is unlikely to be associated with the increased risk of hypertension seen in adults with GH hypersecretion.
A role for life events in the pathogenesis of Cushing's disease
Authors: Sonino Nicoletta , Fava Giovanni A. , Boscaro Marco 
Published: March 2008

SummaryOBJECTIVE We have previously reported on 30 patients with Cushing's syndrome suggesting an aetiological role for stressful life events. The investigation about life events in the year before the first signs of disease onset was extended to a larger population of patients with Cushing's syndrome, allowing us to differentiate patients with pituitary‐dependent and pituitary‐independent forms. DESIGN Case‐control study.PATIENTS Sixty‐six consecutive patients with Cushing's syndrome of various aetiologies (46 with pituitary‐dependent forms and 20 with primary adrenal hyperfunction or ectopic ACTH production) and a control group of 66 healthy subjects, matched for sociodemographic variables, were studied.MEASUREMENTS Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered after the acute phase of illness while in remission.RESULTS Patients with Cushing's syndrome reported significantly more stressful life events (P < 0.001), both events that had an objective negative impact (P < 0.001) and independent events (P < 0.001), than controls, confirming previous findings. Patients with pituitary‐dependent Cushing's disease were compared with their matched controls and reported significantly more total events, events with an objective negative impact and independent events (all at P < 0.001). There were no significant differences between patients with pituitary‐independent forms and their matched controls.CONCLUSIONS These findings indicate a causal role for stressful life events exclusively in pituitary‐dependent Cushing's disease, and suggest a limbic‐hypothalamic involvement in the pathogenesis of this condition. The results are similar to those obtained in major depression, and add to other analogies between the two disorders.
Elevated plasma 19‐hydroxyandrostenedione levels in Cushing's disease: stimulation with ACTH and inhibition with metyrapone
Authors: Mune T. , Morita H. , Yasuda K. , Murayama M. , Yamakitat N. , Miura K. 
Published: March 2008

SummaryOBJECTIVE The regulation of 19‐hydroxyandrostenedione secretion has been suggested to be under the control of both the ACTH‐adrenal axis and renin‐angiotensin system. We undertook the present study to evaluate the effect of the chronic excess of ACTH, or the short‐term excess of ACTH due to metyrapone, on 19‐hydroxyandrostenedione secretion in patients with Cushing's diseaseDESIGN AND PATIENTS We measured plasma 19‐hydroxyandrostenedione levels simultaneously with plasma Δ4‐androstenedione, corticosterone, 11‐deoxycorticosterone, aldosterone and Cortisol levels after HPLC separation in 13 patients with Cushing's disease under basal conditions and during a dexamethasone suppression test or metyrapone test. Seven patients with Cushing's syndrome due to adrenal adenoma were used for comparison.RESULTS The basal levels of 19‐hydroxyandrostenedione in Cushing's disease were elevated (mean ± SD; 323 ± 193 pmol/l, n= 13), while those in Cushing's syndrome due to adrenal adenoma were low (92 ± 24 pmol/l, n= 7), compared to those in normal subjects (117 ± 33 pmol/l, n= 54). The basal levels of Δ4‐androstenedione were mildly elevated In Cushing's disease (9.0 ± 6.5 vs 3.6 ± 2.6 nmol/l of normal subjects) but not in Cushing's syndrome due to adrenal adenoma (3.1 ± 3.0 nmol/l). In the overnight 8 mg dexamethasone suppression test in Cushing's disease (n= 12), plasma levels of 19‐hydroxyandrostenedione and Δ4‐androstenedlone decreased from 277 ± 172 to 156 ± 99 pmol/l and from 9.2 ± 6.8 to 4.7 ± 3.4 nmol/l, respectively, whereas the overnight 1 mg dexamethasone suppression test did not induce significant changes. Metyrapone administration in Cushing's disease (n= 9) increased plasma Δ4‐androstenedione level from 9.5 ± 6.7 to 47.2 ± 28.1 nmol/l, but decreased plasma 19‐hydroxyandrostenedione level from 301 ± 196 to 196 ± 105 pmol/l.CONCLUSIONS These data indicate that plasma levels of 19‐hydroxyandrostenedione in patients with Cushing's disease are elevated due to chronic ACTH excess, and that metyrapone can inhibit 19‐hydroxylation in humans.
Bone mineral density in patients with hyperthyroidism measured by dual energy X‐ray absorptiometry
Authors: Wakasugi Masakiyo , Wakao Rie , Tawata Masato , Gan Naoya , Koizumi Kiyoshi , Onaya Toshimasa 
Published: March 2008

SummaryOBJECTIVE We assessed the changes of bone mass in patients with hyperthyroidism by measuring bone mineral density using a new method, dual energy X‐ray absorptiometry.DESIGN The values of bone mineral density in patients with hyperthyroidism were compared with data obtained from the controls, and we assessed the correlation analysis between bone mineral density and several metabolic parameters.PATIENTS We studied 52 Japanese patients with hyperthyroidism (20 males, 32 females). Healthy normal subjects served to establish the mean bone mineral density In the healthy Japanese population (Shiraki et al. 1991).MEASUREMENT Bone mineral density was assessed by the measurement of lumbar vertebrae and femur by dual energy X‐ray absorptiometry. The bone mineral density of vertebrae for each patient was calculated as the percentage of the mean value (% bone mineral density) obtained from an age and sex‐matched control group. Blood was drawn to measure the levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, free T3, free T4, TSH, TSH receptor antibody, parathyroid hormone, and serum osteocalcin.RESULTS The percentage bone mineral density of vertebrae in patients was 92.6 as compared with that of normal controls, and was inversely correlated with serum TSH receptor antibody, osteocalcin, and alkaline phosphatase.CONCLUSIONS These findings suggest that bone mineral density is decreased in patients with hyperthyroidism and that TSH receptor antibody, osteocalcin, and alkaline phosphatase are sensitive markers of bone metabolism alterations in hyperthyroidism.
Polycystic ovaries are a common finding in untreated female to male transsexuals
Authors: Balen Adam H. , Schachter Morey E. , Montgomery Don , Reid Russell W. , Jacobs Howard S. 
Published: March 2008

SummaryOBJECTIVE We studied the pretreatment hormone profile and ovarian ultrasound appearance of female‐to‐male transsexuals.DESIGN Female‐to‐male transsexuals who were seen in the local Gender Identity Clinic were examined after psychiatric assessment.RESULTS Sixteen patients were assessed. Approximately 50% had symptoms and signs of the polycystic ovary syndrome (PCOS) and 15 had a pelvic ultrasound diagnosis of polycystic ovaries. The endocrine profiles of the patients were not markedly abnormal and were compatible with the diagnosis of PCOS.CONCLUSIONS Polycystic ovaries and the polycystic ovary syndrome are a common finding in female‐to‐male transsexuals who have had no previous exposure to exogenous androgen therapy.
Peptide α‐amidation activity in human plasma: relationship to gastrin processing
Authors: Kapuscinski Mirek , Green Michelle , Sinha Sankar N. , Shepherd Joseph J. , Shulkes Arthur 
Published: March 2008

SummaryOBJECTIVE AND DESIGN C‐terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine α‐amidating mono‐oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des‐glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the post‐secretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins.PATIENTS AND MEASUREMENTS Plasma PAM, gastrin‐amide and gastrin‐gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN‐1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis.RESULTS Patients with MEN‐1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN‐1 subjects with normal circulating G‐NH2 indicating a co‐secretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non‐tumour source (hypergastrinaemic non‐atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non‐amldated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity.CONCLUSION The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.
Longitudinal evaluation of adrenocorticotrophin and β‐lipotrophin plasma levels following bilateral adrenalectomy in patients with Cushing's disease
Authors: Moreira Ayrton C. , Castro Margaret , Machado Helio R. 
Published: March 2008

SummaryOBJECTIVES Bilateral adrenalectomy may be indicated in patients with Cushing's disease in whom hypercortlsolism is not resolved after pituitary microsurgery. However, Nelson's syndrome is a major long‐term complication of such therapy. We have carried out a longitudinal study on patients with Cushing's disease who underwent bilateral adrenalectomy comparing plasma /Mipotrophin (β‐LPH) with ACTH levels.PATIENTS AND METHODS Seven patients unsuccessfully treated by pituitary surgery for Cushing's disease underwent bilateral adrenalectomy. Blood samples were collected on days 8 and 15 and at 1, 2, 3, 6, 9,12,18 and 24 months after adrenalectomy in all patients. Five patients were followed up for the longer periods of 30,33,39,72 and 84 months respectively. Plasma ACTH and β‐LPH were determined by RIA after extraction. Pituitary CT scan was done at 6‐8‐month intervals.RESULTS A pituitary tumour was detected in three patients at 14, 24 and 26 months after adrenalectomy respectively. The basal ACTH (range 8‐21 pmol/l) began to rise between 15 and 30 days and exhibited a sharp increase with a range of 36‐114 pmol/l at 3 months and a range of 53‐187 pmol/l at 6‐9 months after adrenalectomy. The ACTH levels in the three patients who later presented with a pituitary tumour were indistinguishable from those observed in the other patients up to 12 months after adrenalectomy. Only at 12 months or thereafter were their ACTH levels higher than in the other patients (958 ± 252 vs 205 ± 22 pmol/l). β‐LPH concentrations changed in parallel with ACTH levels. The ACTH levels correlated positively with β‐LPH levels (r= 0 76).CONCLUSIONS In patients with Cushing's disease undergoing bilateral adrenalectomy, plasma ACTH and β‐LPH concentrations cannot predict the development of pituitary tumours until 12 months after surgery.