bluuebunny/crossref_metadata_2025 huggingface dataset:
Turner's syndrome with X‐isochromosome and Hashimoto's thyroiditis
Authors: de Kerdanet M. , Lucas J. , Lemee F. , Lecornu M.
Published: March 2008

OBJECTIVE The higher frequency Of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X‐isochromosome, since previous reports of this aspect have included only small numbers of patients.

DESIGN Retrospective study of patients with Turner's syndrome investigated within the past 12 years.

PATIENTS Sixty‐seven cases of Turner's syndrome were reviewed.

MEASUREMENTS Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti‐thyroglobulin and anti‐microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient.

RESULTS A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examinatlon, was established in 20·9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X‐isochromosome (57·3%, 9/16), compared to patients with other karyotypes (9·8%, 5/51) (P = 0·0001).

CONCLUSIONS Our results, obtained by Investigation of a larger number of patients with an X‐isochromosome karyotype than in previous reports, confirm conclusively that patients with X‐isochromosome Turner's syndrome have an increased risk of developing thyroiditis.
Hyperthyroidism associated with metastatic thyroid carcinoma
Authors: Steffensen F. H. , Aunsholt N. Aa.
Published: March 2008

We report a patient with unilateral thyroid carcinoma, who developed hyperfunction of the thyroid gland during the metastatic progression of the thyroid carcinoma. Concurrently with this event, TSI increased and it is suggested that the differentiated aggressive metastatic thyroid neoplasm had initiated the autoimmune disorder leading to TSI production and thus to hyperplasia and hyperfunction of the thyroid resulting in hyperthyroidism.
Insulin sensitivity in non‐diabetic relatives of patients with non‐insulin‐dependent diabetes from two ethnic groups
Authors: Gelding Susan V. , Niththyananthan Ratnam , Chan Siew‐Pheng , Skinner Elizabeth , Robinson Stephen , Gray I. Peter , Mather Hugh , Johnston Desmond G.
Published: March 2008

OBJECTIVE Non‐insulin‐dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non‐insulin‐dependent diabetes from two different ethnic groups.

DESIGN Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test.

PATIENTS Twenty‐four glucose‐tolerant first‐degree relatives of patients with non‐insulin‐dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes.

MEASUREMENTS Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75‐g oral glucose tolerance test. Insulin sensitivity was assessed using a 15‐minute insulin tolerance test (0.05 units/kg).

RESULTS Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 ± 17 vs 40 ± 6 pmol/l, P < 0 05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 ± 9 vs 51 ± 4 μmol/l, P < 0.005), but fasting glucose and non‐esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements.

The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non‐significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 ± 7 vs 139 ± 12μmol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 ± 11 vs 160 ± 11 μmol/l/min).

CONCLUSIONS First‐degree relatives of non‐insulin‐dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non‐insulin‐dependent diabetes in the Asian population.
The effect of low and high sodium diets on plasma atrial natriuretic factor, the renin‐aldosterone system and blood pressure in subjects with essential hypertension
Authors: McKnight J. A. , Roberts G. , Sheridan B. , Atkinson A. B.
Published: March 2008

OBJECTIVE Increasing dietary sodium intake increases blood pressure in some subjects with essential hypertension. Atrial natriuretic factor (ANF) has a potential role in modifying these changes. The purpose of this study was to observe the blood pressure and plasma ANF responses to low and high sodium diets in subjects with essential hypertension to see if the plasma ANF and blood pressure responses were related.

DESIGN An in‐patient study of subjects taking their normal diet (day 1), a 12 mmol sodium diet for 6 days and a 250 mmol diet for 6 days.

PATIENTS Seven men with essential hypertension.

MEASUREMENTS Continuous 24 hour urine collections were analysed for sodium excretion. Blood pressure was recorded at 0900, 1205 and 1700 h on days 1, 7 and 13. Blood was taken at 0900 h (fasting supine overnight) and at 1200 h (after 2 hours erect posture) on the above days for plasma ANF, plasma renin activity (PRA) and serum aldosterone.

RESULTS Urinary sodium excretion was (mean±SEM) 11 ±1 mmol on day 5 of the low sodium diet, and 294 ± 17 mmol during the fifth day of the high sodium diet. Plasma ANF (supine and erect) was significantly lower (2 8±0 6, 1 6 ± 0 2 pmoi/l) on the low sodium diet when compared to the high sodium diet (8 6 ± 2 4, 5 0 ± 1 6 pmol/l (P < 0 05)). Supine and erect PRA and serum aldosterone were significantly higher on the low compared to the high sodium diet. Blood pressure responses were heterogeneous rather than bimodal. Mean arterial blood pressure was 107 ±3 mmHg on the low sodium diet and 111 ±4 mmHg on the high sodium diet (P<0 05). Changes of blood pressure did not correlate with the changes of plasma ANF.

CONCLUSIONS Failure of plasma atrial natriuretic factor to rise with increasing dietary sodium did not therefore determine the blood pressure reponse to the change in dietary sodium. No link was established between plasma atrial natriuretic factor response and sodium sensitivity.
Oncoprotein immunoreactivity in human pituitary tumours
Authors: Raghavan Ravi , Harrison David , Ince Paul G. , James R. A. , Daniels Mark , Birch Peter , Caldwell G. I. , Kendall‐Taylor P.
Published: March 2008

OBJECTIVE and DESIGN The immediate early gene locus AP‐1, incorporating the cellular oncogenes c‐fos and c‐jun (and their oncoprotein products Fos and Jun respectively) play a key role in regulating cell growth and differentiation. The myc‐gene is also known to promote cell growth. In order to investigate the possible role of these oncogenes in human pituitary adenomas, Fos, Jun and Myc oncoprotein immunoreactivities were assessed in surgically resected pituitary adenomas in relation to in‐vivo characteristics (hormone secretion, size and invasiveness) and an in‐vitro index of cell proliferation (Ki‐67 immunoreactivity). Thirty‐three human pituitary adenomas and 16 normal pituitary glands were examined.

MEASUREMENTS Oncoprotein immunoreactivity was recorded as present (+) or absent (‐), and Ki‐67 labelling indices were scored quantitatively. Tumour size was scored from CT scan appearances and radiographic evidence of bone erosion was noted.

RESULTS Oncoprotein immunoreactivity was present in a total of 32/33 cases. Myc immunoreactivity was restricted to the only ACTH‐secreting tumour in the series (1/33). Ki‐67 immunoreactivity was present in 24/32 cases and labelling indices varied from 0.1 to 3.2%.

CONCLUSIONS Oncoprotein immunoreactivity did not correlate with hormonal profile, bone erosion or the size of the proliferating compartment estimated by Ki‐67 labelling indices. Although oncoprotein expression is common in human pituitary adenomas, its significance remains to be elucidated.
Serum FSH and testicular morphology in male infertility
Authors: Bergmann Martin , Behre Hermann M. , Nieschlag Eberhard
Published: March 2008

OBJECTIVE In patients with azoospermia serum FSH helps to differentiate between obstruction or spermatogenetic dysfunction as the possible cause of this condition. The role of FSH in the diagnosis of infertile men with oligoasthenoteratozoospermia is less clearly defined. In order to evaluate the diagnostic significance of serum FSH in the management of male infertility, serum FSH levels were related to testicular morphology from bilateral biopsies of infertile men.

DESIGN AND PATIENTS Testicular biopsies were obtained from 213 infertile men and evaluated in semi‐thin sections. Biopsies were performed either in order to distinguish between obstructive and non‐obstructive azoospermia or because of subnormal semen variables when history, clinical investigation and hormone levels failed to explain infertility. Serum FSH was measured by fluoroimmunoassay.

RESULTS Patients were divided into five groups on the basis of morphological criteria. The mean serum FSH value of patients with obstructive azoospermia and normal histology (group 1, n= 14) was normal (3.0 (2.2–4.1) IU/I) (mean (95% confidence limits)). Serum levels of FSH in non‐obstructive oligo or azoospermia were as follows: group 2: mixed atrophy of tubular tissue without focal Sertoli cell only syndrome (SCO) (n= 104) (4.5 (4.0–5.1) IU/I), group 3: mixed atrophy with unilateral focal Sertoli cell only (n= 39) (7.4 (6.1–90) IU/I), group 4: mixed atrophy with bilateral focal SCO (n= 36) (107 (8.7–13.0) IU/I). Group 5: bilateral or unilateral total Sertoli cell only (n= 20) (16 0 (12 1–20 9) IU/I). Mean serum FSH levels were significantly different between all groups (P<0.05).

CONCLUSIONS Elevation of serum FSH correlates with the appearance of Sertoli cell only tubules. Elevated FSH serum levels make testicular biopsies superfluous for diagnostic purposes, but normal FSH does not exclude severe derangement of spermatogenesis in individual cases.
Prolactin, growth hormone and insulin‐like growth factor‐l in newborn children of smoking mothers*
Authors: Beratis Nicholas G. , Varvarigou Anasiasia , Makri Maria , Vagenakis Apostolos G.
Published: March 2008

OBJECTIVE Since maternal smoking causes fetal circulatory abnormalities, as well as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH and insulin‐like growth factor‐l (IGF‐I) concentrations in the cord and venous blood of neonates of smoking mothers to determine whether or not the tobacco smoke affects the endocrine status of the neonate.

DESIGN The above hormones were measured in the cord blood of the newborns of both smoking and non‐smoking mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in newborns of both groups.

PATIENTS Fifty‐three newborns of smoking and 47 newborns of non‐smoking mothers were investigated. Seventeen of the newborns of the smoking and 21 of the nonsmoking mothers were preterm. The remainder were full‐term.

MEASUREMENTS PRL was measured with a solid‐phase immunoradiometric assay, hGH with a solid‐phase two‐site immunoradiometric assay and IGF‐I with a solid‐phase radioimmunoassay after extraction with acid‐etha‐nol.

RESULTS The median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/l (range 1322‐7230), whereas in the 21 preterm newborns of nonsmoking mothers it was 2013 mU/l (range 243‐4740) (P = 0 0002). The median hGH value in the above subjects was 1020 mU/l (range 35 2‐208 4) and 59 8 mU/l (range 11 6‐134‐2), respectively (P = 0 0039). The median IGF‐I was 580 7 U/l (range 253 2‐4851 1) and 530 6 U/l (range 239 6‐3591 5), respectively (P = 0 429). In the 36 full‐term newborns of smoking mothers the median PRL value was 5171 mU/l (range 2074‐7530), whereas in the 26 full‐term newborns of non‐smoking mothers it was 5081 (range 244‐6540) (P = 0 048). The median hGH was 69 6 mU/l (range 42 3‐280 0) and 32 2 mU/l (range 6 2‐200 0), respectively (P = 0 0031). Also, the median IGF‐I value was 926 3 U/l (range 348 5‐5344 7) and 462 1 U/l (range 250 2‐1578 7), respectively (P = 00024). On the 3rd day the PRL in the preterm neonates of both smoking and non‐smoking mothers showed the same 16‐5% drop, and thus the difference between the groups was maintained. A similar reduction in the hormone levels was observed in the full term neonates.

CONCLUSIONS The findings indicate that the maternal tobacco‐smoking causes disturbances of the endocrine status of the fetus, as shown by the increased levels of PRL, hGH and IGF‐I, which are more pronounced between 30 and 37 weeks of gestation than at term.
The neuroendocrine effects of sumatriptan, a specific ligand for 5‐HT 1‐like receptors
Authors: Facchinetti Fabio , Nappi Rossella E. , Sances Grazia , Fioroni Loredana , Nappi Giuseppe , Genazzani Andrea R.
Published: March 2008

OBJECTIVE A relationship between the serotoninergic and the opiatergic system in the pathogenesis of head pain is supported by several data. This study was carried out to investigate the neuroendocrine effects of sumatriptan, a specific serotonin agonist used in the treatment of migraine, on hypothalamic‐pituitary‐adrenal axis (PHA) hormones.

DESIGN Two consecutive studies were performed. In study A, eight subjects received a subcutaneous (s.c.) injection of sumatriptan (6 mg). In study B, a further six subjects were randomized to receive either sumatriptan or placebo.

SUBJECTS Healthy volunteers recruited within the staff (eight males and six females) were studied.

MEASUREMENT In study A, plasma Cortisol and PRL were measured by direct RIA and β‐endorphin after extraction and chromatography. Samples were collected from 60 minutes before to 120 minutes after the administration of the drug, at 15‐minute intervals. According to the data of the first study, in study B, in addition to Cortisol and β‐endorphin, ACTH was also measured.

RESULTS Significant increases in the mean β‐endorphin and Cortisol concentrations were found in every subject receiving sumatriptan, while no significant changes were observed in prolactin plasma levels. Study B confirmed the activation of the pituitary‐adrenal axis, additionally demonstrating the release of ACTH, and indicated that placebo has no effects.

CONCLUSION Acute s.c. stimulation with sumatriptan activates the pituitary‐adrenal axis.
Immunological findings and thyroid function of untreated Graves' disease patients with undetectable TSH‐binding inhibitor immunoglobulin
Authors: Mukuta T. , Tamai H. , Oshima A. , Morita T. , Matsubayashi S. , Fukata S. , Kuma K.
Published: March 2008

OBJECTIVE TSH‐binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease.

PATIENTS We examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age ± SEM 35 ± 2 years, group A).

MEASUREMENTS We compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age ±SEM 40 ±2 years, group B). T4, TSH, FT4, FT3, 1231 thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit.

RESULTS Serum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P<0 001). The values of TSAb in group A were significantly lower than those in group B (593±67 (mean±SE) vs 2143±280%, respectively, P < 0001). The 1231 thyroid uptake in group A was significantly lower than that in group B (53 1 ±11 vs 61 ‐4±14%, respectively, P<0.01).The thyroid volume in group A was significantly smaller than that in group B (391 ±3 0 vs 51 3±3 3 ml, respectively, P<0 01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit.

CONCLUSION In the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated 123l uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was also confirmed.
α2‐Adrenergic activity is normal in patients with thyroid disease
Authors: Del Rio Graziano , Zizzo Giuseppe , Marrama Paolo , Venneri Maria Grazia , Casa Luciano Delia , Velardo Antonino
Published: March 2008

OBJECTIVE Several studies indicate an inverse relationship between the sympathetic nervous system activity and thyroid function. Altered adrenoceptor sensitivity, particularly α and β, have been described in hypothyroid and hyperthyroid patients. No information in patients with thyroid disease is available on the main mechanism regulating sympathetic nervous system outflow, i.e. the α2‐adrenoceptor pathway. In our study we evaluated α2‐adrenergic activity in patients with thyroid disease by the assessment of cardiovascular and catecholamine response to clonidine, a central a2 adrenergic agonist.

PATIENTS Ten patients with hypothyroidism, six patients with hyperthyroidism before and during adequate therapy, and ten healthy subjects.

MEASUREMENTS After three blood samples for the basal determination of noradrenaline and adrenaline, the subjects swallowed 4 μg/kg body weight of clonidine. Blood pressure and pulse rate were measured 30,60,90,120,130 and 140 minutes after clonidine administration; blood samples for determination of catecholamines were drawn at 120,130 and 140 minutes.

RESULTS At presentation the decrease in plasma noradrenaline after clonidine in the patients was similar to that of the control group (hypothyroids: 1.07 ± 0.23 nmol/l mean±SEM; hyperthyroids: 0.54 ± 0 06 nmol/l; controls: 0.36±0.10 nmol/l; F=1.2, P=NS). No differences were detected in the fall in adrenaline and mean arterial pressure (MAP) after clonidine. The adequate therapy induced in hypothyroid patients a decrease in the basal levels of noradrenaline (1.88±0.28 vs 0.67±0.10 nmol/l; P <0.05) and a lesser fall in mean arterial pressure after clonidine (AMAP 20 4 ± 2 0 vs 9.7 ±2.8 mmHg; P < 0.05). No variations were detected in hyperthyroid patients after therapy either in basal hormones levels or in the magnitude of decrement in MAP and noradrenaline induced by clonidine.

CONCLUSIONS We conclude that in spite of the previously reported abnormalities in α1 and β‐adrenergic receptor activity, the inhibitory α2‐receptor pathway is normal in patients with altered thyroid function.
Prospective evaluation of insulin resistance and lipid metabolism in women receiving oral contraceptives
Authors: Sheu Wayne Huey‐Herng , Hsu Chih‐Hsueh , Chen Yan‐Shiun , Jeng Chii‐Yuang , Fuh Martin Mao‐Tsu
Published: March 2008

OBJECTIVES It has been suggested that normal women receiving oral contraceptives (OC) may develop a series of metabolic side‐effects which relate to the risk of cardiovascular disease. These metabolic disturbances include changes in glucose and insulin metabolism, raised serum lipid and lipoprotein concentrations and elevated blood pressure. All these changes indicate that OC might cause insulin resistance. We have prospectively examined the effect of OC on insulin resistance and lipid metabolism including Lp(a) values.

PATIENTS The study group comprised 13 normally menstruating Chinese women.

DESIGN The study subjects were given a combined triphasic oral contraceptive which was administered on a 21‐day on, 7‐day off medication cyclic regimen, the first pill being administered on day 5 from the beginning of menses. The metabolic investigations were carried out during luteal phase before OC and again the third week of the third month of OC administration.

MEASUREMENTS Metabolic evaluation including insulin secretion and insulin‐mediated glucose uptake were evaluated by oral glucose tolerance test and the modification of insulin suppression test. Fasting triglyceride, cholesterol, HDL‐cholesterol and Lp(a) concentrations were also measured.

RESULTS The plasma glucose and insulin responses during a 75‐g oral glucose challenge increased significantly (P<0 05 and P<003, respectively). The steady‐state plasma glucose (SSPG) concentrations achieved during constant infusion of glucose, insulin and somatostatin increased significantly after 3 cycles of OC administration (glucose 7–5±08 vs 124±07 mmol/l, P<0001) while the steady‐state plasma insulin (SSPI) concentrations were relatively similar (410±14 vs 391 ±7 pmol/l, NS). Plasma triglyceride levels increased significantly (0 81 ±012 vs 1 09±0 19 mmol/l, P<0 03) following OC administration. Fasting plasma cholesterol, HDL cholesterol and calculated LDL cholesterol concentrations did not change as compared with baseline values, nor did the ratio of total cholesterol to HDL cholesterol. The Lp(a) concentrations did not change during the administration of OC (81 ±25 vs 71 ±21 mg/l, NS).

CONCLUSIONS These data indicated that intake of OC for 3 cycles induced glucose intolerance, hyperinsulinaemia and insulin resistance in normal menstruating Chinese women. These changes occurred in association with elevated plasma triglyceride concentrations and no alteration in Lp(a) or other lipid values.
Glucocorticoid responsive ACTH secreting bronchial carcinoid tumours contain high concentrations of glucocorticoid receptors
Authors: Florkowski C. M. , Wittert G. A. , Lewis J. G. , Donald R. A. , Espiner E. A.
Published: March 2008

Cushing's syndrome due to a bronchial ACTH secreting carcinoid tumour may be difficult to distinguish from a pituitary microadenoma (corticotrophinoma) causing Cushing's disease, since in both disorders ACTH secretion may be responsive to glucocorticoids. Why some bronchial carcinoid tumours are responsive is unknown but it could be because of co‐secretion of corticotrophin releasing factor (CRF) and/or expression of glucocorticoid receptors. We report two patients with glucocorticoid responsive ACTH secreting bronchial carcinoid tumours, neither of whom produced or responded to CRF. Significant glucocorticoid receptor binding capacity (92 and 102 pmol/g protein), compared with control lung tissue, was found in extracts from both tumours. These findings suggest that corticotrophinoma‐like responses to glucocorticoids observed in some ACTH secreting bronchial carcinoids result from expression of glucocorticoid receptors and are not necessarily related to the production of CRF.
The value of inferior petrosal sinus sampling in diagnosis and treatment of Cushing's disease
Authors: Landolt Alex M. , Schubiger Othmar , Maurer Robert , Girard Jürg
Published: March 2008

OBJECTIVE While microsurgical selective adenomectomy is the best method available at present for the treatment of Cushing's disease, its success depends to a large degree on precise preoperative intrapituitary microadenoma localization. This study compares the results of intrapituitary adenoma localization obtained with inferior petrosal sampling, computerized tomography and magnetic resonance imaging with the adenoma localization as found at surgery.

DESIGN The results of inferior petrosal sampling for intrapituitary localization of ACTH‐producing pituitary adenomas were compared in a retrospective study with the results of computerized tomography, magnetic resonance imaging, surgical and pathological findings. Special attention was paid to the intersinus ACTH relation.

PATIENTS Thirty‐eight patients (33 women and 5 men) of 11‐68 years of age suffering from pituitary‐dependent Cushing's disease were studied. Patients with ectopic ACTH‐secreting tumours and and recurrent pituitary adenomas were excluded.

MEASUREMENTS Blood samples were obtained simultaneously from both inferior petrosal sinuses and a peripheral vein before and 5, 10, 15 and 20 minutes after stimulation with 60 /μg/m2 human corticotrophin‐releasing hormone (hCRH).

RESULTS of the adenomas in our series, 42% had a diameter of 3 mm or less. Only 6 of 20 adenomas examined by computerized tomography and 11 of 29 examined by magnetic resonance imaging were identified correctly. Inferior petrosal sinus sampling produced significantly better results, particularly when combined with a stimulation test with hCRH: for 29 of 38 adenomas examined, the location was predicted correctly with these techniques. Analysis of the intersinus adrenocorticotrophin concentration ratio showed that the best right‐central‐left discrimination was obtained with values of 1.3 and 1.4.

CONCLUSIONS We conclude that inferior petrosal sinus ACTH sampling after hCRH stimulation is the best method available for the intrapituitary localization of microadenomas causing Cushing's disease provided that the appropriate technique of blood sampling is used meticulously.
Plasma corticotrophin releasing hormone, vasopressin, ACTH and Cortisol responses to acute myocardial infarction
Authors: Donald R. A. , Crozier I. G. , Foy S. G. , Richards A. M. , Livesey J. H. , Ellis M. J. , Mattioli L. , Ikram H.
Published: March 2008

OBJECTIVES We assessed the magnitude and duration of the response of hypothalamic‐pituitary‐adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and Cortisol, during a prolonged medical stress.

DESIGN All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure.

PATIENTS Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily.

MEASUREMENTS Peptide hormones were measured by radioimmunoassay, and Cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll.

RESULTS At the start of the study, mean±SEM plasma AVP (27.9 ± 4.6 pmol/l) was significantly (P<0 001) raised above the mean for the reference range (1.82 ± 0.09 pmol/ I), and 12 patients had values >50 pmol/l. Mean plasma Cortisol (960 ± 89.6 nmol/l) was also raised above the reference range mean (554±28 nmol/l, P<0.001), as was mean plasma CRH (4.97 ± 0.5 pmol/l, reference mean 1.52± 0.09 pmol/l, P<0001). By contrast, mean ACTH (3.88 ± 0.66 pmol/l) was significantly less than the reference mean (10.7 ± 0.7 pmol/l, P<0.001). During the 72‐hour observation period there was a highly significant fall (P<0.001) in plasma CRH, AVP and Cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or Cortisol (P<0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or Cortisol responses to placebo, captopril or enalapril were observed.

CONCLUSIONS Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and Cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and Cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and Cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1, AVP receptor antagonists may have a therapeutic application in limiting infarct size.
The renin‐aldosterone axis in patients with diabetes insipidus
Authors: Antaraki Aspasia , Rangou Despina , Chlouverakis Constantino
Published: March 2008

OBJECTIVE The objective of the present study was to investigate the renin‐aldosterone axis in neurogenic diabetes insipidus in man, in view of the fact that profound abnormalities of this axis have been described in experimental animals with congenital neurogenic diabetes insipidus.

DESIGN AND PATIENTS Nine patients with neurogenic diabetes insipidus and 11 healthy subjects (controls) were examined under basal conditions, following the standard 8‐hour water deprivation test and 1 hour after a subsequent oral rehydration.

MEASUREMENTS Plasma and urine osmolalities were determined by freezing point depression, plasma sodium and potassium by a method using an ion‐selective electrode, plasma AVP, Cortisol, aldosterone and plasma renin activity by radioimmunoassay.

RESULTS Plasma renin activities under basal conditions were significantly higher in patients with diabetes insipidus than in controls (mean ± SEM 23.4 ± 6.6 vs 7.8 ± 1.2 ng/ I min). In the diabetes insipidus group, water deprivation caused a twofold Increase in plasma renin activities (48 ± 13.8 ng/l min), while in the control group plasma renin activity levels were not significantly altered (10.2 ± 1.2 ng/l min). Rehydration did not alter plasma renin activity levels in either group (patients 50.4 ± 13.2, controls 9.0 ± 2.4 ng/l min). Plasma aldosterone concentrations under basal conditions did not differ between the two groups (patients 302.4 ± 37, controls 326.4 ± 36.5 pmol/l) and did not change in patients with diabetes insipidus after water deprivation or rehydration (307.5 ± 67.2 and 385.5 ± 91 pmol/l, respectively). Conversely, controls showed a significant decrease in plasma aldosterone levels after dehydration (201 ± 27.9 pmol/l), which was attributed to the circardian variation in aldosterone secretion, as shown by a parallel decrease in plasma Cortisol levels.

CONCLUSIONS Patients with diabetes insipidus are hyper‐reninaemic, probably because of chronic volume contraction. There is a dissociation between renin and aldosterone in patients with diabetes insipidus under basal conditions, which is exaggerated during water deprivation.
The effects of recombinant human insulin‐like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus
Authors: Cheetham Tim D. , Clayton Kharen L. , Taylor Alistair M. , Holly Jeff , Matthews David R. , Dunger David B.
Published: March 2008

OBJECTIVE It has been proposed that low IGF‐I levels and reduced IGF‐I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM). We have therefore studied the effects of human recombinant insulin‐like growth factor I (rhIGF‐I) administration on GH levels and GH secretion in adolescents with IDDM.

PATIENTS Nine late pubertal adolescents (four male and five female) with IDDM.

DESIGN A double‐blind placebo controlled study of rhIGF‐I administered subcutaneously in a dose of 40 μg/kg body weight at 1800 h.

MEASUREMENTS IGF‐I and GH concentrations were measured at regular intervals throughout the study. Twenty‐two hour GH secretory rates were calculated by deconvolution analysis. Overnight GH profiles were analysed by distribution analysis, and Fourier transformations were performed on both overnight GH concentrations and GH secretory rates.

RESULTS Mean IGF‐I levels over the 22‐hour study period were significantly elevated following rhIGF‐I administration (350 ± 26 vs 205 ± 21 μg/l (mean ± SEM), P<0 001). Mean 22‐hour GH levels were reduced following rhIGF‐I administration (19.4 ± 4.0 compared with 33.6 ± 5.8 mU/l; P= 001). Distribution analysis demonstrated that the reduction in GH levels was due to changes in the proportion of values at both high and low concentrations. Deconvolution analysis also revealed a significant overall reduction in GH secretory rate following IGF‐I administration (1.81 ± 0.30 vs 2.98 ± 0.47 mU/min, P= 0.01) which was still apparent during the final 5.5 hours of the study period (1.51 ± 0.30 vs 2.76 ± 0.61 mU/min, P= 002). The dominant periodicity of GH secretory episodes as determined by Fourier transformation was between 120 and 180 minutes after both IGF‐I and placebo.

CONCLUSIONS In late pubertal adolescents with IDDM the rise in IGF‐I levels following rhIGF‐l administration in a subcutaneous dose of 40 μg/kg body weight leads to a significant reduction in GH levels and GH secretory rate. The reduction in GH secretion is due to changes in pulse amplitude rather than frequency. A reduction in GH secretion was apparent at the beginning and also towards the end of the 22‐hour study period.
Alteration of the circadian rhythm of intact parathyroid hormone following a 96‐hour fast
Authors: Fraser W. D. , Logue F. C. , Christie J. P. , Cameron D. A. , O'Reilly D. St J. , Beastall G. H.
Published: March 2008

OBJECTIVE PTH(1‐84) secretion in normal male subjects follows a circadian rhythm. The control of this rhythm is multifactorial with both neuroendocrine and chemical influences. The aim of this study was to assess the effect of a 96‐hour fast on the circadian rhythm of PTH(1 ‐84), serum calcium, phosphate and nephrogenous cAMP (NcAMP), an index of PTH(1‐84) bioactivity.

DESIGN Blood samples for estimation of all analytes were obtained over a 24‐hour period at 30‐minute intervals. Urine samples were obtained 4 hourly during the daytime and overnight. Each subject was studied on two occasions after being randomized to either (a) normal hospital diet or (b) a 96‐hour fast with water freely available.

SUBJECTS Six healthy adult males aged between 28 and 40 years, mean 32 years.

MEASUREMENTS PTH(1‐84) was measured by an in‐house immunoradiometric assay. Serum calcium, phosphate, albumin, creatinine and urinary creatinine were measured by standard automated techniques. Calcium was adjusted for albumin. Plasma cAMP was estimated by a commercial method and urine cAMP by in‐house radioimmunoassay and NcAMP obtained by calculation. Rhythm parameters were analysed by cosinor techniques. RESULTS There were alterations in the circadian rhythms of serum phosphate, PTH(1–84) and NcAMP following a 96‐hour fast. Fasting abolished the nocturnal rise in phosphate, PTH(1‐84) and NcAMP but had little effect on the pattern of adjusted calcium over a 24‐hour period. The mean concentrations of serum phosphate, adjusted calcium and NcAMP decreased significantly following the fast and mean PTH(1‐84) increased during day time.

CONCLUSIONS Fasting for 96 hours significantly alters the circadian rhythm of PTH(1‐84) secretion by lowering the mean calcium concentration and attenuating the circadian rhythm of serum phosphate.
Detection of dimeric inhibin throughout the human menstrual cycle by two‐site enzyme immunoassay
Authors: Groome N. P. , Illingworth P. J. , O'Brien M. , Cooke I , Ganesan T. S. , Baird D. T. , McNeilly A. S.
Published: March 2008

OBJECTIVE We have developed and validated a two‐site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle.

DESIGN Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32kDa inhibin. Daily samples were assayed from four women through a menstrual cycle.

PATIENTS (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post‐menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25–33.

RESULTS Post‐menopausal women had less than 2ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125ng/l.

During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3‐4ng/l (CI 2.2‐5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1‐81,1)) in the mid‐luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater.

CONCLUSION The human ovary, In particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.
Short‐term fasting in normal women: absence of effects on gonadotrophin secretion and the menstrual cycle
Authors: Soules M. R. , Merriggiola M. C. , Steiner R‐ A. , Clifton D. K. , Toivola B. , Bremner W. J.
Published: March 2008

OBJECTIVE In men and male monkeys, a short‐term fast has been reported to have a major effect on the reproductive axis. In this study we investigated the effects of a short‐term fast (72 hours) on female reproductive hormone secretion and menstrual function.

DESIGN The study consisted of an admission day (control), three successive fasting days (fast 1, 2 and 3) and a refeeding day (post fast).

PATIENTS Eight normal cycling women, ages 21–35, within 10% of ideal body weight, were fasted for 72 hours during the follicular phase of their menstrual cycle.

MEASUREMENTS On the admission day, the last day of the fast and the day of refeeding, blood samples were collected at 10‐minute intervals from 0800 to 2000 h for determination of the LH pulse pattern. Daily determinations of immuno LH, FSH, oestradiol (E) and progesterone (P) were performed throughout the menstrual cycle in which the fast occurred.

RESULTS Throughout the fasting days, the consistently low serum levels of glucose and insulin confirmed that all the subjects were fasting. However, in spite of profound metabolic changes and a significant loss of weight, the short‐term fast did not have discernible effects upon the reproductive hormones studied. Basal mean LH concentrations did not show any significant variation throughout the study period. The mean ± SEM number of LH pulses was 134 ± 1.5/12h on the control day, 12.4 ± 1.2/12h (NS) on the third day of fasting and 11 0 ± 1.5/12 h (NS) the day of refeeding. Each woman maintained a physiological pattern of LH, FSH, E and P throughout the menstrual cycle including the LH surge; ultrasound evidence of normal growth of a dominant follicle; and cycle length consistent with previous cycles.

CONCLUSIONS Our results indicate that in spite of profound metabolic changes, a 72‐hour fast during the follicular phase does not affect the menstrual cycle of normal cycling women. It appears that the female reproductive axis during this phase of the cycle Is more resistant to an acute caloric deprivation than that of men or male monkeys.
Reduced lymphocyte β2‐adrenoceptor density and impaired diastolic left ventricular function in patients with glucocorticoid deficiency
Authors: Allolio Bruno , Ehses Wolfgang , Steffen Hans Michael , Müller Ralf
Published: March 2008

OBJECTIVE Patients with adrenal crisis are at risk of severe hypotension not responding to administration of catecholamines. As glucocorticoids may be a prerequisite for intact β‐adrenoceptor function, impaired adrenoceptor activity may explain the hypotension and reduced cardiac performance in adrenal insufficiency. The aim of our study was, therefore, to further elucidate the permissive action of glucocorticoids on adrenergic function and cardiac performance.

DESIGN Prospective randomized controlled study.

PATIENTS Nine patients with adrenal insufficiency were investigated before and 48 hours after glucocorticoid withdrawal. Mineralocorticoid therapy remained unchanged during the study period.

MEASUREMENTS Lymphocyte β2‐adrenoceptor density, intracellular c‐AMP response to isoprenaline, platelet α2‐receptor density, plasma catecholamines, serum Cortisol, plasma ACTH, echocardiography.

RESULTS Glucocorticoid depletion was demonstrated by a fall in serum Cortisol from mean ± SEM 441 ± 62 to 45 ± 18 nmoI/I. Glucocorticoid withdrawal decreased lymphocyte β2‐receptor density from 798±111 to 498 ± 54 binding sites/cell (P<0.05) and the intracellular c‐AMP response to isoprenaline from 15.0 ± 4.2 to 8.2 ± 1.7 pmol/106 cells (P< 0.05). Echocardiography showed impaired diastolic relaxation after glucocorticoid withdrawal with prolongation of the rapid filling period (80.3 ± 12.5 vs 138.3 ± 11.8 ms, P < 0.05). Plasma catecholamines, platelet α2‐receptor density and systolic left ventricular function were not affected by glucocorticoid deficiency.

CONCLUSIONS This study demonstrates the importance of normal glucocorticoid levels for β2‐adrenoceptor function and helps to explain the decreased responsiveness to catecholamines and the impaired cardiac performance in adrenal crisis.
17β‐Oestradiol counteracts the formation of the more acidic isoforms of follicle‐stimulating hormone and luteinizing hormone after menopause
Authors: Wide Leif , Naessén Tord
Published: March 2008

OBJECTIVE When the gonadotropin levels increase at midcycle, more basic isoforms of FSH and LH appear in the circulation. However, when these gonadotrophins increase at menopause more acidic forms appear. The present study was done to see whether chronic 17β‐oestradiol (E2) administration to post‐menopausal women could counteract the formation of the more acidic isoforms after the menopause.

DESIGN Serum samples were obtained from 16 postmenopausal women, mean age 70 years (range 63‐84 years), 46‐169 days after the subcutaneous insertion of a 20‐mg E2‐implant. FSH, LH and E2 in the sera were measured with fluoroimmunoassays. The median charge and the degree of charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 01% agarose suspension. Sera from an age‐matched control group were analysed in parallel.

RESULTS The E2 levels in the E2‐treated women were 230–570 pmoI/I, within the range expected during the midluteal phase of the normal menstrual cycle. The mean serum FSH and LH levels were similar to normal follicular phase FSH and LH levels (8 6 and 20 8% respectively of the control group). It was estimated that individual serum specimens from both groups contained 20–30 different isoforms for both FSH and LH. The median charges of the isoforms of FSH and LH were more basic in all the E2‐treated subjects than in their corresponding untreated controls. The mean median charge for FSH was close to the values for the follicular and luteal phases and that for LH close to that for the luteal phase. In some E2‐treated women the isoforms were even more basic with a charge similar to that at the midcycle peak. The degree of charge heterogeneity for the E2‐treated group was significantly (P<0.001) larger than for the controls and similar to that during the normal menstrual cycle.

CONCLUSION Chronic E2 administration to post‐menopausal women counteracted the formation of more acidic isoforms of both FSH and LH after the menopause.
Effect of different treatment regimes on linear growth and final height in β‐thalassaemia major
Authors: De Sanctis Vincenzo , Katz Maurice , Vullo Calogero , Bagni Bruno , Ughi Monica , Wonke Beatrix
Published: March 2008

OBJECTIVE The clinical picture of thalassaemia major has changed progressively over the years. Our study is a retrospective analysis of data on growth in a group of patients who have completed puberty spontaneously and have attained their adult height. Our objective was to evaluate the effect of different transfusion regimes and desferrioxamine administration on the growth pattern in β thalassaemia major.

DESIGN AND PATIENTS We studied 64 patients (28 males and 36 females). The patients were divided into three groups (A, B and C) according to the different transfusion regimes and the schedules of chelating therapy. Group A consisted of 16 patients who were transfused regularly at low haemoglobin levels (on average 8 5 g/dl) from an early age and started subcutaneous chelation therapy during adolescence. Group B consisted of 19 patients who were transfused regularly at high haemoglobin levels (on average 10 g/dl) from an early age and started subcutaneous therapy during childhood. Group C consisted of 29 patients who were transfused regularly at high haemoglobin levels (on average 10‐5 g/dl) from an early age and started subcutaneous chelation therapy very early, at a mean age of 2 years. Standard auxological measurements were made at 3‐monthly intervals throughout childhood and puberty until adult height was achieved. For group C patients the data on linear growth are provided only until the age of 12 years.

RESULTS Our study indicates that group A male and female patients did not grow significantly better than those in group B. Group C male and female patients, surprisingly, grew no faster than those who started chelation therapy late in childhood (group A). The most striking feature in the majority of both group A and B patients was reduced spurt in height at puberty. In addition, in both groups, a reduced sitting height due to spinal growth abnormality was found. An inverse correlation between sitting height and serum ferritin levels was observed in group A patients (r=–055, P<0 05), whereas there was a direct correlation in group B patients (r= 0 42, P< 0.05).

CONCLUSIONS These data suggest that an ideal therapeutic regime has yet to be found which avoids the toxic effect of iron overload and on the other hand avoids interference with growth, secondary to desferrioxamine. Therefore we recommend that the growth of thalassaemia patients be monitored routinely at every follow‐up visit and documented on growth velocity charts in order to detect early changes in their growth pattern and to establish an appropriate protocol for investigation and treatment.
Hypothalamic‐pituitary ageing: progressive increase in FSH and LH concentrations throughout the reproductive life in regularly menstruating women*
Authors: Ebbiary N. A. Ahmed , Lenton E. A. , Cooke I. D.
Published: March 2008

OBJECTIVE Reproductive ageing is associated with reduced fertility and endocrine changes that become more pronounced during the perimenopausal period. We aimed to assess changes in gonadotrophin concentrations and the onset of these changes during the reproductive life prior to the perimenopause.

SUBJECTS Ovarian and pituitary hormones were measured and follicle growth monitored In 500 regularly cycling infertile women aged 20–44 years.

MEASUREMENTS Serum levels of FSH and LH were determined during the follicular phase and ultrasonography was used to monitor follicle growth and ovulation. The luteal phase was assessed by sallvary progesterone measurements. Changes In basal FSH and LH with age during ovulatory cycles were assessed.

RESULTS There was a significant progressive increase in FSH levels as early as age 29–30 years which was continued throughout the 30s and became more marked in the early 40s. LH levels showed significant Increase at the age of 35–36 years which was maintained till the age of 40 years and followed by a further increase in women aged > 40 years.

CONCLUSION An increase in FSH and LH concentrations can be detected In women with regular ovulatory cycles quite early during the reproductive life. The Increase In basal FSH (and later LH) may represent the earliest endocrine marker of reproductive ageing. These age‐related increases in FSH and LH can be used as hormonal markers to counsel patients as to the likelihood of their reproductive potential.