bluuebunny/crossref_metadata_2025 huggingface dataset:
Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors
Authors: Martínez‐Mora J. , Sáez J. M. , Torán N. , Isnard R. , Pérez‐Iribarne M. M. , Egozcue J. , Audí L.
Published: March 2008

objective The aim of our study was to establish the definitive diagnosis In an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the ago of 8, based on genetic, clinical and pathological studies

design Hypothalamo–hypophysio–testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro.

patient At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid

measurements LH and FSH were determined pre‐ and post‐gonadectomy. Progesterone, 17‐OH‐progesterone, androstenedione, dehydroepiandrosterone testosterone (1) and oestradlol were determined basally in peripheral and spermatic blood post‐hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5a‐reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. RESULTS LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Ley‐dig‐like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5α‐reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27·0 vs 9·4 ± 0·8 ± mol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low.

conclusions The patient was considered to have an almost complete form of Leydig cell agenesia/hypoplasia in which absence of specific LH binding correlated with total absence of differentiated Leydig cells and Insensitivity of undifferentiated interstitial cells to LH stimulation
Comparison of the effects of ANF 99–126 and ANF 103–126 on captopril‐induced renin release in man
Authors: Lang Chim C. , McMurray John J. , Moyses Christopher , Struthers Allan D.
Published: March 2008

objective The aim was to examine the effects of atrial natriuretic factor (ANF) 99–126 and ANF 103–126, an N‐terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin‐converting enzyme

design Two protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5%d‐glucose (placebo), or ANF 99–126 3 or 10 pmol/kg/min, was administered In a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103–126 either 3 or 10 pmol/kg/min to placebo

subjects Thirty‐three salt‐replete healthy male volunteers aged 21–39 years were studied in the supine position

measurements Plasma renin activity, plasma ANF 99–126 and ANF 103–126 levels, heart rate and blood pressure were measured

results Compared to placebo Infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99–126 infusion (from 755% of baseline to 294% by ANF 99–126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min; P>0·03 and P>0·01 respectively). The comparable findings with ANF 103–126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P>0·01 and P>0·01 respectively).

conclusions The results, taken in conjunction with previous findings, suggest that artrial natriuretic factor inhibits in a non‐selective manner the renin response to all secretagotues so far tested In man. The current results also suggest that the anti‐renin action of atrial natriuretic factor does not depend on the first four N‐terminal amino acids of the native peptide
Influence of sodium valproate on late follicular phase pulsatile LH secretion in normal women
Authors: Abeal J. Lado , Agricola J. Cabezas , Carreira J. M. Paz , Cabezas‐Cerrato J.
Published: March 2008

objective To study whether modulation of the GABAergic system (with sodium valproate) affects pulsatile LH secretion in the late follicular phase of normal women

design Fifteen normal women volunteers were studied over an 8‐hour period in the late follicular phase of two successive menstrual cycles. On each occasion, blood samples were taken every 10 minutes between 1000 and 1800 h. Nine of the volunteers—the short treatment group—were administered 400 mg of sodium valproate every 8 hours on the two days preceding their second session, and a further 400 mg at 0900 h on the day of the session. The other six—the long treatment group—were administered 400 mg of sodium valproate every 8 hours on the seven days preceding their second session and at 0900 and 1400 h on the day of the session

measurements LH, oestradiol and progesterone were determined by radloimmunoassay, and sodium valproate by repolarization fluorescence spectrophotometry. Pulse detection was carried out both by the program ULTRA and by a method developed by the authors

results There were no significant differences In LH pulse amplitude or relative pulse amplitude between records taken in the first and second menstrual cycles, i.e. without or with prior sodium valproate treatment. Short treatment did change interpulse interval and mean secretlon period, but the changes, though statistically significant, were small (about 10 minutes), so that the values for both post‐treatment and control sessions were within the normal range; these parameters were unaffected by long treatment

conclusions Activation of the GABAergic system with sodium valproate had no biologically significant effect on the late follicular phase pulsatile LH secretion of these normal women
Naloxone does not modify fenfluramine‐induced prolactin increase in obese patients
Authors: Argenio G. F. , Bernini G. P. , Vivaldi M. S. , del Corso C. , Santoni R. , Franchi F.
Published: March 2008

objective To evaluate whether the supposed physiological interaction between serotoninergic and opioidergic pathways in the modulation of PRL release is preserved in human obesity, a pathological condition in which these two systems are greatly impaired

design According to a single‐blind randomized procedure, three tests were performed: test A (oral placebo + saline infusion over 5 hours), test B (fenfluramine, a well known serotoninergic drug, 60 mg orally + saline infusion over 5 hours) and test C (fenfluramine at the same dose + naloxone, an opiate receptor antagonist, infusion over 5 hours at a dose of 3 mg/h)

patients Ten obese women (body mass index 34·4±2·3 kg/m2, mean ± SE) and ten normal‐weight sex and age‐matched subjects (body mass index 22·3±2·4 kg/m2) volunteered for the study.

measurements At each test, blood samples for PRL determination were collected in basal conditions (time 0) and every hour for 5 hours. Plasma PRL was determined by radiolmmunoassay

results In controls, naloxone significantly reduced the clear‐cut PRL increase induced by fenfluramine. In obese patients, serotoninergic stimulation caused an increment in PRL levels similar to that in the controls, but oplold receptor blockade by naloxone did not affect this response

conclusions These findings confirm that there is a physiological relationship between the serotoninergic and the opfoiderglc systems in the control of PRL secretion and show that this interaction is not present in obese subjects. Our data provide indirect proof of the functional impairment of these two systems in human obesity
Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1
Authors: Marx Stephen J. , Menczel Jacob , Campbell Gregory , Aurbach Gerald D. , Spiegel Allen M. , Norton Jeffrey A.
Published: March 2008

objective We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroldlsm

design At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration

patients We studied subjects with FMEN1 and primary hyperparathyroldfsm

measurements The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibllity of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume

results The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9·6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1·45

conclusions There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroldlsm
Nephrogenous cyclic AMP in primary hepatocellular carcinoma patients with or without hypercalcaemia
Authors: Panesar N. S. , Au K. M. , Leung Nancy W.Y. , Shek C. C. , Swamlnathan R.
Published: March 2008

objective To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH‐like activity in patients with primary hepatocellular carcinoma

design After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various anaytes and results compared between various groups

patients Fifty‐five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only

measurements Serum calcium, phosphate, aikaline phosphatase, albumin, creatinine and urinary calcium, creatnine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Dioagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods

results Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P > 0·05) phosphate, PTH and TmP/GFR and elevated NcAMP (P > 0·001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P > 0·001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercaicaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH.

conclusion We conciude that a PTH‐like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed
A 64 kDa membrane antigen is a recurrent epitope for natural autoantibodies in patients with Graves' thyroid and ophthalmic diseases*
Authors: Kendler David L. , Rootman Jack , Huber Gerold K. , Davies Terry F.
Published: March 2008

objective We have explored the recently described 64 kDa extraocular muscle antigen that is associated with autoantibodies in the serum of patients with severe Grave's ophthalmopathy. The localization of the antigen and the specificity of autoantibodies for both eye muscle antigens and ophthalmopathy patients were investigated

design Western blotting and immunoprecfpftatlon of metabolically labelled antigen from eye muscle and control tissues with sera from ophthalmopathy, Graves' without ophthalmopathy, and normals were used

patients Sera from normals (n= 9), patients with recent onset Graves' ophthalmopathy (n= 23), and patients with Graves' disease without ophthalmopathy (n= 8) were utilized.

measurements Immunoblots using detergent phase separated (amphiphilic) antigen preparations from fetal eye muscle, skeletal muscle and control tissues were quantitated. Metabolically labelled eye muscle and skeletal muscle antigens were immunoprecipitated using patient and control IgG

results In the eye muscle detergent phase, immuno‐reactivity around 64 kDa was detected in 30% of the patients with ophthalmopathy (n= 23) as well as 38% of patients with Graves' disease and no ophthalmopathy (n= 8) and in 30% of normal sera (n= 9). There was significantly more of this antl‐64 kDa reactivity in sera from the ophthalmopathy patients compared with the normals (P > 0·01). 64 kDa reactivity to detergent phase antigens prepared from human thyroid, skeletal muscle, brain, and liver was also observed with these positive sera indicating the polyreactlvfty of the IgG interactions to conserved antigens in this region.

conclusions We conclude that IgG antibodies binding to a recurrent 64 kDa antigen are present in many normal human sera, with increased concentrations detectable in sera from Graves' ophthalmopathy patients. Such ‘specificity‐crossover’ with similar molecular weight trans‐membrane antigens is likely to be caused by natural autoantibodies reacting with recurrent autoepitopes rather than a factor aetiological in the disease process
The pituitary gland is capable of responding to two successive doses of growth hormone releasing hormone (GHRH)
Authors: Suri D. , Hindmarsh P. C. , Matthews D. R. , Brain C. E. , Brook C. G. D.
Published: March 2008

We have studied the serum growth hormone (GH) response to two consecutive doses of growth hormone releasing hormone (GHRH) (50, 100, 200 μg) given 1, 2 or 3 h apart in seven adult males. The serum GH profile was analysed by deconvolution incorporating a variable half‐life for OH. All three doses of GHRH stimulated maximal GH secretion: 50 μg, 146.0 mU/min (SEM 24.0); 100 μg, 128.1 mU/min (SEM 14.3); 200 μg, 134.1 mU/min (SEM 20.5) (one‐way ANOVA, P = NS). The magnitude of the second secretory burst after the second dose of GHRH was less than that Induced by the first injection of GHRH, particularly when doses of 200 μg were used. Factors influencing the response to the second dose were the GH secretory status at the point that the stimulus was applied and the time interval between administration of the first and second doses. These studies demonstrate that the pituitary gland is capable of responding to two consecutive doses of GHRH although the second response is always less than the first. The data demonstrate the importance of using methods of assessing GH secretion and not relying simply on measured serum GH concentration values

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Testosterone‐secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21‐hydroxylase deficiency
Authors: Leinonen Pekka , Ranta Tapio , Slegberg Rita , Pelkonen Risto , Heikkilä Päivi , Kahri Arvi
Published: March 2008

A 60‐year‐old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17‐hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8–18.4 nmol/l) were remarkably high (normal range 0.7–2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21‐hydroxylated steroids In contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin‐responsive testosterone‐secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21‐hydroxylase activity
Disturbance of osmoregulated thirst and vasopressin secretion in thyrotoxicosis
Authors: Harvey J. N. , Nagl D. K. , Baylis P. H. , Wllkinsont R. , Belchetz P. E.
Published: March 2008

Summary. objective To assess the effect of untreated thyrotoxicosis on osmoregulated thirst sensation and AVP secretion.

design Measurements were made at 30‐minute Intervals while untreated thyrotoxic patients were given sodium chloride 855 mmol/l Intravenously for 2 hours followed by water drinking adlibitum for 2 hours. The protocol was repeated when the patients were euthyroid.

patients Eight newly diagnosed thyrotoxic patients were studied.

measurements Thirst sensation (visual analogue scale), plasma osmolality, AVP and plasma renin activity were measured.

results Prior to osmotic stimulation and after plasma osmolality had been returned to normal by drinking water, thirst sensation was Increased in the thyrotoxic state. Plasma AVP showed an exaggerated response to hypertonic saline in the patients when they were thyrotoxic. Increasing plasma osmolality produced a linear Increase in thirst sensation and log linear increase in plasma AVP. However, in the thyrotoxic state both these relations were altered. The apparent osmolar thresholds for onset of thirst sensation and AVP release were similar (281 and 280 mosm/kg respectively) and were reduced similarly In the thyrotoxic state (269 and 274 mosm/kg respectively).

conclusions The osmostat mechanisms which regulate thirst sensation and AVP release are reset In the thyrotoxic state. The responses of thirst sensation and of plasma AVP to increasing plasma osmolality are altered similarly, suggesting that thyrotoxicosls affects both homeostatic functions by a common mechanism.
Stimulation and suppression of intact parathyroid hormone (PTH1–84) in normal subjects and hyperparathyroid patients
Authors: Lips Paul , Netelenbos J. Coen , Doorn' Lena van , Hackeng Wll H. L. , Llps Cees J. M.
Published: March 2008

Summary. objective Because of an overlap between serum PTH values In healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups.

subjects Subjects were 34 patients with primary hyperparathyroidlsm (PHPT) and 25 healthy controls.

design After stimulation with Intravenous EDTA (10 mg/kg body weight In 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an Intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes.

measurement Serum PTH(1–84) was measured by a double antibody technique.

results The intravenous EDTA test resulted in an average 2‐6‐fold Increase of serum PTH(1–84) In hyperparathyroid patients, whereas it increased 10.5‐fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroldism and controls. The oral calcium dose decreased serum PTH(1–84) In patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1–84) In hyperparathyrold patients to 0.51 and in control subjects to 0.40 of the basal value, and non‐responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium Infusion tests In the patients (r=0.97, P < 0.1). Fasting serum calcium and serum PTH(1–84) showed a positive correlation in PHPT patients (r= 0.75, P< 0.001) and a negative correlation in control subjects (r= ‐0.41, P<0.05). Based on these relationships, hyperparathyrold patients and controls could be completely separated.

conclusion The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests Is less marked In patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroldism.
Prevalence of thyroid deficiency in pregnant women
Authors: Klein R. Z. , Haddow J. E. , Falx J. D. , Brown R. S. , Hermos R. J. , Pulkkinen A. , Mitchell M. L.
Published: March 2008

Summary. objective The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring.

design TSH concentrations were measured In the sera of women at 15—18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest In order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyrold antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and /or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women.

patients The sera were from 2000 consecutive women In Maine being tested for alpha‐fetoprotein concentration at 15–18 weeks of gestation.

results TSH concentrations above 6 mU/l ere found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9–54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty‐eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls.

conclusions Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data Indicate a sufficiently high prevalence of thyroid dysfunction to demand Investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.
Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism
Authors: Price D. E. , O'Malley B. P. , Northover B. , Rosenthal F. D.
Published: March 2008

Summary. objective We have previously reported that, In thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time Interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine.

design and patients

Serum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over‐replaced, as defined by an elevated free T4 and a sub‐normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26–0.32).

results After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 × 0.95 and 12.2 × 1.5 days respectively (mean‐. SEM). The TSH was the first parameter to leave the euthyroid range In all subjects except one in whom the serum TSH was fully suppressed (< 0.05 mU/l) Initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 × 0.8 and 9.4 × 0.7 days respectively). In contrast, In the over‐replaced group serum TSH and STI became elevated after 12.4 × 1.0 days (P < 0.005 vs euthyrold group) and 16.0 × 2.7 days (P < 0.05 vs euthyroid group) respectively. There was no delay In the fall in serum T4 or T3 in the over‐replaced group when compared with the euthyrold group. CONCLUSIONS in the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal In advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these Individuals.
Glucocorticoid receptors in lymphocytes in anorexia nervosa
Authors: Glrardln E. , Garoscio‐Cholet M. , Dechaud H. , Lejeune H. , Carrier E. , Tourniaire J. , Pugeat M.
Published: March 2008

Summary. objective The aim was to explore the down‐regulation of the glucocortlcoid receptors during hypercortlsolaemla in anorexia nervosa.

design Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were Isolated for receptor binding studies.

patients Sixteen anorexic patients, aged 16–27 years, with a meanSEM body mass Index of 14.2.2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain.

measurements The binding capacity and affinity of the glucocorticold receptors were measured with dexamethasone as llgand on lymphocytes.

results In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of giucocorticold receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687.1750 vs 7347.1285 sites/cell; Kd: 7.7.2.4 vs 7.4.1.7 nM at 24.C). After weight gain (14.2 to 16.2 kg/ m2), receptor numbers were 8421 .2126 (pre) and 9011 . 500 (post) sites/cell, which are not significantly different (p>0.2); the Kd was unchanged (9.3.2.6 vs 9.2.2.4 nM).

conclusions Hypercortlsolaemla does not down‐regulate the lymphocyte glucocorticoid receptors In anorexia nervosa and a post‐receptor defect might be Involved in peripheral tissue resistance to the effects of gtucocortlcold hormones in undernutrition.
Association between autoimmune thyroid disease and Familial Alzheimers disease
Authors: Ewins David L. , Rossor Martin N. , Butler Joan , Rogues Penelope K. , Mullen Michael J. , McGregor Alan M.
Published: March 2008

Summary. objective To determine the prevalence of autoimmune thyroid disease in Familial Alzheimer's Disease kindreds and to ascertain whether there is any evidence for genetic linkage between the two conditions.

design Retrospective study of Familial Alzheimer's Disease kindreds.

patients Seventy affected and unaffected family members from 12 kindreds.

measurements Antl‐thyroglobulin and anti‐microsomal autoantibody status was determined using an enzyme‐linked immunosorbent assay. Thyrotrophin levels were determined by an Immunoradiometric assay.

results Of the family members, 41.4% had evidence of autoimmune thyroid disease, with significant co‐segregation between the presence of thyroid autoantibodles and the development of Alzheimer's disease (p<0.01).

conclusions This study demonstrates a very high prevalence of autoimmune thyroid disease In Familial Alzhelmer's Disease kindreds and suggests that a genetic factor contributing towards the development of auto‐Immune thyroid disease may be located on chromosome 21 within close proximity to the Familial Alzheimer's Disease gene.
Clonidine pretreatment modifies the growth hormone secretory pattern induced by shortterm continuous GRF infusion in normal man
Authors: Lima L. , Arce V. , Diaz M. J. , Tresguerres J. A. F. , Devesa J.
Published: March 2008

Summary. objective The aim of this study was to Investigate the effect of a single dose of clonidlne on the pattern of GH release in response to a 10‐hour continuous GRF infusion in normal man.

design Plasma GH was analysed In samples withdrawn at 20‐mlnute Intervals, from 0900 to 1900 h, according to the following protocols: in a control study, a placebo was given at 1000 h; in other experiments, clonidlne (300 μg, oraily) was given at 1000 h, alone or together with a continuous intravenous Infusion of GRF 1–29 (0.3 μg/kg/h) starting at this time. In another experiment, the continuous Infusion of GRF 1–29 was preceded by placebo administration at 1000 h.

patients

Eight normal volunteers (four women and four men), aged 19–24 years were studied. MEASUREMENTS Plasma GH levels were measured by RIA. Analysis of the pattern of GH secretion was performed using cluster analysis.

results

Clonidlne induced a slight but significant increase In plasma GH values, peaking 60 to 120 minutes later; however, no significant changes were observed in Indices of total and pulsatile GH release for the whole sampling period in this study. Continuous GRF administration led to increased episodic GH secretion, by augmentIng GH peak amplitude, although peak frequency was not modified. An increase in interpulse GH values was also observed during GRF infusion. Pretreatment with clonidine clearly changed the pattern of GH release during GRF infusion: the amount of GH secreted was significantly higher, the number of GH peaks significantly Increased, and almost all the GH was secreted within them.

conclusions

These data concord with our previous demonstration that clonidlne disrupts the hypothalam‐somatotroph rhythm by Inhibiting the hypothaiamic release of somatostatin. Given that clonidlne pretreatment induced a more physiological episodic pattern of GRF‐ induced GH release, the possibility of combining clonidipe and GRF therapy for short stature In children is envisaged.
Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients
Authors: Valcavl R. , Dieguez C. , Zini M. , Page M. D. , Dottl C. , Portioli I. , Scanlon M. F.
Published: March 2008

Summary. objective We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion.

design Pyridostigmine was given orally, then GHRH injected i.v., and levels were measured. In a separate study, pirenzepine was injected i.v., then GHRH, and growth hormone levels were measured. PATIENTS Thyrotoxic patients were compared with normal subjects.

measurements

GH was measured from – 30 to + 120 minutes at intervals of 15 minutes.

results Pyridostigmine markedly increased GH responses to GHRH in normal subjects, but not in thyrotoxic patients. Pirenzepine abolished the GH response to GHRH in thyrotoxic patients.

conclusions GH responses to GHRH in hyperthyroid patients were suppressed by cholinergic muscarlnic receptor blockade with pirenzepine. Activation of cholinergic pathways with pyridostigmine did not increase GH responses to GHRH In these patients. This may be a consequence of increased hypothalamic cholinergic function or reduced hypothalamic GHRH activity in hyperthyroidism. Our findings demonstrate a further mechanism by means of which thyroid status may affect the secretory activity of the somatotroph.
Laron‐type dwarfism with apparently normal high affinity serum growth hormone‐binding protein
Authors: Buchanan C. R. , Maheshwari H. G. , Norman M. R. , Morrell D. J. , Preece M. A.
Published: March 2008

Summary. objective Normal serum contains a high affinity GH‐binding protein, which appears to be Identical with the extracellular domain of the GH receptor. It Is normally absent from the serum of patients with Laron‐type dwarf‐ism. We wished in this study to define the serum GH‐binding protein status of a family with Laron‐type dwarf‐ism.

design and patients

We performed an open case study of an Asian family In which three sisters (aged 3 to 15 years) had the phenotype of Laron‐type dwarfism. Sera from a fourth, unrelated girl with Laron‐type dwarfism and subjects without endocrine disorders were used as control samples.

measurements Laron‐type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF‐I levels on Immunoassay, with serum IGF‐I levels falling to rise during treatment with GH. Serum GH‐binding proteins were characterized using gel chromatography on Sephacryl S‐100HR following Incubation of serum with 125I‐GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross‐linking to 125I‐GH.

results

All members of the family had high affinity serum GH‐binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH‐binding protein activity in the unrelated child with Larontype dwarfism and previous reports of serum GH‐binding protein levels In this disorder.

conclusions

The affected patients may possess a novel biochemical defect which results in GH‐resistance and reduced production of IGF‐I in the presence of normal serum GH‐binding protein levels.
Influence of thyroxine treatment on thyroid size and anti‐thyroid peroxidase antibodies in Hashimoto's thyroiditis
Authors: Hegedüs Laszlo , Hansen Jens Melholm , Feldt‐Rasmussen Ulla , Hansen Bo Melholm , Høier‐Madsen Mimi
Published: March 2008

Summary.objectiveit has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto's thyroiditis but no objective data are available. We have therefore Investigated the Influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxldase antibodies.

designConsecutive patients with goitrous Hashimoto's thyroiditis was studied.

patientsThirteen women participated; all had goitrous thyroiditis.

treatment

To render them euthyroid thyroxine was given for 24 months.

measurements

Thyroid size was measured ultra‐sonically and antithyroid peroxidase antibodies were measured using a commercial radloimmunological method.

resultConcomitant with the gradual increase in serum free thyroxine and free triiodothyronlne Index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 ± 6.8 ml (mean ± SEM) to 34.1 ± 5.7 ml (32%),P< 0.001 was demonstrated. Anti‐thyroid peroxidase antibodies were present In high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after. Initiation of treatment.

conclusion

A clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved duringl‐thyroxine treatment of hypothyrold goitrous Hashimoto's thyroiditis.
The short Synacthen test in acute hospital admissions
Authors: Patel S. R. , Selby C. , Jeffcoate W. J.
Published: March 2008

Summary. objective We wished to define the cortisol response to 250 μg intramuscular tetracosactrin (Synacthen) in acute hospital admissions, using a modern Immunoassay for cortisol.

design We performed a prospective study of, as near as possible, a consecutive series of 161 admissions to a single unit.

patients We studied 50 patients (age range 67–98, mean 80.3 years, 31‐female, 19‐male) admitted as an emergency, from whom it was possible to obtain informed consent, and whom it was possible to study within 24 hours of admission.

measurements

We measured baseline, increment and peak serum cortisol following administration of 250 μg intramuscular tetracosactrin between 0800 and 0900 hours.

results Baseline cortisol concentrations ranged from 288 to 1585 nmol/I (mean 706; median 665). Peak cortisol concentrations ranged from 602 to 2265 nmol/I (mean 1076; median 999). Baseline and peak cortisol concentrations showed a significant correlation (P < 0.001). Increment varied from 10 to 747 nmol/I (mean 374; median 336) and did not correlate with baseline.

conclusions In acute hospital admissions, baseline serum cortisol between 0800 and 0900 hours should exceed 250 nmol/I. Peak serum cortisol after 250 μg intramuscular tetracosactrin should exceed 600 nmol/I. Calculation of the increment is of no value.
Antisperm antibodies in the polyglandular autoimmune (PGA) syndrome type I: response to cyclical steroid therapy
Authors: Tsatsoulis A. , Shalet S. M.
Published: March 2008

Summary. objective To determine if cyclical intermediate dose steroid therapy could Improve semen parameters In an Infertile man with sperm autolmmunity associated with the polyglandular autolmmune (PGA) syndrome.

design Sperm agglutination studies performed before, during and after three courses of cyclical intermediate dose prednisolone therapy.

patient A twenty‐six‐year old man with polyglandular autolmmune syndrome, consisting of Addison's disease, hypoparathyroidism, chronic mucocutaneous candidiasis and alopecia totalis, presented with Infertility. He had normal endocrine testicular function but severe exocrine failure evidenced by a low sperm count (4.5 ± 104/ml), zero motility and universal sperm agglutination.

measurements Sperm agglutination tests.

results At presentation the gelatin agglutination test (GAT) was strongly positive in serum (1/1204) and seminal plasma (1/64) as was the tray agglutination test (TAT) (1/32). The patient's wife had a regular menstrual cycle with normal luteal phase progesterone levels.

Following three courses of cyclical prednisolone (20 mg twice daily on days 1–10 of wife's cycle, and 5 mg on days 11 and 12), sperm quantity and motility Improved consider‐ably (12 ± 106/ml, 40% respectively) and sperm agglutination tests became negative. After a fourth course of therapy the patient's wife became pregnant. Three months post‐treatment sperm motility was very low again and agglutinating activity in serum and seminal plasma increased.

conclusions This is the first case of male infertility due to sperm autoimmunity in association with the PGA syndrome type 1. The Immunosuppressive action of cyclical intermediate dose steroid therapy led to a significant quantitative and qualitative Improvement in semen parameters.
Cholesterol fractions and apolipoproteins during endometriosis treatment by a gonadotrophin releasing hormone (GnRH) agonist implant or by danazol
Authors: Lemay André , Brideau Natalie‐Anne , Forest Jean‐Claude , Dodin Sylvie , Maheux Rodolphe
Published: March 2008

Summary. objective The evaluation of cholesterol fractions and apoproteins during ovarian suppression by a GnRH agonist implant vs danazol in the treatment of endometriosis

design A randomized study in 33 patients comparing goserelin (3.6 mg/4 weeks s.c., n= 20) with danazol (2 ± 400 mg/day p.o., n= 13) in patients with a laparoscopic diagnosis of endometriosis and treated for 6 months.

measurements

Triglycerides, cholesterol (C), LDL‐C, HDL‐C subtractions and apoproteins A‐1 and B were measured at admission, at months 2, 4 and 6 of treatment and at month 2 post‐treatment.

results After 1 month of therapy, serum oestradiol levels were maintained in the menopausal range with goserelin and in the early follicular phase range with danazol. Goserelin induced a significant elevation in HDL‐C (by 31.4%), in HDL2‐C (24.6%) and in HDL3‐C (45.7%) but no significant change in LDL‐C or in ApoA‐1 and ApoB. By contrast, danazol caused significant diminutions in HDL‐C (23.9%), HDL,‐C (56.6%) and ApoA‐1 (35.6%). Moreover, danazol increased LDL‐C (10.5%) and ApoB (29.0%, P < 0.05). The lipoprotein changes during goserelin had a favourable effect on the atherogenic index (cholesterol/HDL‐C) and ApoA‐1/ApoB ratio whereas those of danazol had opposite effects. These changes reverted 2 months after danazol while HDL was still elevated after goserelin.

conclusions In relation to cholesterol, goserelin is a safe medication. The significance of temporary adverse changes in cholesterol fractions due to danazol Is still unknown.
The secretory granule peptides 7B2 and CCB are sensitive biochemical markers of neuro‐endocrine bronchial tumours in man
Authors: Vieau D. , Rojas‐Miranda' A. , Verley' J. M. , Lenne F. , Bertagna And X.
Published: March 2008

Summary. Objective Bronchial tumours are the most frequent cause of the ectopic ACTH syndrome. Two types of tumours are classically responsible: the relatively benign carcinoids and the highly aggressive small cell carcinomas. Both have neuro‐endocrine features and are thought to originate from the endocrine component of the bronchial tree. Our objective was to assess the sensitivity of 7B2 and secretogranin 1 as new biochemical markers of neuro‐endocrine differentiation in these tumours In comparison with gastrin releasing peptide.

Methods Tissue concentration of 7B2, secretogranin 1 fragments (GAWK and CCB), gastrin releasing peptide and 8‐endorphin were measured in normal human lung (n=4), bronchial carcinoid tumours with (n=5) and with‐out (n=15) the ectopic ACTH syndrome, small cell carcinomas (n=2), squamous cell carcinomas (n=11) and adenocarcinomas (n=6). Molecular weight forms of Immunoreactive ‐ACTH, ‐GAWK, ‐gastrin releasing peptide, and ‐7B2 were also examined using gel exclusion chromatography and Western blot analysis.

Results We detected 7B2 immunoreactivity in 19 of 22 neuro‐endocrine lung tumours (with values ranging from <5 to 555 fmol/mg wet weight tissue), CCB immunoreactivity in 20 of 22 tumours with neuro‐endocrine features (with values ranging from <5 to 19 875 fmol mg wet weight tissue) and gastrin releasing peptide immunoreactivity In 10 of 22 neuro‐endocrine lung tumors (with values ranging from <5 to 11132 fmol/mg wet weight tissue). Immunoreactive 7B2 and CCB were detected neither In tumours with non‐endocrine features, nor in the four normal lung specimens. Differing molecular weight forms of Immuno‐reactive 7B2 in two bronchial carcinoids associated with the ectopic ACTH syndrome showed a predominant signal corresponding to a molecular weight of 22 kDa; in addition, a second signal of 19 kDa was also present. The differing molecular weight forms of Immunoreactive ACTH related peptides In the five tumours responsible for the ectopic ACTH syndrome showed, in addition to ACTH1‐35, the constant presence In variable proportions of corticotrophin‐like Intermediary lobe peptide (or ACTH15‐39). The differing molecular weight forms of Immunoreactive GAWK showed heterogeneous results with materials eluting at Kav of 0, 0.3 and 0.4 respectively. In the three bronchial carcinoids studied, two immunoreactive gastrin releasing peptide molecular weight forms were always found at Kav of 0.5 and 0.85 corresponding to gastrin releasing peptide and its fragment 14‐27 respectively.

Conclusion Our results show that 7B2 and the two fragments of secretogranin 1 (GAWK and CCB) are the best biochemical markers of neuro‐endocrine differentiation in human lung tumours.
Inhibin and age in men
Authors: MacNaughton Judith A. , Bangah' Mohan L. , McCloudt Philip I. , Burger Henry G.
Published: March 2008

Summary. objective Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine If changes in testicular function occur over the age range 19–80 years.

design Single fasting blood samples were obtained between 0800 and 0900 h.

patients Working men In a large Industrial company between the ages of 19 and 60 years participated in the study.

measurements fsh,

serum immunoreactive Inhibin and total testosterone were measured, the latter two as measurements of Sertoll and Leydig cell function respectively.

results

The mean baseline serum Immunoreactive inhibin level was significantly lower in men from the older age groups, 31–40 years (479 U/I), 41–50 years (439 U/I) and 51–60 years (415 U/I) than in men from the youngest age group, 21–30 years (613 U/I) while serum FSH was higher in men from the older age groups, 41–50 years (3.7 IU/I) and 51–60 years (6.1 IU/I) than In men from the youngest age group, 21–30 years (2.6 IU/I). There appears to be a change in both FSH and inhibin production, consistent with a primary decline In testicular function.

There was no significant difference in testosterone levels between the older age group, age 51–60 years and the younger age group, age 21–30 years. However, testosterone levels were significantly lower in the 41–50 year age group, when compared with the 21–30 year, this significance levelling out at about age 45 years.

conclusion

The data are consistent with the hypothesis that Immunoreactive inhibin reflects Inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.
Levels of GH binding activity, IGFBP‐1, insulin, blood glucose and cortisol in intensive care patients
Authors: Ross Richard J. M. , Miell John P. , Holly Jeff M. P. , Maheshwari Hlralal , Norman Mike , Abdulla A. Farhana , Buchanan Charles R.
Published: March 2008

Summary. objective To Investigate levels of serum GH binding activity, Insulin‐like growth factor binding protein‐1 (IGFBP‐1), blood glucose, serum insulin, and cortisol in patients on the Intensive Therapy Unit.

design Case‐control study of severely Ill patients admitted to the Intensive Therapy Unit.

patients Six critically ill patients (51–78 years) who required ventilatory and nutritional support and six healthy age, sex, height and weight matched controls.

measurements Patients and controls were studied for two 24‐hour periods; the patients before and after commencing parenteral nutrition, the controls whilst fasted and on a second occasion when fed a diet equal In protein and calories to that of the patients' parenteral nutrition. Samples were taken hourly for measurement of IGFBP‐1, blood glucose, serum Insulin and cortisol. Growth hormone binding activity was measured at 0 hours.

results Blood glucose levels were higher in the patients than controls in both the fasted (mean SEM 5.1 ±0.5 vs 3.8± 0.2 mmol/1, p= 0.04) and fed states (10.1 ± 1.6 vs 5.0±0.1 mmol/1, p= 0.02) and patients' insulin levels were also higher when fed (81.5±31.6 vs 24.2±4.8 mU/1, p=0.046) although there were no significant differences between patients and controls when fasted. IGFBP‐1 levels were Inversely related to insulin levels in both the patients and controls; mean IGFBP‐1 concentrations were higher In fasted patients than In controls (123.38 vs 52.9, p=0.046) but when fed, both groups had similar mean levels. Serum GH binding activity was low in the patients and did not change with feeding. Mean 24‐hour cortisol levels were higher in the patients than In controls, whether fasted or fed, and showed no nyctohemeral rhythm.

conclusions We have previously reported that critically patients have low levels of 1GF‐1 with augmented basal levels of GH. The present results demonstrate that these changes in the GH–IGF‐1 axis are associated with insulin resistance with respect to blood glucose and high levels of IGFBP–1 when patients are fasted. However, when fed, the Inverse relationship of IGFBP–1 to insulin is preserved. Patients have low levels of GH binding activity and Increased mean cortisol levels. Interventional studies in this patient group with GH and IGF‐1 must take account of these changes in binding protein and cortisol levels.