bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with subclinical autonomous cortisol hypersecretion: a prospective clinical study
Authors: Reznik Y. , Lefebvre H. , Rohmer V. , Charbonnel B. , Tabarin A. , Rodien P. , Lecomte P. , Bardet S. , Coffin C. , Mahoudeau J. 
Published: September 2004

Summarybackground  Incidentally discovered adrenal tumours are frequently associated with subclinical autonomous cortisol hypersecretion of unknown origin. Aberrant hormone receptors have been observed in case reports of overt Cushing's syndrome. The question arises as to whether such receptors may be present in the functioning adrenal incidentaloma, which is common and might be a subclinical stage of Cushing's syndrome.patients and methods  Twenty‐one consecutive patients with a unilateral incidentaloma, the biochemical features of subclinical cortisol hypersecretion and/or the scintigraphic features of an autonomously functioning adrenal adenoma were investigated for plasma cortisol responses to various stimuli: upright posture, meal, combined hypothalamic‐hormones, the vasopressin analogue terlipressin, glucagon, angiotensin II, the serotonin 5‐HT4 agonist cisapride, and ACTH. Six normal controls were similarly investigated. All subjects were studied during 8 mg per day dexamethasone in order to avoid any ACTH‐dependent variation of plasma cortisol.results  The most constant responses in adrenal incidentalomas were observed after stimulation by terlipressin (18/20 patients, 28–415% cortisol increase) and cisapride (17/21 patients, 25–364% cortisol increase). Eighteen out of 21 patients responded to several stimuli (cortisol increase ≥ 25%), and all responded to at least one stimulus other than ACTH, while such responses were absent in the controls. Plasma ACTH remained suppressed in all subjects throughout the study.conclusions  Aberrant membrane receptors detected by in vivo stimulation tests appear to be common in autonomously functioning unilateral adrenocortical adenomas. These receptors may be involved in the modulation of cortisol secretion in adrenal incidentaloma, with potential therapeutic consequences for the control of subclinical cortisol hypersecretion.
Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury
Authors: Aimaretti Gianluca , Ambrosio Maria Rosaria , Di Somma Carolina , Fusco Alessandra , Cannavò Salvatore , Gasperi Maurizio , Scaroni Carla , De Marinis Laura , Benvenga Salvatore , Uberti Ettore Carlo degli , Lombardi Gaetano , Mantero Franco , Martino Enio , Giordano Giulio , Ghigo Ezio 
Published: September 2004

Summaryobjective  Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic–pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations.aim  To clarify the occurrence of hypopituitarism in patients after traumatic brain injury (TBI) or subarachnoid haemorrhage (SAH) 3 months after the BI.subjects and methods  The occurrence of hypopituitarism in conscious patients after traumatic brain injury [TBI, n = 100, 31 women, 69 men; age 37·1 ± 1·8 years; body mass index (BMI) 23·7 ± 0·4 kg/m2; Glasgow Coma Scale (GCS) 3–15] or subarachnoid haemorrhage [SAH, n = 40, 14 men, 26 wpmen, 51·0 ± 2·0 years; 25·0 ± 0·6 kg/m2; Fisher's scale 1–4] was studied in a multicentre study 3 months after the BI. All patients underwent wide basal hormonal evaluation; the GH/IGF‐I axis was evaluated by GHRH + arginine test and IGF‐I measurement.results  In TBI patients, some degree of hypopituitarism was shown in 35%. Total, multiple and isolated deficits were present in 4, 6 and 25%, respectively. Diabetes insipidus was present in 4%. Secondary adrenal, thyroid and gonadal deficit was present in 8, 5 and 17%, respectively. Severe GH deficiency (GHD) was the most frequent pituitary defect (25%). In SAH patients, some degree of hypopituitarism was shown in 37·5%. Despite no total hypopituitarism, multiple and isolated deficits were present in 10 and 27·5%, respectively. Diabetes insipidus was present in 7·5%. Secondary adrenal, thyroid and gonadal deficit was present in 2·5, 7·5 and 12·5%, respectively. Severe GHD was the most frequent defect (25%).conclusions  TBI and SAH are conditions associated with high risk of acquired hypopituitarism. The pituitary defect is often multiple and severe GHD is the most frequent defect. Thus neuroendocrine evaluations are always mandatory in patients after brain injuries.
Both intrauterine growth restriction and postnatal growth influence childhood serum concentrations of adiponectin
Authors: López‐Bermejo Abel , Casano‐Sancho Paula , Fernández‐Real José Manuel , Kihara Shinji , Funahashi Tohru , Rodríguez‐Hierro Francisco , Ricart Wifredo , Ibañez Lourdes 
Published: September 2004

Summaryobjective  Insulin resistance has been linked to intrauterine growth restriction; adiponectin is a strong determinant of insulin sensitivity. We aimed at studying the contributions of birthweight and insulin sensitivity to circulating adiponectin in children born small for gestational age (SGA).design  Cross‐sectional, hospital‐based study dealing with insulin sensitivity in SGA children.patients  Thirty‐two prepubertal children born SGA (age 5·4 ± 2·9 years) and 37 prepubertal children born appropriate for gestational age (AGA, age 5·9 ± 3·0 years).measurements  Serum levels of fasting glucose, serum lipids, insulin (immunometric assay) and adiponectin concentrations (ELISA) were assessed, and insulin resistance (IR) and insulin secretion (β‐cell) were calculated by the homeostasis model of assessment (HOMA).results  SGA children had similar HOMA‐IR, HOMA‐β‐cell and adiponectin concentrations than AGA children. However, in a separate analysis of subjects older than 3 years of age, SGA children showed higher HOMA‐IR after adjusting for sex, age and body mass index (BMI) standard deviation score (SDS). Circulating adiponectin was higher in SGA children [adjusted means: 14·5 mg/l (95% CI 12·9–16·1) and 18·7 mg/l (95% CI 17·0–20·3) for AGA and SGA children, respectively; P < 0·0001]. Further analysis revealed that the group of overweight SGA (arbitrarily defined as being in the higher quartile for the BMI SDS distribution in the sample) had decreased serum concentrations of adiponectin, compared to lean SGA children [adjusted means: 12·9 mg/l (95% CI 9·3–16·5) vs. 19·0 (95% CI 16·8–21·3), respectively; P = 0·001]. In a multiple regression model, HOMA‐IR and SGA status explained 35% and 15% of adiponectin variance, respectively.conclusions  Prenatal growth restriction is associated with insulin resistance but relatively increased adiponectin concentrations, provided overweight does not ensue. The contributions of circulating adiponectin to the increased risks for developing insulin resistance and type‐2 diabetes in formerly SGA subjects merit further studies.
Metabolism of chylomicrons in patients with congenital lipoatrophic diabetes: a study with emulsion models of chylomicrons
Authors: Wajchenberg Bernardo L. , Amâncio Rosângela F. , Santomauro Ana T. , Maranhão Raul C. 
Published: September 2004

Summarybackground  Lipoatrophic diabetes is characterized by the near absence of adipose tissue and the presence of insulin‐resistant diabetes. Fasting hypertriglyceridaemia and increased postprandial lipidaemia are also present, but the metabolism of chylomicrons, the triglyceride‐rich lipoproteins in the circulation that carry the dietary fats absorbed by the intestine, was not specifically investigated. Because both the activity of insulin‐dependent lipoprotein lipase that catalyses the chylomicron lipolysis and the storage of the lipolysis products are affected in the disease, it is important to evaluate how those changes may ultimately affect the chylomicron lipolysis and removal of chylomicron remnants from the circulation.objective  The aim of the study was to evaluate the chylomicron intravascular metabolism in patients with lipoatrophic diabetes.patients  Six patients with lipoatrophic diabetes (four females, two males) aged 22·2 ± 4·4 years, with body mass index (BMI) 21·6 ± 3·6 kg/m2, were compared with 12 healthy control subjects (seven females, five males) aged 24·3 ± 2·1 years with BMI 22·5 ± 2·7 kg/m2.measurements  The plasma kinetics of intravenously injected chylomicron‐like emulsions labelled with 3H‐triglycerides (3H‐TG) and with 14C‐cholesteryl esters (14C‐CE) were determined, the former tracing the chylomicron lipolysis by lipoprotein lipase and the latter the removal of chylomicron remnants from the plasma.results  Triglyceride values (8·3 ± 9·2 mmol/l) in the patients were higher (P < 0·005) and high density lipoprotein (HDL) cholesterol values (0·8 ± 0·2 mmol/l) lower (P < 0·0005) than in controls (0·7 ± 0·2 and 1·3 ± 0·4 mmol/l, respectively) whereas total cholesterol, apoprotein B (apo B) and apo A1 were similar. The fractional clearance rate (FCR, in min−1) of 3H‐TG was 0·014 ± 0·016 and the FCR of 14C‐CE was 0·008 ± 0·012 in the patients and 0·046 ± 0·024 and 0·024 ± 0·012 in the controls, respectively (P < 0·05). Thus FCRs of both emulsion labels were markedly reduced in the patients, indicating that lipolysis and remnant removal were diminished. Diminished remnant removal may be due to either deficient lipolysis or deficient removal mechanisms.conclusion  The metabolism of chylomicrons tested by the emulsion method is impaired in lipoatrophic diabetes.
Insulin‐like growth factor‐1 deficiency determines increased intima–media thickness at common carotid arteries in adult patients with growth hormone deficiency
Authors: Colao Annamaria , Di Somma Carolina , Filippella Mariagiovanna , Rota Francesca , Pivonello Rosario , Orio Francesco , Vitale Giovanni , Lombardi Gaetano 
Published: September 2004

Summaryobjective  To investigate the role of IGF‐1 on intima–media thickness (IMT) at common carotid arteries by Doppler ultrasonography.subjects  Thirty‐nine patients (17 women, 22 men, aged 25–70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF‐1 levels, and 39 sex‐, age‐ and body mass index (BMI)‐matched healthy controls.results  Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0·88 ± 0·26 vs. 0·69 ± 0·14 mm, P < 0·001), and systolic and diastolic peak velocity (P < 0·001) compared to controls. Eight patients (18%) and one control (2·1%, P = 0·04) had well‐defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0·78, P < 0·001). In both controls (r = −0·82; P < 0·0001) and patients with GHD (r = −0·84, P < 0·0001), serum IGF‐1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH‐deficient patients were total cholesterol levels (t = 5·2, P < 0·001), followed by disease duration (t = 2·4, P = 0·02), while in controls the variables most significantly related to IMT were IGF‐1 levels (t = −9·9, P < 0·001), followed by low density lipoprotein (LDL)‐cholesterol levels (t = −2·3, P = 0·02). Compared to patients with normal IGF‐1 levels, those with low IGF‐1 levels had lower high density lipoprotein (HDL)‐cholesterol levels (1·0 ± 0·2 vs. 1·3 ± 0·2 mmol/l, P = 0·0002), and higher glucose (54·3 ± 6·1 vs. 48·9 ± 5·9 mmol/l, P = 0·008), insulin (25·2 ± 6·8 vs. 18·8 ± 6·0 mUl/l, P = 0·004), total cholesterol (7·1 ± 1·1 vs. 4·9 ± 0·6 mmol/l, P < 0·0001), total/HDL‐cholesterol ratio (7·2 ± 1·8 vs. 3·9 ± 0·7, P < 0·0001), fibrinogen levels (319·8 ± 56·9 vs. 241·8 ± 53·0 mg/dl, P < 0·0001) and mean IMT at common carotid arteries (1·05 ± 0·25 vs. 0·69 ± 0·07 mm, P < 0·0001). Atherosclerotic plaques were found only in GH‐deficient patients with low IGF‐1 levels.conclusions  GH‐deficient patients have alterations in lipid profile with an increase in the total/HDL‐cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF‐1 deficiency have increased IMT.
Weight‐related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency
Authors: Mah Peak M. , Jenkins Richard C. , Rostami‐Hodjegan Amin , Newell‐Price John , Doane Anita , Ibbotson Victoria , Tucker Geoffrey T. , Ross Richard J. 
Published: September 2004

Summaryobjective  The objective of this study was to examine the variables determining hydrocortisone (HC) disposition in patients with adrenal insufficiency and to develop practical protocols for individualized prescribing and monitoring of HC treatment.design and patients  Serum cortisol profiles were measured in 20 cortisol‐insufficient patients (09·00 h cortisol < 50 nmol/l) given oral HC as either a fixed or ‘body surface area‐adjusted’ dose in the fasted or fed state. Endogenous cortisol levels were measured in healthy subjects. Pharmacokinetic analysis was performed using P‐Pharm software, and computer simulations were used to assess the likely population distribution of the data.results  Body weight was the most important predictor of HC clearance. A fixed 10‐mg HC dose overexposed patients to cortisol by 6·3%, whereas weight‐adjusted dosing decreased interpatient variability in maximum cortisol concentration from 31 to 7%, decreased area under the curve (AUC) from 50 to 22% (P < 0·05), and reduced overexposure to < 5%. Food taken before HC delayed its absorption. Serum cortisol measured 4 h after HC predicted cortisol AUC (r2 = 0·78; P < 0·001).conclusions  We recommend weight‐adjusted HC dosing, thrice daily before food, monitored with a single serum cortisol measurement using a nomogram. This regimen was prospectively examined in 40 cortisol‐insufficient patients, 85% of whom opted to remain on the new thrice‐daily treatment regimen.
Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels
Authors: Carosa Eleonora , Martini Paolo , Brandetti Fulvia , Di Stasi Savino M. , Lombardo Francesco , Lenzi Andrea , Jannini Emmanuele A. 
Published: September 2004

objective  Lack of sexual activity due to erectile dysfunction (ED) decreases testosterone (T) levels through a central effect on the hypothalamic–pituitary axis. In this paper we studied the effect of different type V phosphodiesterase (PDE5) inhibitor treatments for ED on the reversibility of this endocrine pattern.design  Open‐label, retrospective study.patients  Seventy‐four consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and tadalafil (Tad) 20 mg.measurements  The success in sexual intercourse was recorded and total (tT) and free testosterone (fT) levels were studied before and after 3 months of treatment.results  Basal level of tT and fT were at the bottom of the normal range and LH levels were at the top of the high normal range. After treatments, this endocrine pattern was reversed in both groups. However, the T increase in Sild‐treated patients was significantly lower than in those treated with Tad (4·7 ± 2·7 vs. 5·1 ± 0·9, P < 0·001). fT levels followed a directly proportional pattern, while the inverse was found when LH production was studied. The intercourse rate reflected this effect: in fact, the Sild group showed a 4·9 ± 2·9/month full sexual intercourse rate while in the Tad group a significantly higher rate of sexual intercourse was found (6·9 ± 4·6/month, P = 0·04). However, drug consumption was comparable between the groups (Sild 4·9 ± 2·9 vs. Tad 4·4 ± 2·8 pills/month, P = 0·72).conclusions  As it is unlikely that the two drugs have a different direct effect on the pituitary–testis axis, this effect is probably due to the higher frequency of full sexual intercourse in the Tad‐treated group, because of the drug's longer half‐life.
Neurosteroids: The StAR Protein in the Brain
Authors: Sierra A. 
Published: September 2004

AbstractThe nervous system is a well‐known target for steroid hormones, as these hormones regulate brain functions that include neuronal survival and differentiation, myelination, neurogenesis, plasticity and repair after injury. Furthermore, the brain is also a steroidogenic tissue because it possesses the enzymes required to metabolize the common precursor, cholesterol, into steroids, named ‘neurosteroids’. The rate‐limiting step in the synthesis of steroid hormones is the access of cholesterol, accumulated in the outer mitochondrial membrane, to the first steroidogenic enzyme, P450scc (cholesterol side‐chain cleavage enzyme), located in the inner mitochondrial membrane. In the ovary and the adrenal gland, which comprise classic steroidogenic tissues, this process requires the steroidogenic acute regulatory protein (StAR) to facilitate the shuttle of cholesterol through the intermembrane space. The mechanism used by the brain to regulate the first stage of steroidogenesis remains unknown. Recently, several groups have investigated the potential presence of StAR in the nervous tissue and have concluded that StAR is widely expressed throughout the brain, although restricted to specific cell populations. New results concerning localization, regulation and possible functions of StAR in the brain are discussed.
Activation of Arylalkylamine N‐Acetyltransferase by Phorbol Esters in Bovine Pinealocytes Suggests a Novel Regulatory Pathway in Melatonin Synthesis
Authors: Schomerus C. , Laedtke E. , Korf H.‐W. 
Published: September 2004

AbstractIn all mammalian species investigated, noradrenaline activates a β‐adrenoceptor/cAMP/protein kinase A‐dependent mechanism to switch on arylalkylamine N‐acetyltransferase and melatonin biosynthesis in the pineal gland. Other compounds which are known to influence the melatonin‐generating system are phorbol esters. The effect of phorbol esters on regulation of melatonin synthesis has been mainly investigated in rat pinealocytes. In these cells, phorbol esters do not increase cAMP levels and arylalkylamine N‐acetyltransferase on their own; however, phorbol esters potentiate the effects on cAMP and AANAT activity induced upon β‐adrenoceptor stimulation. In the present study, we investigated the effect of phorbol esters on the regulation of melatonin synthesis in bovine pinealocytes. We show that, in these cells, the phorbol esters 4β‐phorbol 12‐myristate 13‐acetate (PMA) or phorbol 12,13‐dibutyrate have a direct stimulatory effect and induced 4–10‐fold increases in AANAT protein levels, AANAT activity and melatonin production. The extent of these effects was similar to those induced by noradrenaline. Notably, responses to PMA were not accompanied by increases in cAMP levels. Northern blot analysis showed that Aanat mRNA levels did not change upon PMA treatment indicating that phorbol esters control AANAT at a post‐transcriptional level. The effects on AANAT and melatonin production were reduced by use of protein kinase C inhibitors, but not by blockade of the cyclic AMP/protein kinase A pathway. Our results point towards a novel mechanism in the regulation of melatonin production that is cAMP‐independent and involves protein kinase C. The study is of particular interest because regulation of melatonin biosynthesis in bovines may resemble that in primates more closely than that in rodents.
Fos Expression after Mating in Noradrenergic Cells of the A1 and A2 Areas of the Medulla is Altered by Adrenalectomy
Authors: Cameron N. M. , Ha G. K. , Erskine M. S. 
Published: September 2004

AbstractIn the female rat, the integrity of the ventral noradrenergic bundle (VNAB) is necessary to carry stimuli from the uterine cervix and vagina to brain areas involved in mating‐induced pseudopregnancy. Because adrenal hormones are known to alter noradrenergic function, we examined whether adrenalectomy altered mating‐induced Fos expression in the A1 and A2 noradrenergic cell groups that project through the VNAB. Ovariectomized females were adrenalectomized (ADX) or sham‐operated (Sham) and, 2 weeks after surgery, were given oestrogen and progesterone and mated. They received 15 intromissions, five intromissions or 15 mounts‐without‐intromission (mounts‐only) from a male. Two hours after mating, rats were perfused and brains were collected; controls were perfused after being taken directly from their home cage. After immunocytochemical staining, Fos‐immunoreactive (Fos‐IR) and dopamine‐β‐hydroxylase‐immunoreactive (DBH‐IR) cells and the percentage of DBH cells that were labelled with Fos (% DBH/Fos) were counted. In the A1 area, Fos‐IR and percentage DBH/Fos were not affected by adrenalectomy. Although an overall effect of mating treatment was found for both measures, no specific mating treatment increased labelled cells above home cage levels. In the caudal, middle and rostral A2, 15 intromissions induced a significant increase in Fos‐IR in Sham females above all other groups and a higher percentage of DBH/Fos in the middle and rostral A2 areas. ADX females showed no rise in either Fos‐IR or percentage DBH/Fos after 15 intromissions. However, in the middle and rostral A2, ADX females showed significantly increased Fos‐IR and percentage DBH/Fos after mounts‐only treatment above Sham mounts‐only females and all other ADX groups. These results demonstrate that adrenal hormones suppress activation of A2 cells to mounts‐only stimuli but contribute to A2 activation in response to intromissions from males. The latter effect may result from stress associated with receipt of vaginocervical stimulation during mating.
Behavioural and Neuroendocrine Adaptations to Repeated Stress during Puberty in Male Golden Hamsters
Authors: Wommack J. C. , Salinas A. , Melloni R. H. , Delville Y. 
Published: September 2004

AbstractIn adult animals, the consequences of stress are often severe and long lasting. Repeated subjugation in adult male golden hamsters inhibits aggression and increases submissive and avoidant behaviours. By contrast, subjugation during puberty enhances offensive aggression. The goals of this study were to characterize behavioural and neuroendocrine responses of naïve and repeatedly subjugated juveniles to social defeat and to assess potential recovery from social stress. From the onset of puberty on postnatal day 28 (P28) to mid puberty (P42), animals were either socially subjugated or placed in a clean and empty cage for 20 min daily. The subjugated and control groups were further divided into subgroups and sacrificed under basal conditions or after social defeat on P28, P35 (early puberty), P45 (mid puberty) and P70 (early adulthood). On P35 and P45, repeatedly subjugated juveniles showed a complete inhibition of olfactory investigation (i.e. risk assessment) towards aggressive adults. Repeatedly subjugated also animals had lower postdefeat cortisol levels than controls on P45. Interestingly, basal cortisol levels increased gradually during puberty but did not differ between treatment groups at any point. Repeated subjugation was also associated with increased tyrosine hydroxylase immunoreactivity (ir‐TH) within the extended medial amygdala. After a 4‐week recovery period, none of these variables differed between subjugated and control groups. In an additional experiment, subjugated adults also had increased ir‐TH in the medial extended amygdala, suggesting that these neurones are particularly responsive to social stress. In conclusion, puberty may be a developmental period characterized by behavioural and neuroendocrine plasticity in stress responsiveness. Furthermore, peri‐pubertal changes in stress hormones may explain why juvenile hamsters are more resilient to social stress than adults.