Pituitary Volume Research Articles

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis (n = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis (n = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients (P = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced (P = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids.

Duration of untreated psychosis/illness and brain volume changes in early psychosis

The time period during which patients manifest psychotic or unspecific symptoms prior to treatment (duration of untreated psychosis, DUP, and the duration of untreated illness, DUI) has been found to be moderately associated with poor clinical and social outcome. Equivocal evidence exists of an association between DUP/DUI and structural brain abnormalities, such as reduced hippocampus volume (HV), pituitary volume (PV) and grey matter volume (GMV). Thus, the goal of the present work was to examine if DUP and DUI are associated with abnormalities in HV, PV and GMV. Using a region of interest (ROI) based approach, we present data of 39 patients from the Basel FePsy (Früherkennung von Psychosen, early detection of psychosis) study for which information about DUP, DUI and HV, PV and GMV data could be obtained. Twenty-three of them were first episode psychosis (FEP) and 16 at-risk mental state (ARMS) patients who later made the transition to frank psychosis. In unadjusted analyses, we found a significant positive correlation between DUP and PV in FEP patients. However, when adjusted for covariates, we found no significant correlation between DUP or DUI and HV, PV or GMV anymore. There only was a trend for decreasing GMV with increasing DUI in FEP. Our results do not comprehensively support the hypothesis of a “toxic” effect of the pathogenic mechanism underlying untreated psychosis on brain structure. If there is any effect, it might rather occur very early in the disease process, during which patients experience only unspecific symptoms.

Extra-pituitary Cerebral Anomalies in Pediatric Patients of Ectopic Neurohypophysis: An Uncommon Association.

Context:Ectopic neurohypophysis (EN) refers to an interrupted, nonvisualized, and thinned out pituitary stalk with ectopic location of the posterior pituitary gland. Concurrent extra-pituitary cerebral and extra-cranial anomalies have been rarely reported in patients of EN.Aim:The aim of this study was to evaluate the magnetic resonance imaging (MRI) findings of extra-pituitary cerebral anomalies in pediatric patients of EN.Settings and Design:A hospital-based cross-sectional study was conducted in a tertiary care center.Subjects and Methods:The study group comprised eight pediatric patients of EN associated with extra-pituitary cerebral or vascular anomalies. Clinical and biochemical assessment was done in all patients.Results:Out of the total eight patients with EN, MRI showed interrupted pituitary stalk in five patients (62.5%) and nonvisible pituitary stalk in three patients (37.5%). Ectopic posterior pituitary bright spot was demonstrated in median eminence in six patients (75%), faintly visualized in one patient (12.5%) and nonvisualized in another one patient. Statistical significant association was noted between pituitary gland height and patient's body height with the pituitary gland volume (P < 0.001). Varied extra-pituitary cerebral anomalies encountered in our patients ranged from isolated anomalies such as optic nerve hypoplasia in three patients (37.5%), corpus callosum dysplasia in four patients (50%), agyria-pachygyria complex in two patients (25%), and intracranial vascular anomalies in two patients to syndromic association of tuberous sclerosis in one patient.Conclusion:Identifying and reporting of associated extra-pituitary cerebral anomalies in patients with EN are crucial in assessing the overall neurological outcome of such patients.

3D Volumetric Measurements of GH Secreting Adenomas Correlate with Baseline Pituitary Function, Initial Surgery Success Rate, and Disease Control.

There is scarce data on the clinical utility of volume measurement for growth hormone (GH)-secreting pituitary adenomas. The current study objective was to assess the association between pituitary adenoma volumes and baseline endocrine evaluation, initial surgical success rate, and disease control among patients with acromegaly. A retrospective cohort study was conducted at a clinical research center including patients with acromegaly due to GH-secreting pituitary adenomas. Baseline hormonal evaluation and adenoma characteristics according to MRI were collected. Volumetric measurements of pituitary adenomas were performed using a semi-automated lesion segmentation and tumor-volume assessment tools. Rates of post-operative medical treatment, radiation therapy, and re-operation were gathered from the patients' medical records. Twenty seven patients (11 females) were included, median age 21.0 years (interquartile range 29 years, range 3-61 years). Patients harboring adenomas with a volume <2 000 mm3 had higher chance to achieve disease remission [94.1% (n=16) vs. 50.0% (n=4), p<0.05]. Adenoma volumes positively correlated with baseline plasma GH levels before and after oral glucose administration, and with plasma IGF-I and PRL levels. Adenoma volume had negative correlation with morning plasma cortisol levels. Finally, patients harboring larger adenomas required 2nd surgery and/or medical treatment more often compared with subjects with smaller adenomas. Accurate 3D volume measurement of GH-secreting pituitary adenomas may be used for the prediction of initial surgery success and for disease control rates among patients with a GH-secreting pituitary adenomas and performs better than standard size assessments.

Pituitary volume reduction in schizophrenia following cognitive behavioural therapy

Cognitive behavioural therapy (CBT) for psychosis (CBTp) aims to lower the stress of psychotic symptoms. Given that the pituitary is involved in stress regulation, CBT-led stress reduction may be accompanied by a change in pituitary volume. This study aimed to determine whether CBTp reduces pituitary volume in schizophrenia. The relation between pre-therapy memory and CBTp-led pituitary volume change was also examined given that poor memory relates to a blunted cortisol awakening response, denoting impaired stress response, in schizophrenia. Pituitary volume was measured at baseline in 40 schizophrenia or schizoaffective disorder patients and 30 healthy participants before therapy. Pituitary volume was measured again 6–9months after patients had either received CBTp in addition to standard care (CBTp+SC, n=24), or continued with standard care alone (SC, n=16). CBTp+SC and SC groups were compared on pituitary volume change from baseline to follow-up. Pre-therapy memory performance (Hopkins Verbal Learning and Wechsler Memory Scale – Logical memory) was correlated with baseline-to-follow-up pituitary volume change. Pituitary volume reduced over time in CBTp+SC patients. Additionally, pre-therapy verbal learning correlated more strongly with longitudinal pituitary volume reduction in the CBTp+SC group than the SC group. To conclude, CBTp reduces pituitary volume in schizophrenia most likely by enhancing stress regulation and lowering the distress due to psychotic symptoms.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

Objectives:Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume.Design:Prospective controlled study in an outpatient clinic.Methods:Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC.Results:Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects.Conclusions:The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

Fanconi anemia: correlating central nervous system malformations and genetic complementation groups

Congenital central nervous system abnormalities in children with Fanconi anemia are poorly characterized, especially with regard to specific genetic complementation groups. To characterize the impact of genetic complementation groups on central nervous system anatomy. Through chart review we identified 36 patients with Fanconi anemia with available brain MRIs at the University of Minnesota (average age, 11.3years; range, 1-43 years; M:F=19:17), which we reviewed and compared to 19 age- and sex-matched controls (average age, 7.9years; range, 2-18 years; M:F=9:10). Genotypic information was available for 27 patients (15 FA-A, 2 FA-C, 3 FA-G, and 7 FA-D1 [biallelic mutations in BRCA2 gene]). Of the 36 patients, 61% had at least one congenital central nervous system or skull base abnormality. These included hypoplastic clivus (n=12), hypoplastic adenohypophysis (n=11), platybasia (n=8), pontocerebellar hypoplasia (n=7), isolated pontine hypoplasia (n=4), isolated vermis hypoplasia (n=3), and ectopic neurohypophysis (n=6). Average pituitary volume was significantly less in patients with Fanconi anemia (P<0.0001) than in controls. Basal angle was significantly greater in Fanconi anemia patients (P=0.006), but the basal angle of those with FA-D1 was not significantly different from controls (P=0.239). Clivus length was less in the Fanconi anemia group (P=0.002), but significance was only observed in the FA-D1 subgroup (P<0.0001). Of the seven patients meeting criteria for pontocerebellar hypoplasia, six belonged to the FA-D1 group. Patients with Fanconi anemia have higher incidences of ectopic neurohypophysis, adenohypophysis hypoplasia, platybasia and other midline central nervous system skull base posterior fossa abnormalities than age- and sex-matched controls. Patients with posterior fossa abnormalities, including pontocerebellar hypoplasia, are more likely to have biallelic BRCA2 mutations.

Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome

BackgroundPrader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS.MethodsTwenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus.ResultsChildren with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed.ConclusionsWe report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.

A Comparative Study of Pituitary Volume Variations in MRI in Acute Onset of Psychiatric Conditions.

The growing belief that endocrine abnormalities may underlie many mental conditions has led to increased use of imaging and hormonal assays in patients attending to psychiatric OPDs. People who are in an acute phase of a psychiatric disorder show Hypothalamic Pituitary Adrenal (HPA) axis hyperactivity, but the precise underlying central mechanisms are unclear. To assess the pituitary gland volume variations in patients presenting with new onset acute psychiatric illness in comparison with age and gender matched controls by using MRI. The study included 50 patients, with symptoms of acute psychiatric illness presenting within one month of onset of illness and 50 age and gender matched healthy controls. Both patients and controls were made to undergo MRI of the Brain. A 0.9 mm slices of entire brain were obtained by 3 dimensional T1 weighted sequence. Pituitary gland was traced in all sagittal slices. Anterior pituitary and posterior pituitary bright spot were measured separately in each slice. Volume of the pituitary (in cubic centimetre- cm3) was calculated by summing areas. Significance of variations in pituitary gland volumes was compared between the cases and controls using Analysis of Covariance (ANOVA). There were significantly larger pituitary gland volumes in the cases than the controls, irrespective of psychiatric diagnosis (ANOVA, f=15.56; p=0.0002). Pituitary volumes in cases were 15.36% (0.73 cm3) higher than in controls. There is a strong likelihood of HPA axis overactivity during initial phase of all mental disorders along with increased pituitary gland volumes. Further studies including hormonal assays and correlation with imaging are likely to provide further insight into neuroanatomical and pathological basis of psychiatric disorders.

Age and sex related differences in normal pituitary gland and fossa volumes.

This study investigates the influence of age and sex on the volumes of the pituitary fossa and gland in 91 males and 108 females from Croatia who underwent magnetic resonance imaging of the endocranium for complaints not related to the pituitary gland. Isometric 3DT1 MPRAGE and 3DT1 MPR sequences were obtained on 1.5. Tesla and analysed on ISSA software. The volumes were obtained from the sum of all the areas multiplied by the thickness of the section. The mean volume of the pituitary fossa for males was 1111.1.4 mm3, for females 1354.4.2 mm3. Correlation analysis showed a significant negative correlation (P=0.0.09) between age of the patient, and pituitary volume. Age of the patient and free volume demonstrate a significant positive correlation (P=0.0.01) indicating that the amount of unoccupied space in the pituitary fossa significantly increases with age. Determining general morphological values, as well as variations of pituitary depth and the occupation of the fossa with the pituitary gland is of great help in everyday diagnostic and therapeutic approach.

Acromegaly: the effect of somatostatin analogues on tumour volume shrinkage

Acromegaly is a rare disease, caused by growth hormone (GH) hypersecretion and secondarily elevated insulin-like growth hormone 1 (IGF-1) level. Nearly all patients with acromegaly suffer from somatotroph pituitary adenoma. The main goal of treatment is to normalise both GH and IGF-1 levels, which reduces symptoms, complications and mortality. Transsphenoidal selective adenomectomy performed by an experienced neurosurgeon is the first-line therapy of choice. Therapy with somatostatin analogues (SSA) is used as a neoadjuvant treatment prior to surgery and in a persistent disease following the surgery. The long-acting somatostatin analogues reduce serum GH/IGF-1 levels and tumour volume. In this clinical review, mechanisms and role of 1st and 2nd generation somatostatin analogues in the treatment of patients with acromegaly are presented, with particular emphasis on the effects on somatotroph pituitary adenoma volume reduction.

Evidence for the changes of pituitary volumes in patients with post-traumatic stress disorder

In pubertal and postpubertal patients with post-traumatic stress disorder (PTSD), significantly greater pituitary gland volumes have been reported. Moving from this point, in the present study, we aimed to investigate pituitary gland volumes in patients with PTSD and hypothesized that volumes of the gland would be structurally changed. Volumetric magnetic resonance imaging of the pituitary gland was performed among sixteen patients with PTSD and fifteen healthy control subjects. We found that the mean volume of the pituitary gland was statistically significant and smaller than that of healthy subjects (0.69±0.08cm3 for patient group and 0.83±0.21 for control subjects). Consequently, in the present study, we found that patients with PTSD had smaller pituitary gland volumes than those of healthy controls like other anxiety disorders. It is important to provide support for this finding in future longitudinal investigations.

Пациенты с макроаденомами гипофиза: на что же они жалуются и кого посещают в первую очередь?

Aim: to evaluate the primary complaints of patients with pituitary macroadenomas and “first-referred” specialists for them. Material and Methods. 351 with pituitary macroadenomas (at least one size >10 mm) were examined: 144 non-functional adenomas (NFA), 65 macroprolactinomas, 142 somatotropinomas. A pituitary adenoma was considered as giant if at least one of the sizes was >40 mm. MRI with an impact study of the pituitary was performed on high field instrument Intera Achieva (PHILIPS company) 3.0 TL, with intravenous extracellular gadolinium contrast agents. Statistical analysis of the results was carried out using the IBM statistical program SPSS Statistics 20 for Windows 7.0 with variation statistics methods for nonparametric data. The data are expressed as Mе [25%, 75%]. Results. The patients’ age ranged from 20 to 80 years and were: NFA 60 [51; 66] y.o., prolactinomas 44 [35; 59] y.o. and somatotropinomas 57 [47; 66] y.o. (р<0.001). Pituitary tumour volumes were: NFA 5,526 [2,460; 11,774] mm3, prolactinomas 5,275 [1,408; 10,566]) mm3 and somatotropinomas 2,814 [1,226; 4,708] mm3 (р<0.001). First patients’ complaints were: NFA – headache (61.7%) and visual disorders (34.8%), prolactinomas – headache (36.8%) and menstrual disorders (27.3%), somatotropinomas – appearance change (31.1%) and headache (32.8%). There was no correlation found between headache and tumour volume however significant correlation was revealed between visual disorders and tumour volume as well as vertical and sagittal sizes of the tumour. The most often “first referred” specialists were: NFA – neurologist (43%) and ophthalmologist (20%), prolactinomas – gynecologist (36.4% of patients of reproductive age) and neurologist (31%); somatotropinomas – endocrinologist (28%) and therapist (25%). Among macroadenomas 32 giant tumors were found: 18 NFA (12.5% of all NFA group), 8 (12.3%) prolactinomas, 6 (4.2%) somatotropinomas. The median age of patients with giant macroadenomas were: NFA 54 [38; 68] y.o., prolactinomas 29 [25; 43] y.o. and somatotropinomas 34 [24; 46] y.o. Tumour volumes of giant adenomas were: NFA 28,190 [21,143; 44,896] mm3; prolactinomas 38,592 [15,994; 78,606] мм3; and somatotropinomas 51,209 [36,703; 102,207] mm3 (p<0.001). Main complaints for patient with giant pituitary tumours were visual impairment (60%, 18 patients – 11 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and headache (44%, 14 patients – 8 patients with NFA, 5 prolactinomas and 1 patient with somatotropinoma). The most often “first referred” specialists were ophthalmologist (50%, 16 patients – 9 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and neurologist (34.4%, 11 cases – 8 patients with NFA, 2 with prolactinomas and 1 with somatotropinoma). Conclusions. Headache and visual impairment were the most often complaints in our cohort of macroadenoma patients, however there were some discrepancies between groups of tumours with different hormonal activity. Neurologist and ophthalmologist should be aware of patients with pituitary macroadenomas, headache and visual disorders should be strong indications for pituitary MRI especially in patients younger than 50.

Patients with pituitary macroadenomas: what do they complain about and whom do they visit first?

Aim: to evaluate the primary complaints of patients with pituitary macroadenomas and “first-referred” specialists for them.Material and Methods. 351 with pituitary macroadenomas (at least one size &gt;10 mm) were examined: 144 non-functional adenomas (NFA), 65 macroprolactinomas, 142 somatotropinomas. A pituitary adenoma was considered as giant if at least one of the sizes was &gt;40 mm. MRI with an impact study of the pituitary was performed on high field instrument Intera Achieva (PHILIPS company) 3.0 TL, with intravenous extracellular gadolinium contrast agents. Statistical analysis of the results was carried out using the IBM statistical program SPSS Statistics 20 for Windows 7.0 with variation statistics methods for nonparametric data. The data are expressed as Mе [25%, 75%].Results. The patients’ age ranged from 20 to 80 years and were: NFA 60 [51; 66] y.o., prolactinomas 44 [35; 59] y.o. and somatotropinomas 57 [47; 66] y.o. (р&lt;0.001). Pituitary tumour volumes were: NFA 5,526 [2,460; 11,774] mm3, prolactinomas 5,275 [1,408; 10,566]) mm3 and somatotropinomas 2,814 [1,226; 4,708] mm3 (р&lt;0.001). First patients’ complaints were: NFA – headache (61.7%) and visual disorders (34.8%), prolactinomas – headache (36.8%) and menstrual disorders (27.3%), somatotropinomas – appearance change (31.1%) and headache (32.8%). There was no correlation found between headache and tumour volume however significant correlation was revealed between visual disorders and tumour volume as well as vertical and sagittal sizes of the tumour. The most often “first referred” specialists were: NFA – neurologist (43%) and ophthalmologist (20%), prolactinomas – gynecologist (36.4% of patients of reproductive age) and neurologist (31%); somatotropinomas – endocrinologist (28%) and therapist (25%). Among macroadenomas 32 giant tumors were found: 18 NFA (12.5% of all NFA group), 8 (12.3%) prolactinomas, 6 (4.2%) somatotropinomas. The median age of patients with giant macroadenomas were: NFA 54 [38; 68] y.o., prolactinomas 29 [25; 43] y.o. and somatotropinomas 34 [24; 46] y.o. Tumour volumes of giant adenomas were: NFA 28,190 [21,143; 44,896] mm3; prolactinomas 38,592 [15,994; 78,606] мм3; and somatotropinomas 51,209 [36,703; 102,207] mm3 (p&lt;0.001). Main complaints for patient with giant pituitary tumours were visual impairment (60%, 18 patients – 11 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and headache (44%, 14 patients – 8 patients with NFA, 5 prolactinomas and 1 patient with somatotropinoma). The most often “first referred” specialists were ophthalmologist (50%, 16 patients – 9 patients with NFA, 4 prolactinomas and 3 somatotropinomas) and neurologist (34.4%, 11 cases – 8 patients with NFA, 2 with prolactinomas and 1 with somatotropinoma). Conclusions. Headache and visual impairment were the most often complaints in our cohort of macroadenoma patients, however there were some discrepancies between groups of tumours with different hormonal activity. Neurologist and ophthalmologist should be aware of patients with pituitary macroadenomas, headache and visual disorders should be strong indications for pituitary MRI especially in patients younger than 50.

Pituitary lacks sexual dimorphism and displays reduced signal intensity on T1-weighted MRI in adolescents with histories of heavy prenatal alcohol exposure

Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure. Pituitary gland volume and maximum signal intensity were examined for group differences. Control female adolescents presented with significantly greater pituitary volume compared to males, as has been previously reported. However, this sexual dimorphism was absent in adolescents with histories of prenatal alcohol exposure. Alcohol-exposed adolescents, regardless of sex, demonstrated reduced pituitary maximum signal intensity compared to controls. The lack of a sex difference in pituitary volumes within the alcohol-exposed group suggests such exposure may interfere with adolescent typical sexual dimorphism of the pituitary. Signal intensity in the posterior pituitary may reflect vasopressin storage. Our findings suggest vasopressin activity should be evaluated in alcohol-exposed adolescents.

Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs.

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures including volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups - heavy binge alcohol (HBA; 2.5g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5g/kg/treatment ethanol and 10mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ∼280mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4-41; choline was administered on GD 4-148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures.

Stress et transition psychotique : revue de la littérature

BackgroundPsychiatric disorders are consistent with the gene x environment model, and non-specific environmental factors such as childhood trauma, urbanity, and migration have been implicated. All of these factors have in common to dysregulate the biological pathways involved in response to stress. Stress is a well-known precipitating factor implicated in psychiatric disorders such as depression, bipolar disorder, anxiety, and possibly schizophrenia. More precisely, psychosocial stress induces dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and could modify neurotransmission, which raises the question of the involvement of stress-related biological changes in psychotic disorders. Indeed, the literature reveals dysregulation of the HPA axis in schizophrenia. This dysregulation seems to be present in the prodromal phases (UHR subjects for ultra-high risk) and early schizophrenia (FEP for first episode psychosis). Thus, and following the stress–vulnerability model, stress could act directly on psychotic onset and precipitate the transition of vulnerable subjects to a full-blown psychosis. ObjectiveThe present paper reviews the literature on stress and onset of schizophrenia, with consideration for the causal role vs. associated role of HPA axis dysregulation in schizophrenia and the factors that influence it, in particular during prodromal and earlier phases. We also discuss different methods developed to measure stress in humans. MethodologyWe performed a bibliographic search using the keywords ‘cortisol’, ‘glucocorticoid’, ‘HPA’ with ‘UHR’, ‘CHR’, ‘at-risk mental state’, ‘first episode psychosis’, ‘schizotypal’, ‘prodromal schizophrenia’ in Medline, Web of Knowledge (WOS), and EBSCO completed by a screening of the references of the selected articles. ResultsStress has been studied for many years in schizophrenia, either by subjective methods (questionnaires), or objective methods (standardized experimental protocols) with biological sampling and/or brain imaging methods. These methods have suggested a link between dysregulation of the HPA axis and psychotic symptoms both through abnormal basal levels of cortisol and flattened reactivity to social stress. Imaging results suggest indirect modifications, including abnormal pituitary or hippocampal volume. Several factors dysregulating the HPA axis have also been highlighted, such as consumption of drugs (i.e. cannabis), childhood trauma or genetic factors (such as COMT, or MTHFR variants). Psychological stress induces subcortical dopaminergic activation attributable to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is present in the prodromal phase (UHR) in patients who have experienced a first psychotic episode (FEP) and in siblings of schizophrenic patients. Stress dysregulation is a plausible hypothesis to understand the psychosis onset. DiscussionThe effect of stress on brain pathways could participate to the mechanisms underlying the onset of psychotic symptoms, both as a precipitating factor and as a marker of a predisposing vulnerability. This dysregulation fits into the gene x environment model: in subjects with genetic predispositions, stressful environmental factors can modify biological pathways implicated in psychiatric disorders, promoting the emergence of symptoms. However, many confounding factors obscure the literature, and further studies are needed in schizophrenic patients, UHR and FEP patients to clarify the precise role of stress in psychotic transition. Identification of stress biomarkers could help diagnosis and prognosis, and pave the way for specific care strategies based on stress-targeted therapies.

The Diagnostic Approach to Central Adrenocortical Insufficiency (CAI) in Thalassemia.

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Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study

Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically.Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats.Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

Pasireotide Therapy of Multiple Endocrine Neoplasia Type 1-Associated Neuroendocrine Tumors in Female Mice Deleted for an Men1 Allele Improves Survival and Reduces Tumor Progression.

Pasireotide, a somatostatin analog, is reported to have anti-proliferative effects in neuroendocrine tumors (NETs). We therefore assessed the efficacy of pasireotide for treating pancreatic and pituitary NETs that develop in a mouse model of multiple endocrine neoplasia type 1 (MEN1). Men1+/− mice were treated from age 12 mo with 40 mg/kg pasireotide long-acting release formulation, or PBS, intramuscularly monthly for 9 mo. The Men1+/− mice had magnetic resonance imaging at 12 and 21 mo, and from 20 mo oral 5-bromo-2-deoxyuridine for 1 mo, to assess tumor development and proliferation, respectively. NETs were collected at age 21 mo, and proliferation and apoptosis assessed by immunohistochemistry and TUNEL assays, respectively. Pasireotide-treated Men1+/− mice had increased survival (pasireotide, 80.9% vs PBS, 65.2%; P < .05), with fewer mice developing pancreatic NETs (pasireotide, 86.9% vs PBS, 96.9%; P < .05) and smaller increases in pituitary NET volumes (pre-treated vs post-treated, 0.803 ± 0.058 mm3 vs 2.872 ± 0.728 mm3 [pasireotide] compared with 0.844 ± 0.066 mm3 vs 8.847 ±1.948 mm3 [PBS]; P < .01). In addition, pasireotide-treated mice had fewer pancreatic NETs compared with PBS-treated mice (2.36 ± 0.25 vs 3.72 ± 0.32, respectively; P < .001), with decreased proliferation in pancreatic NETs (pasireotide, 0.35 ± 0.03% vs PBS, 0.78 ± 0.08%; P < .0001) and pituitary NETs (pasireotide, 0.73 ±0.07% vs PBS, 1.81 ± 0.15%; P < .0001), but increased apoptosis in pancreatic NETs (pasireotide, 0.42 ± 0.05% vs PBS, 0.19 ± 0.03%; P < .001) and pituitary NETs (pasireotide, 14.75 ± 1.58% vs PBS, 2.35 ± 0.44%; P < .001). Thus, pasireotide increased survival and inhibited pancreatic and pituitary NET growth, thereby indicating its potential as an anti-proliferative and pro-apoptotic therapy.