Pituitary Gland Volume Research Articles

Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping

Ambitious international efforts are underway to produce gene-knockout mice for each of the 25,000 mouse genes, providing a new platform to study mammalian development and disease. Robust, large-scale methods for morphological assessment of prenatal mice will be essential to this work. Embryo phenotyping currently relies on histological techniques but these are not well suited to large volume screening. The qualitative nature of these approaches also limits the potential for detailed group analysis. Advances in non-invasive imaging techniques such as magnetic resonance imaging (MRI) may surmount these barriers. We present a high-throughput approach to generate detailed virtual histology of the whole embryo, combined with the novel use of a whole-embryo atlas for automated phenotypic assessment. Using individual 3D embryo MRI histology, we identified new pituitary phenotypes in Hesx1 mutant mice. Subsequently, we used advanced computational techniques to produce a whole-body embryo atlas from 6 CD-1 embryos, creating an average image with greatly enhanced anatomical detail, particularly in CNS structures. This methodology enabled unsupervised assessment of morphological differences between CD-1 embryos and Chd7 knockout mice (n=5 Chd7+/+ and n=8 Chd7+/-, C57BL/6 background). Using a new atlas generated from these three groups, quantitative organ volumes were automatically measured. We demonstrated a difference in mean brain volumes between Chd7+/+ and Chd7+/- mice (42.0 vs. 39.1mm3, p<0.05). Differences in whole-body, olfactory and normalised pituitary gland volumes were also found between CD-1 and Chd7+/+ mice (C57BL/6 background). Our work demonstrates the feasibility of combining high-throughput embryo MRI with automated analysis techniques to distinguish novel mouse phenotypes.

Pituitary gland volume among heroin users stabilised on substitution pharmacotherapy

While long-term heroin addiction is associated with hypothalamus–pituitary–adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine-treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity.

Pituitary volume in patients with bipolar disorder and their first-degree relatives

Background Hypothalamic–pituitary–adrenal (HPA) axis dysregulation has been reported in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have yielded inconsistent findings. In addition, the contribution of genetic factors to the pituitary changes in BD remains largely unknown. Method We used MRI to investigate the pituitary volume in 29 remitted patients with BD, 49 of their first-degree relatives (of whom 15 had a diagnosis of Major Depressive Disorder), and 52 age- and gender-matched healthy controls. Results BD patients had a significantly larger pituitary volume compared with their relatives and healthy controls. Pituitary volume did not differ between controls and healthy relatives or relatives diagnosed with major depression. Limitations Direct measures of HPA function (i.e., hormonal levels) were not available. Conclusions These findings suggest that enlarged pituitary volume is associated with disease expression but not genetic susceptibility to BD.

The effect of atypical antipsychotics on pituitary gland volume in patients with first-episode psychosis: A longitudinal MRI study

Background Pituitary volume is currently measured as a marker of hypothalamic-pituitary-adrenal hyperactivity in patients with psychosis despite suggestions of susceptibility to antipsychotics. Qualifying and quantifying the effect of atypical antipsychotics on the volume of the pituitary gland will determine whether this measure is valid as a future estimate of HPA-axis activation in psychotic populations. Aims To determine the qualitative and quantitative effect of atypical antipsychotic medications on pituitary gland volume in a first-episode psychosis population. Method Pituitary volume was measured from T1-weighted magnetic resonance images in a group of 43 first-episode psychosis patients, the majority of whom were neuroleptic-naïve, at baseline and after 3 months of treatment, to determine whether change in pituitary volume was correlated with cumulative dose of atypical antipsychotic medication. Results There was no significant baseline difference in pituitary volume between subjects and controls, or between neuroleptic-naïve and neuroleptic-treated subjects. Over the follow-up period there was a negative correlation between percentage change in pituitary volume and cumulative 3-month dose of atypical antipsychotic ( r = − 0.37), i.e. volume increases were associated with lower doses and volume decreases with higher doses. Conclusions Atypical antipsychotic medications may reduce pituitary gland volume in a dose-dependent manner suggesting that atypical antipsychotic medication may support affected individuals to cope with stress associated with emerging psychotic disorders.

Increased pituitary volume in patients with established bipolar affective disorder

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age = 38.4 years) and 24 matched controls (7 males and 17 females, mean age = 38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.

Smaller pituitary volume in adult patients with obsessive–compulsive disorder

Another structure in the obsessive-compulsive disorder (OCD) circuit may be the pituitary gland because of the fact that limbic-hypothalamic-pituitary-adrenal (LHPA) axis abnormality has been reported in patients with OCD. There has been only one prior study, however, concerning pituitary volumetry, in which the sample was a pediatric group. The purpose of the present study was therefore to investigate this in an adult OCD patient group using magnetic resonance imaging (MRI). Pituitary volume was measured in 23 OCD patients and the same number of healthy control subjects. Volumetric measurements were made on T1-weighted coronal MRI, with 2.40-mm-thick slices, at 1.5 T, and were done blindly. A statistically significantly smaller pituitary volume was found in OCD patients compared to healthy controls (age and intracranial volume as covariates). With regard to gender and diagnosis, there was a significant difference in pituitary gland volume (F = 4.18, P < 0.05). In addition, post-hoc analysis indicated near-significant difference in men with OCD as compared with women with OCD (P = 0.07) and significant difference between control men and control women (F = 10.96, P < 0.001). Taking into consideration that the prior study found decreases in pituitary volume in pediatric patients with OCD as compared with healthy control subjects, future large MRI studies should investigate pituitary size longitudinally, with a careful characterization of hypothalamo-pituitary-adrenal (HPA) function in conjunction with anatomic MRI evaluation.

HPG-axis hormones during puberty: A study on the association with hypothalamic and pituitary volumes

During puberty, the hypothalamus-pituitary-gonadal (HPG) axis is activated, leading to increases in luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex steroids (testosterone and estradiol) levels. We aimed to study the association between hypothalamic and pituitary volumes and development of pubertal hormones in healthy pubertal children. Hormone levels of LH, FSH, estradiol (measured in urine) and testosterone (measured in saliva) were assessed in 85 healthy children (39 boys, 46 girls) between 10 and 15 years of age. Hypothalamic and pituitary gland volumes were segmented on high resolution structural MRI scans. Since sex hormone production is regulated in a sex-specific manner, associations between hormones, hypothalamus and pituitary were analyzed in boys and girls separately. LH, estradiol and testosterone levels all increased with age in both sexes, whereas FSH level did not. Pituitary volume also increased with age and explained 12%, 10% and 8% of the variance in female estradiol, testosterone and LH levels respectively. Corrected for age, pituitary volume explained 17% of FSH level in girls (not boys). Hypothalamic volume did not change with age and did not significantly explain variance in any hormonal level. Our study suggests that a larger pituitary volume is related to higher FSH production, but this association seems independent of pubertal development. The positive association between estradiol, LH and testosterone and pituitary volume is related to age-related pubertal development. With respect to the hypothalamus, we did not find convincing evidence for a larger structure to be involved in elevated hormonal production.

Pituitary gland volume in currently depressed and remitted depressed patients

Major depressive disorder (MDD) has been associated with increased pituitary gland volume (PGV), which is thought to reflect stress-related dysregulation related to hypothalamic-pituitary-adrenal (HPA) axis activity. However, it is unclear whether PGV alteration reflects a “dynamic” change related to current mood instability or if it is a stable marker of illness vulnerability. In this study we investigated PGV in currently depressed patients (cMDD) ( n = 31), remitted depressed patients (rMDD) ( n = 31) and healthy controls ( n = 33), using 1.5 Tesla magnetic resonance imaging (MRI). The groups were matched for age and gender. We found no significant PGV, intra-cranial volume (ICV) or whole brain volume (WBV) differences between cMDD patients, rMDD patients and healthy controls. Furthermore, PGV was not correlated with clinical features of depression (e.g., age of onset; number of episodes; and scores on subscales of the Beck Depression Inventory, the Positive Affect and Negative Affect Scale, and the Mood and Anxiety Symptom Questionnaire). In conclusion, PGV does not appear to be a marker of current or past MDD in adult patients.

Increased pituitary volume in schizophrenia spectrum disorders

While hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been implicated in psychotic disorders, previous magnetic resonance imaging (MRI) studies of the pituitary gland volume in schizophrenia have yielded controversial results. It is also unknown whether patients with schizophrenia spectrum such as schizotypal disorder exhibit pituitary volume changes. In this study, we investigated the pituitary volume using MRI in 47 schizotypal disorder patients (29 males, mean age=25.0 years), 72 schizophrenia patients (38 males, mean age=26.2 years), and 81 age and gender matched healthy controls (46 males, mean age=24.5 years). Both patient groups had a larger pituitary volume compared with controls, but no difference was found between the schizophrenia and schizotypal patients. The pituitary volume was larger in females than in males for all diagnostic groups. There was no association between the pituitary volume and type (typical versus atypical), daily dosage, or duration of antipsychotic medication in either patient group. These findings are consistent with a stress-diathesis model of schizophrenia and further suggest that the schizotypal patients share HPA axis hyperactivity with young established schizophrenia patients reflecting a common vulnerability to stress within the schizophrenia spectrum.

No pituitary gland volume change in medication-free depressed patients

Increased serum cortisol levels and a hyperactive hypothalamo-pituitary-adrenal (HPA) axis have been proposed to play an important role in the pathophysiology of Major Depressive Disorder (MDD). However, there are inconsistent results regarding pituitary gland volume (PGV), which is one of the key elements of the HPA axis evaluated by MRI in depressed patients. In this study, we analyzed the PGV of medication-free moderately depressed MDD patients ( N = 34) and age and sex matched healthy controls ( N = 39). PGV did not differ between MDD patients and healthy controls [mean volume ± S.D.; 0.76 ± 0.17 cm 3 and 0.75 ± 0.14 cm 3; ANCOVA, F 1,69 = 1.25 p > 0.05; respectively]. Our results confirm that volumetric PGV changes are not crucial for depression pathophysiology among unmedicated, moderately depressed adults.

An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic–pituitary–adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Pituitary gland volume in adolescent and young adult bipolar and unipolar depression

Few studies have examined pituitary gland size in mood disorders, particularly in adolescents. We hypothesized increase in the pituitary gland size in early-onset mood disorders. Thirty subjects between the ages of 13 and 20 years participated in the study. Three groups (control, bipolar I depression and unipolar depression) of 10 subjects each (4 male, 6 female) underwent volumetric magnetic resonance imaging at 1.5 T. Analysis of covariance (covarying for age, sex and intracranial volume) revealed a significant difference in pituitary gland volume amongst the groups [F(2,24) = 7.092, p = 0.014]. Post hoc analysis revealed that controls had a significantly smaller pituitary gland volume than both bipolar patients (p = 0.019) and depressed patients (p = 0.049). Bipolar and depressed subjects did not differ significantly from each other with regard to pituitary gland volume (p = 0.653). Control females had larger pituitary glands than control males [F(1,8) = 10.523, p = 0.012], but no sex differences were noted in the mood disorder groups. Pituitary glands are enlarged in adolescents with mood disorders compared to controls. Healthy young females have larger pituitary glands than males, but such a difference is not evident in individuals with unipolar depression or bipolar disorder. These findings provide new evidence of abnormalities of the pituitary in early onset mood disorders, and are consistent with neuroendocrine dysfunction in early stages of such illnesses.

Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury

The objective was to study the anatomical changes in the pituitary gland following acute moderate or severe traumatic brain injury (TBI). Retrospective, observational, case-control study. Neurosciences Critical Care Unit of a university hospital. Forty-one patients with moderate or severe TBI who underwent magnetic resonance imaging (MRI) during the acute phase (less than seven days) of TBI. MRI scans of 43 normal healthy volunteers were used as controls. None. Patient demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Injury Severity Score (ISS), post-resuscitation Glasgow Coma Score (GCS), Glasgow Outcome Score (GOS), mean intracranial pressure (ICP), mean cerebral perfusion pressure (CPP), computed tomography (CT) data, pituitary gland volumes and structural lesions in the pituitary on MRI scans. The pituitary glands were significantly enlarged in the TBI group (the median and interquartile range were as follows: cases 672 mm3 (range 601-783 mm3) and controls 552 mm3 (range 445-620 mm3); p value<0.0001). APACHE II, GCS, GOS and ICP were not significantly correlated with the pituitary volume. Twelve of the 41 cases (30%) demonstrated focal changes in the pituitary gland (haemorrhage/haemorrhagic infarction (n=5), swollen gland with bulging superior margin (n=5), heterogeneous signal intensities in the anterior lobe (n=2) and partial transection of the infundibular stalk (n=1). Acute TBI is associated with pituitary gland enlargement with specific lesions, which are seen in approximately 30% of patients. MRI of the pituitary may provide useful information about the mechanisms involved in post-traumatic hypopituitarism.

Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls ( n = 20) and the total BPD cohort ( n = 20). However, within the BPD cohort, those exposed to childhood trauma ( n = 9) tended to have smaller pituitaries (− 18%) than those with no history of childhood trauma ( n = 10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic–pituitary–adrenal axis dysfunction.

P.1.e.020 Pituitary gland volumes in major depressive disorder patients

P.1.e.020 Pituitary gland volumes in major depressive disorder patients

Effect of antipsychotics on pituitary gland volume in treatment-naïve first-episode schizophrenia: A pilot study

The objective of this study was to examine the effect of antipsychotics on pituitary volume in schizophrenic subjects. Pituitary volumes were measured in 16 patients with schizophrenia at baseline and 12 months after treatment with an antipsychotic medication using magnetic resonance imaging (MRI). A group of 12 healthy controls was evaluated at baseline and after 12 months. Pituitary volume significantly increased in the schizophrenic subjects after treatment (12% increase). This appeared to be specific to the prolactin-elevating drugs. In controls, pituitary volume did not change significantly (3% decrease). Pituitary volume may be a useful biomarker for treatments that affect neuroendocrine function.

Visual documentation of ovine pituitary gland development with magnetic resonance imaging following zeranol treatment

The objective of the current study was to determine whether magnetic resonance imaging (MRI) could be successfully utilized to document the effect of an oestrogenic anabolic agent on pituitary gland growth. The experimental animals consisted of two 1/2 sibling Suffolk wethers (castrated rams), which received either no implant (control, n = 1) or a 24 mg zeranol implant at day 0 and day 42 (zeranol; n = 1). Animals were anaesthetized with propofol and supported with oxygen during the MRI procedure. A mobile MRI unit with a 0.5 tesla (T), superconducting magnet was used to obtain 3 mm thick, non-contrast enhanced, T1-weighted (TR 500-600, TE25) sagittal, transverse and dorsal images of the pituitary gland. Sagittal images were recorded only when the mesencephalic aqueduct and infundibulum were distinctly visible in the same image. Pituitary glands were imaged at 14-day intervals for 70 days to determine if and when the anabolic effects of zeranol on pituitary gland growth could be visualized using MRI techniques. Three separate measurements of the pituitary gland dimensions made with the on-screen cursor were averaged to calculate pituitary gland dimensions and volume. A computer-assisted image analysis system and laser film images were used to determine pituitary gland area. Increases in pituitary gland volume for control and zeranol-treated animals were evident within 14 days, and by the end of the 70-day study, the increase in pituitary volume for the zeranol-treated animal was three times greater than that of the control animal. Overall, our results indicate that MRI technology can be successfully used to document the development of the pituitary gland in vivo. Application of knowledge gained from this novel approach to study the growth, development and function of endocrine glands over time, and within the same animal, will enhance human and animal endocrine diagnostic procedures.

Development and sexual dimorphism of the pituitary gland

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91 ± 5.89 years) and females were 7 to 35 years of age (16.75 ± 5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups ( F = 3.55, df = 2, 143, p = 0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups ( p = 0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.

Intraobserver and interobserver agreement, reproducibility, and accuracy of computed tomographic measurements of pituitary gland dimensions in healthy dogs

To determine the reproducibility and accuracy of computed tomographic (CT) measurements of pituitary gland dimensions in healthy dogs. 35 healthy sexually intact adult dogs. 2 observers independently viewed CT images of the skull in 35 dogs twice. Pituitary gland height, width, length, and volume and pituitary gland height-to-brain area ratio (P:B ratio) were measured or calculated. Intraobserver and interobserver agreement indexes (AIs) were calculated for pituitary gland dimensions. Computed tomography was performed also on 5 phantoms, and both observers measured phantom dimensions twice. True-value AIs were calculated for the phantom study. The mean +/- SD interobserver AI between observer 1 and 2 for pituitary gland height and the P:B ratio was 0.90 +/- 0.07. The intraobserver AI for pituitary gland height and the P:B ratio was 0.97 +/- 0.04 for observer 1 and 0.94 +/- 0.04 for observer 2. The intra and interobserver AIs for the other dimensions were lower than those for pituitary gland height and the P:B ratio. All phantom dimensions on CT images were underestimated significantly, compared with their true values. The intra- and interobserver AIs for pituitary gland dimension measurements on CT images were high. However, the same observer preferably should perform serial measurements. Window settings influence pituitary gland dimension measurements, and predetermined window settings are recommended to make comparisons among dogs. Pituitary gland dimension measurements made from CT images in our study underestimated the true values.

Pituitary Volume in Treatment-Naïve Pediatric Major Depressive Disorder

Prior pilot investigation identified a larger pituitary gland volume (PGV) in pediatric patients with major depressive disorder (MDD) compared with healthy pediatric control subjects that was most prominent in boys with MDD. In this independent sample, we focus on gender differences in pituitary volume in a larger sample of pediatric patients with MDD. Volumetric magnetic resonance imaging studies were conducted in 35 psychotropic drug-naïve children (15 boys, 20 girls), ages 8-17 years, and 35 case-matched healthy control subjects. The MDD boys had larger PGV (19%) compared with male control subjects. No significant diagnostic group differences in pituitary volume were observed in girls. Healthy boys had significantly smaller PGV (27%) than healthy girls, whereas MDD boys did not differ from girls with MDD. Nonfamilial (without a family history of mood disorder) boys with MDD had significantly larger PGV (35%) than male healthy control subjects and tended to have a larger PGV (27%) than familial (at least one first-degree relative with MDD) boys with MDD. Boys with familial MDD did not differ from control subjects. These findings provide new evidence of increased pituitary volume in psychotropic-naïve pediatric patients with MDD that seems to be more prominent in male patients with nonfamilial MDD.