Pituitary Morphology Research Articles

Delayed onset arginine vasopressin deficiency after traumatic brain injury.

Delayed arginine vasopressin deficiency (AVP-D) can present in patients following traumatic brain injury (TBI) and may occur years after the trauma, presenting with nonspecific symptoms. The objective of this case is to highlight the importance of considering the delayed onset AVP-D in patients with a history of TBI. We report a case of a patient who had sustained severe traumatic brain injury 8 years before and who presented with polydipsia, behavioural disorder and frequent falls during the last 3 months. The diagnosis of AVP-D was confirmed by water restriction with a positive response to desmopressin, and pituitary MRI showed an absent spontaneous posterior hyperintensity on T1WI. Follow-up confirmed permanent diabetes insipidus as well as a suspected anterior pituitary deficiency. Pituitary dysfunction occurs following TBI and is correlated with severity. As in our case, symptoms are generally non-specific and are difficult to explore given the patient's neurologic sequelae. MRI 8 years post trauma showed changes in pituitary morphology. Some authors have proposed the need for active screening of post-TBI patients. This case highlights the need for clinicians to be aware that AVP-D can occur years after traumatic brain injury. Delayed onset post-traumatic arginine vasopressin deficiency may occur in patients with TBI and is correlated with the severity. The clinical picture is usually non-specific and diagnosis of AVP-D is challenging in non-verbal patients. An active screening for pituitary dysfunction is warranted in TBI patients and should be extended should one hormone deficit be identified.

The influence of pituitary volume on the growth response in growth hormone-treated children with growth hormone deficiency or idiopathic short stature.

Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to determine if pituitary volume (PV) can distinguish patients with growth hormone (GH) deficiency from those with idiopathic short stature (ISS), (2) to validate an association between PV and severity of GH deficiency, and (3) to compare PV between good and poor response groups in children with GH deficiency or ISS after 1 year of treatment. Data were collected from the medical records of 152 children with GH deficiency or ISS who underwent GH stimulation test, sella MRI, and GH treatment for at least 1 year. Estimated PVs were calculated using the formula of an ellipsoid. We compared the PVs in patients with GH deficiency with those of patients with ISS. In addition, we assessed the association between PV and severity of GH deficiency, and we assessed growth response after treatment. No difference was observed in PV between patients with GH deficiency and those with ISS. The severity of the GH deficiency seemed to be associated with PV (P=0.082), and the height of the pituitary gland was associated with severity of GH deficiency (P<0.005). The PV in the good response group was less than that of the poor response group in patients with GH deficiency (P<0.005), and PV showed no association with responsiveness to GH treatment in patients with ISS (P=0.073). The measurement of PV cannot be used for differential diagnosis between GH deficiency and ISS. In patients with GH deficiency, PV tended to be smaller as the severity of GH deficiency increased, but the difference was not significant. PV may be a good response predictor for GH treatment. Further studies, including a radiomics-based approach, will be helpful in elucidating the clinical implications of pituitary morphology in patients with short stature.

Cushing’s Disease of Unknown Etiology: A Clinical Case Report

Cushing’s disease (CD) remains a diagnostic and therapeutic challenge. Different subtypes may be recognized that will offer insight in this complex situation. We describe an atypical case that we assume is a common variation albeit with no previous formal description. A young female patient presented with minimal clinical features of CD, but increased adrenocorticotropic hormone (ACTH) and cortisol levels, with maintained circadian rhythm that was not suppressed either after the rapid dexamethasone or the prolonged low-dose dexamethasone tests, but suppressed with the prolonged high-dose dexamethasone test and presented a flat ACTH and cortisol response after the corticotropin-releasing hormone (CRH) test. A diffuse enlarged pituitary gland with thickened pituitary stalk was present and a mixed corticotroph adenoma was removed. CD persisted despite now normal pituitary morphology, except for pituitary stalk widening. Plasma levels of CRH were low and no abnormalities were found in the coding region or flanking introns of glucocorticoid receptor (GCR) gene ( NR3C1 ). Somatostatin receptors were not present in the octreoscan, and treatment with cabergoline or somatostatin analogs was ineffective. Morbidity and mortality are increased in CD even in patients successfully treated and in remission. Despite early success in over 80% of the patients, in the long term CD recurs in almost 50% of the patients. Defining subtypes of CD may help elucidate mechanisms of the disease. We propose a new variant that we assume is common. Furthermore adaptation to chronic hypercortisolism is present. J Endocrinol Metab. 2022;12(1):40-48 doi: https://doi.org/10.14740/jem784

Altered pituitary morphology as a sign of benign hereditary chorea caused by TITF1/NKX2.1 mutations

Benign hereditary chorea (BHC) is a rare genetically heterogeneous movement disorder, in which conventional neuroimaging has been reported as normal in most cases. Cystic pituitary abnormalities and features of empty sella have been described in only 7 patients with BHC to date. We present 4 patients from 2 families with a BHC phenotype, 3 of whom underwent targeted pituitary MR imaging and genetic testing. All four patients in the two families displayed a classic BHC phenotype. The targeted pituitary MR imaging demonstrated abnormal pituitary sella morphology. Genetic testing was performed in three patients, and showed mutations causing BHC in three of the patients, as well as identifying a novel nonsense mutation of the TITF1/NKX2-1 gene in one of the patients. The presence of the abnormal pituitary sella in two affected members of the same family supports the hypothesis that this sign is a distinct feature of the BHC phenotype spectrum due to mutations in the TITF1 gene. Interestingly, these abnormalities seem to develop in adult life and are progressive. They occur in at least 26% of patients affected with Brain-lung-thyroid syndrome. As a part of the management of these patients we recommend to perform follow-up MRI brain with dedicated pituitary imaging also in adult life as the abnormality can occur years after the onset of chorea.

MRI Findings of Pituitary Gland in Growth Hormone-Deficient Children and Their Correlation with Growth Hormone Peak during Growth Hormone Stimulation Tests.

This study aims to explore the magnetic resonance imaging (MRI) findings of the pituitary gland (PG) in children with growth hormone deficiency (GHD) and their correlation with the growth hormone (GH) peak during clinical GH stimulation tests. Sixty-one children with GHD diagnosed and treated between December 2018 and December 2021 were retrospectively analyzed in terms of clinical and pituitary morphological MRI data. MRI measurements of various diameters of the adenohypophysis (AH) were obtained to analyze the differences of the measured values in different genders and age groups, as well as their relationship with the GH peak in GH stimulation tests. Among the 61 children with GHD, the superior PG margin was protuberant in 2 cases, flat in 13 cases, and concave in 46 cases. The three age groups showed similar pituitary morphology and stalk (P > 0.05). On T1-weighted images, the proportion of isointensity was lower while the proportion of slightly-low signal intensity was higher in the anterior pituitary gland (APG) of children aged >10 compared with those aged 7–10. The comparison of AH linear parameters and GH peak values of male patients among different age groups showed that the anteroposterior (sagittal) diameter of AH and GH peak were the highest in the >10-year-old group and the lowest in the ≤6-year-old group, with those of the 7–10-year-old group in between (P < 0.05). In females, the anteroposterior (sagittal) diameter and GH peak were higher in the 7–10-year-old group and >10-year-old group compared with the ≤6-year-old group (P < 0.05). The MRI coronal and sagittal heights of PG in children with GHD were positively correlated with the GH peak value. In conclusion, in GHD patients, the coronal and sagittal heights as well as the coronal width of AH do not change with sex or age, but the coronal and sagittal heights of PG are positively correlated with the GH peak of GH stimulation tests, which has high application value in the diagnosis of children with GHD.

Dedicated sellar magnetic resonance imaging protocols without contrast enhancement in girls with central precocious puberty: prevalence of pathologic lesions and clinical correlation.

Contrast-enhanced brain magnetic resonance imaging (MRI) is routinely performed in children with central precocious puberty (CPP). We evaluated the value of a dedicated sellar MRI protocol without contrast enhancement in girls with CPP. This study included 261 girls diagnosed with CPP. We performed sellar MRI scanning without gadolinium enhancement of the hypothalamic-pituitary area (HPA) at the pituitary level, including additional T2-weighted imaging of whole-brain scans to check for other lesions. We evaluated the prevalence of intracranial lesions via this MR protocol. In addition,the correlation between the clinical parameters and morphology of the pituitary gland on the images was assessed. Intracranial lesions were detected in 17 (6.5%) of the 261 girls. Of the 17 girls with abnormalities, 16 (94.1%) had findings in brain areas other than the HPA. The weight, height, Tanner stage of patients were significantly (p < 0.05) higher in the group with greater pituitary height. Patient weight and height, Tanner stage of breast development, and luteinizing hormone (LH) levels were significantly (p < 0.05) greater in those with a higher pituitary grade as determined on sellar MRI. A dedicated unenhanced sellar MRI protocol provides valuable information on brain lesions and pituitary morphology. We found a significantly low prevalence of brain lesions among girls with CPP. Analysis of the height or shape of the pituitary gland on sellar MRI revealed significant correlations with the weight, height, Tanner stage, and LH levels of the patients.

Clinical and Biochemical Phenotype of Indian Children with Different Types of Idiopathic Growth Hormone Deficiency and their Association with Pituitary Height on MRI.

Background and Objectives:Differentiation of growth hormone deficiency (GHD) into various types has been made based on peak stimulated growth hormone levels and other hormone axis involvement. The data regarding how this classification is associated with variation in clinical and biochemical phenotype and how these findings associate with pituitary morphology remains sparse, especially in the Indian population. Therefore, we aimed to ascertain the differences in the pattern of auxological, clinical features including pituitary hypoplasia, and endocrinological profile among patients with severe GHD, partial GHD, and MPHD in the Indian population and to evaluate the association of pituitary height with various clinical and hormonal parameters.Materials and Methods:We conducted a cross-sectional study in 100 patients with idiopathic GHD. Patients were grouped into severe GHD, partial GHD, and MPHD to observe the differences in clinical, biochemical, and MRI findings. The pituitary height findings were correlated clinical and biochemical presentation.Results:MPHD subjects had a significantly higher frequency of breech delivery, neonatal jaundice, neonatal hypoglycemia, and micropenis. A significant difference was observed in the chronological age, bone age retardation (CA-BA), height SDS, weight SDS, peak GH response, IGF-1, IGF-1 SDS, and prevalence of pituitary hypoplasia, pituitary height, and pituitary height SDS among these three groups. In the composite population of GHD, pituitary height SDS was correlated with peak GH, basal IGF-I SDS, and body height SDS.Conclusion:The clinical and biochemical phenotype differs significantly among the various types of GHD. Pituitary height correlates with these findings and is helpful in further assessment of these patients.

Central nervous system lesions in Fanconi anemia: Experience from a research center for Fanconi anemia patients.

Brain atrophy, abnormal pituitary morphology, corpus callosum, and posterior fossa abnormalities have been described in patients with Fanconi anemia (FA). We aimed to provide an overview of cranial neuroimaging findings and to evaluate the clinical implications in FA patients. Cranial magnetic resonance imaging (MRI) studies of 34 patients with FA were retrospectively evaluated, and patients' clinical data were correlated with the imaging findings. The patients' median age was 17.6 (range, 3.9-28) years. At least one pathological brain imaging finding was demonstrated in 22 (65%) patients. These findings included corpus callosum abnormalities and other related supratentorial malformations in nine, pituitary abnormalities in eight, craniovertebral junction and posterior fossa abnormalities in eight, vascular lesions in six, and intracerebral calcifications in two patients. Among the 22 patients who had abnormal cranial MRI findings, six (27%) had mild to moderate intellectual disability (ID), three (14%) had epilepsy, one (5%) had mild hearing loss, and one patient (5%) had hemiplegia. Among these 34 patients, 14 (41%) were transfusion dependent. There was no significant difference between patients with congenital and acquired neuroimaging findings and patients with normal neuroimaging regarding transfusion dependency. Acquired abnormalities in brain tissue, such as white matter intensity changes, white matter T2 hyperintense discrete foci, or infarcts along with congenital abnormalities, were identified in this study. Variable abnormal brain imaging findings in FA patients, although some were not associated with clinical neurological manifestations, suggest that brain imaging could be part of screening in FA.

Mutations Within the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency

Objective:Mutations of the genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation may lead to combined pituitary hormone deficiency (CPHD). PROP1 gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of this study was to describe the phenotypes of Turkish CPHD patients and define the frequency of PROP1 mutations.Methods:Fifty-seven CPHD patients from 50 families were screened for PROP1 mutations. The patients were affected by growth hormone (GH) and additional anterior pituitary hormone deficiencies.Results:All patients had GH deficiency. In addition, 98.2% had central hypothyroidism, 45.6% had hypogonadotropic hypogonadism, 43.8% had adrenocorticotropic hormone deficiency and 7.1% had prolactin deficiency. Parental consanguinity rate was 50.9% and 14 cases were familial. Mean height standard deviation score (SDS) and weight SDS were -3.8±1.4 and -3.1±2.0, respectively. Of 53 patients with available pituitary imaging, 32 (60.4%) showed abnormalities. None had extra-pituitary abnormalities. Eight index patients had PROP1 gene mutations. Five sporadic patients were homozygous for c.301_302delAG (p.Leu102CysfsTer8) mutation, two siblings had exon 2 deletion, two siblings had complete gene deletion and two siblings were homozygous for the novel c.353A>G (p.Q118R) mutation. The frequency of the PROP1 mutations was 16% in our cohort. Mutation rate was significantly higher in familial cases compared to sporadic cases (42.8% vs 11.6%; p<0.01).Conclusion:Phenotype of patients regarding hormonal deficiencies, pituitary morphology, presence of extra-pituitary findings, family history of CPHD and parental consanguinity are important for deciding which pituitary transcription factor deficiency should be investigated. PROP1 mutation frequencies vary in different populations and its prevalence is high in Turkish CPHD patients.

Hypopituitarism in Patients with Blepharophimosis and FOXL2 Mutations

Background: FOXL2 is the gene involved in blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). There have been few single case reports of growth hormone deficiency (GHD) with this syndrome, and Foxl2 is known to be involved in pituitary development in mice. Our aim was to analyze the prevalence of FOXL2 gene alteration in a series of patients with congenital hypopituitarism and eyelid anomalies. Methods: FOXL2 was analyzed in 10 patients with hypopituitarism (ranging from isolated GHD to complete pituitary hormone deficiency) and eyelid anomalies (typical BPES in 4 patients and milder anomalies in 6 patients). In patients with an FOXL2 mutation, we ruled out other possible molecular explanations by analyzing a panel of 20 genes known to be associated with hypopituitarism, and a candidate gene approach was used for patients without an FOXL2mutation. Results: Three patients had an FOXL2mutation. All 3 had typical BPES. Their pituitary phenotype varied from GHD to complete pituitary hormone deficiency and their pituitary morphology ranged from normal to an interrupted pituitary stalk. No mutations were found in genes previously associated with hypopituitarism. Conclusion: Our study shows that some patients with BPES have hypopituitarism with no molecular explanation other than FOXL2 mutation. This points toward an involvement of FOXL2 in human pituitary development.

Fertility and Pregnancy in Women With Hypopituitarism: A Systematic Literature Review

Human reproduction is mainly governed from the hypothalamic-adrenal-gonadal (HPG) axis, which controls both ovarian morphology and function. Disturbances in the secretion of other anterior pituitary hormones (and their respective endocrine axes) interfere with HPG activity and have been linked to fertility problems. In normal pregnancy, maintenance of homeostasis is associated with continuous changes in pituitary morphology and function, which need to be considered during hormone replacement in patients with hypopituitarism. We conducted a systematic PubMed literature review from 1969 to 2019, with the following keywords: fertility and hypopituitarism, pregnancy and hypopituitarism, and ovulation induction and hypopituitarism. Case reports or single-case series of up to 2 patients/4 pregnancies were excluded. Eleven publications described data on fertility (n = 6) and/or pregnancy (n = 7) in women with hypopituitarism. Women with hypopituitarism often need assisted reproductive treatment, with pregnancy rates ranging from 47% to 100%. In patients achieving pregnancy, live birth rate ranged from 61% to 100%. While glucocorticoids, levothyroxine, and desmopressin are safely prescribed during pregnancy, growth hormone treatment regimens vary significantly between countries, and several publications support a positive effect in women seeking fertility. In this first systematic review on fertility, ovulation induction, and pregnancy in patients with hypopituitarism, we show that while literature is scarce, birth rates are high in patients achieving pregnancy. However, prospective studies are needed for evaluating outcomes in relationship to treatment patterns. Replacement therapy in hypopituitarism should always mimic normal physiology, and this becomes challenging with changing demands during pregnancy evolution.

Volumetric and three-dimensional examination of sella turcica by cone-beam computed tomography: reference data for guidance to pathologic pituitary morphology.

The aim of the study was to assess the dimensions and volume of sella turcica in healthy Caucasian adults with normal occlusion and facial appearance from cone-beam computed tomography (CBCT) images. CBCT images of 80 Caucasian adult patients (40 males, 40 females) with normal facial appearance and occlusion taken previously for diagnostic purposes were evaluated. Two groups were constructed in accordance to gender. The volume, length, diameter, and depth of the sella turcica were measured by Romexis software programme. Mann-Whitney U test and Independent t-tests were used for statistical analysis. The mean lengths of the sella were 9.9 mm and 10.2 mm, depths were 9.2 mm and 8.8 mm and diameters were 12.3 mm and 12.1 mm in female and male groups, respectively. Between the genders, no statistically significant differences were found for any of the measurements. There were significantly higher values for the volume of sella turcica in males than in females (1102 ± 285.3 mm3 and 951.3 ± 278.5 mm3, respectively). The dimensions of sella turcica in healthy Caucasian adults with normal occlusion and facial appearance revealed nonsignificant differences between the genders. Individual variability in dimensions and gender differences in the volume are of importance in comparison of patients with craniofacial syndromes and aberrations. Knowledge concerning the dimensions and volume of sella turcica will be clinically relevant for a guidance to consciously realize pituitary disorders.

Changes in body composition in male adolescents with childhood‐onset GH deficiency during transition

Restarting rhGH in adolescents with childhood-onset (CO-) GHD is usually based on GH retest, IGF-1, additional pituitary hormone deficiencies, pituitary morphology and history. Short-term changes in body composition in adolescents with CO-GHD when off rhGH may contribute to the identification of those in need of treatment continuation. This is a longitudinal single-centre study. The body composition of 90 male adolescents with low-likelihood severe GHD of adolescence was measured by DXA at the time of rhGH discontinuation and 6months thereafter. At diagnosis, mean age was 5.4years, height was -2.68 SDS and stimulated GH peak was 5.1ng/mL. RhGH treatment was stopped at 16.7years at near-final height of -0.44 SDS. The adolescents were re-examined after 3months off rhGH using both IGF-1 and GHRH-arginine tests. Severe GHD of adolescence was defined both by stimulated GH<16ng/mL and by IGF-1<-1.90 SDS. Males with severe GHD of adolescence (n=8) gained more relative and absolute fat mass and lost significantly more relative lean body mass after 6months off rhGH than healthy individuals (n=82; P<0.001). The sum of absolute fat mass gain and lean body mass loss (=body composition changes score; BCC score) correlated highly with the GH peak (R=0.17; P<0.001). A BCC score >7.0kg was 88% sensitive and 94% specific for detecting severe GHD of adolescence (AUC=0.975). Short-term body composition changes when off rhGH are good clinical markers of severe GHD in male adolescents. The novel BBC score is an aggregate of these changes.

Transcriptional profiling and pathway analysis reveal differences in pituitary gland function, morphology, and vascularization in chickens genetically selected for high or low body weight

BackgroundThough intensive genetic selection has led to extraordinary advances in growth rate and feed efficiency in production of meat-type chickens, endocrine processes controlling these traits are still poorly understood. The anterior pituitary gland is a central component of the neuroendocrine system and plays a key role in regulating important physiological processes that directly impact broiler production efficiency, though how differences in pituitary gland function contribute to various growth and body composition phenotypes is not fully understood.ResultsGlobal anterior pituitary gene expression was evaluated on post-hatch weeks 1, 3, 5, and 7 in male broiler chickens selected for high (HG) or low (LG) growth. Differentially expressed genes (DEGs) were analyzed with gene ontology categorization, self-organizing maps, gene interaction network determination, and upstream regulator identification to uncover novel pituitary genes and pathways contributing to differences in growth and body composition. A total of 263 genes were differentially expressed between HG and LG anterior pituitary glands (P ≤ 0.05 for genetic line-by-age interaction or main effect of line; ≥1.6-fold difference between lines), including genes encoding four anterior pituitary hormones. Genes involved in signal transduction, transcriptional regulation, and vesicle-mediated transport were differentially expressed and are predicted to influence expression and secretion of pituitary hormones. DEGs involved in immune regulation provide evidence that inflammation and response to cellular stressors may compromise pituitary function in LG birds, affecting their ability to adequately produce pituitary hormones. Many DEGs were also predicted to function in processes that regulate organ morphology and angiogenesis, suggesting pituitary gland structure differs between the divergently selected lines.ConclusionsThe large number of DEGs within the anterior pituitary gland of birds selected for high or low body weight highlights the importance of this gland in regulating economically important traits such as growth and body composition in broiler chickens. Intracellular signaling, transcriptional regulation, and membrane trafficking are important cellular processes contributing to proper hormone production and secretion. The data also suggest that pituitary function is intimately tied to structure, and organization of the gland could influence hypothalamic and systemic metabolic inputs and delivery of hormones regulating growth and metabolism into peripheral circulation.

Genetic analysis of IRF6, a gene involved in craniofacial midline formation, in relation to pituitary and facial morphology of patients with idiopathic growth hormone deficiency

IntroductionGrowth hormone is secreted by the pituitary gland, which forms part of the craniofacial midline. IRF6 encodes a transcription factor involved in the development of the craniofacial midline and mutations in IRF6 are known to disturb craniofacial development. Craniofacial and pituitary development are closely related. After whole exome sequencing revealed a new mutation in IRF6 in a family with Idiopathic Growth Hormone Deficiency (IGHD), we screened the remainder of our IGHD cohort for mutations in this gene and related their genotypes to pituitary and craniofacial morphology.Materials and methodsWe sequenced all coding exons and exon–intron boundaries of IRF6 in 81 patients with IGHD. We performed a multiplex ligation-dependent probe amplification (MLPA) in order to exclude copy number variations in IRF6. We analyzed facial measurements taken from standardized digital pictures of 48 patients.ResultsWe found two new variants and eleven polymorphisms. Apart from the new mutation found in the index family (p.Arg233Cys), we found one other new heterozygous missense mutation in IRF6 (Pro456Ser). p.Arg233Cys was reported as extremely rare in exome databases (1 allele out of 120.852 alleles sequenced), strictly conserved among species and was predicted deleterious by all variant predictor programs. Pro456Ser was predicted to be benign. MLPA did not reveal any exon deletions or duplications in any of the patients.ConclusionThis is the first report of IRF6 analysis in an IGHD cohort. We found one new mutation which, based on in silico analysis, could be of functional relevance. However, we did not find any mutations in the other patients. Therefore, we conclude that IRF6 defects are rare in IGHD patients and further research should focus on new candidate genes.

Analysis of Factors Related to Hypopituitarism in Patients with Nonsellar Intracranial Tumor.

Previous studies have suggested that postoperative hypopituitarism in patients with nonsellar intracranial tumors is caused by traumatic surgery. However, with development of minimally invasive and precise neurosurgical techniques, the degree of injury to brain tissue has been reduced significantly, especially for parenchymal tumors. Therefore, understanding preexisting hypopituitarism and related risk factors can improve perioperative management for patients with nonsellar intracranial tumors. Chart data were collected retrospectively from 83 patients with nonsellar intracranial tumors admitted to our hospital from May 2014 to April 2015. Pituitary function of each subject was determined based on results of preoperative serum pituitary hormone analysis. Univariate and multivariate logistic regression methods were used to analyze relationships between preoperative hypopituitarism and factors including age, sex, history of hypertension and secondary epilepsy, course of disease, tumor mass effect, site of tumor, intracranial pressure (ICP), cerebrospinal fluid content, and pituitary morphology. A total of 30 patients (36.14%) presented with preoperative hypopituitarism in either 1 axis or multiple axes; 23 (27.71%) were affected in 1 axis, and 7 (8.43%) were affected in multiple axes. Univariate analysis showed that risk factors for preoperative hypopituitarism in patients with a nonsellar intracranial tumor include an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H2O), and mass effect (P < 0.05). Multivariate logistic regression analysis showed that mass effect is an independent risk factor for preoperative hypopituitarism in patients with nonsellar intracranial tumors (P < 0.05; odds ratio, 3.197). Prevalence of hypopituitarism is high in patients with nonsellar intracranial tumors. The occurrence of hypopituitarism is correlated with factors including an acute or subacute course (≤3 months), intracranial hypertension (ICP >200 mm H2O), and mass effect (P< 0.05). Mass effect is an independent risk factor for hypopituitarism.

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.

Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement

Background: Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Aims: Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. Methods: The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. Results: GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. Conclusions: GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology.

Effect of inhibiting connexin 43 expression on the expression of rat glial cell growth factors in prolactinomas

Objective To investigate the effect of inhibiting connexin 43 (Cx43) expression on the expression of rat glial cell growth factor in prolactinomas. Methods Forty-eight female rats were randomly assigned to normal, simple estradiol, estradiol+ carbenoxolone, and simple carbenoxolone groups by the completely randomized method (n=12 in each group). A model of rat prolactinoma was induced by estradiol. The normal group did not accept drug treatment; the simple estradiol group was injected estradiol intramuscularly (3 000 mg/kg, once a week, for 13 weeks); 10 weeks after injection of estradiol, the estradiol+ carbenoxolone group injected carbenoxolone via subarachnoid (once a week, for 3 weeks); and the simple carbenoxolone group only injected carbenoxolone for 3 weeks. The changes of body mass of pituitary and histomorphology were observed. Western blot was used to detect the expression levels of Cx43 and glial growth factor (GGF). Results The pituitary weights of the normal, simple estradiol, estradiol+ carbenoxolone and simple carbenoxolone groups were 51.0±0.4 mg, 93.3±1.0 mg, 52.7±2.1 mg and 68.5±1.3 mg, respectively. There were significant differences (F=786.73, P<0.01); the relative expression quantities of Cx43 were 8.0±2.2%, 34.7±4.0, .9.3±3.1%, and 15.3 ±3.8%, respectively, and the relative expression quantities of GGF were 17.7±5.2%, 46.9±1.4%, 15.8±3.6%, and 20.0±2.3%, respectively. There were significant differences (F=1051.51. P<0.01; F=806.58, P<0.01). The pituitary histopathological morphology of the estradiol+ carbenoxolone group was close to the normal group and the simple carbenoxolone group. Conclusions Inhibition of pituitary Cx43 expression may inhibit the GGF expression, thereby inhibiting the growth of pituitary prolactinomas in rats. Key words: Prolactinoma; Gap junction proteins; Gap junction inhibitor; Glial cell growth factor; Rats

Pituitary Morphology and Function in 43 Children with Central Diabetes Insipidus.

Objective. In pediatric central diabetes insipidus (CDI), etiology diagnosis and pituitary function monitoring are usually delayed. This study aimed to illustrate the importance of regular follow-up and pituitary function monitoring in pediatric CDI. Methods. The clinical, hormonal, and neuroradiological characteristics of children with CDI at diagnosis and during 1.5–2-year follow-up were collected and analyzed. Results. The study included 43 CDI patients. The mean interval between initial manifestation and diagnosis was 22.29 ± 3.67 months (range: 2–108 months). The most common complaint was polyuria/polydipsia. Causes included Langerhans cell histiocytosis, germinoma, and craniopharyngioma in 2, 5, and 4 patients; the remaining were idiopathic. No significant changes were found during the 1.5–2 years after CDI diagnosis. Twenty-three of the 43 cases (53.5%) had ≥1 anterior pituitary hormone deficiency. Isolated growth hormone deficiency was the most frequent abnormality (37.5%) and was not associated with pituitary stalk diameter. Multiple pituitary hormone deficiencies were found in 8 cases with pituitary stalk diameter > 4.5 mm. Conclusion. Diagnosis of CDI is usually delayed. CDI with a pituitary stalk diameter > 4.5 mm carries a higher risk of multiple pituitary hormone deficiencies. Long-term MRI and pituitary function follow-ups are necessary for children with idiopathic CDI.