Posterior Pituitary Research Articles

Orexin‐A and orexin‐B are differently localized in the pars nervosa and pars distalis of the white‐spotted conger and Japanese eel pituitaries

AbstractThe distribution of orexin‐A and orexin‐B immunoreactivity was examined in the pituitaries of the white‐spotted conger (Conger myriaster) and the Japanese eel (Anguilla japonica) using immunohistochemical techniques. Orexin‐A‐immunoreactive puncta were dispersed in the pars nervosa of the neurointermediate lobe, and a part of these puncta were immuno‐positive for galanin. In contrast, orexin‐B immunoreactive cells were observed in the proximal part of the pars distalis, and these cells were immuno‐positive for luteinizing hormone. Considering the present results and previous findings, orexin‐A and orexin‐B may modulate the secretion of α‐melanocyte‐stimulating hormone and growth hormone, respectively, and participate in the regulation of energy homeostasis.

Breastfeeding—An Essential Newborn Nutrient

AbstractBreastfeeding is an art/skill. Globally, it is gaining a steady prominence as World Health Organization (WHO) and United Nations International Children's Emergency Fund (UNICEF) have specified exclusive breastfeeding for the initial half year. They have likewise offered significance to initiation of breastfeeding within half an hour to 1 hour after birth that has a critical effect on the developing infant as the colostrum in the breast milk supports immunity in the developing baby and newborn child, following birth helps in invigorating the posterior pituitary, release of Oxytocin and thus helps in uterine contraction and forestalls postpartum hemorrhage in postnatal mothers.Analysis of data from 123 countries shows that babies are breastfed at some point in their lives. However, the rate shifts between low-income, middle-income and high-income countries. It is evaluated that in low- and middle-income countries, approximately 4% of children are never breastfed, while in high-income countries it is 21%. As indicated by the WHO, in excess of 20 million infants are born weighing under 2.5 kg and unfortunately developing nations are facing the brunt of this.One of the WHO Global Targets 2025 is to increase the rate of exclusive breastfeeding in the first 6 months up to at least 50% to improve maternal, infant, and young child nutrition. Unfortunately, only 38% of infants aged 0 to 6 months are exclusively breastfed globally.Numerous factors contribute to produce a positive situation for breastfeeding. Within the health care organizations, mothers need information and support to breastfeed immediately after birth and beyond. Indeed, studies have discovered that implementation of breastfeeding interventions within the health care organizations and community can possibly expand the rates by 2.5 times.In India, government has implemented 6 months maternity leave that benefit many working mothers to exclusive breast feed their newborns.Breastfed children perform better intelligence tests, and are less likely to be overweight and diabetic in later life. If the breastfeeding rate improves in compared to the current rates, then additional 20,000 deaths can be prevented due to breast and ovarian cancer. Studies have found that exclusive breastfeeding can have influence on development of milestones. An ability that a child must achieve by a certain age is developmental milestone. The milestones can be physical, social, emotional, cognitive and communication skills like walking, sharing, expressing emotions, identifying familiar sounds, and talking.·

Morphometric comparison of Fisch type A and endoscopic endonasal far-medial supracondylar approaches to the jugular foramen.

The jugular foramen (JF) is one of the most complex and challenging skull base regions to approach surgically. The extreme medial approach to access the JF provides the approach angle from an anterior direction and does not require dissection and sacrifice of the jugular bulb (JB) to reach the pars nervosa. The authors compared the Fisch type A approach to the extreme medial approach to access the JF and evaluated the usefulness of the extreme medial approach. This study was performed at the Anatomical Laboratory for Visuospatial Innovations in Otolaryngology and Neurosurgery of The Ohio State University. For the comparison of surgical maneuverability and visualization, two angles were measured: 1) the angle of attack (AoA), defined as the widest angle of movement achieved with a straight dissector; and 2) the angle of endoscopic exposure (AoEE), defined as the widest angle of movement in the nasal cavity. The differences in eustachian tube (ET) management, approach angle, surgical maneuverability, and surgical application of the Fisch type A approach to the extreme medial approach were compared. There was no difference between ET mobilization and transection regarding cranial-caudal (CC) or medial-lateral (ML) AoA (p = 0.646). The CC-AoA of the Fisch type A approach was significantly wider than the CC-AoA of the extreme medial approach (p = 0.001), and the CC-AoEE was significantly wider than the CC-AoA of the extreme medial approach (p < 0.001). There was no significant difference between the CC-AoA of the Fisch type A approach and the CC-AoEE. The ML-AoA of the Fisch type A approach was significantly wider than the ML-AoA of the extreme medial approach (p = 0.033), and the ML-AoEE was significantly wider than ML-AoA in the extreme medial approach (p < 0.001). The ML-AoEE was significantly wider than the ML-AoA in the Fisch type A approach (p = 0.033). The surgical maneuverability of the extreme medial approach was not inferior to that of the Fisch type A approach. The extreme medial approach can provide excellent surgical field visualization, while preserving the JB. Select cases of chordomas, chondrosarcomas, and JF schwannomas should be considered for an extreme medial approach. These two approaches are complementary, and a case-by-case detailed analysis should be conducted to decide the best approach.

Oestrogen-dependent hypothalamic oxytocin expression with changes in feeding and body weight in female rats

Oxytocin (OXT) is produced in the hypothalamic nuclei and secreted into systemic circulation from the posterior pituitary gland. In the central nervous system, OXT regulates behaviours including maternal and feeding behaviours. Our aim is to evaluate whether oestrogen regulates hypothalamic OXT dynamics. Herein, we provide the first evidence that OXT dynamics in the hypothalamus vary with sex and that oestrogen may modulate dynamic changes in OXT levels, using OXT-mRFP1 transgenic rats. The fluorescence intensity of OXT-mRFP1 and expression of the OXT and mRFP1 genes in the hypothalamic nuclei is highest during the oestrus stage in female rats and decreased significantly in ovariectomised rats. Oestrogen replacement caused significant increases in fluorescence intensity and gene expression in a dose-related manner. This is also demonstrated in the rats’ feeding behaviour and hypothalamic Fos neurons using cholecystokinin-8 and immunohistochemistry. Hypothalamic OXT expression is oestrogen-dependent and can be enhanced centrally by the administration of oestrogen.

Pituitary Stalk Interruption Syndrome in a Newborn with Encephalopathy: A Case Report

Background: Pituitary Stalk Interruption Syndrome is a rare midline brain anomaly involving the pituitary gland that leads to a variable degree of pituitary hypofunction with a classic neuroimaging finding of the ectopic posterior pituitary, thin or absent pituitary stalk, and anterior pituitary hypoplasia. Case Presentation: We present the case of a term newborn who developed encephalopathy and respiratory distress during the neonatal period and was later diagnosed with Pituitary Stalk Interruption Syndrome. Conclusion: Genetic defects have been identified in 5% of cases, and at times there are associated extra pituitary malformations. In spite of being a welldescribed syndrome, a detailed description of its neonatal presentation and course is lacking in the literature.

Whole Exome Sequencing in Patients With Ectopic Posterior Pituitary.

Ectopic posterior pituitary (EPP), a condition in which the posterior pituitary gland is displaced due to defective neuronal migration, is frequently associated with hypopituitarism. Genetic variants play a role, but many cases remain unexplained. A large EPP cohort was studied to explore the importance of genetic variants and how they correlate with clinical findings. Whole exome sequencing was performed on a discovery sample of 27 cases to identify rare variants. The variants that met the criteria for rarity and biological relevance, or that were previously associated with EPP (ROBO1 and HESX1), were then resequenced in the 27 cases plus a replication sample of 51 cases. We identified 16 different variants in 12 genes in 15 of the 78 cases (19.2%). Complete anterior pituitary deficiency was twice as common in cases with variants of interest compared to cases without variants (9/15 [60%] vs 19/63 [30.1%], respectively; Z test, P = 0.06). Breech presentation was more frequent in the variant positive group (5/15 vs 1/63; Z test, P = 0.003). Four cases had variants in ROBO1 and 1 in HESX1, genes previously associated with EPP. The ROBO1 p.S18* variant has not been reported previously; ROBO1 p.Q1227H has not been associated with EPP previously. EPP cases with variants of interest identified in this study were more likely to present with severe clinical disease. Several variants were identified in genes not previously associated with EPP. Our findings confirm that EPP is a multigenic disorder. Future studies are needed to identify additional genes.

Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.

Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss of function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double; heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.

Extra-pituitary midline structural abnormalities associated with ectopic posterior pituitary detected on a new rapid MRI protocol (FAST1.2).

Test if the MRI FAST1.2 protocol can detect extra-pituitary midline structural brain abnormalities in patients with ectopic posterior pituitary (EPP), and highlighting their radiological-laboratory correlations. Cross-sectional study of patients with EPP and control group. All individuals were submitted to FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. We evaluated 36 individuals with EPP and 78 as control group. Pituitary stalk (PS) was identified in 7/36 patients in EPP group by FAST1, and in 24/36 patients in FAST1.2 (p < 0.001). FAST1 failed to detect PS in one individual in the control group, while the FAST1.2 defined the PS in all individuals. In EPP group, eleven had interhypothalamic adhesion (IHA), three septo-optic dysplasia, and one cerebellar malformation. We didn't observe higher frequency of panhypopituitarism or developmental delay in patients with IHA. In control group, three had pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. FAST1.2 allows confident recognition of midline structural abnormalities, including the pituitary stalk and IHA, thereby making MRI acquisition faster and with no need for contrast administration. IHA could be associated with defects in neuronal migration, as occur in patients with EPP, with no clinical significance.

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.

Oxytocin suppresses CXCL10 production in TNF-α-stimulated human dental pulp stem cells.

Oxytocin (OX) is a posterior pituitary hormone secreted into the blood from axon terminals projecting from the posterior pituitary. Recent reports indicate OX plays an important role in the progression of inflammatory diseases such as rheumatoid arthritis. Pulpitis is caused by the activation of the biological defense mechanism of the dental pulp against cariogenic bacteria. However, the role of OX in the pathogenesis of pulpitis remains unknown. The aim of this study was to examine the effect of OX on CXC chemokine ligand 10 (CXCL10) production in human dental pulp stem cells (HDPSCs). Expression of the oxytocin receptor (OXR) on HDPSCs was detected by Western blot analysis and immunofluorescence. CXCL10 production in HDPSCs was measured using an enzyme-linked immunosorbent assay kit. Western blot analysis was performed to determine the phosphorylation levels of signal transduction molecules, including nuclear factor kappa B, mitogen-activated protein kinases (MAPKs), and Akt in HDPSCs. HDPSCs expressed OXR. OX significantly decreased CXCL10 production in tumor necrosis factor (TNF)-α-stimulated HDPSCs. The p38 MAPK and Akt pathways were related to the OX-suppressed CXCL10 production in TNF-α-stimulated HDPSCs. These results indicate that OX appears to modulate the immune response in pulpitis via suppression of CXCL10 production by HDPSCs.

Recording and manipulation of the maternal oxytocin neural activities in mice

Pulsatile release of the hormone oxytocin (OT) mediates uterine contraction during parturition and milk ejection during lactation.1-3 These pulses are generated by the unique activity patterns of the central neuroendocrine OT neurons located in the paraventricular and supraoptic hypothalamus. Classical studies have characterized putative OT neurons by invivo extracellular recording techniques in rats and rabbits.1,4-10 Due to technical limitations, however, the identity of OT neurons in these previous studies was speculative based on their electrophysiological characteristics and axonal projection to the posterior pituitary, not on OT gene expression. To pinpoint OT neural activities among other hypothalamic neurons that project to the pituitary11,12 and make better use of cell-type-specific neuroscience toolkits,13 a mouse model needs to be developed for the studies of parturition and lactation. We herein introduce viral genetic approaches in mice to characterize the maternal activities of OT neurons by fiber photometry. A sharp photometric peak of OT neurons appeared at approximately 520s following simultaneous suckling stimuli from three pups. The amplitude of the peaks increased as the mother mice experienced lactation, irrespective of the age of the pups, suggesting the intrinsic plasticity of maternal OT neurons. Based on a mono-synaptic input map to OT neurons, we pharmacogenetically activated the inhibitory neurons in the bed nucleus of the stria terminalis and found the suppression of the activities of OT neurons. Collectively, our study illuminates temporal dynamics in the maternal neural activities of OT neurons and identifies one of its modulatory inputs.

The company that one keeps: An interplay between growth hormone and other pituitary hormones

Short stature is defined as a height &lt;2 SD from the mean height for a child of the same sex, ethnicity and chronological age. We present a case series of proportionate short stature whose associated endocrinological deficits left us intrigued. A 9 ½-year-old boy presented with poor growth-velocity (GV) for 5 years and central diabetes insipidus (on the treatment for 1 year). His height was 118 cm (−2.6 SD) and his weight was 20 kg (−2.03 SD). MRI brain showed hypoplastic anterior pituitary with absent bright spot and growth hormone (GH) dynamics proved GH deficiency. A 10-year-4-month-old girl presented with poor GV. Her height was 106 cm (−4.44 SD) and her weight was 15 kg (−3.74 SD). Targeted investigations revealed multiple pituitary hormone deficiencies (central hypothyroidism, secondary adrenal insufficiency and GH deficiency). MRI brain showed reduced pituitary height with ectopic posterior pituitary. GH therapy commenced only after coverage with hydrocortisone. A 1-year-old boy was admitted with failure to gain weight and height for 4 months of age. His length was 57 cm (−7.89 SD) and weight: was 4.6 kg (−5.86 SD) with immature facies, frontal bossing and midfacial hypoplasia. Low GH values at the time of critical sample (blood glucose = 36 mg/dl) revealed GH deficiency. MRI brain demonstrated a hypoplastic pituitary gland. All proportionate short-statured children without obvious dysmorphism need detailed evaluation. GH deficiency can present as a spectrum from isolated deficiency to multiple pituitary (anterior and posterior) deficiencies and so the order of correction of the deficiencies is equally important.

The effect of glucose dynamics on plasma copeptin levels upon glucagon, arginine, and macimorelin stimulation in healthy adults

PurposeNon-osmotic stimulation tests using glucagon, arginine, or macimorelin were recently evaluated for their ability to assess posterior pituitary function. Glucagon and arginine, but not macimorelin, stimulated copeptin secretion (a surrogate marker of vasopressin) and, therefore, provide novel tests to assess the posterior pituitary. The exact underlying mechanism behind their stimulatory effect remains elusive.MethodsThis analysis combined data from three diagnostic studies conducted at the University Hospital Basel, Switzerland. In total, 80 healthy adults underwent the glucagon (n = 22), arginine (n = 30), or macimorelin (n = 28) stimulation tests. The primary objective was to investigate glucose course upon glucagon, arginine, and macimorelin stimulation tests and its effect on plasma copeptin release.ResultsUpon glucagon stimulation, the median [IQR] glucose level at baseline was 5.0 [4.6, 5.2] mmol/l, peaked at 8.1 [7.2, 9.4] mmol/l after 30 min and decreased to a minimum of 3.8 [3.5, 4.5] mmol/l after 120 min. The median copeptin increase upon glucagon stimulation was 7.7 [2.6, 28.0] pmol/l. Upon arginine, the glucose level at baseline was 4.9 [4.8, 5.5] mmol/l, peaked at 6.0 [5.2, 6.4] mmol/l after 30 min and decreased to a minimum of 4.3 [3.8, 4.8] mmol/l after 60 min. The median copeptin increase upon arginine stimulation was 4.5 [2.9, 7.5] pmol/l. Upon macimorelin, glucose levels showed no notable dynamics over the 120 min, and no major change in copeptin was observed.In the pooled dataset, a decrease in glucose levels was significantly correlated with copeptin increase (ρ = 0.53, p < 0.01).ConclusionA similar course in plasma glucose was observed in the copeptin-stimulating test, i.e., after glucagon and arginine, while macimorelin had no effect on glucose and copeptin levels. We hypothesize that a drop in glucose levels observed upon glucagon and arginine might stimulate copeptin.

Electron microscopic study on the effect of chronic fluoxetine treatment on pituitary gland and the possible therapeutic effect of adipose-derived mesenchymal stem cells in adult male albino rats

ABSTRACT Background: Adipose-derived mesenchymal stem cells (ADSCs) have therapeutic potential for the treatment of a variety of disorders due to their self-renewal and multipotential differentiation capabilities. Aim of the work: This study was planned to demonstrate the electron microscopic structure of the pituitary gland after chronic fluoxetine treatment and the possible therapeutic effect of ADSCs. Materials and methods:Thirty healthy male adult albino rats were classified into Control group (Group I). Fluoxetine treated (Group II) received 24 mg/kg/day of fluoxetine dissolved in 1.0 mL of tap water once a day. Fluoxetine group treated with ADSCs (Group III) received fluoxetine as group (II) for 30 days and then was injected once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) received fluoxetine for 30 days and then received no treatment till the end of the experiment. Results: The ultrastructural observations of the fluoxetine-treated group revealed major histological changes in both the pars distalis and nervosa. Pars distalis revealed cells with different shapes, sizes, nuclei, and variable profiles of the cytoplasm. Pars nervosa, on the other hand, revealed pituicytes with electron-lucent cytoplasm and small apoptotic nuclei. Administration of ADSCs greatly improved the microscopic appearance of cells, while the recovery group showed similar histological changes as the fluoxetine group. Conclusion: Fluoxetine caused various deleterious changes in the pituitary gland of albino rats, as evidenced by electron microscopy. These changes were almost corrected by the ADSCs treatment. .

Links between posterior pituitary activity, psychometric profile and other endocrine abnormalities in anorexia nervosa: a multimodal evaluation

IntroductionOpioid system activity was found disturbed in several reward circuit areas in restrictive anorexia nervosa (AN) patients but also at the pituitary level. The role of this specific abnormality in AN physiopathology remains unknown.OObjectivesWe aimed to evaluate the relationship of upper mentioned AN abnormality with its classical pituitary features and eating behavior traits.MethodsPET [11C] diprenorphin binding potential (BPND) were processed for each pituitary part in three groups of young women: 12 AN, 11 recovered AN patients (ANrec), and 12 Controls. Anterior pituitary hormones and neurohypophysis (NH) 12 points circadian profile including copeptin and oxytocin, psychological scores were evaluated in these subjects as well as in 13 bulimic (BN) patients.Results[11C] diprenorphin pituitary binding was found to be fully localized in NH. Only AN patients’ NH present lower [11C] diprenorphin BPND than Controls, interpreted as a higher opioid tone. Both AN and ANrec show lower copeptin/24h than in Controls but no difference in oxytocin. BN showed increased copeptin and low oxytocin. In AN patients copeptin inversely correlate with Restrained Eating while oxytocin correlate with the External Eating score. NH [11C] diprenorphin BPND correlated with leptin but not with copeptin or oxytocin.ConclusionsNeurohypopysis opioid tone in anorexia nervosa seem not to impact the vasopressin or oxytocin release but still may interfere in gonadal axis regulation. Copeptin, a good indicator of hydration state, may be a good tool to detect hidden restrictive or purging behaviors. Specific correlates with AN psychologic features still suggest a physiopathological involvement.DisclosureNo significant relationships.

Estimate incidence and predictive factors of pediatric central diabetes insipidus in a single-institute study

ObjectiveThis study provided a rough estimate incidence of primary pediatric central diabetes insipidus (CDI) and examines the diagnostic factors between pediatric CDI and primary polydipsia (PP). MethodsWe collected 27 patients with chief complaints of polyuria and/or polydipsia from January 2014 to December 2018 in the Department of Pediatrics, Our University Hospital. ResultsWe diagnosed type 1 diabetes mellitus (T1DM) in 16 patients, CDI in 5, PP in 5, and nocturnal enuresis in 1. The rough estimate incidence rate of pediatric CDI was 0.71/100,000/year. The diagnostic factors were a body mass index (BMI), urine gravity in the morning, urine volume and intake volume over 24 h, and bright spots in the posterior pituitary in a magnetic resonance image (MRI). The cutoff value of urine gravity in the morning for CDI was <1.010, with a sensitivity of 100 % and specificity of 100 %. The cutoff value of urine volume over 24 h for CDI was >2299 mL/m2, with a sensitivity of 100 % and specificity of 85.7 %. No pediatric CDI patients had the bright spot in the posterior pituitary of their MRI, using a type 1–weighted image; however, only 1 out of 4 PP patients did not show the bright spot. ConclusionThe rough estimate incidence of pediatric CDI with polydipsia and polyuria under the limited condition was 0.71/100,000/year, which was very low. Distinguishable factors between CDI patients and PP patients were BMI, urine and intake volumes over 24 h, and a bright spot on an MRI. Further studies with multiple institutes and more patients are required to confirm these findings.

A full-system study of neuroendocrine regulation of fish reproduction

The participation of the hypothalamo-hypophysial neurosecretory system (HHNS) in the initiation of energy-consuming migration and spawning behaviors and the completion of spawning by suppressing the hyperactivity of the target glands, which ensures the body transition to energy-saving plastic metabolism was established by ecological-histophysiological full-system studies. The analysis of the HHNS key role in these processes made it possible to develop a constructive working scheme for the neuroendocrine integration of fish reproduction on the principle of self-regulation. In order to increase the fish factory reproduction biotech efficiency new methods for controlling of its biotechnology have been developed on this basis. The technology of preparation and the results of industrial tests of the effectiveness pituitary preparations developed to enhance fish maturation: isolated anterior and posterior pituitary lobes (APL and PPL) of the pituitary gland are presented in this part of the research. The increase degree of the of fish farming producers use average of 15% was proved by production (industrial) tests of the effectiveness of the use of the drug APL at sturgeon fish breeding plants of the lower rivers Volga and Don. To increase the effectiveness of the drug APL usage, its dependence on the degree of preparedness of females for puberty and ovulation was established by the most objective assessment of their individual fish-breeding qualities by the degree of the oocyte nucleus polarization. The most important indicators of the producers physiological state and offspring are stored after the use of APL not only within the production norm, but also qualitatively exceed the “control” — the whole pituitary gland. In order to avoid significant production loss of pituitary dry matter (especially when removing PPL) and the high consumption (35–40%) of the pituitary glands to stimulate the maturation of fish males a “Method for stimulating puberty of male fish” by the isolated posterior pituitary lobe was developed, providing waste-free technology for the preparation and usage of both drugs. Possible prospects for improving methods of stimulating sexual maturity of fish breeders are discussed.

Adding T2-Weighted Images to FAST1 Protocol to Evaluate the Anatomy of the Hypothalamic-Pituitary Region

Introduction: Ectopic posterior pituitary (EPP) is a malformation of the hypothalamic-pituitary region presented as a spectrum from isolated growth hormone deficiency (GHD) to multiple pituitary hormone deficiencies (MPHDs). Our goal was to establish whether the FAST1.2 protocol, which combines the FAST1 protocol with 3D-T2 DRIVE images, could identify the pituitary stalk (PS) and the regional anatomy more accurately. Methods: A retrospective study of 36 individuals with EPP and hypopituitarism and a control group of 78 individuals with eutopic posterior pituitary was conducted. All individuals were submitted to FAST1.2. The position and size of the pituitary lobes were described, and the presence/absence of the PS was confirmed. Results: FAST1 identified the PS in 19% of individuals with EPP, while FAST1.2 identified the PS in 67% (p < 0.001). In the FAST1.2 protocol, the PS was visible in all control individuals. All EPP patients with isolated GHD had visible PS in FAST1.2, while only 58.6% of MPHD cases had visible PS. The size of the anterior lobe and the anteroposterior length of the posterior pituitary were smaller in the EPP group versus controls (p < 0.001). We noticed a reduced anterior pituitary lobe in both diameters in MPHD patients (p < 0.05). Six patients acquired new pituitary hormone deficiencies not recognized at the time of MRI; in this group, only 1 patient had a PS not visible in FAST1.2. Discussion/Conclusion: The FAST1.2 protocol could prevent the misdiagnosis of idiopathic GHD in patients with short stature and could also be important in the progression to MPHD. The PS could be considered a predictor of hypopituitarism, but its use as an isolated indicator for the progression to MPHD is not recommended. Our results reinforce the use of the size of the anterior lobe as a predictor of hypopituitarism and a possible predictor of the degree of pituitary insufficiency. The FAST1.2 protocol could be used as an alternative to gadolinium administration, as a cheaper and faster method, while eliminating the potential risks associated with the administration of contrast media.

NUCLEAR PARATHYROID HORMONE‐RELATED PROTEIN IS NECESSARY FOR PITUITARY SOMATOTROPHS AND GROWTH HORMONE PRODUCTION Waleed J. Hashmi1, Noriko Kantake2, Shiu Yuan2,3, Ibiaghani Max Harry2,3, Nathan K. Hoggard1, Alex H. Fishbach2, Ramiro E. Toribio4, Thomas J. Rosol2,3, Department of Biomedical Sciences, Translation Biomedical Sciences Program, Ohio University, Athens, 45701, OH1,Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University2, Department of

Parathyroid hormone‐related protein (PTHrP) is an important regulator of bone growth, energy metabolism, and lung development. PTHrP is expressed by the pituitary endocrine cells. The pituitary gland plays an important role in homeostasis, energy metabolism, and development. The first phylogenetic identification of PTHrP in animals has shown that it originally developed as a secretory pituitary hormone in fishes. PTHrP is both a secreted and nuclear protein. A novel knock‐in mouse (PTHrP∆/∆) with a lack of the nuclear localization sequence (NLS) of PTHrP was developed. The mice fail to grow and die 4 to 5 days after birth. We hypothesized that the nuclear localization sequence (NLS) of PTHrP was necessary to many tissues for normal development and physiological processes. Histological analysis was performed to study the morphological structure of the pituitaries in these mice. Compared to the wildtype and heterozygote mice(PTHrP+/∆), the pituitary pars distalis from 1‐day‐old PTHrP∆/∆ mice was hypocellular, with a decreased density of pituitary epithelial cells throughout the gland (hypoplasia of the pituitary pars distalis). Occasional pituitary epithelial cells were apoptotic with shrunken pyknotic or fragmented nuclei, with increased cytoplasmic eosinophilia. The pituitary pars intermedia, pars nervosa, and rathke pouch epithelium was unaffected. Immunohistochemistry using GH primary antibody showed decreased GH secretion in somatotrophs which may contribute to early senescence in the mice. Immunoreactivity to GH was strongest in the pituitary epithelial cells within lateral areas of the pars distalis in PTHrP+/∆ mice. The GH immunoreactive cells in the pituitary epithelial cells of PTHrP∆/∆ mice was low compared to PTHrP+/∆ mice. The GH is expressed at low levels in the pituitaries from the PTHrP∆/∆ mice compared to PTHrP+/∆mice as verified by PCR. Understanding the mechanisms and functions of nuclear PTHrP in the pituitary provides the platform for improved medical therapies for endocrine diseases as well as novel insights into the impact of the PTHrP on processes such as growth and metabolism.

Abstract #1176767: A Rare Case of Incidental Ectopic Posterior Pituitary in an Adult

Ectopic posterior pituitary (EPP) is a rare anomaly that is usually diagnosed in childhood and typically associated with aberrant pituitary stalk development, anterior pituitary hypoplasia and functional deficits, and craniofacial abnormalities. We present a case of incidental EPP diagnosed in an adult patient. A 57-year-old female underwent MRI for evaluation of headache and right ocular pain. A normal-sized anterior pituitary was present in the sella turcica, but the pituitary stalk could not be visualized and T1 weighted high-signal corresponding to the neurohypophysis was ectopically adjacent to the superior margin of the anterior pituitary. The patient reported an unremarkable gestation and birth, was of slightly below average stature for a woman in the United States (163 cm, 64 in), had two children and no problems with infertility, and denied polyuria and nocturia. She reported an automobile accident with head trauma at age 20 years, though she was not informed of head imaging abnormalities. Primary hypothyroidism was well compensated on supplemental thyroxine, and gonadotropins were appropriately elevated for postmenopausal status. Measurements of IGF-1 and prolactin were within their respective laboratory reference ranges, but 8 AM cortisol (0.9 μg/dL, expected > 15) and ACTH level (< 5 pg/mL, 10-65) indicated isolated secondary adrenal insufficiency (AI). Diagnosis of AI was confirmed by a 250 μg Cosyntropin™ stimulation test (30 min stimulated cortisol 4.3 μg/dL, 60 min 6.1 μg/dL, expected > 18). There was no history of recent or extended treatment with exogenous glucocorticoids. EPP may result from incomplete inferior extension of the diencephalon during embryologic development or occur after events such as pituitary surgery or severe head injury that result in transection of the pituitary stalk. Mutations in multiple genes involved in neuronal migration and pituitary development, including HESX1, GLI2, and PROP1, have been identified in congenital cases of EPP. Anterior pituitary deficits were identified in over 80% of patients in one pediatric series of EPP patients, with corticotroph axis deficiencies in approximately two-thirds of patients. Diabetes insipidus is uncommon and occurs in fewer than 10% of EPP cases. This patient’s case of EPP is highly unusual because it was diagnosed incidentally and well into adulthood. Remote head trauma may have been the inciting event for EPP to occur, though this cannot be confirmed. The diagnosis of isolated secondary adrenal insufficiency in this patient’s case illustrates the importance of screening anterior pituitary function in all patients with EPP.