Lobe Of Pituitary Research Articles

The First Pituitary Proteome Landscape From Matched Anterior and Posterior Lobes for a Better Understanding of the Pituitary Gland

To date, very few mass spectrometry (MS)–based proteomics studies are available on the anterior and posterior lobes of the pituitary. In the past, MS-based investigations have focused exclusively on the whole pituitary gland or anterior pituitary lobe. In this study, for the first time, we performed a deep MS-based analysis of five anterior and five posterior matched lobes to build the first lobe-specific pituitary proteome map, which documented 4090 proteins with isoforms, mostly mapped into chromosomes 1, 2, and 11. About 1446 differentially expressed significant proteins were identified, which were studied for lobe specificity, biological pathway enrichment, protein–protein interaction, regions specific to comparison of human brain and other neuroendocrine glands from Human Protein Atlas to identify pituitary-enriched proteins. Hormones specific to each lobe were also identified and validated with parallel reaction monitoring–based target verification. The study identified and validated hormones, growth hormone and thyroid-stimulating hormone subunit beta, exclusively to the anterior lobe whereas oxytocin–neurophysin 1 and arginine vasopressin to the posterior lobe. The study also identified proteins POU1F1 (pituitary-specific positive transcription factor 1), POMC (pro-opiomelanocortin), PCOLCE2 (procollagen C-endopeptidase enhancer 2), and NPTX2 (neuronal pentraxin-2) as pituitary-enriched proteins and was validated for their lobe specificity using parallel reaction monitoring. In addition, three uPE1 proteins, namely THEM6 (mesenchymal stem cell protein DSCD75), FSD1L (coiled-coil domain–containing protein 10), and METTL26 (methyltransferase-like 26), were identified using the NeXtProt database, and depicted tumor markers S100 proteins having high expression in the posterior lobe. In summary, the study documents the first matched anterior and posterior pituitary proteome map acting as a reference control for a better understanding of functional and nonfunctional pituitary adenomas and extrapolating the aim of the Human Proteome Project towards the investigation of the proteome of life.

Pituitary stem cells: what do we know?

The pituitary gland is defined as a highly “plastic” gland, capable of adapting to the changing needs of the body over the course of a lifetime. In 1969, the first putative pituitary stem cells were isolated, defined as chromophobe cells because of their inability to secrete/incorporate hormones. Since then, studies have improved and have confirmed the presumed existence of a side population characterized by SOX2 expression in both the anterior and marginal pituitary lobes. From the numerous studies conducted to unravel the biological significance of these stem populations, it is currently believed that these cells, at least in the adult basal gland, are highly quiescent; however, their functions are still not well understood. This review reports the major advances achieved in recent years towards developing protocols for the isolation of pituitary stem cells from healthy tissue and pituitary adenomas, as well as the first studies on their use in regenerative medicine.

RF13 | PMON146 Molecular determinants of cavernous sinus invasion by pituitary adenomas: functional in vitro studies and in vivo investigations in a rat model of invasive pituitary tumorigenesis obtained by stereotactic pituitary GC cells injection

Abstract Context Surgical removal is the primary treatment option for pituitary adenomas. However, pituitary surgery is frequently incomplete because of invasion of extrasellar cerebral structures. In particular, the vicinity with the carotid artery hinders the radical surgical excision of the adenoma portion invading the cavernous sinus. Our objective was to study the molecular bases of the cavernous sinus invasion by pituitary adenomas. Methods We obtained a unique tissue collection of 19 invasive pituitary adenomas with a sample from the intrasellar portion and a sample from the portion invading the cavernous sinus for each adenoma. We used RNA-sequencing to compare the gene expression patterns of the invading and intrasellar portions. The implication of one differentially expressed candidate gene in the invasive behavior was first analyzed in vitro using Transwell Assay to study the impact of its pharmacologic inhibition on cell migration and invasion. These experiments were conducted in murine lactosomatotroph GH3 cells and gonadotroph LbT2 cell. To further study the role of this gene on tumor growth and behavior in vivo, we elaborated a model of invasive pituitary adenomas by stereotactic injection of murine somatotroph GC cell into the lobes of the pituitary gland of female Wistar Furth rats. Twelve rats (10-12 week-old) received 20.000 GC cells in each pituitary lobe. After surgery, rats were monitored weekly, tumor development was assessed fortnightly by 3 successive 7Tesla MRI and analyzed by Horos software. Rats were sacrificed 7 weeks after GC cells injection. Six of the 12 rats were treated during this period with the pharmacological inhibitor of the candidate gene. Results RNA-sequencing identified 159 up-regulated genes and 11 down-regulated genes in the invasive adenoma portion. In vitro pharmacological inhibition of the candidate gene decreased cell migration and invasion in GH3 cells (p=0.0205 and p=0.0038) and LbT2 cell (p=0.0345 and p=0.0131). Amongst the 12 injected animals, 11 (92%) rats developed invasive pituitary tumors. Tumor growth was rapid, causing death from intracranial hypertensions before the theoretical end of the study protocol in 7 animals. Pharmacological inhibition tended to slow tumor growth from 30.3 mm3/week to 7.8 mm3/week (p=0.12) and decreased cumulative mortality (83% in untreated animals versus 33% in treated animals, p=0.08). Conclusion We described the molecular signature associated with the invasive behavior of pituitary adenomas and identified a therapeutic target, which is related to pituitary cells migration and invasion in functional in vitro studies. Pharmacologic inhibition of this target tended to decrease tumor growth and mortality from intracranial hypertension in vivo, however larger numbers of animals are necessary to confirm this observation. Our original approach of orthotopic cell injection into rat pituitaries resulting in tumor development provides a new tool for molecular studies of pituitary tumorigenesis and for the screening of new therapeutic agents. Presentation: Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Research Article: Development of the Control System for Artificial Reproduction of Fish Populations Based on a Complex of Neroendocrinological Research and Biotech Innovations

The participation of the hypothalamic-hypophysial neurosecretory system (HHNS) in fish reproduction using light, electron microscopy and immunocytochemistry was established by ecologo-histophysiological studies for the first time in the world literature. At the beginning of passing fish migrations a violation of the HHNS basic osmoregulative function, causing habitat change is revealed. Simultaneously the HHNS causes the neurotropic effect on the central nervous system (CNS) arousal in the form of a dominant state of "Migration impulse." At the beginning of spawning, HHNS also initiates spawning behavior and completes it by participating in the body's protective-adaptive reactions to natural physiological stress. The functional role of the HHNS in fish reproduction is to initiate energy-intensive (reproductive) processes of migratory and spawning behaviors and to complete spawning by suppressing the hyperactivity of target glands, which ensures the body's transition to energy-saving plastic exchange. The analysis of the key role of the HHNS in the integration of fish reproduction by the self-regulation principle has allowed the development of a constructive working scheme. New biotech methods of managing breeding time, rates of survival and growth of valuable fish species were developed on this basis. They are presented in the form of 10 inventions. To stimulate sex maturation, drugs of isolated anterior and posterior pituitary lobes were developed and introduced in sturgeon industry, increasing the extent of their fish-breeding use by 15% and saving the pituitary up to 40%. To delay puberty, a method of industrial fish breeders reservation in the critical salinity habitat of 4-8‰, both in seawater and in table salt solutions has been developed. On this basis, a full-system method of sturgeon and salmon fish populations reproduction, covering all stages of farm biotechnology has been developed. It is carried out by mass breeders reservation in sea cages, obtaining there offspring and, after the river fish-farm growing youngs to their readiness for migration, the final cultivation them in sea cages gardens till large life-resistant youngs. For the implementation of the proposed industrial biotechnology and year-round fish farming a new installation of recirculating aquaculture systems (RAS) hatcheries and farms was developed by means of the off-season underground conditioning of fish cultivation habitat and by the principle of natural-industrial engineering ecology. Due to the general aim ‒ increasing the efficiency biotechnology of reproduction and logical relationships, all developments are integrated into the system of biotech management of fish population reproduction.

Review Article: Systemic Lupus Erythematosus in Gynecology

The participation of the hypothalamic-hypophysial neurosecretory system (HHNS) in fish reproduction using light, electron microscopy and immunocytochemistry was established by ecologo-histophysiological studies for the first time in the world literature. At the beginning of passing fish migrations a violation of the HHNS basic osmoregulative function, causing habitat change is revealed. Simultaneously the HHNS causes the neurotropic effect on the central nervous system (CNS) arousal in the form of a dominant state of "Migration impulse." At the beginning of spawning, HHNS also initiates spawning behavior and completes it by participating in the body's protective-adaptive reactions to natural physiological stress. The functional role of the HHNS in fish reproduction is to initiate energy-intensive (reproductive) processes of migratory and spawning behaviors and to complete spawning by suppressing the hyperactivity of target glands, which ensures the body's transition to energy-saving plastic exchange. The analysis of the key role of the HHNS in the integration of fish reproduction by the self-regulation principle has allowed the development of a constructive working scheme. New biotech methods of managing breeding time, rates of survival and growth of valuable fish species were developed on this basis. They are presented in the form of 10 inventions. To stimulate sex maturation, drugs of isolated anterior and posterior pituitary lobes were developed and introduced in sturgeon industry, increasing the extent of their fish-breeding use by 15% and saving the pituitary up to 40%. To delay puberty, a method of industrial fish breeders reservation in the critical salinity habitat of 4-8‰, both in seawater and in table salt solutions has been developed. On this basis, a full-system method of sturgeon and salmon fish populations reproduction, covering all stages of farm biotechnology has been developed. It is carried out by mass breeders reservation in sea cages, obtaining there offspring and, after the river fish-farm growing youngs to their readiness for migration, the final cultivation them in sea cages gardens till large life-resistant youngs. For the implementation of the proposed industrial biotechnology and year-round fish farming a new installation of recirculating aquaculture systems (RAS) hatcheries and farms was developed by means of the off-season underground conditioning of fish cultivation habitat and by the principle of natural-industrial engineering ecology. Due to the general aim ‒ increasing the efficiency biotechnology of reproduction and logical relationships, all developments are integrated into the system of biotech management of fish population reproduction.

A Randomized Trial of Comparative Dosimetric Study of Radiotherapy in High Grade Gliomas Based on the Guidelines of 2019-NRG and EORTC Target Delineation

<h3>Purpose/Objective(s)</h3> Postoperative radiotherapy is important for high-grade glioma (WHO Grade 3-4), but the optimal way for contouring the target area for radiotherapy is still unclear. The purpose of this randomized trial was to compare the dosimetric differences in radiation treatment plans (TPS) generated based on the European Organization for Research and Treatment of Cancer (EORTC) and NRG consensus (NRG-2019) guidelines to provide evidence for optimal target delineation for high-grade glioma. <h3>Materials/Methods</h3> Patients with diagnosis of high-grade glioma were randomly assigned (1:1) to receive postoperative radiotherapy based on either EORTC guideline or NRG-2019 guideline. We report the result of dosimetric comparison first. In 13 high grade glioma patients, both EORTC and NRG-2019 radiation treatment plans were generated for dosimetric comparison. For EORTC group, the prescription dose was 95% PTV 60 Gy in 30 fractions. The gross tumor volume (GTV) including resection cavity and residual tumor encompassed the T1-weighted images (T1WI) and T2 FLAIR contrast-enhancing lesion. For NRG-2019group, GTV involved the T1-weighted images (T1WI) and T2 FLAIR contrast-enhancing foci and peritumoral edema on the preoperative CT or MRI. The prescription dose of PTV1 was 46 Gy in 23 fractions. The areas were then diminished to contain merely the contrast enhancing foci with a 2.5 cm margin as CTV2, and PTV2 was equal the CTV2 plus 0.3 cm margin for additional prescription dose was 14 Gy in 7 fractions. It should be noted that CTV1 and CTV2 were trimmed according to the anatomical barriers, falx, ventricles, etc. This trial is registered with chictr.org.cn, number ChiCTR2100046667. <h3>Results</h3> The median volume for PTV of EORTC plans, PTV1 of NRG-2019 plans, PTV2 of NRG-2019 plans were 336.6 cm³ (range 161.1-511.5 cm³), 365.3 cm³ (range 123.4-535.0 cm³), and 263.2 cm³ (range 116.8-497.7 cm³), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different. There was no significant difference in the volume percent of brain irradiated to 30 Gy, 46 Gy, and 60 Gy according to different target delineations (P = 0.397, P = 0.590 and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brainstem, optic chiasm, optic nerve, lens, eyes, pituitary, and temporal lobes (P = 0.858, P = 0.858, 0.701, P = 0.794, P = 0.701, P = 0.427, P = 0.489, P = 0.898, P = 0.626, P = 0.942 and P = 0.161, respectively). <h3>Conclusion</h3> Compared with EORTC guidelines for postoperative radiotherapy for high-grade glioma, the NRG-2019 target area delineation guidelines were able to include peritumor edema in the CTV without increasing the radiation dose to organs at risk (OARs). This study further provides a foundation for the application of the NRG-2019 consensus in radiotherapy for patients with high-grade gliomas.

Regulation of fenestra formation via actin-dynamin2 interaction in rat pituitary endothelial cells.

Endothelial fenestrae are transcellular pores divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP). They function as a channel for peptide hormones and other substances. Invagination of the plasma membrane is necessary for the fenestra formation. The actin cytoskeleton is essential for scission of endocytic vesicles from the invaginated plasma membrane. Therefore, we examined the involvement of the actin cytoskeleton in fenestra formation in cultured endothelial cells isolated from the anterior lobe (AL) of the rat pituitary, using immunofluorescence and scanning electron microscopy. Inhibition of polymerization and depolymerization of the actin cytoskeleton by latrunculin A and jasplakinolide, respectively, remarkably increased the PLVAP-positive sieve plate area and number of fenestrae. Jasplakinolide significantly affected the arrangement of the fenestra on the cell surface, resulting in parallel serpentine furrows of the fenestra. These results suggest that the actin cytoskeleton not only induces fenestra formation but also regulates cell arrangement. Dynamin is a scission protein of the invaginated plasma membrane and interacts with the actin cytoskeleton. We found that dynamin2 is mainly expressed in the endothelial cells of the rat AL. We then investigated the function of dynamin2 by the treatment with dyngo-4a, a potent inhibitor of dynamin1 and dynamin2, on the fenestra formation. As a result, the PLVAP-positive area is significantly increased by the treatment. These results show that the actin-dynamin2 interaction is essential for the control of the fenestra formation in endothelial cells of rat AL. In conclusion, the actin cytoskeleton and dynamin2 function as regulators of endothelial fenestra formation.

Light and electron microscopic studies on the influence of stress on prolactin-immunoreactivity in rat anterior pituitary lobe.

An increasing number of evidence suggests an important role of prolactin in the modulation of stress response. However, the mechanisms of its action on the HPA axis are not yet understood. Glucocorticoids, liberated from adrenal cortex due to hormonal signals from pituitary corticotrophs are known to play a key role in systemic stress response. Previously we found evidence that corticosteroid-binding globulin (CBG) is involved in rapid, membrane-mediated actions of adrenal steroids. Here we studied qualitatively immunostainings for prolactin and CBG in pituitaries of male rats that had been subjected to osmotic challenge. We also examined late pregnant, parturient and early lactating rats, assuming that parturition represents a strong physiological stress. We employed double immunofluorescencent staining of semithin sections and immunoelectron microscopy. In stressed males we found increased prolactin immunofluorescence associated with membranes while in controls this staining was predominantly cytoplasmatic. CBG immunofluorescence was found in almost all prolactin cells of stressed males while such double staining was only occasionally observed in controls. Similar observations were made in females: While parturient rats showed intense membrane associated double staining for both antigens, late pregnant and early lactating animals showed patterns similar to that of male controls. Immunoelectron microscopy revealed increased exocytosis of prolactin containing vesicles in lactating rats. CBG was localized on cell membranes and additionally within prolactin vesicles. Our observations suggest prolactin liberation from pituitary lactotrophs along with CBG upon systemic stress response. Membrane effects of glucocorticoids mediated by CBG may be linked to stimulus secretion of prolactin.

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.

TBIO-03. Angiogenesis in Pituitary Adenoma

The role of angiogenesis in pituitary tumor development used to be questioned, since pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to nonin- vasive and microprolactinomas. We should know VEGF was found firstly in pituitary anterior lobe, then tumor angiogenesis must occur. Meanwhile the vascular arrange- ment raised by VEGF is irregular, that sometimes lead to pituitary apoplexy. In this chapter, hypoxia inducible factors (HIF), transcription factors regulating expression of several genes related to oxygen homeostasis are in response to hypoxic stress. We focus on tumor angiogenesis regulated by the signaling cascade in tumor angiogenesis in pituitary tumor.

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.

Effects of pituitary hormones deficiency from the specific pituitary lobes on learning, memory and survival behavior in the Wistar rat

The role of the different adenohypophyseal hormones (GH, PRL, ACTH, TSH, LH and FSH) and neurohypophyseal (AVP and OXY) hormones on animal behavior, memory and learning have been stablished, however the role of lobe‐specific hormones on these cerebral functions has been not completely dilucidated. Here we study the specific pituitary hormone deficiencies in hypophysectomized (HYPOX), with anterior lobectomized (AL) and neurointermediate lobectomized (NIL) rats, subject to novel object recognition (NOR), forced swim (FS) and prepulse inhibition (PPI) tests. For comparisons the intact control (IC) and sham operated (SHAM) groups were also included. The NOR test that evaluate different phases of learning and memory in rodents, showed that memory discrimination index (DI) significantly increased in the NIL group, indicating that AVP and OXY deficiency negatively affect the ability of short and medium‐term memory. The FS test assess survival and motivation behavior; results showed that AL, NIL and HYPOX groups induced a loss in motivation and will to survive (increased immobility time); these observations may be partially explained by: 1) the significant deficiency of metabolic hormones (GH, ACTH‐corticosterone, TSH‐thyroid hormones and LH‐FSH‐testosterone hormones) whose decrease also induced significant loss in both mass muscle and body weight in AL and HYPOX groups and, 2) the decreased survival and motivational behavior induced by the AVP and OXY deficiency (NIL‐induced), thus supporting the view of the motivational and survival role of these hormones. The IPP test evaluates the rat ability to respond to potentially harmful acoustic stimuli and long‐term memory; results showed that AL animals did not show any sign of learning (expressed as very low inhibition percentage), whereas, interestingly, the HYPOX group (without any pituitary hormones) the long‐term memory was not significantly affected. In conclusion these results support the important role of the several pituitary hormones mainly neurohypophyseal hormones (AVP and OXY) controlling important brain functions necessary for learning, memory, and survival. These experimental models will allow in the future to study specifically the role of each pituitary hormone on the different aspects of animal behavior such as memory, motivation, generosity, adaptation, among others.

Establishment and Application of an Index System for the Risk of Drug Shortages in China: Based on Delphi Method and Analytic Hierarchy Process.

At present, the avoidance of drug shortages mainly relies on expert experience. This study aimed to establish an evaluation index system for the risk of drug shortages in medical institutions in China and to apply the system to guide the graded management of drugs in short supply. A two-round Delphi process was conducted to determine the indicators in the index system. The weight value of each indicator was calculated using analytic hierarchy process (AHP) methods. The data of drugs in short supply from January 1 to December 31, 2020 in Hunan province were collected and evaluated using this index system. The evaluation scores, which ranged from 0 to 100, were calculated. A three-level index system with four first-level indicators, 11 second-level indicators, and 36 third-level indicators was constructed by the two rounds of the Delphi process. The expert authority coefficient (Cr) of the first and second rounds of consultation were 0.88 and 0.90, respectively. The Kendall's coefficients of concordance (Kendall's W) for the two rounds of consultation were 0.44 and 0.50, respectively (P<.05). For the first-level indicators 'supply stability,' 'causes of shortage,' 'medicine availability in medical institution' and 'pharmaceutical properties,' the weight values were 0.3253, 0.2489, 0.2398, and 0.1860, respectively. Based on the risk evaluation score, drugs (dosage strength) at high risk of shortage included sodium thiosulfate (0.64 g), posterior pituitary lobe hormones (1 mL:6 IU), protamine sulfate (5 mL:50 mg), thrombin (500 U), urokinase (10 WU), and rotundine sulfate (2 mL:60 mg). An indexed system for the risk assessment of drug shortages in China was established to guide the graded response to drug shortages in medical institutions and the implementation of differential management strategies to address these shortages.

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update.

BackgroundAccidental hypothermia (AH) is an unintended decrease in body core temperature (BCT) to below 35°C. We present an update on physiological/pathophysiological changes associated with AH and rewarming from hypothermic cardiac arrest (HCA).Temperature Regulation and MetabolismTriggered by falling skin temperature, Thyrotropin-Releasing Hormone (TRH) from hypothalamus induces release of Thyroid-Stimulating Hormone (TSH) and Prolactin from pituitary gland anterior lobe that stimulate thyroid generation of triiodothyronine and thyroxine (T4). The latter act together with noradrenaline to induce heat production by binding to adrenergic β3-receptors in fat cells. Exposed to cold, noradrenaline prompts degradation of triglycerides from brown adipose tissue (BAT) into free fatty acids that uncouple metabolism to heat production, rather than generating adenosine triphosphate. If BAT is lacking, AH occurs more readily.Cardiac OutputAssuming a 7% drop in metabolism per °C, a BCT decrease of 10°C can reduce metabolism by 70% paralleled by a corresponding decline in CO. Consequently, it is possible to maintain adequate oxygen delivery provided correctly performed cardiopulmonary resuscitation (CPR), which might result in approximately 30% of CO generated at normal BCT.Liver and CoagulationAH promotes coagulation disturbances following trauma and acidosis by reducing coagulation and platelet functions. Mean prothrombin and partial thromboplastin times might increase by 40–60% in moderate hypothermia. Rewarming might release tissue factor from damaged tissues, that triggers disseminated intravascular coagulation. Hypothermia might inhibit platelet aggregation and coagulation.KidneysRenal blood flow decreases due to vasoconstriction of afferent arterioles, electrolyte and fluid disturbances and increasing blood viscosity. Severely deranged renal function occurs particularly in the presence of rhabdomyolysis induced by severe AH combined with trauma.ConclusionMetabolism drops 7% per °C fall in BCT, reducing CO correspondingly. Therefore, it is possible to maintain adequate oxygen delivery after 10°C drop in BCT provided correctly performed CPR. Hypothermia may facilitate rhabdomyolysis in traumatized patients. Victims suspected of HCA should be rewarmed before being pronounced dead. Rewarming avalanche victims of HCA with serum potassium > 12 mmol/L and a burial time >30 min with no air pocket, most probably be futile.

Autoimmune pituitary inflammation

Autoimmune Hypophysitis (AH) is often refereed in the literature as lymphocytic pituitary inflammation. It is the most common form of rare, chronic inflammation states affecting this gland. In most cases it has autoimmune character. Symptoms of pituitary inflammation are mostly headaches, dysfunction of anterior and/or posterior pituitary lobe and visual disturbances. Diagnostics is extremely difficult and inflammation itself is probably diagnosed too rare. Autoimmune Hypophysitis coexist with other autoimmune endocrinopathies. The golden standard in Autoimmune Hypophysitis diagnosis is biopsy and magnetic resonance imaging (MRI) is also used. In relation to rare occurrence of the Autoimmune Hypophysitis, varied clinical picture and lack of standardized research on large group of patients there are no described standards of conduct with those patients.

Treatment of functioning pituitary macroadenoma with endoscopic transsphenoidal surgery: a case report

Pituitary macroadenomas are benign tumors in the pituitary gland measuring more than 1 cm in diameter. Pituitary adenomas account for 8 to 10% of all intracranial tumors and occur primarily in the anterior pituitary lobe and rarely in the posterior lobe. Most pituitary macroadenomas are non-functioning tumors, which show clinical symptoms due to tumor pressure and do not increase hormonal activity. In this case, a 40 y.o. woman was diagnosed with a pituitary macroadenoma after showing clinical symptoms of a functioning tumor, namely acromegaly, prognathism, and large, beefy hands and feet, for the past 4 years. Complaints were accompanied by amenorrhea, intermittent cephalgia, and hemianopsia in the right eye. Blood laboratory tests revealed increased levels of prolactin and growth hormone, while the results of computed tomography (CT) scans and magnetic resonance imaging (MRI) of the head indicate the presence of a pituitary macroadenoma. Endoscopic transsphenoidal surgery, a minimally invasive procedure, was performed with minimal complications.

Congenital hypopituitarism due to novel compound heterozygous POU1F1 gene mutation: A case report and review of the literature

Failure to thrive is one of the most common complaints in the endocrinology and genetics clinic. An 8-month-old girl with presentation of motor developmental delay, failure to thrive, and midline facial defects, with history of hypoglycemia at birth and central congenital hypothyroidism (CCH), was brought to our genetic clinic. Hormone test demonstrated combined pituitary hormone deficiency with growth hormone deficiency (GHD), central hypothyroidism, and hypoprolactinemia. Brain magnetic resonance imaging (MRI) showed anterior pituitary hypoplasia (APH), abnormal pituitary stalk, and preserved posterior pituitary lobe. Whole exome sequence (WES) identified a compound heterozygous mutation of the POU1F1 gene: c.649C>T (p.Arg217Ter) and c.662T>C (p.Ile221Thr), which are de novo mutation and inherited from mother, respectively. The patient's phenotype was consistent clinically with congenital hypopituitarism due to the POU1F1 gene mutation. Based on our literature review, this is the first report of the c.662T>C mutation, to the best of our knowledge. Our study demonstrates the power of WES for early diagnosis of congenital hypopituitarism with its relative phenotype for improving prognosis and preventing irreversible deficit.

New insights into the role and origin of pituitary S100β-positive cells.

In the anterior pituitary, S100β protein (S100β) has been assumed to be a marker of folliculo-stellate cells, which are one of the non-hormone-producing cells existing in the parenchyma of the adult anterior lobe and are composed of subpopulations with various functions. However, recent accumulating studies on S100β-positive cells, including non-folliculo-stellate cells lining the marginal cell layer (MCL), have shown the novel aspect that most S100β-positive cells in the MCL and parenchyma of the adult anterior lobe are positive for sex determining region Y-box 2 (SOX2), a marker of pituitary stem/progenitor cells. From the viewpoint of SOX2-positive cells, the majority of these cells in the MCL and in the parenchyma are positive for S100β, suggesting that S100β plays a role in the large population of stem/progenitor cells in the anterior lobe of the adult pituitary. Reportedly, S100β/SOX2-double positive cells are able to differentiate into hormone-producing cells and various types of non-hormone-producing cells. Intriguingly, it has been demonstrated that extra-pituitary lineage cells invade the pituitary gland during prenatal pituitary organogenesis. Among them, two S100β-positive populations have been identified: one is SOX2-positive population which invades at the late embryonic period through the pituitary stalk and another is a SOX2-negative population that invades at the middle embryonic period through Atwell's recess. These two populations are likely the substantive origin of S100β-positive cells in the postnatal anterior pituitary, while S100β-positive cells emerging from oral ectoderm-derived cells remain unclear.

Two Cases of Hypovascular Pituitary Metastases and Literature Review

Pituitary metastasis,a rare kind of intracranial malignant tumor,is characterized by metastasis from all parts of the body to the pituitary.The common tumors metastatic to pituitary are abundant with blood supply,located in the posterior pituitary lobe and/or the pituitary stalk.The lesion shows infiltrative growth,and mainly demonstrates low signal on T1 weighted imaging and high signal on T2 weighted imaging.It is usually enhanced significantly after iodinated contrast administration.The metastatic tumor with poor blood supply is similar to pituitary macroadenoma on magnetic resonance image,which makes it difficult to be differentiated.We reported two cases of pathologically diagnosed pituitary metastasis with poor blood supply and reviewed related papers,aiming to provide the imaging differentiation points of hypovascular pituitary metastasis.