Posterior Pituitary Research Articles

Clinical Features and Analysis in Pituitary Stalk Interruption Syndrome.

Pituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Because the etiology and clinical cognition of PSIS remain elusive, we analyzed the clinical features of PSIS in Chinese patients. A retrospective analysis was conducted on the clinical presentation, laboratory data, imaging examination, and management of 24 PSIS inpatients from our center over 10 years. Among the 24 PSIS patients, there were 22 males (91.7%) and 2 females (8.3%). Growth hormone deficiency was present in all 24 cases (100%), hypogonadism in 24 cases (100%), secondary adrenal insufficiency in 22 cases (91.2%), and hypothyroidism in 21 cases (87.5%). 20 cases (83.3%) of PSIS patients exhibited deficiencies in four anterior pituitary hormones, 3 cases (12.5%) exhibited deficiencies in three anterior pituitary hormones, and 1 case (4.2%) exhibited deficiencies in two anterior pituitary hormones, with none exhibiting deficiencies in posterior pituitary hormones. Among the 24 PSIS patients, 12 had a history of growth hormone therapy before admission, and 12 had no such history. Additionally, 19 cases (79.2%) with PSIS were complicated by dyslipidemia, 15 cases (62.5%) were complicated by nonalcoholic fatty liver disease, and 9 cases (37.5%) were complicated by hyperuricemia. PSIS often presents with growth retardation and hypogonadotropic hypogonadism, but in some cases, short stature is not exhibited. PSIS is prone to complications such as dyslipidemia, nonalcoholic fatty liver disease, and hyperuricemia, increasing the risk of cardiovascular and cerebrovascular diseases. In clinical practice, the diagnostic ability of PSIS should be improved, and pituitary function and complications should be evaluated in a timely manner to avoid delayed treatment.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report

BackgroundAlthough vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported.Case presentationAn 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 μg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 μIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient’s disease course was stable with continued thyroid and adrenal corticosteroid supplementation.ConclusionsHerein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

WNK1 is a central osmolality sensor for arginine vasopressin release and acts through the OSR1/SPAK kinase cascade

Background: Maintaining internal osmolality constancy and water homeostasis is essential for life. The circumventricular organs (CVOs) of the brain, including the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO), lack a blood-brain barrier. Neurons in OVLT and SFO detect increases in serum osmolality that stimulate the production of vasopressin (AVP) in paraventricular nuclei (PVN) to be released in the posterior pituitary. We have recently reported that WNK1 in sensory neurons in CVOs functions as an osmolality sensor for AVP release (Jin et al., JCI, 2023). WNK1 activates Kv3.1 to increase action potential, traveling down to PVN to increase AVP synthesis for release from the posterior pituitary. Here, we propose that OSR1/SPAK acts as the downstream kinase for WNK1 in regulating AVP release. We further investigated the regulation of vasopressin release by the WNK1-OSR1/SPAK cascade in response to extracellular hyperosmolality. Methods: Cre recombinase-carrying retrograde AAV virus was stereotaxically injected into PVN nuclei from normal mice and SPAK-null mice with a homozygous OSR1-floxed allele (SAPK−/−;OSR1flox/flox). Metabolic cage studies were performed on mice. Urine output, water intake, serum osmolality, serum AVP, and copeptin levels were measured. K+ currents were measured from the OVLT neurons by whole-cell patch clamp. Results: Increased osmolality, either by water restriction or mannitol injection, activated OSR1/SPAK in OVLT, as evident by increased serine-373 phospho-SPAK and serine-325 phospho-OSR. Like the WNK1 deletion, the double deletion of OSR/SPAK in OVLT caused polyuria with decreased urine osmolality that persisted in water restriction. Circulating levels of AVP and copeptin were increased by water restriction in control mice. In contrast, water restriction failed to increase the levels in OSR/SPAK-deletion mice. Knockdown of the Kv3.1 channel in OVLT by shRNA showed the central diabetes insipidus (DI) phenotype as well. Hypertonicity increased K+ currents and WNKs inhibitor prevented the increase in OVLT neurons. Conclusions: Mice with neuronal-specific OSR1/SPAK deletion have water homeostasis defects consistent with partial central DI; Evidence supporting that OSR1/SPAK acts downstream of WNK1 to regulate AVP release; WNK1-OSR1/SPAK activates Kv3.1 to increase firing frequency of neurons projecting from CVOs to PVN. Our findings reveal that an intracellular protein acts as a sensor for extracellular tonicity and provide fresh insights into the mechanisms by which the body maintains osmolality constancy. Future studies will investigate how OSR1/SPAK regulates Kv3.1 channels. NIDDK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Anterior and Posterior Pituitary Function in Patients with Sheehan Syndrome - Combining the use of Insulin Tolerance Test and Copeptin Assay.

Sheehan syndrome (SS) typically involves the loss of anterior pituitary cells and rarely affects the posterior pituitary. The water deprivation test (WDT) is the gold standard for diagnosing central diabetes insipidus (CDI), but it is cumbersome. Serum copeptin measurements are an alternative for CDI diagnosis. In this study, we measured hypoglycaemia-stimulated serum copeptin in SS patients to assess posterior pituitary function alongside anterior pituitary hormone levels. This study recruited 43 patients with SS on stable hormonal replacement except for growth hormone (GH), 18 patients with CDI, and 19 body mass index (BMI) and parity-matched controls. All patients with SS and four patients with CDI underwent an insulin tolerance test (ITT), and hypoglycaemia-stimulated copeptin levels were measured at 0, 30, 45, and 90 minutes after insulin injection. The mean serum copeptin level among patients with SS (26.01 ± 12.41 pmol/L) was significantly lower than that in healthy controls (31.92 ± 7.85 pmol/L) and higher than that in patients with CDI (1.81 ± 0.14 pmol/L). Using pre-defined cut-offs for CDI, basal serum copeptin <2.69 pmol/L and stimulated levels <4.92 pmol/L for complete central DI, and basal copeptin levels >2.69 pmol/L and stimulated copeptin <4.92 pmol/L for partial central DI, 9.2% (n = 4) of patients with SS had CDI, of which half had complete CDI and half had partial CDI. A significant number of patients with SS who are on hormone replacement therapy show involvement of the posterior pituitary, despite not displaying symptoms.

Characterisation of a Novel Osmosensitive Pathway from the Supraoptic Nucleus to the Median Preoptic Nucleus

The Supraoptic Nucleus (SON) is well regarded for the neuroendocrine release of vasopressin and oxytocin through the posterior pituitary gland. Evidence also exists for extra-pituitary efferent projections of SON neurons, mainly collaterals to the lateral hypothalamus and central amygdala. The objective of this study was to examine the existence of a central SON projection to the median preoptic nucleus (MnPO) of the hypothalamus. Microinjections of the retrograde tracer Cholera Toxin B Subunit (CTb) into the MnPO of male Wistar rats (n = 3) retrogradely labelled SON neurons. Fluorescence immunohistochemistry revealed equal involvement of vasopressin (AVP) and oxytocin (OXT) — producing SON neurons (n = 107 AVP+/CTb+, n = 110 OXT+/ CTb+, n = 417 total CTb+ neurons). This major collateral projection was also examined in an animal model of Polycystic Kidney Disease, the Lewis Polycystic Kidney (LPK) rat (n = 3 animals; n = 104 AVP+/CTb+, n = 41 OXT+/CTb+, n = 372 total CTb+ neurons) and its healthy Lewis control (n = 3 animals; n = 115 AVP+/CTb+, n = 100 OXT+/CTb+, n = 430 total CTb+ neurons). Although the function of this projection is currently unclear, preliminary data in a subset of LPKs shows these SON neurons with MnPO collateral projections are activated by osmotic stressors (e.g., hypertonic saline). In summary, we report a major collateral projection from the SON to MnPO that is activated by osmotic stress. Given the well-known role of the MnPO in drinking behaviour, we suggest this SON-MnPO circuit may be involved in the coordination of fluid regulation and drinking behaviour. This project was funded by Macquarie University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Generation of an Inducible Avp Knockout Mouse Line Using CRISPR/Cas9 and Cre/LoxP

Background: Arginine vasopressin (AVP) is a peptide hormone coded by the Avp gene, synthesized in the hypothalamus and secreted by the posterior pituitary. Dysregulation of AVP secretion contributes to a variety of human diseases. Previous studies of functional roles of AVP have been largely dependent on the use of Brattleboro rats, which manifest a spontaneous mutation in the Avp gene and lack circulating AVP. Despite their utility, Brattleboro rats are diffcult to breed owing largely to the fixed nature of the Avp mutation, resulting in increased neonatal death and behavioral effects in the adults. Consequently, commercial breeders have ceased production, despite a continued need. To fill this need, we have now created a mouse model with a tamoxifen-inducible deletion of AVP. Methods: We employed CRISPR/Cas9 to target the desired regions (first intron and 3' downstream) within the Avp gene. Successful insertion of the two loxP sites was confirmed by PCR using primers flanking the targeted regions. Restriction enzymes BamHI or EcoRI were used to confirm correct targeting. For additional confirmation, PCR products were cloned into the TA-cloning vector and sequenced. Mice harboring the floxed allele were mated to B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J mice that globally express a tamoxifen-inducible Cre recombinase. Results: The resultant homozygous conditional knockout mice ( Cre+ Avpflx/ flx) are viable, fertile, and show no signs of polydipsia or polyuria prior to induction, indicating that the conditional alleles retain their wild-type function. Induction of Cre-mediated recombination by administration of tamoxifen (2-3 mg q.d., i.p. for 5 days) in 8-week-old mice resulted in a decrease in urine osmolality from 2076±138 to 122±6 mOsm/kgH2O on day 31 after induction (p&lt;0.0001). Sanger sequencing demonstrated the expected 1245 bp deletion at the Avp locus. The kidney parenchyma was structurally normal with no evidence of medullary atrophy 6 weeks after induction. Immunoblotting of AQP2 in the inner medulla showed a significant decrease in AQP2 band density in Cre+ Avpflx/ flx mice to 27±14 % of values in Cre− floxed control mice (p&lt;0.05). Conclusion: We developed an inducible AVP knockout mouse line ( Cre+ Avpflx/ flx) that will be shared with the research community and are likely to be useful for further study of regulation of water balance and polycystic kidney disease, as well as neural, vascular, and metabolic roles of vasopressin. The work was funded by the Division of Intramural Research, National Heart, Lung and Blood Institute. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Membrane-Targeted palGFP Predominantly Localizes to the Plasma Membrane but not to Neurosecretory Vesicle Membranes in Rat Oxytocin Neurons.

Recent advances in viral vector technology, specifically using adeno-associated virus (AAV) vectors, have significantly expanded possibilities in neuronal tracing. We have utilized the Cre/loxP system in combination with AAV techniques in rats to explore the subcellular localization of palmitoylation signal-tagged GFP (palGFP) in oxytocin-producing neurosecretory neurons. A distinctive branching pattern of single axons was observed at the level of the terminals in the posterior pituitary. Despite challenges in detecting palGFP signals by fluorescent microscopy, immunoelectron microscopy demonstrated predominant localization on the plasma membrane, with a minor presence on the neurosecretory vesicle membrane. These findings suggest that membrane-anchored palGFP may undergo exocytosis, translocating from the plasma membrane to the neurosecretory vesicle membrane. In this study, we observed characteristic axon terminal structures in the posterior pituitary of oxytocin neurons. This study indicates the importance of understanding the plasma membrane-specific sorting system in neuronal membrane migration and encourages future studies on the underlying mechanisms.

Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion.

Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle and glucose production by the liver. The balance between the secretions of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet β-cells and α-cells can sense variations in glycemia and respond by an appropriate secretory response. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime. The central nervous system (CNS), which has an almost absolute requirement for glucose as a source of metabolic energy and thus a vital interest in ensuring that glycemic levels never fall below ∼5 mM, is equipped with populations of neurons responsive to changes in glucose concentrations. These neurons control pancreatic islet cell secretion activity in multiple ways: through both branches of the autonomic nervous system, through the hypothalamic-pituitary-adrenal axis, and by secreting vasopressin (AVP) in the blood at the level of the posterior pituitary. Here, we present the autonomic innervation of the pancreatic islets; the mechanisms of neuron activation by a rise or a fall in glucose concentration; how current viral tracing, chemogenetic, and optogenetic techniques allow integration of specific glucose sensing neurons in defined neuronal circuits that control endocrine pancreas function; and, finally, how genetic screens in mice can untangle the diversity of the hypothalamic mechanisms controlling the response to hypoglycemia.

Imaging and quantification of neuropeptides in mouse pituitary tissue by atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry.

Atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) mass spectrometry has enabled the untargeted analysis and imaging of neuropeptides and proteins in biological tissues under ambient conditions. Sensitivity in AP-MALDI can be improved by using sample-specific preparation methods. A comprehensive and detailed optimization strategy including instrument parameters, matrix spraying and sample tissue washing pretreatment was implemented to enhance the sensitivity and coverage of neuropeptides in mouse pituitary tissues by commercial AP-MALDI mass spectrometry imaging (MSI). The sensitivity of a commercial AP-MALDI system for endogenous neuropeptides in mouse pituitary was enhanced by up to 15.2-fold by shortening the transmission gap from the sample plate to the inlet, attaching copper adhesive tape to an indium tin oxide-coated glass slide, optimizing the matrix spray solvent and using sample tissue washing pretreatment. Following careful optimization, the distributions of nine endogenous neuropeptides were successfully visualized in the pituitary. Furthermore, the quantitative capability of AP-MALDI for neuropeptides was evaluated and the concentrations of neuropeptides oxytocin and vasopressin in the pituitary posterior lobe were increased approximately twofold under hypertonic saline stress. Mouse pituitary neuropeptides have emerged as important signaling molecules due to their role in stress response. This work indicates the potential of modified AP-MALDI as a promising AP MSI method for in situ visualization and quantification of neuropeptides in complex biological tissues.

Single-cell analysis of mesenchymal cells in permeable neural vasculature reveals novel diverse subpopulations of fibroblasts

BackgroundIn the choroid plexus and pituitary gland, vasculature is known to have a permeable, fenestrated phenotype which allows for the free passage of molecules in contrast to the blood brain barrier observed in the rest of the CNS. The endothelium of these compartments, along with secretory, neural-lineage cells (choroid epithelium and pituitary endocrine cells) have been studied in detail, but less attention has been given to the perivascular mesenchymal cells of these compartments.MethodsThe Hic1CreERT2 Rosa26LSL−TdTomato mouse model was used in conjunction with a PdgfraH2B−EGFP mouse model to examine mesenchymal cells, which can be subdivided into Pdgfra+ fibroblasts and Pdgfra− pericytes within the choroid plexus (CP) and pituitary gland (PG), by histological, immunofluorescence staining and single-cell RNA-sequencing analyses.ResultsWe found that both CP and PG possess substantial populations of distinct Hic1+ mesenchymal cells, including an abundance of Pdgfra+ fibroblasts. Within the pituitary, we identified distinct subpopulations of Hic1+ fibroblasts in the glandular anterior pituitary and the neurosecretory posterior pituitary. We also identified multiple distinct markers of CP, PG, and the meningeal mesenchymal compartment, including alkaline phosphatase, indole-n-methyltransferase and CD34.ConclusionsNovel, distinct subpopulations of mesenchymal cells can be found in permeable vascular interfaces, including the CP, PG, and meninges, and make distinct contributions to both organs through the production of structural proteins, enzymes, transporters, and trophic molecules.

Suprasellar granular cell tumor: A rare case report

Granular cell tumor (GCT) originating from the sellar and suprasellar regions, specifically from the neurohypophysis, is a rare neoplasm. Symptomatic GCT of the neurohypophysis is exceedingly rare, being &lt;70 cases described so far. GCTs predominantly exhibit benign behavior, while the malignancy rate remains at 2%. Imaging is quite unspecific and diagnosis is difficult to establish preoperatively. Histopathology and immunohistochemistry serve as the definitive diagnostic approach for GCTs and help in distinguishing GCT from other pituitary tumors, including pituitary adenoma, pituicytoma, and spindle cell oncocytoma. These tumors are resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment modality. Due to the potential absence of distinct tumor masses and local tissue infiltration by tumor cells, complete excision is crucial, with resection extent extending beyond areas of infiltration. Here, we present a rare case of GCT originating from the posterior pituitary in the suprasellar region. On immunohistochemistry, tumor cells expressed diffusely thyroid transcription factor-1, S-100 protein, and vimentin confirming the diagnosis of supra-sellar GCT. The reported case is noteworthy for the rarity of the clinicopathological entity.

Gross morpho-biometry, histometry and immunohistochemical investigations of pituitary gland in the juvenile and adult male African giant rats (Cricetomys gambianus)

This work was designed to investigate the morphometry and immunohistochemical features of pituitary glands in the African Giant Rats (AGR). Adult and juvenile AGR were sacrificed and their brains harvested, and the pituitary glands were carefully dissected. The weight, length and width of brains and pituitary glands were subsequently measured. Sections were prepared and stained using Haematoxylin and Eosin (H&amp;E), Cresyl-violet and periodic-acid-Schiff (PAS) for histological analysis. Immunohistochemical analysis was carried out with Glial-Fibrillary-Acidic-Protein (GFAP) and Ionized-Calcium-Binding-Adapter-Molecule 1 (Iba1). Grossly, the AGR pituitary gland is a somehow laterally extended, saddle-shaped organ that is dorso-ventrally flattened. The gray-coloured adenohypophysis (anterior-pituitary lobe) was bigger in size than the whitish neurohypophysis (posterior-pituitary lobe) on physical examination. Histometrically, the adenohypophyseal length was noticeably greater than that of neurohypophysis in both juvenile and adult. Similarly, the adenohypophyseal and neurohypophyseal width in adult were found to be more than that of juvenile. Also, the histological staining of the neurohypophysis and adenohypophysis were distinct. In the neurohypophysis, fibrous and protoplasmic pituicytes were observed among fibres and Herring-bodies. Chromophils and chromophobes were identified in the adenohypophysis and melanotrophs in the intermediate lobe. Immunohistochemistry showed pituicytes in the neurohypophysis, which was positive with GFAP-antibody. With Iba1-antibody, the neurohypophysis expressed a stronger positive immunolabelling to microglia as compared to macrophages in the adenohypophysis. In conclusion, the gross and microscopic characteristics of pituitary glands of the AGR are found to be similar to other rodents and mammals. We recommend further study to compare morphometrical parameters between male and females of this model.

Neural control of fluid homeostasis is engaged below 10°C in hibernation.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) hibernate for several months each winter without access to water,1 but the mechanisms that maintain fluid homeostasis during hibernation are poorly understood. In torpor, when body temperature (TB) reaches 4°C, squirrels decrease metabolism, slow heart rate, and reduce plasma levels of the antidiuretic hormones arginine vasopressin (AVP) and oxytocin (OXT).1 Squirrels spontaneously undergo interbout arousal (IBA) every 2weeks, temporarily recovering an active-like metabolism and a TB of 37°C for up to 48 h.1,2 Despite the low levels of AVP and OXT during torpor, profound increases in blood pressure and heart rate during the torpor-IBA transition are not associated with massive fluid loss, suggesting the existence of a mechanism that protects against diuresis at a low TB. Here, we demonstrate that the antidiuretic hormone release pathway is activated by hypothalamic supraoptic nucleus (SON) neurons early in the torpor-arousal transition. SON neuron activity, dense-core vesicle release from the posterior pituitary, and plasma hormone levels all begin to increase before TB reaches 10°C. Invivo fiber photometry of SON neurons from hibernating squirrels, together with RNA sequencing and c-FOS immunohistochemistry, confirms that SON is electrically, transcriptionally, and translationally active to monitor blood osmolality throughout the dynamic torpor-arousal transition. Our work emphasizes the importance of the antidiuretic pathway during the torpor-arousal transition and reveals that the neurophysiological mechanism that coordinates the hormonal response to retain fluid is active at an extremely low TB, which is prohibitive for these processes in non-hibernators.

Alpha-synuclein expression in oxytocin neurons of young and old bovine brains.

Understanding of central nervous system mechanisms underlying age-related infertility remains limited. Fibril α-synuclein, distinct from its monomeric form, is implicated in age-related diseases. Notably, fibril α-synuclein spreads among neurons, similar to prions, from damaged old neurons in cortex and hippocampus to healthy neurons. However, less is known whether α-synuclein propagates into oxytocin neurons, which play crucial roles in reproduction. We compared α-synuclein expression in the oxytocin neurons in suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), paraventricular hypothalamic nucleus (PVN), and posterior pituitary (PP) gland of healthy heifers and aged cows to determine its role in age-related infertility. We analyzed mRNA and protein expression, along with Congo red histochemistry and fluorescent immunohistochemistry for oxytocin and α-synuclein, followed by confocal microscopy with Congo red staining. Both mRNA and protein expressions of α-synuclein were confirmed in the bovine cortex, hippocampus, SCN, SON, PVN, and PP tissues. Significant differences in α-synuclein mRNA expressions were observed in the cortex and hippocampus between young heifers and old cows. Western blots showed five bands of α-synuclein, probably reflecting monomers, dimers, and oligomers, in the cortex, hippocampus, SCN, SON, PVN, and PP tissues, and there were significant differences in some bands between the young heifers and old cows. Bright-field and polarized light microscopy did not detect obvious amyloid deposition in the aged hypothalami; however, higher-sensitive confocal microscopy unveiled strong positive signals for Congo red and α-synuclein in oxytocin neurons in the aged hypothalami. α-synuclein was expressed in oxytocin neurons, and some differences were observed between young and old hypothalami.

Cases: Decompensated Heart Failure Secondary to Hypopituitarism in an Elderly Patient.

Hypopituitarism is difficult to diagnose because of its non-specific symptoms, especially in the presence of comorbidities. A 77-year-old woman with worsening anorexia and exertional dyspnea was initially diagnosed with decompensated dry cold-type heart failure. Hormonal laboratory tests indicated secondary hypothyroidism as a part of the evaluation of heart failure. Furthermore, pituitary magnetic resonance imaging revealed thickening of the pituitary stalk and a loss of signal intensity in the posterior pituitary, thus suggesting lymphocytic hypophysitis. Oral hydrocortisone and levothyroxine improved the persistent anorexia. In this case, hypopituitarism occasionally presented as dry cold-type heart failure, thus making a prompt diagnosis challenging in the setting of concurrent heart failure.

Pituitary Metastasis Masquerading as Pituitary Macroadenoma-from a Primary Follicular Thyroid Malignancy

Background: Metastasis to the pituitary is very rare. Thyroid carcinoma as a primary source of pituitary metastasis is uncommon. Pituitary metastasis is common in posterior pituitary. Metastasis can also occur to anterior pituitary with varied presentations. Case Description: A 47-year-old lady presented with galactorrhoea, ptosis, diminished vision of the right eye, and headache from 6 months. She had a pituitary macroadenoma with suprasellar, para-sellar and infrasellar extension on evaluation. She underwent initial transnasal transsphenoidal decompression followed by pteronial craniotomy with decompression of the residual tumour. The histopathology was metastatic tumor of sella. Further evaluation showed a thyroid nodule and bilateral lung nodules. With suspicion of a primary thyroid malignancy, total thyroidectomy was performed and biopsy report of the thyroid showed follicular carcinoma. Conclusion: Metastasis to the pituitary can be a rare presentation of thyroid cancer. It may masquerade a pituitary adenoma. Key-words: Sella, Pituitary metastases, Parasellar, Suprasellar, Diabetes Insipidus, Thyroid.

Https://fz.kiev.ua/index.php?abs=2034

Investigation of the mechanism of neuronal communication underlies the fundamental discoveries that promote health. The studies of oxytocin signaling in neurons from or within different brain areas are directed to explore the role of this neurohormonal modulator in the regulation of synaptic transmission and plasticity, neuronal excitability that contributes to the reproduction, social behavior and learning capacity, anxiety, inflammation and differentiation in the brain. Oxytocin is synthesized in supraoptic and paraventricular nuclei of the hypothalamus and when secreted into the bloodstream from the posterior pituitary, it produces a significant effect on uterine contraction and lactation. At the same time this nonapeptide being released within the limbic system and brain cortex modulates neuronal activity by affecting ion channels on their membranes. The oxytocin receptor is primarily coupled to Gq/11 proteins causing phospholipase C activation, Ca2+ release and store-operated Ca2+ entry. These pathways are central for the regulation of the activity of different types of TRP channels, especially of the canonical subfamily (TRPC). Here we highlight the link between oxytocin signaling, which is particularly well investigated in the myometrium, and receptor-operated TRPC4 and multimodal TRPV4 ion channels that participate in oxytocin-dependent regulation of the uterine smooth muscle contractility under various conditions. Importantly, similarly to oxytocin, these channels have been implicated in neuropathic pain behavior, anxiety, fear and depression. Since similar signal transduction pathways are likely to be functional in neuronal cells, we propose that future studies of oxytocin effects in the CNS should also consider the role of these Ca2+-permeable channels.

A Rare Case of Hypophysitis Due to Tuberculosis with an Atypical Presentation of Normal Pituitary Markers

Abstract Hypophysitis developing secondary to tuberculosis is a very rare clinical entity. Hypophysitis occurs because of inflammation and it may affect the anterior, infundibulum, posterior, or entire pituitary gland. Here, we are presenting a case of a young male having tubercular meningitis who was taking antitubercular treatment for the last 2 months and was having disseminated tuberculosis. The patient presented with severe headache with fever and 4–5 episodes of vomiting. The patient presented with the affection of consciousness in the form of confusion, irritability, and disorientation. High-resolution CT thorax was suggestive of pulmonary tuberculosis (Koch’s) with centrilobular nodules and a tree-in-bud appearance. Magnetic resonance imaging brain showed prominent leptomeningeal enhancement with an enlarged pituitary gland with enlarged enhancing stalk suggestive of hypophysitis. The hypophysitis case developing secondary to tuberculosis as a very rare entity is discussed in this case report. This case is also an atypical presentation wherein the pituitary markers are normal in hypophysitis.

Trio-based whole exome sequencing in patients with ectopic posterior pituitary.

Ectopic posterior pituitary (EPP) is a rare congenital abnormality, sometimes associated with other midline defects, such as pituitary stalk interruption syndrome (PSIS), in which thin or absent pituitary stalk and anterior pituitary hypoplasia are combined to EPP. Most cases are sporadic, with few reports of familial cases, and many congenital hypopituitarism (CH) cases remain unsolved. To search for candidate genes associated with this condition, we performed trio-based whole-exome sequencing (WES) on patients with EPP, including two familial cases. This study included subjects with EPP and PSIS diagnosed by a simple MRI protocol (FAST1.2). We performed two distinct analyses in the trio-based WES. We looked for previously described genes associated with pituitary development. Next, we investigated the whole exome for variants inherited in a pattern consistent with a monogenic etiology. Ten families were evaluated; eight were composed of a child with EPP and healthy parents, one has two affected siblings, and one family has a son and mother with EPP. When analyzing the previously described candidate variants associated with pituitary development, we found variants in GLI2 and FGFR1 in three families. We also found six other variants of interest in three patients: KMT2A, GALR3, RTN4R, SEMA3A, NIPBL, and DSCAML1. The analysis allowed us to find previously reported and not reported GLI2 variants, all inherited from healthy parents, which reinforces the incomplete penetrance pattern of GLI2 variants in the development of EPP and draws attention to possible future functional studies of those variants that have a recurrent expression in CH. We also found novel FGFR1 and SEMA3A variants that suggest an oligogenic mechanism in PSIS and EPP, as seen in patients with hypogonadotropic hypogonadism. We report the first case of a patient with Wiedemann-Steiner syndrome and PSIS, suggesting that the KMT2A gene may be related to pituitary development. Furthermore, the trios' analysis allowed us to find five other variants of interest. Future investigations may clarify the roles of these variants in the etiology of EPP and PSIS.

Diagnosing and treating anterior pituitary hormone deficiency in pediatric patients.

Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.