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The Journal of Headache and Pain May 2024Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately...
BACKGROUND
Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells.
METHODS
The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca imaging of intact trigeminal ganglion (TG).
RESULTS
Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways.
CONCLUSIONS
Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance.
Topics: Animals; Pituitary Adenylate Cyclase-Activating Polypeptide; Mast Cells; Male; Mice; Stress, Psychological; Receptors, G-Protein-Coupled; Trigeminal Ganglion; Headache; Mice, Knockout; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38802819
DOI: 10.1186/s10194-024-01786-3 -
Reviews in Endocrine & Metabolic... Jun 2024Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical... (Review)
Review
Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.
Topics: Humans; Hypopituitarism; Prevalence; Hospitalization; Morbidity; Hospital Mortality
PubMed: 38802643
DOI: 10.1007/s11154-024-09888-8 -
Biomedical Reports Jul 2024During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of... (Review)
Review
During the coronavirus disease 2019 (COVID-19) pandemic, cognitive impairment of varying degrees of severity began to be observed in a significant percentage of patients. The present study discussed the impact of immunological processes on structural and functional changes in the central nervous system and the related cognitive disorders. The purpose of the present review was to analyse and discuss available information from the scientific literature considering the possible relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection and cognitive impairment, including NeuroCOVID, frontal syndrome and cytokine storm. A systematic literature review was conducted using: Google Scholar, Elsevier and the PubMed database. When searching for materials, the following keywords were used: 'cognitive dysfunctions', 'SARS-CoV-2', 'COVID-19', 'Neuro-SARS2', 'NeuroCOVID', 'frontal syndrome', 'cytokine storm', 'Long COVID-19'. A total of 96 articles were included in the study. The analysis focused on the characteristics of each study's materials, methods, results and conclusions. SARS-CoV-2 infection may induce or influence existing cognitive disorders of various nature and severity. The influence of immunological factors related to the response against SARS-CoV-2 on the disturbance of cerebral perfusion, the functioning of nerve cells and the neuroprotective effect has been demonstrated. Particular importance is attached to the cytokine storm and the related difference between pro- and anti-inflammatory effects, oxidative stress, disturbances in the regulation of the hypothalamic-pituitary-adrenal axis and the stress response of the body.
PubMed: 38800038
DOI: 10.3892/br.2024.1791 -
Journal of Clinical Biochemistry and... May 2024Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the...
Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supplementation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling.
PubMed: 38799134
DOI: 10.3164/jcbn.23-127 -
Problemy Endokrinologii Oct 2023DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a... (Review)
Review
DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a dusfunction of the endoribonuclease DICER, which plays an important role in the processing of microRNAs with subsequent regulation of the control of the expression of oncogenes and tumor suppressor genes. Clinical manifestations of dyseropathies is very different and may include both endocrine manifestations - multinodular goiter, differentiated thyroid cancers, ovarian stromal tumors, pituitary blastoma, and non-endocrine formations - pleuropulmonary blastoma, cystic nephroma, pineoblastoma. The presence of somatic mutations of the DICER1 gene is a resultant stage in the pathogenesis of dyseropathies, determining the further path of oncogenesis. At present, DICER1 syndrome is diagnosed extremely rarely, which leads to late detection of the components of the disease in the patient, late diagnosis of neoplasms, lack of family counseling. Diagnosis at the early stages of the disease, the development of screening programs for the management of these patients allows minimizing the risks of developing more malignant, aggressive forms of the disease.
Topics: Humans; Ribonuclease III; DEAD-box RNA Helicases; Mutation; Female; Thyroid Neoplasms; Goiter, Nodular; Pulmonary Blastoma
PubMed: 38796764
DOI: 10.14341/probl13383 -
Problemy Endokrinologii Sep 2023Polydipsia is a pathologically increased thirst, satisfied by the intake of water in large quantities, which can manifest itself in various somatic or mental diseases...
Polydipsia is a pathologically increased thirst, satisfied by the intake of water in large quantities, which can manifest itself in various somatic or mental diseases and at first glance is similar to a true vasopressin deficiency. Central diabetes insipidus (CDI) is a disease of the hypothalamic-pituitary region characterized by the inability of the kidneys to reabsorb water and concentrate urine, which is based on a defect in the synthesis or secretion of vasopressin and is manifested by severe thirst and excretion of large amounts of hypotonic urine. The prevalence of the disease in the population is 1:25,000, which characterizes it as a fairly rare pathology of the hypothalamic-pituitary region. The peak incidence is between 30 and 40 years of age. According to various literary sources, the disease is not characterized by gender differences in prevalence, however, on the example of the Moscow population, women prevailed in the incidence structure of CND in a ratio of 2.2:1. Insidiousness, with apparent absences in the difficulty of diagnosing primary polydipsia, lies in the manifestations of water intoxication, thus this condition requires knowledge of clear diagnostic criteria by healthcare professionals and an interdisciplinary approach in the treatment of this condition. On the example of this clinical case, we will try to highlight the differential diagnostic criteria for psychogenic polydipsia in comparison with the true deficiency of arginine vasopressin (AVP) or central diabetes insipidus (CDI), which can be applied in real clinical practice.
Topics: Humans; Polydipsia, Psychogenic; Female; Adult; Diagnosis, Differential; Male; Thirst; Polydipsia; Water Intoxication
PubMed: 38796762
DOI: 10.14341/probl13359 -
Problemy Endokrinologii Sep 2023Thyrotropin-secreting pituitary adenomas (TSH-PA) are a rare cause of thyrotoxicosis and account for 0.5-2% of all pituitary adenomas. Taking into account the rarity of...
BACKGROUND
Thyrotropin-secreting pituitary adenomas (TSH-PA) are a rare cause of thyrotoxicosis and account for 0.5-2% of all pituitary adenomas. Taking into account the rarity of the disease, it is extremely important to analyze each case of TSH-PA.
AIM
To analyze the clinical characteristics and treatment outcomes of patients with TSH-PA, as well as to determine preoperative and early postoperative factors that predict long-term remission.
MATERIALS AND METHODS
In a single-center retrospective study we analyzed clinical signs, laboratory and instrumental studies, as well as the treatment outcomes of patients with TSH-PA from 2010 to 2023. Preoperative factors, as well as TSH level measured on day 3 postoperatively, were evaluated for their ability to predict long-term remission when comparing groups of patients with and without remission.
RESULTS
The study included 45 patients with TSH-PA (14 men, 31 women), with a median age of 45 years [30; 57]. The most common clinical manifestations of TSH-PA were: cardiac arrhythmia in 37 (82.2%) patients, thyroid pathology in 27 (60%), neurological disorders in 24 (53.35%). Most PAs were macroadenomas (n=35, 77.8%). Preoperatively, 28 (77.8%) patients received somatostatin analogs, and 20 (71.4%) patients were euthyroid at the time of surgery. Surgical treatment was performed in 36 (80%) patients, postoperative remission was achieved in 31 cases (86.1%). Administration of somatostatin analogues to patients with no remission/relapse after surgery lead to the remission in 100% of cases (4/4). A 1 mm increase in PA size raised the odds of recurrence/no remission by 1.15-fold,and PA invasion during surgery - by 5.129 fold. A TSH level on day 3 postoperatively above 0.391 mIU/L (AUC, 0.952; 95% CI 0.873-1.000; standard error 0.04; p<0.001) identifies patients with relapse/absence of remission after surgical treatment (sensitivity = 100%, specificity = 88.9%).
CONCLUSION
The TSH-PA in the structure of PAs is extremely rare, and as a result, most of them are misdiagnosed and detected already at the stage of macroadenoma. The most effective method of treatment is transnasal transsphenoidal adenomectomy. Somatostatin analogues can be used as second-line therapy if surgical treatment is ineffective. We have proposed a possible model for postoperative TSH levels (>0.391 mU/l) to predict recurrence of TSH-PA, which requires validation on an expanded number of cases.
Topics: Humans; Male; Female; Pituitary Neoplasms; Middle Aged; Thyrotropin; Adult; Retrospective Studies; Adenoma; Treatment Outcome; Somatostatin
PubMed: 38796758
DOI: 10.14341/probl13325 -
Problemy Endokrinologii Sep 2023Hyperprolactinemia accompanies growth hormone hypersecretion in approximately 25-39% of cases. There is a recommendation to determine the level of prolactin in clinical... (Observational Study)
Observational Study
BACKGROUND
Hyperprolactinemia accompanies growth hormone hypersecretion in approximately 25-39% of cases. There is a recommendation to determine the level of prolactin in clinical guidelines for diagnosis and treatment of acromegaly. However, there is no understanding of the necessity to investigate the IGF-1 level in patients with hyperprolactinemia and a pituitary adenoma.
AIM
Determining the proportion of patients with hyperprolactinemia and pituitary adenoma, who were examined for IGF-1 levels, and identifying the proportion of patients with acromegaly among this cohort.
MATERIALS AND METHODS
Between December 2019 and December 2022 a single-center observational single-stage single-sample uncontrolled study was conducted. At the first stage of the study, the proportion of patients with pituitary adenoma and hyperprolactinemia with studied IGF-1 levels was determined, according to medical records. At the second stage of the study, patients without known indicators of IGF-1 were determined. The concentration of growth hormone was studied during the oral glucose load in the case of increased IGF-1 levels.
RESULTS
At the first stage, 105 patients were included in the study. The level of IGF-1 was determined in 41/105 (39%) cases. There were 22/41 (53.7%) cases in the subgroup with pituitary incidentalomas and 19/64 (29.7%) cases in the subgroup with hyperprolactinemia among them. At the second stage, the IGF-1 level was additionally determined in 53 patients with hyperprolactinemia and pituitary adenoma (total 94 patients). The level of IGF-1 was elevated in 11/94 patients, further acromegaly was confirmed in 3/94 patients (3.2%).
CONCLUSION
In real clinical practice the level of IGF-1 is studied only in 39% of cases in patients with pituitary adenoma and hyperprolactinemia. The disease was detected in 3 cases (3.2%) out of 94 people with hyperprolactinemia and pituitary adenoma without clinical manifestations of acromegaly. We consider the study of IGF-1 levels justified as a screening for acromegaly in patients with hyperprolactinemia and pituitary adenoma.
Topics: Humans; Hyperprolactinemia; Female; Acromegaly; Male; Pituitary Neoplasms; Adult; Insulin-Like Growth Factor I; Middle Aged; Adenoma; Human Growth Hormone
PubMed: 38796756
DOI: 10.14341/probl13344 -
Translational Psychiatry May 2024In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic...
In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic-pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.
Topics: Oxytocin; Animals; Hippocampus; Male; Cognitive Dysfunction; Hypothalamus; MAP Kinase Signaling System; Amyloid beta-Peptides; Neurons; Disease Models, Animal; Mice; Phosphorylation
PubMed: 38796566
DOI: 10.1038/s41398-024-02930-y