-
The Journal of Clinical Endocrinology... Jun 2024Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive,...
Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis. Consequent "primary stress system disorders" were popularly accepted, with phenotypes based on conditions such as Cushing syndrome, pheochromocytoma, and adrenal insufficiency. Cardiometabolic and major depressive disorders are candidates for hypercortisolemic etiology, contrasting the "hypocortisolemic symptom triad" of stress sensitivity, chronic fatigue, and pain. However, acceptance of chronic stress etiology requires cause-and-effect associations, and practical utility such as therapeutics altering stress system function. Inherent predispositions to stress system perturbations may be relevant. Glucocorticoid receptor (GR) variants have been associated with metabolic/neuropsychological states. The SERPINA6 gene encoding corticosteroid-binding globulin (CBG), was the sole genetic factor in a single-nucleotide variation-genome-wide association study linkage study of morning plasma cortisol, a risk factor for cardiovascular disease, with alterations in tissue-specific GR-related gene expression. Studies showed genetically predicted high cortisol concentrations are associated with hypertension and anxiety, and low CBG concentrations/binding affinity, with the hypocortisolemic triad. Acquired CBG deficiency in septic shock results in 3-fold higher mortality when hydrocortisone administration produces equivocal results, consistent with CBG's role in spatiotemporal cortisol delivery. We propose some stress system disorders result from constitutional stress system variants rather than stressors themselves. Altered CBG:cortisol buffering may influence interstitial cortisol ultradian surges leading to pathological tissue effects, an example of stress system variants contributing to stress-related disorders.
PubMed: 38941154
DOI: 10.1210/clinem/dgae412 -
BMC Pulmonary Medicine Jun 2024Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between...
BACKGROUND
Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.
METHODS
This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.
RESULTS
Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).
CONCLUSION
PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.
Topics: Humans; Male; Female; Pulmonary Embolism; Retrospective Studies; Middle Aged; Fibrin Fibrinogen Degradation Products; Sex Factors; Adult; Aged; China; Antipsychotic Agents; Risk Factors; Mental Disorders; Hyperprolactinemia; Prevalence
PubMed: 38937698
DOI: 10.1186/s12890-024-03122-6 -
Zhonghua Wai Ke Za Zhi [Chinese Journal... Jun 2024The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular...
The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the gene.
PubMed: 38937132
DOI: 10.3760/cma.j.cn112139-20240102-00002 -
Brain Research Bulletin Jun 2024Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and... (Review)
Review
Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.
PubMed: 38936669
DOI: 10.1016/j.brainresbull.2024.111022 -
Acta Clinica Belgica Jun 2024Sarcoidosis is a multi-system granulomatous disease of unknown origin. It is mainly thought of as a lung disease but it can affect any organ system. Sinus and endocrine...
OBJECTIVES
Sarcoidosis is a multi-system granulomatous disease of unknown origin. It is mainly thought of as a lung disease but it can affect any organ system. Sinus and endocrine dysfunctions are described but are rare and seldomly linked with sarcoidosis.
METHODS
Here we describe a case of a young Caucasian man who already visited multiple care givers for sinusitis, erectile dysfunction and anorexia. He presented at the emergency department with fever and emaciation, polyuria and polydipsia. The results of the blood sampling revealed a hypercalcaemia as well as abnormal thyroid function.
RESULTS
After biochemical, radiological and histopathological workup, he was diagnosed with pulmonary sarcoidosis. Treatment with corticosteroids resulted in resolution of the sinusitis and normalisation of the calcemia, as well as the thyroid function while the impotence, polydipsia and polyuria remained. Elaboration revealed extra-pulmonary involvement of the sarcoidosis with dysfunction of the hypothalamic-pituitary axis with hypogonadotropic hypogonadism and diabetes insipidus due to a sellar mass.
CONCLUSION
This is a rare case of systemic sarcoidosis with both thoracic and extra thoracic manifestations, with pituitary and sinus involvement. It shows that sarcoidosis can affect any organ system and diagnosis can be difficult in case of extrapulmonary manifestations.
PubMed: 38934586
DOI: 10.1080/17843286.2024.2366714 -
Frontiers in Medicine 2024Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is...
BACKGROUND
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is speculated that for HRLCC infertility women with multiple uterine leiomyomas, preimplantation genetic testing may help block transmission of mutated FH gene during pregnancy.
CASE PRESENTATION
We present the case of a 26-year-old nulligravida with a history of early-onset uterine leiomyomatosis had a heterozygous nonsense mutation [NM_000143.4 (FH): c.1027C > T(p.Arg343Ter)] in the HRLLC gene. After ovulation induction and fertilization, preimplantation genetic testing for monogenic disorders (PGT-M) on embryos revealed the absence of the pathogenic allele in two blastomeres. Uterine fibroids were identified before embryo transfer, leading to a submucosal myomectomy and long period of pituitary suppression by Gonadotropin-releasing hormone analog (GnRHa). The patient achieved a healthy live birth after the second cycle of frozen-thawed embryo transfer.
CONCLUSION
This case details the successful treatment of an infertile patient with an HRLLC family history, resulting in a healthy birth through myomectomy and PGT-M selected embryo transplantation. Our literature search indicates the first reported live birth after HRLLC-PGT-M.
PubMed: 38933105
DOI: 10.3389/fmed.2024.1400694 -
Medicina (Kaunas, Lithuania) Jun 2024Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This...
Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor ( gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess gene expression in the duodenum, vertebrae, and kidneys. In Group S, Prlr gene expression was notably decreased in the duodenum ( < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum ( < 0.01) alongside elevated expression in the vertebrae and kidneys. In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.
Topics: Animals; Hyperprolactinemia; Sulpiride; Rats, Wistar; Female; Vitamin D; Rats; Calcium; Duodenum; Receptors, Prolactin; Gene Expression
PubMed: 38929559
DOI: 10.3390/medicina60060942 -
Biomedicines Jun 2024Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests... (Review)
Review
A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.
Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.
PubMed: 38927579
DOI: 10.3390/biomedicines12061372 -
Biomedicines Jun 2024Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow...
Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.
PubMed: 38927575
DOI: 10.3390/biomedicines12061368 -
Acta Pharmacologica Sinica Jun 2024Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two...
Somatostatin receptor 5 (SSTR5) is highly expressed in ACTH-secreting pituitary adenomas and is an important drug target for the treatment of Cushing's disease. Two cyclic SST analog peptides (pasireotide and octreotide) both can activate SSTR5 and SSTR2. Pasireotide is preferential binding to SSTR5 than octreotide, while octreotide is biased to SSTR2 than SSTR5. The lack of selectivity of both pasireotide and octreotide causes side effects, such as hyperglycemia, gastrointestinal disturbance, and abnormal glucose homeostasis. However, little is known about the binding and selectivity mechanisms of pasireotide and octreotide with SSTR5, limiting the development of subtype-selective SST analog drugs specifically targeting SSTR5. Here, we report two cryo-electron microscopy (cryo-EM) structures of SSTR5-Gi complexes activated by pasireotide and octreoitde at resolutions of 3.09 Å and 3.24 Å, respectively. In combination with structural analysis and functional experiments, our results reveal the molecular mechanisms of ligand recognition and receptor activation. We also demonstrate that pasireotide preferentially binds to SSTR5 through the interactions between Tyr(Bzl)/Trp of pasireotide and SSTR5. Moreover, we find that the Q, N, F and ECL2 of SSTR2 play a crucial role in octreotide biased binding of SSTR2. Our results will provide structural insights and offer new opportunities for the drug discovery of better selective pharmaceuticals targeting specific SSTR subtypes.
PubMed: 38926478
DOI: 10.1038/s41401-024-01314-8