Emotionality vs. Other Biobehavioural Traits: A Look at Neurochemical Biomarkers for Their Differentiation

This review highlights the differential contributions of multiple neurochemical systems to temperament traits related and those that are unrelated to emotionality, even though these systems have a significant overlap. The difference in neurochemical biomarkers of these traits is analysed from the perspective of the neurochemical model, Functional Ensemble of Temperament (FET) that uses multi-marker and constructivism principles. Special attention is given to a differential contribution of hypothalamic–pituitary hormones and opioid neuropeptides implicated in both emotional and non-emotional regulation. The review highlights the role of the mu-opioid receptor system in dispositional emotional valence and the role of the kappa-opioid system in dispositional perceptual and behavioural alertness. These opioid receptor (OR) systems, microbiota and cytokines are produced in three neuroanatomically distinct complexes in the brain and the body, which all together integrate dispositional emotionality. In contrast, hormones could be seen as neurochemical biomarkers of non-emotional aspects of behavioural regulation related to the construction of behaviour in fast-changing and current situations. As examples of the role of hormones, the review summarised their contribution to temperament traits of Sensation Seeking (SS) and Empathy (EMP), which FET considers as non-emotionality traits related to behavioural orientation. SS is presented here as based on (higher) testosterone (fluctuating), adrenaline and (low) cortisol systems, and EMP, as based on (higher) oxytocin, reciprocally coupled with vasopressin and (lower) testosterone. Due to the involvement of gonadal hormones, there are sex and age differences in these traits that could be explained by evolutionary theory. There are, therefore, specific neurochemical biomarkers differentiating (OR-based) dispositional emotionality and (hormones-based) body’s regulation in fast-changing events. Here we propose to consider dispositional emotionality associated with OR systems as emotionality in a true sense, whereas to consider hormonal ensembles regulating SS and EMP as systems of behavioural orientation and not emotionality.

Pituitary Hormones mRNA Abundance in the Mediterranean Sea Bass Dicentrarchus labrax: Seasonal Rhythms, Effects of Melatonin and Water Salinity

In fish, most hormonal productions of the pituitary gland display daily and/or seasonal rhythmic patterns under control by upstream regulators, including internal biological clocks. The pineal hormone melatonin, one main output of the clocks, acts at different levels of the neuroendocrine axis. Melatonin rhythmic production is synchronized mainly by photoperiod and temperature. Here we aimed at better understanding the role melatonin plays in regulating the pituitary hormonal productions in a species of scientific and economical interest, the euryhaline European sea bass Dicentrarchus labrax. We investigated the seasonal variations in mRNA abundance of pituitary hormones in two groups of fish raised one in sea water (SW fish), and one in brackish water (BW fish). The mRNA abundance of three melatonin receptors was also studied in the SW fish. Finally, we investigated the in vitro effects of melatonin or analogs on the mRNA abundance of pituitary hormones at two times of the year and after adaptation to different salinities. We found that (1) the reproductive hormones displayed similar mRNA seasonal profiles regardless of the fish origin, while (2) the other hormones exhibited different patterns in the SW vs. the BW fish. (3) The melatonin receptors mRNA abundance displayed seasonal variations in the SW fish. (4) Melatonin affected mRNA abundance of most of the pituitary hormones in vitro; (5) the responses to melatonin depended on its concentration, the month investigated and the salinity at which the fish were previously adapted. Our results suggest that the productions of the pituitary are a response to multiple factors from internal and external origin including melatonin. The variety of the responses described might reflect a high plasticity of the pituitary in a fish that faces multiple external conditions along its life characterized by marked daily and seasonal changes in photoperiod, temperature and salinity.

Neuroimaging Assessment of Aggressive Pituitary Adenomas

Aggressive pituitary adenomas (APA) are adenomas that show rapid growth, invasiveness, frequent or multiple relapses, or are resistant to conventional therapies. Clinical-imaging assessment of aggressive pituitary adenomas with the aid of magnetic resonance imaging (MRI) plays an important role in early prediction, further disease outcomes and aggressive behavior of adenomas. Purpose of the Study: was to assess the correlation of neuroimaging data with the hormonal activity of APA. Materials and Methods: The study included 74 patients with aggressive pituitary adenomas. The average age of the patients was from 12 to 69. The patients underwent a basal assessment of the level of pituitary hormones: prolactin (PRL), GH (growth hormone), insulin-like growth factor-1 (IGF-1) and blood cortisol by the RIA method, as well as an MRI study. Knop's classification was used to assess the invasion. Results: The hormonal workup showed prevalence of inactive pituitary adenomas among aggressive adenomas. No correlation was found between the hormonal activity of aggressive adenomas and the volume of pituitary adenomas. Moreover, MRI data indicated that invasion into the cavernous sinus of the III degree and heterogeneity of the adenoma may be considered equivalents of aggressiveness. Conclusion: The established patterns support the need for visualization assessment of aggressive pituitary adenomas and strongly suggest the evaluation of the degree of aggression based on tumor heterogenecity, chiasm compression, hypo- and iso-intensity in T1 mode and hyperintensity in T2 modes.

A Perplexing Case of Pituitary Apoplexy Masquerading as Meningoencephalitis

Pituitary apoplexy (PA) is extremely rare in children and adolescents. It is a life-threatening condition usually results from sudden hemorrhage or infarction induced swelling in a pituitary adenoma. The clinical manifestations of PA include severe headaches, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Therefore, the presence of meningeal irritation may lead to misdiagnosis as a case of meningoencephalitis or spontaneous subarachnoid hemorrhage, and delay in the proper management of the disease. We report a case of 17-year-old pubertal boy who developed sudden severe headache, vomiting, slurring of speech and abnormal behaviour followed by impaired sensorium with fever. The patient who was initially diagnosed with meningoencephalitis (ME) based on clinical presentation and cerebrospinal fluid (CSF) analysis, which was consistent with bacterial meningitis. MRI of brain was performed, confirming a pituitary macroadenoma with hemorrhage and ischemic changes in both basal ganglia and pons. A complete analysis of the pituitary hormones revealed decreased cortisol and thyroid hormone level and hyperprolactinemia and he was subsequently started on placement corticosteroid and L-thyroxine therapy and cabergoline. After 14/ days of antimicrobial therapy with ceftriaxone and ampicillin, the patient improved and was discharged on hormone replacement therapy and surgical advised. Hereby, we report our case with a review of literatures. Bangladesh J Medicine July 2022; 33(1) : 85-88

Hypothalamic-pituitary hormones will be affected by the interaction between 5q13-14-rs2239670 (CARTPT) gene variants and diet in different obesity phenotypes

Objective Evidence show that cocaine and amphetamine regulated transcript-prepropeptide (CART-PT) gene variants may affect obesity related traits, but little is known about its end points. In the current study, we aimed to evaluate the interaction of CARTPT gene polymorphism with diet quality indices including dietary approaches to stop hypertension (DASH) and Mediterranean diet score (MDS) on cardio-metabolic risk factors. This cross sectional study recruited 288 apparently healthy obese individuals. Diet quality indices including DASH and MDS were evaluated using semi quantitative food frequency questionnaire (FFQ). Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) was used for CARTPT genotypes. Results No significant differences was reported for general characteristics and biochemical parameters across genotypes except for QUICKI among females (P = 0.01) and it was higher in heterozygous genotype. There was significant CARTPT-DASH interactions affecting serum fasting glucose level (P = 0.049). However, in relation to CERTPT-MDS interactions, the highest level of insulin (P = 0.003) and HOMA-IR (P = 0.003) values were shown among AA carriers in high adherence to MDS, while AA carriers in high compliance to MDS experienced decreased level of QUICKI (P = 0.001).

Acute Secondary Adrenal Insufficiency Misdiagnosed as Acute Cholecystitis

Hypopituitarism refers to insufficient secretion of the pituitary hormones. Patients with acute adrenocorticotropic hormone (ACTH) deficiency may be presented with fatigue, dizziness, orthostatic hypotension, hypoglycemia, nausea, vomiting, or nonspecific abdominal pain. This study described an unusual case of hypopituitarism in a patient who presented with general abdominal pain, abdominal tenderness, nausea, vomiting, hypotension, and hypoglycemia. At first, the patient was admitted with the diagnosis of acute cholecystitis, but after treatment of hypopituitarism and adrenal insufficiency, his symptoms resolved completely, without the need for surgery. Hypopituitarism and secondary adrenal insufficiency should be considered in the differential diagnosis of the patients who present with acute abdomen, hypotension, or hypoglycemia.

Isolated Adrenocorticotropic Hormone Deficiency Caused by Camrelizumab in a Patient with Lung Sarcoma: A Case Report and Literature Review

Background Immune checkpoint inhibitors significantly increase survival in some malignant tumors, but they also lead to a variety of immune-related adverse events that affect multiple organs, including the liver, lung and endocrine system. Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare pituitary disorder characterized by secondary adrenal insufficiency with low or absent cortisol production but the normal secretion of pituitary hormones other than ACTH. IAD caused by atezolizumab, pembrolizumab and nivolumab therapy had been reported, but none is reported in camrelizumab, a new immune checkpoint inhibitor (ICI). Clinicians may not be aware of this unusual side effect. Case presentation: Here, we describe a 70-year-old male patient who had lung sarcoma and was treated with camrelizumab. After nine months of treatment, he developed immune-related pneumonia and hepatitis associated with camrelizumab. The patient discontinued the drug and recovered soon after administration of glucocorticoids. But he subsequently appeared severe hyponatremia, and was diagnosed with late-onset IAD induced by camrelizumab. His symptoms alleviated after glucocorticoid replacement therapy. Conclusion Regular monitoring serum sodium levels and testing endocrine function should be beneficial for cancer patients not only during the treatment of camrelizumab but also after discontinuation of the ICI. Clinicians should consider IAD induced by ICIs when hyponatremia occurs in the patients.

Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis

Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.

Cardiomyopathy Associated With Tertiary Adrenal Insufficiency Manifesting as Refractory Heart Failure, Shock, and Sudden Cardiac Death: A Case Report

Dilated cardiomyopathy is an etiologically heterogeneous disorder. Early diagnosis and prompt treatment of the underlying disease are of great significance. Primary and secondary adrenal insufficiency are considered quite rare causes of dilated cardiomyopathy. However, to the best of our knowledge, no case of cardiomyopathy associated with tertiary adrenal insufficiency has been reported. Herein, we described a 68-year-old woman with a 15-year history of seasonal dermatitis presented with frequent heart failure and shock. At first, she was diagnosed with idiopathic dilated cardiomyopathy, but standard heart failure and antishock treatment failed. Given her long-term use of dexamethasone for treating seasonal dermatitis, and clinical manifestations consistent with adrenal insufficiency, we tested her basal plasma cortisol, simultaneous corticotropin, and other pituitary hormones, confirming that she had tertiary adrenal insufficiency. Additionally, abdominal enhanced computed tomography revealed atrophic bilateral adrenal glands, indicating long-standing and severe adrenal insufficiency. Then hydrocortisone replacement therapy was initiated, and she recovered rapidly. During the next 2 years of follow-up, she never experienced any episodes of heart failure and shock. Unfortunately, she refused the implantation of defibrillator with cardiac resynchronization therapy (CRT-D) and died of sudden cardiac death 2 years later. Although we could not exclude the coincidence of idiopathic dilated cardiomyopathy with tertiary adrenal insufficiency with 100% certainty, her unique clinical course strongly indicated that her cardiomyopathy resulted from tertiary adrenal insufficiency. This case demonstrates that patients on corticosteroids are at risk for tertiary adrenal insufficiency, which may result in refractory cardiomyopathy and even sudden cardiac death.

Principles of Neuroendocrinology and Hypothalamic Function

The hypothalamus is the neural center of the endocrine system, the regulator of the autonomic nervous system, and the circadian and seasonal clock for behavioral and sleep-wake functions. The hypothalamus maintains homeostasis by integrating cortical, limbic, and spinal inputs and by affecting hormone release, temperature regulation, intake of food and water, sexual behavior and reproduction, emotional responses, and diurnal rhythms. As the link from the nervous system to the endocrine system, the hypothalamus synthesizes and secretes neurohormones that stimulate or inhibit the secretion of pituitary hormones.