Adrenal Activity Research Articles

Positive Correlation Between Fecal Estrogen and Glucocorticoid Metabolites in a Female Clouded Leopard.

Clouded leopards are notoriously difficult to manage under human care due to their tendency toward high stress, intersex aggression, and limited reproductive success. This case study investigated the endocrinological interplay between adrenal and ovarian steroids and describes a positive correlation between concentrations of fecal estrogen and glucocorticoid metabolites in a female clouded leopard. The female was monitored through two sampling periods approximately 16 months apart, and each data set yielded similar results using a simple linear regression model. The finding of a significant positive correlation between the two steroids represents a novel finding in felids and a hitherto unidentified potential interplay between adrenal and ovarian steroid activity. It also adds to our collective understanding of the effects of estrus on female clouded leopards, impacting conservation efforts as we encourage reproduction in this vulnerable species.

Perinatal running training reversed postnatal anxiety and depressive-like behavior and cognitive impairment in mice following prenatal subchronic variable stress.

Pregnancy is a very complex and highly stressful time in women. Despite the high prevalence of postpartum depression, more than 50 % of mothers are undiagnosed or untreated, showing an urgent need to explore an effective preventive strategy. Regular physical activity has been suggested to be associated with an increased quality of life in pregnant and postpartum women. The purpose of this study was to determine whether perinatal running training can affect maternal care stress-related anxiety, depressive-like behavior, and cognitive changes in postpartum dams and to explore the possible underlying mechanism. 40 female C57BL/6J mice were divided into four groups: prenatal control (NC) and running training (EX) group (NC+EX), prenatal control and nonrunning training (RE) group (NC+RE), prenatal subchronic variable stress (SCVS) and running training group (SCVS+EX) and prenatal SCVS and non-running training group (SCVS+RE). Mice in prenatal stress groups were subjected to SCVS after pregnancy confirmed. Mice in running training groups subjected to running training throughout pregnancy and lactation. Then after the delivery, maternal behavior, cognitive changes, anxiety and depressive-like behaviors were tested. Then we measured the serum prolactin (PRL), hypothalamic-pituitary adrenal (HPA) axis activity, and adult hippocampus neurogenesis (AHN) in dams. Compared to NC+RE, prenatal SCVS caused cognitive impairments, the decrease in maternal behavior, and anxiety and depressive-like behavior in SCVS+RE dams, accompanying increase in HPA axis activity and decreased the PRL levels and AHN in postpartum period. Then compared to SCVS+RE, perinatal running training mitigates cognitive impairments, increased maternal behavior, and alleviates anxiety and depressive-like behavior in SCVS+EX dams, accompanying the decreased HPA axis activity, and the increased PRL levels and AHN in postpartum period. Overall, this study suggests that perinatal running training might improve maternal care and reverse prenatal stress-related cognitive impairment and anxiety and depressive-like behavior in postpartum dams.

Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice

Rapid glucose supply is crucial for animal survival during stress response. How the timescale of stress-induced glucose release precisely controlled by hypothalamic corticotropin-releasing hormone (CRH) neurons remains unclear. Here, we show that stress-induced hyperglycemia can be divided into at least two stages in male mice: the first fast stage is mediated by hypothalamus (paraventricular to ventromedial hypothalamus)-sympathetic (raphe pallidus nucleus to intermediolateral nucleus)-liver (HSL) axis activity; the second delayed stage is mediated by adrenal activity. Blocking the activity of HSL axis impairs predatory evoked flight responses, indicating that the HSL pathway activity is necessary for stress coping. We further reveal the intracellular signal cascade for CRH signal in the hypothalamus, which is mediated by GABAA receptor β3 subunit phosphorylation at S408/409, results in prevention of GABAA receptor membrane recruitment. Thus, we uncovered the precise timescale of glucose supply during stress which is mediated by adrenal independent HSL and adrenal dependent pathway respectively.

12325 Adrenocortical Carcinoma Masquerading As Pheochromocytoma In A Patient With Congenital Adrenal Hyperplasia

Abstract Disclosure: E.M. Niedzialkowska: None. A.A. Banka: None. Introduction: The development of adrenocortical carcinoma (ACC) in patients with congenital adrenal hyperplasia (CAH) is rare. The patients with CAH are at increased risk of adrenal tumors which is attributed to ACTH stimulation of adrenal gland if the disease is not appropriately treated. ACC cases mistaken for pheochromocytomas have been reported in the literature and are attributed to the variety of immunohistochemical markers expressed by the tumors. Case description:59 y.o female with salt-wasting CAH diagnosed at the age of 2 (21-hydroxylase deficiency) on hydrocortisone supplementation reported to the hospital due to episodes of sweating, tachycardia and hypertension. Work up revealed mildly elevated plasma normetanephrine 1 nmol/l (N <0.9), urine normetanephrine 1762 mcg (N<899), VMA 11.2 mcg/24hr (N 3.3-7.2). MRI of the abdomen revealed 2 left adrenal masses of 3.7 and 2.4 cm, right adrenal gland hyperplasia and low T1 and T2 enhancement. I-123 MIBG revealed increased activity and thickness of the right adrenal gland and no significant uptake on the left with nodular masses. The patient underwent left adrenalectomy with pathological report consistent with pheochromocytoma due to positive chromogranin and synaptophysin staining and moderate Ki activity. A year later follow up imaging showed an enhancing mass up to 7 cm at the suprarenal fossa invading the left kidney that was positive for nodular adrenocortical hyperplasia per pathology report. The patient continued to have elevated 17-OH- progesterone (2740 ng/l, N <51) despite compliance with her steroid therapy and suppressed ACTH. She underwent mass resection along with nephrectomy, splenectomy, partial colectomy and partial pancreatectomy. Pathology report was positive for adrenocortical carcinoma (positive chromogranin, synaptophysin, CAM 5.2, polycystic cytokeratin, Ki positive in greater than 10% of the tumor cells) with renal and regional lymph node invasion and colonic metastases. The patient was started on mitotane therapy but a year later PET scan was positive for liver and omental metastases and was subsequently started on carboplatin/etoposide followed by streptozocin/adriamycin with initial good response, however repeat PET a year afterwards showed progression of the liver lesions, metastases to omentum and metastatic lesion to calvarium and the patient expired soon afterwards. Discussion: CAH predisposes patients to adrenal tumors which is attributed to increased ACTH stimulation of the adrenal gland but ACC in this population is extremely rare. In very rare cases ACC can present clinically as pheochromocytoma with elevated catecholamine levels and positive synaptophysin and chromogranin staining which poses a clinical challenge. Both CAH and ACC can lead to increased androgen levels and ACTH levels can help to differentiate the origin of the hyperandrogenemia. Presentation: 6/2/2024

8563 Pheochromocytoma Screening In A Patient With Neurofibromatosis Type I And Medication-Resistant Hypertension

Abstract Disclosure: E. Mora: None. A. Bolduc, MD: None. G. Elshimy: None. Title: Pheochromocytoma Screening in a Patient With Neurofibromatosis Type I and Medication-Resistant Hypertension Background: Patients with neurofibromatosis type I (NF1) have a higher risk of pheochromocytoma and it may be missed if no screening done, thus placing the patient at risk of stroke and/or myocardial infarction. The prevalence of pheochromocytoma in patients with NF1 is 2.9% according to a retrospective cohort study by Gruber et al. We present a case of biochemically silent pheochromocytoma in a patient with NF1 and resistant hypertension Clinical case: A 74-year woman with NF1 presented with episodic headaches and labile systolic blood pressure (BP) in the 170-200s mm Hg on three different antihypertensives consistent with pheochromocytoma. Initial tests for renal artery stenosis and pheochromocytoma showed normal plasma MN (0.43 nmol/L, n< 0.50 nmol/L) and NM (0.86 nmol/L, n< 0.90 nmol/L), and normal flow in both renal hila by color Doppler and no large suprarenal masses identified on retroperitoneal US. Duplex imaging of the bilateral kidneys showed no evidence of renal artery stenosis. CT of abdomen/pelvis with and without IV contrast showed a 1.6 cm nodule on Right (RT) adrenal gland that measured 36 HU on unenhanced phase with an absolute washout of 67%. No discrete nodule in Lt adrenal gland. Dotatate PET/CT revealed a Rt adrenal nodule with elevated asymmetric activity (measured 28.1 standardized uptake values (SUV), n for liver: max 12.3, spleen: max 23.5) relative to the normal physiologic activity of the Leftt adrenal gland, which is concerning for pheochromocytoma. The patient was then referred to our endocrine clinic for further evaluation 6 months after the initial presentation. Labs showed normal aldosterone (5.8 ng/dL, n≤39.2 ng/dL), cortisol (7.66 mcg/dL, n: 3.09-22.40 mcg/dL), ACTH (20 pg/mL, n: 7.2-63 (AM collection), and DHEA-S (28 mcg/dL, n:5.3-124 mcg/dL). Normal repeat plasma MN (0.38 nmol/L, n< 0.50 nmol/L) and NM (0.46 nmol/L, n< 0.90 nmol/L). Repeat CT adrenal washout redemonstrated 1.4 cm Rt adrenal nodule that measured 39 HU on non- contrast image with an absolute washout of 68%. Patient will have a surgical resection of the Rt adrenal biochemically silent pheochromocytoma next week and she has been receiving an alpha-blocker prior to surgery to decrease risk for labile BP. Discussion and Conclusion: This case illustrates how CT and DOtatate scan findings can alert providers to the presence of a pheochromocytoma, even in biochemically negative patients. We recommend pheochromocytoma screening in all patients with NF1 to prevent delayed diagnosis and complications of untreated pheochromocytoma. Presentation: 6/1/2024

7963 Analysis of the inhibition of adrenal synthesis and peripheral metabolism of corticosteroids by oteseconazole and two preclinical tetrazole antifungals

Abstract Disclosure: M. Jäger: None. V. González-Ruiz: None. F.L. Joos: None. D.V. Winter: None. J. Boccard: None. T. Degenhardt: Employee; Self; Mycovia Inc. S. Brand: Employee; Self; Mycovia Inc.. S. Rudaz: None. G.R. Thompson: None. A. Odermatt: None. The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia by blocking adrenal cortisol synthesis and its peripheral inactivation [1]. Mechanisms of pseudohyperaldosteronism include inhibition of adrenal cytochrome P450 enzymes CYP11B1 and CYP17A1, as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazole compounds have been developed [2]. Here, we used adrenal H295R cells and enzyme activity assays to assess the inhibition of steroidogenesis by the tetrazoles oteseconazole, VT-1129 and VT-1598. In addition, the three tetrazoles were tested for inhibition of 11β-HSD2. Steroidomic footprint analyses of H295R cell supernatants using untargeted LC-HRMS with steroid annotation indicated common features of the oteseconazole and VT-1129 patterns with that of the triazole itraconazole, and similarities between VT-1598 and the triazole isavuconazole. Targeted quantification of nine adrenal steroids by UHPLC-MS/MS in supernatants of treated H295R cells showed an overall inhibition of steroidogenesis by the tetrazoles and the triazoles itraconazole and isavuconazole. Experiments using recombinant human enzymes suggested that this effect is not caused by direct inhibition of steroidogenic enzymes because no or very weak inhibition could be observed. Furthermore, oteseconazole, VT-1129 and VT-1598 did not inhibit 11β-HSD2, suggesting that they unlikely cause pseudohyperaldosteronism. Further research needs to uncover the exact mechanism for the observed overall inhibition of steroidogenesis by the tetrazoles as well as itraconazole and isavuconazole, and whether concentrations reached in patients are high enough to cause adrenal insufficiency and hyperplasia.

Effects of dopamine β-hydroxylase inhibition in pressure overload-induced right ventricular failure.

Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β-hydroxylase (DβH) inhibition with BIA 21-5337 improved right ventricular (RV) function or remodeling in pressure overload-induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21-5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate-reducing effects of BIA 21-5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure-volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21-5337 reduced adrenal gland DβH activity and 24-h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end-of-study, there were no differences in RV function or RV remodeling between BIA 21-5337 and vehicle-treated rats. In conclusion, treatment with BIA 21-5337 did not have any beneficial-nor adverse-effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity.

Expression of tryptophan hydroxylase in rat adrenal glands: Upregulation of TPH2 by chronic stress

It has been shown that chronic restraint stress (CRS) increases adrenal 5-HT levels and turnover through a mechanism that appears unrelated to tryptophan hydroxylase (TPH). In the present study we re-analyzed the effects of CRS (20 min/day) for 14 days relative to control (CTRL) conditions on TPH expression, distribution, and activity in rat adrenal glands. On day 15, adrenal glands were collected for TPH1 and TPH2 immunohistochemistry, Western blot, and RT-PCR; TPH activity was estimated by quantification of 5-hydroxytryptophan (5-HTP) and, indirectly, through measurement of 5-HT and 5-hydroxindolacetic acid (5-HIAA) levels and turnover (5-HIAA/5-HT ratio) by HPLC. TPH expression and activity in the dorsal raphe nucleus (DRN) were also determined for comparison. TPH1 and TPH2 immunostaining was observed in the adrenal medulla, and measurable levels of TPH1 and TPH2 protein and mRNA were detected in rat adrenal glands from CTRL animals. CRS exposure noticeably increased TPH2- but not THP1-immunostaining in the medulla and the outer adrenocortical areas of left (LAG) but not of right adrenal glands (RAG). In addition, CRS exposure increased TPH2 protein and mRNA levels in LAG; however, both measures decreased in DRN. Finally, CRS treatment produced an increase and a decrease of TPH activity and 5-HT turnover in LAG and DRN, respectively. Results indicate that TPH is indeed expressed in rat adrenal glands. Exposure to CRS upregulates TPH2 in LAG, while inducing downregulation of it in the DRN. Then, the increased levels of 5-HT in LAG from CRS-exposed animals likely results from TPH2-mediated synthesis.

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

Previous assessments of faecal glucocorticoid metabolites in Cape mountain zebra (Equus zebra zebra) were flawed

Abstract Steroid hormones, especially glucocorticoids (GCs), are widely used to assess physiological responses to stressors. As steroid hormones are heavily metabolised prior to excretion, it is essential to validate enzyme immunoassays (EIAs) for measuring faecal glucocorticoid metabolites (fGCMs). Although problems with unvalidated assays have been raised repeatedly, their use persists widely. Lea et al. (2017) used an unvalidated corticosterone assay (CJM006) to relate fGCM concentrations to habitat quality, demography and population performance in the Cape mountain zebra (Equus zebra zebra). Here, we revisit their findings and evaluate the validity of their conclusions using a validated EIA. First, we evaluate the biological sensitivity of six EIAs (three group‐specific metabolite assays and three corticosterone assays, including CJM006) through a biological validation experiment (translocation) for two sub‐species of mountain zebra, Cape mountain and Hartmann's mountain zebra (E. z. hartmannae). Second, we reanalyse the faecal extracts from Lea et al. (2017) using a validated EIA. fGCM concentrations consistently increased following translocation, when using two 11‐oxoaetiocholanolone (lab codes: 72T and 72a) and an 11ß‐hydroxyaetiocholanolone (69a) EIA, but did not with three different corticosterone EIAs. All corticosterone EIAs (including CJM006) failed to detect an increase in fGCMs within the critical 48–72‐h period post translocation. Therefore, the CJM006 EIA utilised in Lea et al. (2017) does not sensitively measure hypothalamic–pituitary–adrenal (HPA) axis activity in CMZ faeces. Using a validated assay (72T), fGCM concentrations were no longer associated with adult sex ratio or habitat quality (measured by grassiness) and these variables were dropped from predictive models. fGCM concentrations now varied between seasons and were negatively associated with female fecundity (foal:mare ratio). Consequently, we can conclude that the results of the previous study are unreliable. We introduce the terms “insensitive” and “sub‐optimal” to categorise assays that are tested but fail validation, and assays that are comparatively poor at detecting relevant hormone changes, respectively. We discuss how both “insensitive” and “sub‐optimal” assays could lead to incorrect inferences about population stressors and counterproductive conservation recommendations. Read the free Plain Language Summary for this article on the Journal blog.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19

BackgroundThe effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. MethodsThe comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FindingsThe demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. InterpretationCritical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

Is social disadvantage a chronic stressor? Socioeconomic position and HPA axis activity among older adults living in England

IntroductionLiving in socioeconomic disadvantage has been conceptualised as a chronic stressor, although this contradicts evidence from studies using hair cortisol and cortisone as a measure of hypothalamus-pituitary-adrenal (HPA)11HPA axis: Hypothalamus Pituitary Adrenal axis axis activity. These studies used complete case analyses, ignoring the impact of missing data for inference, despite the high proportion of missing biomarker data. The methodological limitations of studies investigating the association between socioeconomic position (SEP)22SEP: Socio-economic Position defined as education, wealth, and social class and hair cortisol and cortisone are considered in this study by comparing three common methods to deal with missing data: (1) Complete Case Analysis (CCA),33CCA: Complete Case Analysis (2) Inverse Probability Weighting (IPW) 44IPW: Inverse Probability Weightingand (3) weighted Multiple Imputation (MI).55MI: Multiple Imputation This study examines if socioeconomic disadvantage is associated with higher levels of HPA axis activity as measured by hair cortisol and cortisone among older adults using three approaches for compensating for missing data. MethodCortisol and cortisone levels in hair samples from 4573 participants in the 6th wave (2012–2013) of the English Longitudinal Study of Ageing (ELSA)66ELSA: English Longitudinal Study of Ageing were examined, in relation to education, wealth, and social class. We compared linear regression models with CCA, weighted and multiple imputed weighted linear regression models. ResultsSocial groups with certain characteristics (i.e., ethnic minorities, in routine and manual occupations, physically inactive, with poorer health, and smokers) were less likely to have hair cortisol and hair cortisone data compared to the most advantaged groups. We found a consistent pattern of higher levels of hair cortisol and cortisone among the most socioeconomically disadvantaged groups compared to the most advantaged groups. Complete case approaches to missing data underestimated the levels of hair cortisol in education and social class and the levels of hair cortisone in education, wealth, and social class in the most disadvantaged groups. ConclusionThis study demonstrates that social disadvantage as measured by disadvantaged SEP is associated with increased HPA axis activity. The conceptualisation of social disadvantage as a chronic stressor may be valid and previous studies reporting no associations between SEP and hair cortisol may be biased due to their lack of consideration of missing data cases which showed the underrepresentation of disadvantaged social groups in the analyses. Future analyses using biosocial data may need to consider and adjust for missing data.

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

Unique and interactive effects of threat and deprivation on latent trait cortisol among emerging adults.

Though considerable work supports the Dimensional Model of Adversity and Psychopathology, prior research has not tested whether the dimensions-threat (e.g., abuse) and deprivation (e.g., neglect)-are uniquely related to salivary trait indicators of hypothalamic pituitary adrenal (HPA) axis activity. We examined the unique and interactive effects of threat and deprivation on latent trait cortisol (LTC)-and whether these effects were modified by co-occurring adversities. Emerging adults (n=90; Mage=19.36 years; 99.88% cisgender women) provided salivary cortisol samples four times a day (waking, 30 min and 45 min postwaking, bedtime) over three 3-day measurement waves over 13 weeks. Contextual life stress interviews assessed early adversity. Though the effects varied according to the conceptualization of early adversity, overall, threat-but not deprivation, nor other co-occurring adversities-was uniquely associated with the across-wave LTC. Specifically, the incidence and frequency of threat were each negatively related to the across-wave LTC. Threat severity was also associated with the across-wave LTC, but only among those with no deprivation. Finally, the effects of threat were modified by other co-occurring adversities. Findings suggest that threat has unique implications for individual differences in HPA axis activity among emerging adults, and that co-occurring adversities modify such effects.

Effect of resuscitation of cryopreserved porcine adrenal glands at 26 °C on their recovery and functioning under xenotransplantation

The study is devoted to the effect of lowered resuscitation temperature (26 °C) on cryopreserved porcine adrenal glands functional activity in vitro and in vivo under xenotransplantation. The adrenals were collected from newborn pigs, cryopreserved with 5 % DMSO at a rate of 1 °C/min, resuscitated at 26 or 37 °C for 48 h (5 % CO2, DMEM), embedded into small intestinal submucosa, and transplanted to bilaterally adrenalectomized rats. It has been shown that the glands resuscitated at 26 °C have suppressed free-radical processes and can produce cortisol and aldosterone in vitro, and may lead to elevated blood levels of these hormones. Moreover, the adrenal grafts maintain blood glucose levels and promote the formation of glycogen stores. Thus, the resuscitation at 26 °C can improve the quality of grafts and favor the introduction and application of the cryopreserved organs and tissues for transplantation in clinical and experimental practice.

Hair cortisol concentrations in pregnant women with bipolar, depressive, or schizophrenic spectrum disorders

PurposeMaternal cortisol levels in pregnancy may support the growth of or adversely affect fetal organs, including the brain. While moderate cortisol levels are essential for fetal development, excessive or prolonged elevations may have negative health consequences for both the mother and the offspring. Little is known about predictors of altered hypothalamic–pituitary–adrenal (HPA) axis activity during pregnancy. This study examined maternal hair cortisol concentration (HCC) in the 3rd trimester of pregnancy in relation to severe psychopathology.MethodsHair samples were collected from 69 women, 32 with a lifetime diagnosis of severe mental disorders (bipolar I or II disorder, moderate or severe depressive disorder, schizophrenic spectrum disorder), and 37 non-clinical controls. Hair samples were collected during the 3rd trimester, and liquid chromatography tandem mass spectrometry was used for cortisol assessment. Psychiatric diagnosis and current level of symptomatic functioning were assessed using the structured clinical interview from the DSM-5 and the global assessment of functioning scale.ResultsWomen with a lifetime diagnosis of severe mental illness had significantly elevated HCC compared to controls. Poorer current symptomatic functioning was also significantly associated with elevated HCC in pregnancy.ConclusionsThe implications of alterations in HCC on both maternal and infant health need further study.

Adrenal and metabolic hormones demonstrate risk-reward trade-offs for African elephants foraging in human-dominated landscapes.

A key driver of the African savannah elephant population decline is the loss of habitat and associated human-elephant conflict. Elephant physiological responses to these pressures, however, are largely unknown. To address this knowledge gap, we evaluated faecal glucocorticoid metabolite (fGCM) concentrations as an indicator of adrenal activity and faecal thyroid metabolite (fT3) concentrations as an indicator of metabolic activity in relation to land use, livestock density, and human landscape modification, while controlling for the effects of seasonality and primary productivity (measured using the normalized difference vegetation index). Our best-fit model found that fGCM concentrations to be elevated during the dry season, in areas with higher human modification index values, and those with more agropastoral activities and livestock. There was also a negative relationship between primary productivity and fGCM concentrations. We found fT3 concentrations to be higher during the wet season, in agropastoral landscapes, in locations with higher human activity, and in areas with no livestock. This study highlights how elephants balance nutritional rewards and risks in foraging decisions when using human-dominated landscapes, results that can serve to better interpret elephant behaviour at the human-wildlife interface and contribute to more insightful conservation strategies.

Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

X-linked adrenoleukodystrophy and primary adrenal insufficiency.

X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder caused by a congenital defect in the ATP-binding cassette transporters sub-family D member 1 gene (ABCD1) producing adrenoleukodystrophy protein (ALDP). According to population studies, X-ALD has an estimated birth prevalence of 1 in 17.000 subjects (considering both hemizygous males and heterozygous females), and there is no evidence that this prevalence varies among regions or ethnic groups. ALDP deficiency results in a defective peroxisomal β-oxidation of very long chain fatty acids (VLCFA). As a consequence of this metabolic abnormality, VLCFAs accumulate in nervous system (brain white matter and spinal cord), testis and adrenal cortex. All X-ALD affected patients carry a mutation on the ABCD1 gene. Nevertheless, patients with a defect on the ABCD1 gene can have a dramatic difference in the clinical presentation of the disease. In fact, X-ALD can vary from the most severe cerebral paediatric form (CerALD), to adult adrenomyeloneuropathy (AMN), Addison-only and asymptomatic forms. Primary adrenal insufficiency (PAI) is one of the main features of X-ALD, with a prevalence of 70% in ALD/AMN patients and 5% in female carriers. The pathogenesis of X-ALD related PAI is still unclear, even if a few published data suggests a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of adrenal cell membrane function and ACTH receptor activity. The reason why PAI develops only in a proportion of ALD/AMN patients remains incompletely understood. A growing consensus supports VLCFA assessment in all male children presenting with PAI, as early diagnosis and start of therapy may be essential for X-ALD patients. Children and adults with PAI require individualized glucocorticoid replacement therapy, while mineralocorticoid therapy is needed only in a few cases after consideration of hormonal and electrolytes status. Novel approaches, such as prolonged release glucocorticoids, offer potential benefit in optimizing hormonal replacement for X-ALD-related PAI. Although the association between PAI and X-ALD has been observed in clinical practice, the underlying mechanisms remain poorly understood. This paper aims to explore the multifaceted relationship between PAI and X-ALD, shedding light on shared pathophysiology, clinical manifestations, and potential therapeutic interventions.

SARS-CoV-2 Affects Thyroid and Adrenal Glands: An 18F-FDG PET/CT Study.

Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by 18F-FDG PET/CT. We retrospectively evaluated the 18F-FDG PET/CT scans of COVID-19 patients admitted by three different centres, either in a low-intensity department or in the intensive care unit (ICU). A visual assessment and a semi-quantitative evaluation of areas of interest in thyroid and adrenal glands were performed by recording SUVmax and SUVmean. The 18F-FDG PET/CT uptake in COVID-19 patients was compared with those observed in normal age-matched controls. Between March 2020 and March 2022, 33 patients from three different centres (twenty-eight patients in a low-intensity department and five patients in ICU), were studied by 18F-FDG PET/CT during active illness. Seven of them were also studied after clinical remission (3-6 months after disease onset). Thirty-six normal subjects were used as age-matched controls. In the thyroid gland, no statistically significant differences were observed between control subjects and COVID-19 patients at diagnosis. However, at the follow-up PET/CT study, we found a statistically higher SUVmax and SUVmean (p = 0.009 and p = 0.004, respectively) in the thyroid of COVID-19 patients. In adrenal glands, we observed lower SUVmax and SUVmean in COVID-19 patients at baseline compared to control subjects (p < 0.0001) and this finding did not normalize after clinical recovery (p = 0.0018 for SUVmax and p = 0.002 for SUV mean). In our series, we observed persistent low 18F-FDG uptake in adrenal glands of patients at diagnosis of COVID-19 and after recovery, suggesting a chronic hypofunction. By contrast, thyroid uptake was comparable to normal subjects at disease onset, but after recovery, a subgroup of patients showed an increased metabolism, thus possibly suggesting the onset of an inflammatory thyroiditis. Our results should alert clinicians to investigate the pituitary-adrenal axis and thyroid functionality at the time of infection and to monitor them after recovery.