ACTH

A Practical Strategy for Primary Aldosteronism Subtyping: Leveraging the Unilateral Adrenal Vein Sampling Index When Bilateral Cannulation Fails.

Qing-Rong Deng, Xiang Cao, Jun Deng +9 more

Adrenal vein sampling (AVS) is the standard procedure for identifying unilateral primary aldosteronism (uPA) in surgical candidates. However, many patients undergo non-diagnostic or partially successful AVS, which may preclude them from curative surgery. This study aimed to evaluate the diagnostic utility of the unilateral AVS index for identifying uPA.

Racial and ethnic variations of metabolic indicators associated with childhood obesity: a comparative cross-sectional study.

Jing Wu, Zhenran Xu, Li Xi +3 more

Susceptibility to adult metabolic diseases varies significantly across ethnicities. Asian adults exhibit elevated risks associated with obesity at lower body mass index (BMI) levels; whether similar patterns occur in pediatric populations remains unclear. This study aimed to evaluate how metabolic indicators associated with childhood obesity vary across diverse racial/ethnic groups.

Ectopic ACTH-dependent Cushing syndrome due to mature ovarian teratoma.

Naseem Eisa

Ectopic adrenocorticotropic hormone (ACTH) secretion accounts for 10%-20% of ACTH-dependent Cushing syndrome, with ovarian teratomas being an exceptionally rare source. We present a female in her early 40s with severe Cushing syndrome due to ectopic ACTH secretion from a mature ovarian teratoma. She presented with progressive weight gain, moon facies, dorsocervical fat pad, proximal muscle weakness, hypertension and new-onset diabetes. Biochemical evaluation confirmed ACTH-dependent hypercortisolism with elevated cortisol, plasma ACTH, late-night salivary cortisol, urinary free cortisol and failure of dexamethasone suppression. Bilateral inferior petrosal sinus sampling (IPSS) confirmed an ectopic source. After negative pituitary and thoracoabdominal imaging, pelvic imaging identified a large right ovarian mass. Laparoscopic salpingo-oophorectomy was performed, and histopathology confirmed a mature cystic teratoma with ACTH-positive neuroendocrine cells. Postoperatively, the patient achieved complete clinical and biochemical remission with full hypothalamic-pituitary-adrenal axis recovery at 1 year follow-up. This case underscores the systematic diagnostic approach required for ectopic ACTH syndrome-including biochemical confirmation, IPSS to distinguish pituitary from ectopic sources and comprehensive imaging-as well as the importance of considering uncommon tumour sites, including ovarian teratomas, when standard thoracoabdominal imaging is unrevealing.

Absent nocturnal cortisol decline in Pheochromocytoma: A retrospective study.

Yahan Sun, Mitsuhiro Kometani, Ko Aiga +5 more

Pheochromocytoma is a catecholamine-producing tumor that may exhibit atypical hormonal profiles. Emerging evidence suggests an association with cortisol dysregulation in the absence of overt Cushing syndrome; however, systematic cortisol evaluation is not routinely performed. This study investigated the prevalence and clinical characteristics of absent nocturnal cortisol decline in pheochromocytoma. This retrospective study included 53 patients with histologically confirmed pheochromocytoma treated between 2011 and 2024. All eligible patients diagnosed during the study period were included. Among them, 22 had paired morning (8:00 AM) and midnight serum cortisol measurements for analysis of nocturnal cortisol decline. Adrenocorticotropic hormone (ACTH) and the 1-mg dexamethasone suppression test (DST) were assessed when available. Patients were stratified by midnight cortisol level (≥1.8 µg/dL vs < 1.8 µg/dL). Among the 22 patients, 18 (82%) had elevated midnight cortisol, indicating absent nocturnal decline (mean midnight, 5.1 µg/dL; mean morning, 13.7 µg/dL). The elevated group (n = 18) was older than the normal group (n = 4) (median, 64 vs 43 years). Metabolic comorbidities were more frequent in the elevated group, including diabetes (50% vs. 25%), dyslipidemia (61% vs. 25%), and cardiovascular disease (44% vs. 0%). DST was performed in 10 patients and showed adequate suppression in 7 of 8 patients with paired cortisol measurements, arguing against autonomous cortisol secretion. No patients had clinical features of overt Cushing syndrome. Absent nocturnal cortisol decline was common and may reflect a pseudo-Cushing state associated with catecholamine excess. These findings support further evaluation of cortisol regulation and its clinical implications.

Diagnostic challenges of Cushing's syndrome in pregnancy.

Fariha Tahir, Brendan Browne, Melina Kostoula +1 more

SummaryWe report a rare case of Cushing's syndrome in a pregnant woman carrying twins. Interestingly, the patient did exhibit many of the classic clinical features typically associated with hypercortisolism, including Cushingoid facies, violaceous striae, insulin-dependent diabetes, raised central adiposity, chronic hypertension and peripheral myopathy. Her case was less straightforward given her previous gastric sleeve bariatric surgery, which led to rapid weight loss prior to pregnancy. The occurrence of an atraumatic fracture of the femoral neck in a young woman with a medical history of type 2 diabetes mellitus, chronic hypertension and possible severe osteoporosis raised clinical suspicion of a unifying diagnosis, prompting further evaluation.Biochemical testing, including elevated cortisol and suppressed adrenocorticotropic hormone levels, alongside imaging studies, confirmed the diagnosis of adrenal Cushing's syndrome. This case prompted a deeper investigation into the physiological changes of the hypothalamic-pituitary-adrenal axis during normal pregnancy, as well as the unique challenges in diagnosing and managing Cushing's syndrome during pregnancy.This case highlights the need for a high index of suspicion and a multidisciplinary approach in diagnosing and managing complex presentations in pregnancy. Early recognition and treatment of Cushing's syndrome are critical to optimising maternal and fetal outcomes.Cushing's syndrome during pregnancy is a rare but serious hormonal syndrome characterised by elevated cortisol levels. This hypercortisolism may be a result of functional adrenal or pituitary tumours, or iatrogenic. Though uncommon, it poses a significant threat to both maternal and fetal health due to the high risk of complications. This case study aims to provide a current overview of the diagnosis and management of Cushing's syndrome in pregnancy, with an emphasis on minimising associated maternal and fetal morbidity. The case report highlights missed differential diagnoses of Cushing's syndrome in the pre-pregnancy period despite the presence of type 2 diabetes, hypertension and morbid obesity in a young patient. Bariatric surgery further complicated the differential diagnosis.

A Rare Case of Takotsubo Cardiomyopathy Responsive to Fludrocortisone in Secondary Adrenal Insufficiency.

Waqar Khalid, Muhammad Usman Khan, Maheen Khoso +3 more

We present a case of a middle-aged woman with a prolonged history of diarrhea, vomiting, and abdominal pain. Upon admission to the ICU, she exhibited hypotension and hypoglycemia. Based on presenting gastrointestinal complaints, she was initially treated for acute gastroenteritis; however, continuous refractory hypotension led to an echocardiographic assessment. A left ventricular ejection fraction (LVEF) of 30-35% with apical akinesis and distinct apical ballooning was visualized on a transthoracic echocardiogram, suggestive of takotsubo cardiomyopathy. An increasing inotropic demand raised concerns regarding alternative etiologies. Further evaluation revealed decreased adrenocorticotropic hormone and cortisol levels, leading to a diagnosis of secondary adrenal insufficiency. Treatment with fludrocortisone significantly improved her adrenal insufficiency and her cardiomyopathy. This case highlights secondary adrenal insufficiency as a rare but potential cause of takotsubo cardiomyopathy in Pakistan, with the use of fludrocortisone as a treatment option in a carefully selected patient.

Unruptured Giant Internal Carotid Artery Aneurysm Compressing the Pituitary Gland Leading to Panhypopituitarism.

Sapna Sharma, Madhav Acharya, Sara Bean +2 more

Internal carotid artery aneurysms are rare and can lead to hypopituitarism due to their mass effect. Hypopituitarism triggered by aneurysmal compression may persist, and postsurgical restoration of pituitary function is challenging, often necessitating long-term hormone replacement therapy. We herein report a case of hypopituitarism caused by intrasellar aneurysm.

Post-ACTH peak cortisol response is associated with genotype in children with nonclassic congenital adrenal hyperplasia.

Allie N Dayno, Marissa J Kilberg, Erin Gonter +4 more

Suboptimal cortisol levels after ACTH stimulation have been recently reported in approximately 30% of patients with nonclassic congenital adrenal hyperplasia (NCCAH). There is little information on the role of genotype on cortisol secretion in NCCAH. The aim of this study is to investigate the association between genotype (i.e compound heterozygote for one mild and one severe CYP21A2 variant vs. homozygous for two mild variants) and peak cortisol response after ACTH stimulation in a pediatric population with NCCAH.

Small-cell carcinoma of the cervix with acute-onset psychotic symptoms associated with clinically diagnosed ectopic ACTH production: a case report.

Kanako Ozaki, Junya Fujino, Kaoru Niimi +11 more

Small-cell carcinoma of the cervix (SCCC) is a rare and highly aggressive histological subtype of cervical cancer, associated with poor prognosis. SCCC is histologically classified as a neuroendocrine tumor and has the potential to produce ectopic hormones, leading to various paraneoplastic syndromes. This report is a rare case of recurrent SCCC presenting with psychiatric symptoms due to endogenous Cushing's syndrome caused by ectopic adrenocorticotropic hormone (ACTH) production. The patient initially developed mood and behavioral disturbances as the disease progressed, leading to hospitalization under the suspicion of a primary psychiatric disorder. However, further evaluation, prompted by the discovery of severe hypokalemia, revealed Cushing's syndrome associated with clinically diagnosed ectopic ACTH production in the setting of recurrent disease. Her psychiatric symptoms rapidly remitted following the administration of a cortisol synthesis inhibitor. This case highlights the importance of considering endocrine disorders as potential causes of psychiatric manifestations in patients with cancer, particularly those with neuroendocrine tumors such as SCCC. Acute and marked elevation of endogenous cortisol can induce distinct psychiatric symptoms, such as manic features and grandiose delusions, that often respond better to endocrine treatment aimed at normalizing cortisol levels rather than to antipsychotic therapy alone. Clinicians should be aware of this rare but important clinical presentation as timely diagnosis and management can improve patient outcomes.

Surgical resection of an adrenocorticotropic hormone-producing pulmonary typical carcinoid with mediastinal lymph node metastasis and high programmed death-ligand 1 expression.

Masakazu Matsuda, Fumihiko Kinoshita, Yukina Takeichi +9 more

The programmed death-ligand 1 positivity rate in typical carcinoid is generally low; however, cases with programmed death-ligand 1 expression are more frequently associated with lymph node metastasis and have a poorer prognosis. While immune checkpoint inhibitors were incorporated into adjuvant chemotherapy regimens for programmed death-ligand 1-positive non-small cell lung cancer, their efficacy in pulmonary carcinoids remains unclear. A 47-year-old woman presented to a local clinic with moon face. Laboratory testing revealed elevated levels of adrenocorticotropic hormone and cortisol and adrenocorticotropic hormone-dependent Cushing's syndrome was suspected. For further evaluation, the patient was referred to our hospital. Computed tomography revealed a nodule in the left lower lobe of the lung and enlargement of the left hilar lymph node, suggesting ectopic Cushing's syndrome. Left lung cancer (cT1bN1M0, cStage IIB) was suspected, and the patient underwent robot-assisted thoracoscopic left lower lobectomy with ND2a-2 lymph node dissection for diagnostic and therapeutic purposes. Pathological examination confirmed a diagnosis of typical carcinoid (pT1bN2M0, pStage IIIA) with high programmed death-ligand 1 expression. Considering the presence of mediastinal lymph node involvement and programmed death-ligand 1 expression, the patient received four courses of cisplatin and vinorelbine, followed by treatment with atezolizumab. Postoperatively, her adrenocorticotropic hormone levels normalized, and the patient has been alive 18 months postoperatively without recurrence. Programmed death-ligand 1-positive typical carcinoids are associated with a higher frequency of lymph node metastasis and poorer prognosis. Additional case investigations are required to assess the efficacy of immune checkpoint inhibitors in typical carcinoid.

Symptom management with osilodrostat in multiple endocrine neoplasia type 1 with a Cushing syndrome presentation.

Hasan Frookh Jamal

Multiple endocrine neoplasia type 1 (MEN1) syndrome is a rare autosomal dominant disorder characterized by predisposition to a multitude of endocrine neoplasms. Cushing syndrome (CS) within MEN1 presents complex diagnostic and therapeutic challenges. We report a case of a 36-year-old male with adrenocorticotropic hormone (ACTH)-dependent Cushing disease and MEN1 syndrome with thymic and pancreatic neuroendocrine tumors. The patient presented with weight gain, weakness and proximal myopathy. Biochemical testing confirmed ACTH-dependent hypercortisolism. Imaging revealed a pituitary microadenoma, a large anterior mediastinal mass, and pancreatic lesions. Genetic analysis confirmed a pathogenic heterozygous MEN1 frameshift variant. After thymectomy, he declined further surgery. Treatment with thymectomy and octreotide long-acting release (LAR) was ineffective. Initiation of osilodrostat (titrated to 5 mg twice daily) resulted in a 76% reduction in urinary cortisol levels and a 47 kg weight loss, with significant functional improvement. Pancreatic and pituitary lesions remained stable. This is the first reported case of successful symptom management of MEN1-associated Cushing disease with osilodrostat, establishing it as an effective therapeutic option for medically complex MEN1 cases where surgery is not feasible or is declined.

Endocrine Modulation of Inflammation: The Role of Adrenocorticotropic Hormone and Cortisol.

Maritza Vidal, Nancy E Lane

The melanocortin system, derived from pro-opiomelanocortin processing, represents a crucial neuroendocrine-immune interface that regulates inflammatory and metabolic pathways. Through its 5 melanocortin receptors (MCRs), MCR1 to MCR5, this system exerts widespread endocrine, paracrine, and autocrine functions across the central nervous system, skin, adipose tissue, bone, and immune cells. Activation of melanocortin signaling produces potent anti-inflammatory effects by modulating cytokine release, leukocyte trafficking, and transcriptional control of proinflammatory mediators. Adrenocorticotropic hormone (ACTH), via the hypothalamic-pituitary-adrenal axis and direct interaction with MCR2, stimulates both cortisol synthesis and mediates steroid-independent immunomodulation in extra-adrenal tissues. It should be taken into account that ACTH is the only ligand for MCR2 inducing steroidogenesis, cell proliferation and anti-inflammatory effects. Synthetic and natural ACTH formulations, such as repository corticotropin injection (Acthar® Gel) and Purified Cortrophin Gel, have demonstrated clinical benefit in refractory inflammatory diseases, as their efficacy may extend beyond classic glucocorticoid pathways. Recent preclinical studies of selective MCR agonists, including MCR1-targeted compounds like dersimelagon, highlight novel therapeutic possibilities for autoimmune and fibrotic disorders. Understanding the dual steroidogenic and nonsteroidogenic actions of melanocortins provides a framework for developing targeted therapies with improved safety profiles compared with conventional glucocorticoids.

Clinical characteristics, diagnosis, and treatment of Cushing's syndrome: analysis of a multicenter registry in Antioquia, Colombia.

Wilfredo Antonio Rivera-Martínez, María Johana Ramírez Castaño, Stefanía Cruz Calderón +9 more

Cushing's syndrome (CS) is a rare endocrine disorder caused by long-term exposure to excess cortisol and is linked to significant morbidity. Data from multiple centers in Latin America remains limited.

Discordant Cortisol Responses to Spontaneous Hypoglycaemia Versus Adrenocorticotropic Hormone Stimulation: A Diagnostic Challenge for Hypothalamic-Pituitary-Adrenal Axis Assessment.

Pushpa Machineni, Asha Ranjan, Adlyne R Asirvatham +1 more

The hypothalamic-pituitary-adrenal (HPA) axis is a critical regulator of cortisol secretion, assessed via dynamic tests such as the insulin tolerance test and adrenocorticotropic hormone (ACTH) stimulation test. Discordant cortisol responses in recurrent hypoglycaemia that is, blunted secretion during hypoglycaemia but preserved under ACTH stimulation, pose a diagnostic challenge in evaluating adrenal insufficiency (AI).

Uncommon tumor, uncertain course: functional oncocytic adrenocortical neoplasm with mild autonomous cortisol secretion.

Fatima Hallak, Kendra Frey, Maria Ortega Abad +3 more

Oncocytic adrenocortical neoplasms are rare adrenal tumors that are usually discovered incidentally. Although most are nonfunctional, about one-third secrete hormones, most often cortisol. We present the case of a 59-year-old man with a right adrenal mass and long-standing, difficult-to-control hypertension. Biochemical testing revealed a 1 mg dexamethasone suppression test (DST) of 2.8 μg/dL (77.25 nmol/L) (reference range: <1.8 μg/dL; <50 nmol/L), a repeated 1 mg DST of 2.3 μg/dL (63.44 nmol/L), a baseline adrenocorticotropic hormone of 6.5 pg/dL (1.4 pmol/L) (reference range: 7.2-63.3 pg/mL; 1.6-13.9 pmol/L), and a dehydroepiandrosterone of 66.5 μg/dL (1.80 μmol/L) (reference range: 51.7-295 μg/dL; 1.4-8.0 μmol/L); consistent with mild autonomous cortisol secretion. Adrenal computed tomography (CT) showed a stable 21 mm indeterminate adrenal nodule with an unenhanced CT attenuation of 22 Hounsfield units. The patient underwent laparoscopic adrenalectomy, and pathology confirmed an oncocytic adrenocortical neoplasm of uncertain malignant potential. Postoperatively, a 1 mg DST was within normal limits, confirming the resolution of mild autonomous cortisol secretion. He is currently under surveillance with annual CT imaging. This case underscores the need to consider oncocytic adrenocortical neoplasms in the differential diagnosis of adrenal incidentalomas and highlights the importance of further research into this rare entity.

Pulmonary neuroendocrine tumour-associated ectopic Cushing's syndrome: diagnostic challenges and multidisciplinary management.

Rubén D Carrasco B, Alba Juanes, Carmen Marrón +3 more

Ectopic adrenocorticotropic hormone (ACTH) secretion is a rare cause of Cushing's syndrome (CS), often associated with neuroendocrine tumours (NETs). Early diagnosis can be difficult due to variable clinical manifestations and psychiatric symptoms that may obscure the underlying endocrine disorder. We report a case of severe ectopic ACTH-dependent Cushing's syndrome secondary to a pulmonary NET, highlighting the importance of multidisciplinary management, advanced imaging with positron emission tomography/computed tomography with gallium-68-labelled DOTA-D-Phe-Tyr-octreotide (68Ga-DOTATOC PET-CT) and aggressive biochemical control to enable curative surgery and full clinical recovery.

Hypothalamic-pituitary-adrenal axis activity and neurotrophic factors in drug-naive children and adolescents with attention-deficit/hyperactivity disorder.

Hurşit Ferahkaya, Necati Uzun, Hasibe Ağır +5 more

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a complex and not fully understood etiology. Increasing evidence suggests that neurotrophic factors involved in neurodevelopment and synaptic plasticity, as well as hormones of the hypothalamic-pituitary-adrenal (HPA) axis that regulate the stress response, may contribute to the pathophysiology of ADHD.

Transient adrenocorticotropic hormone elevation with a disproportionate cortisol response prior to the onset of immune checkpoint inhibitor-related hypophysitis.

Hina Inui-Yasuda, Hironori Bando, Miki Watanabe +10 more

Central Hypothyroidism and Impaired Growth Hormone Secretion Due to Subclinical Cushing's Syndrome: A Case Report.

Masahito Katahira, Taku Tsunekawa, Akira Mizoguchi +4 more

A 34-year-old Chinese woman presenting with general fatigue was found to have central hypothyroidism and low-normal insulin-like growth factor 1 (IGF-1). Although she had no cushingoid features, her adrenocorticotropic hormone levels were suppressed, while her serum cortisol levels were normal. Cortisol secretion was not suppressed following a 1-mg dexamethasone suppression test, and computed tomography revealed a left adrenal tumor. After adrenalectomy, her thyroid function, growth hormone (GH) secretion, and IGF-1 levels were normalized. A histopathological examination confirmed adrenocortical adenoma. This case demonstrates that mild autonomous cortisol secretion can impair GH secretion and cause central hypothyroidism even in the absence of any overt cushingoid features.

Psychosocial and Biological Factors Associated with Non-Suicidal Self-Injury in Chinese Child and Adolescent Inpatients with Major Depressive Disorder.

Chao Liu, Xue-Yan Zhu, Yan-Ni Shi +8 more

This study assessed the prevalence and associated psychosocial and biological factors of non-suicidal self-injury (NSSI) in Chinese child and adolescent inpatients diagnosed with major depressive disorder (MDD) by DSM-5 criteria.

Clinical and Metabolic Outcomes of Adrenalectomy Versus Conservative Management in Mild Autonomous Cortisol Secretion.

Seda Karslı, Selin Çelik, Özge Şahin Kimyon +3 more

Adrenalectomy and conservative management are therapeutic approaches for mild autonomous cortisol secretion; however, their comparative clinical impact in routine practice remains uncertain. We aimed to evaluate real-world hormonal, clinical, and metabolic outcomes according to the treatment strategy in patients with mild autonomous cortisol secretion. This single-center retrospective observational study included consecutive patients with adrenal incidentaloma fulfilling guideline-based diagnostic criteria for mild autonomous cortisol secretion between January 2015 and December 2024. Sixty-five patients with complete hormonal evaluation and follow-up data were analyzed and classified into surgery (n=23) and conservative (n=42) groups. Demographic characteristics, adenoma features, comorbidities, hormonal parameters, and metabolic outcomes were assessed at baseline and at the final follow-up. The median follow-up duration was approximately 3 years and similar between groups (p>0.05). At baseline, the body mass index, adenoma size, and cortisol levels after the 1-mg dexamethasone suppression test were significantly higher, while adrenocorticotropic hormone levels were lower in the surgery group (p=0.02, p=0.02, p=0.036, and p<0.01, respectively). During the follow-up, adrenocorticotropic hormone levels increased and post-dexamethasone suppression test cortisol levels significantly decreased after adrenalectomy (p=0.001 and p=0.036, respectively), whereas metabolic parameters and comorbidity profiles remained largely unchanged. In the conservative group, total cholesterol increased modestly over time (p=0.048), with no significant changes in other clinical outcomes. No significant difference in comorbidity progression was observed between treatment strategies. In this real-world cohort, adrenalectomy resulted in clear hormonal improvement without parallel short-term metabolic or clinical benefits compared with conservative management. These findings highlight the heterogeneous clinical expression of mild autonomous cortisol secretion and underscore the importance of individualized patient selection for surgery.

Early hypocortisolism with persistent remission following osilodrostat in a patient with long-standing Cushing disease.

Liat Sasson, Ilan Shimon

Cushing syndrome is a disorder of endogenous hypercortisolism characterized by increased morbidity and mortality; when surgery is not curative or feasible, medical therapies targeting pituitary adrenocorticotropic hormone or adrenal cortisol production are essential. We report a case of early-onset hypocortisolism and sustained remission following a brief osilodrostat therapy in a 70-year-old woman with Cushing disease who had been treated for many years with pasireotide and metyrapone. Ten days after initiating osilodrostat, she developed clinical signs of adrenal insufficiency and a low morning serum cortisol of 2.8 µg/dL (SI: 76 nmol/L) (reference range 7-25 µg/dL [SI: 193-690 nmol/L]); osilodrostat was discontinued, and glucocorticoid replacement was initiated, remaining glucocorticoid-replacement dependent at low doses for 2 months. Over subsequent follow-up of over 20 months, her 24-hour urinary free cortisol normalized, and she maintained persistent biochemical and clinical eucortisolism off all Cushing therapy, with no relapse of hypercortisolism. She also experienced weight loss of 16.5 kg and marked improvement in diabetes control, enabling discontinuation of insulin and glucagon-like peptide-1 (GLP-1) receptor agonist therapy. This is among the earliest documented cases of osilodrostat-induced hypocortisolism with long sustained hormonal remission after treatment discontinuation, emphasizing the need for early monitoring and prolonged follow-up.

The potential role of aging on acute phase proteins and hypotalamus-pituitary-adrenal axis: A representative cohort study in pregnant mares.

Deborah La Fauci, Pietro Medica, Esterina Fazio +3 more

Pregnancy in mares triggers physiological adaptations involving changes in inflammatory biomarkers, particularly acute-phase proteins (APPs), and the activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, the extent to which these responses are influenced by maternal age remains unclear. The hypothesis of this study was that both APP profile and HPA axis activity during gestation are modulated by the age of the mare. Accordingly, the objective was to evaluate these variables throughout pregnancy and assess the impact of age on their physiological regulation. A total of 41 Spanish Purebred mares were evaluated: n. 31 were pregnant (n. 15 of ≤10 years; n. 16 of >10 years old) and n. 10 were non-pregnant mares. Pregnant mares were monitored monthly throughout gestation, to assess temporal changes in APPs and HPA axis activity. Blood samples were collected to measure serum amyloid A (SAA), haptoglobin (Hp), C-reactive protein (CRP), adrenocorticotropic hormone (ACTH), and cortisol (CORT) concentrations. Statistical analysis included repeated measures ANOVA, and t-tests to assess biomarker differences by age and pregnancy status. Pregnant mares, particularly older individuals, showed elevated concentrations of inflammatory and endocrine markers compared to non-pregnant ones (p < 0.05). These findings demonstrate that pregnancy significantly alters inflammatory and endocrine biomarkers in mares; therefore, older pregnant individuals showed more pronounced and sustained increases compared to both younger pregnant and non-pregnant mares. This suggests that maternal age influences the physiological adaptation to pregnancy, particularly in the regulation of the HPA axis and acute-phase response.

Resting neuroendocrine markers in relation to acute mental stress-induced adrenergic reactivity profiles in adults: The SABPA study.

Dewald Naudé, Wayne Smith, Roland von Känel +1 more

Stress-induced hemodynamic reactivity was categorized as predominant alpha (α)- and beta (β)-adrenergic reactivity profiles. Within these profiles, we investigated resting neuroendocrine markers, their associations with hemodynamic reactivity, and odds of an α- or β-adrenergic reactivity profile. We included 375 teachers (20-65 years) and recorded one-minute beat-to-beat hemodynamic reactivity during Stroop-Color-Word-Conflict-test. We categorized α-responders [lowest-quartile ∆%CO, ∆%Cwk; n = 49], β-responders [highest-quartile ∆%CO, ∆%Cwk; n = 69], mixed-α/β-responders [remaining n = 257]. Baseline fasting serum adrenocorticotropic hormone (ACTH), cortisol, urinary norepinephrine-to-creatinine (u-NE/Cr), and epinephrine-to-creatinine (u-EPI/Cr) ratios were measured. Predominant α-responders were older with greater hypertension prevalence than other responders. In α-responders, u-NE/Cr inversely, and ACTH and cortisol positively associated with ∆%CO and ∆%Cwk (all p ≤ 0.044). In β-responders, u-NE/Cr positively associated with ∆%CO, u-EPI/Cr inversely with ∆%CO, and positively with ∆%Cwk (all p ≤ 0.045). Odds of an α-profile were higher with u-NE/Cr, ACTH, and cortisol in the highest-quartile (all p ≤ 0.004). Odds of a β-profile were higher with u-NE/Cr in the highest-quartile and ACTH and cortisol in the lowest-quartile (all p ≤ 0.006). Predominant α-responders exhibited higher u-NE/Cr, ACTH, and cortisol, suggesting vascular risk through peripheral vasoconstriction. Predominant β-responders showed higher u-NE/Cr only, suggesting adaptive cardiac performance via catecholaminergic drive. These findings reveal distinct neuroendocrine underpinnings with implications for personalized acute stress cardiovascular phenotyping.

[Modern capabilities of contrast-enhanced computed tomography in the diagnosis of adrenal adenomas].

N V Tarbaeva, A Chevais, A V Manaev +5 more

 Adrenal incidentalomas are common, with a detection rate of up to 7% in patients over 70 years of age. Of these, up to 25% are functionally active, leading to the development of severe clinical manifestations. Challenges of insufficient diagnosis and a lack of a personalized approach to the management of such patients persist. To overcome these challenges, the use of CT image analysis is proposed to develop criteria for non-invasive diagnosis, which is a pathway towards improving personalized patient management.

Effect of Normal Level Endocrine Hormones and Hypothalamic Neuropeptides on Obesity in Women of Childbearing Age.

Yingying Tang, Xiukun Zhang, Lei Fan +4 more

To explore the association of endocrine hormones and hypothalamic neuropeptides fluctuations within normal level with obesity in women of childbearing age.

Reversible Cardiomyopathy Induced by Adrenal Insufficiency: A Case Report.

Nehad M Makki, Amjad A Bugis, Amr E Waly +2 more

Adrenal insufficiency, though rare, can cause serious cardiovascular complications such as reversible cardiomyopathy. We present the case of a 56-year-old woman admitted to the intensive care unit with bradycardia, hypotension, and hypoglycemia, followed by hemodynamic instability and subsequent development of supraventricular tachycardia requiring stabilization. Endocrine assessment performed after stabilization demonstrated panhypopituitarism with radiological evidence of an empty sella, central hypothyroidism, and biochemical findings consistent with central adrenal insufficiency, confirmed by low morning cortisol with low adrenocorticotropic hormone levels. On admission, echocardiography showed biventricular dysfunction with a reduced ejection fraction and severe tricuspid regurgitation. Following initiation of intravenous hydrocortisone and supportive therapy, repeat echocardiography at one month demonstrated significant improvement, with recovery of systolic function and marked reduction in valvular regurgitation, consistent with reversible cardiomyopathy. This case highlights the importance of adrenal insufficiency as a potential cause of unexplained cardiomyopathy. The patient's cardiac function improved markedly following appropriate endocrine therapy, with normalization of ejection fraction and resolution of valvular abnormalities. These findings underscore the value of early endocrine evaluation and timely management in preventing irreversible cardiac damage and achieving complete functional recovery.

Incidentally Discovered Adrenal Mass With Mild Autonomous Cortisol Secretion and Pheochromocytoma.

Padala Ravi Kumar, Sai Madhav Reddy Duggempudi, Deepak K Dash +2 more

Adrenal incidentalomas are adrenal masses detected on imaging performed for conditions unrelated to suspected adrenal disease. While pheochromocytomas and adrenal cortical adenomas are well-recognized entities, their coexistence with autonomous cortisol secretion (ACS) within a single lesion is rare and presents diagnostic and therapeutic challenges. A 53-year-old woman was incidentally found to have a left adrenal mass during imaging performed for evaluation of obstructive jaundice. She had hypertension but no classic symptoms of pheochromocytoma or overt Cushing's syndrome. Adrenal-protocol non-contrast CT showed an attenuation of -13 Hounsfield units (HU), suggestive of a benign adrenal adenoma. Biochemical evaluation revealed non-suppressible cortisol on the overnight dexamethasone suppression test (ONDST) and low-dose dexamethasone suppression test (LDDST), along with suppressed adrenocorticotropic hormone (ACTH), consistent with mild autonomous cortisol secretion (MACS). Additionally, 24-hour urinary fractionated normetanephrine levels were elevated, with normal fractionated metanephrine levels, confirming catecholamine excess. Preoperatively, she was managed with alpha- and beta-blockade, followed by open left adrenalectomy. Intraoperatively, she developed hypertension requiring nitroprusside infusion, and postoperatively she experienced transient hypotension, which was managed with intravenous fluids and hydrocortisone. Histopathology revealed a collision tumor with features of adrenal cortical adenoma and pheochromocytoma. Postoperatively, her requirement for antihypertensive drugs decreased from three to one. Repeat 24-hour urinary fractionated normetanephrine levels were normal at four weeks after surgery. This case highlights the importance of comprehensive biochemical and imaging assessment in adrenal incidentalomas. The tumor's dual-secretory nature necessitated meticulous perioperative management to prevent complications, and recognition of such rare entities is crucial for optimizing surgical and medical outcomes.

Metachronous Bilateral Adrenal Adenomas Causing Adrenocorticotropic Hormone-Independent Cushing's Syndrome: A Case Report.

I-Ting Hsiao, Chieh-Hua Lu

Bilateral adrenal adenomas (BAAs) represent an uncommon etiology of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS); however, metachronous BAAs, where the adenomas present years apart, are exceptionally rare, with only a few cases previously reported. We present the case of a 53-year-old woman who developed ACTH-independent CS from a left adrenal cortical adenoma 19 years ago, treated successfully with a left-sided adrenalectomy. Nineteen years after the first episode, she presented with classic hypercortisolism symptoms, including central obesity, striae, and osteoporosis. Workup confirmed recurrent ACTH-independent CS with a low baseline ACTH level and a failure of both low- and high-dose dexamethasone suppression tests to suppress cortisol. Laparoscopic-assisted right-sided adrenalectomy was performed after image confirmation. Adrenal cortical adenoma was diagnosed by histological examination. Following the adrenalectomy, the patient required permanent glucocorticoid and mineralocorticoid replacement therapy. Serial brain magnetic resonance imaging (MRI) scans were initiated for Nelson's syndrome (NS) surveillance. Over 38 months of follow-up, the patient's clinical symptoms improved, and no signs of NS were noted. This case represents the longest detailed reported case with an interval of 19 years between the diagnosis and surgical treatment of metachronous BAAs causing ACTH-independent CS. This rarity highlights the critical importance of long-term and regular follow-up for patients with unilateral adrenal adenoma to monitor for subsequent contralateral masses.

A rare case report of familial glucocorticoid deficiency type 4 (GCCD4) with dilated cardiomyopathy: a 3-year follow-up study.

Zeli Xun, Yan'an Du, Ting Zhao +1 more

Familial glucocorticoid deficiency type 4 (GCCD4), caused by nicotinamide nucleotide transhydrogenase (NNT) gene mutations, represents a rare multisystem disorder with poorly characterized cardiac manifestations.

The Association Between Suicidal Ideation, Personality Traits, and Stress Hormones in Final-Year Medical Students.

Feyza Nur Ozbahar, Hamit Sirri Keten, Seyithan Taysi

This study aims to investigate the relationship between suicide risk, personality traits, and stress-related hormone levels among final-year medical students.