We report a woman in her 20s with congenital adrenal hyperplasia (CAH) due to a clinical diagnosis of 11β-hydroxylase deficiency, bilateral ovarian adrenal rest tumours (OARTs), autoimmune Addison's disease and premature ovarian insufficiency. Despite the combination of CAH and OARTs, she conceived spontaneously twice, with complete regression of the tumours under glucocorticoid therapy. Years later, she developed an Addisonian crisis confirmed by positive 21-hydroxylase antibodies and subsequently manifested ovarian failure and mineralocorticoid deficiency. This case illustrates the rare coexistence of distinct adrenal and ovarian pathologies, highlights the potential reproductive impact of OARTs and underscores the need for further study and standardised management strategies.

Extreme cold exposure has emerged as a significant global public health challenge to cognitive function among populations such as military personnel, polar workers, and residents of high-latitude regions. However, the complex mechanisms underlying cold environment-induced cognitive impairment remain to be systematically elucidated. This systematic review synthesizes the effects of cold exposure (CE) on cognitive function and the potential biological mechanisms involved. CE impairs cognition through four interconnected pathways: neuroendocrine dysregulation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. The dual dysregulation of the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-thyroid axis constitutes the core neuroendocrine mechanism, wherein excessive glucocorticoids mediate hippocampal structural damage through mitochondrial reactive oxygen species bursts, autophagic dysregulation, and synaptic plasticity impairment. Oxidative stress is characterized by ROS accumulation and a collapse of antioxidant defenses, with time-dependent decompensation of the Nrf2 pathway exacerbating lipid peroxidation and oxidative modification of synaptic proteins. Neuroinflammation features hippocampal microglial activation and a positive feedback loop involving the HMGB1-NLRP3 inflammasome, driving the cascade release of pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-α. Mitochondrial dysfunction manifests as suppressed biogenesis, imbalanced dynamics (Drp1-mediated excessive fission), and decreased oxidative phosphorylation efficiency, leading to neuronal energy crisis and apoptosis. These four pathways amplify each other through positive feedback cycles, ultimately culminating in synaptic plasticity collapse and hippocampal-dependent memory deficits. Based on these mechanisms, this review proposes comprehensive protective strategies, including cold acclimatization training, pharmacological interventions, and targeted therapies. Current research faces challenges such as high heterogeneity in exposure parameters, lack of core body temperature monitoring, and insufficient mechanistic validation. Future efforts should establish standardized research paradigms, quantitatively delineate the relationship between CE intensity/duration and neural injury, and explore precision intervention targets based on the neuroendocrine-immune-metabolic interaction network, thereby providing theoretical foundations and practical approaches for brain health protection in extreme environments.

Painless thyroiditis is a destructive disorder associated with immune dysregulation. Although an abrupt reduction in corticosteroid activity has been implicated, the precipitating role of endogenous adrenal insufficiency remains unclear. A 66-year-old woman was admitted to a referring hospital with anorexia, vomiting, and hyponatremia and was diagnosed with syndrome of inappropriate antidiuresis (SIAD). Despite correction of serum sodium levels, anorexia persisted. Two months later, she developed fever, tachycardia, impaired consciousness, and severe hypercalcemia and was transferred to our institution. Laboratory evaluation revealed marked thyrotoxicosis with suppressed thyroid-stimulating hormone and elevated free thyroxine levels, along with inappropriately low adrenocorticotropic hormone (ACTH) and cortisol levels. The patient met the diagnostic criteria for thyroid crisis. Thyroid antibody testing and imaging findings were consistent with painless thyroiditis. Secondary adrenal insufficiency was confirmed by a blunted cortisol response to a rapid ACTH stimulation test. Treatment with intravenous hydrocortisone and empiric potassium iodide resulted in rapid clinical improvement. This case suggests an association between unrecognized secondary adrenal insufficiency initially diagnosed as SIAD and the subsequent occurrence of painless thyroiditis and thyroid crisis. Evaluation of adrenal function should be considered in patients with hyponatremia and thyrotoxicosis.

A 22-year-old man with untreated congenital adrenal hyperplasia (CAH) developed an acute adrenal crisis following bilateral orchiectomy for testicular adrenal rest tumors. The patient survived into adulthood without treatment until progressive testicular masses led to surgery due to misinterpretation of malignancy. Eighteen days postoperatively, he presented with severe asthenia, hyponatremia, and hyperkalemia. Diagnostic evaluation revealed markedly elevated 17-hydroxyprogesterone, androstenedione, and adrenocorticotropic hormone levels, with bilateral adrenal hyperplasia on imaging. Genetic testing identified a homozygous pathogenic variant in the CYP21A2 gene. Following glucocorticoid and mineralocorticoid replacement, the patient achieved clinical stability. This case illustrates that surgical removal of testicular adrenal rest tumors in untreated individuals can precipitate severe acute adrenal insufficiency, highlighting these tumors as a critical sentinel finding for late-diagnosis congenital adrenal hyperplasia.

Opioid-induced adrenal insufficiency (OIAI) is a known, but often overlooked complication associated with chronic opioid use. It is important to recognize OIAI as, if untreated, can lead to increased morbidity and mortality.

BACKGROUND Multiple endocrine neoplasia type 2A (MEN 2A) is a rare autosomal-dominant genetic syndrome characterized by mutations in the RET gene and tumors of endocrine glands, including pheochromocytomas. Pheochromocytoma is a benign primary endocrine tumor of the adrenal glands that produces catecholamines and in rare cases is complicated by pheochromocytoma multisystem crisis (PMC), a life-threatening endocrine emergency caused by severe catecholamine overproduction. This report describes a 42-year-old woman presenting with PMC associated with bilateral pheochromocytomas and MEN2A. CASE REPORT The patient presented with a sudden onset of back pain and dyspnea with severe shock. An enhanced computed tomography examination revealed bilateral adrenal gland tumors, and she was diagnosed with PMC complicated by multiple organ failure and catecholamine-induced cardiomyopathy. We introduced simultaneous veno-venous extracorporeal membrane oxygenation and continuous hemodiafiltration. A definitive operation for PMC was performed on hospital day 12, with the intent of complete resection of bilateral pheochromocytomas. The patient was weaned from continuous hemodiafiltration on hospital day 21st day and was finally weaned from artificial ventilation on hospital day 30. Genetic examination revealed a pathogenic RET mutation (Cys634Arg, C634R), leading to the diagnosis of MEN2A. She is now undergoing rehabilitation, with intensive surveillance for thyroid medullary carcinoma and hyperparathyroidism. CONCLUSIONS PMC can easily lead to multiple organ failure within a few days. A multidisciplinary approach to PMC can rescue these patients by making surgical pheochromocytoma resection possible. If synchronous bilateral pheochromocytomas are detected, MEN2A should be suspected.

Adrenal crisis is a life-threatening condition which is caused by an insufficient level of glucocorticoids in the body. Most patients have preexisting adrenal insufficiency, and physical or emotional stress triggers the adrenal crisis. This includes acute illness and surgery. It is important that patients receive a life-saving emergency injection of 100 mg hydrocortisone immediately and a continuous supplementation afterwards. This article focuses on the pathophysiology, trigger factors, prevention and emergency treatment of adrenal crisis in adult patients. By adjusting the regular dosage of glucocorticoids in stressful situations, adrenal crisis can be prevented. Patients at risk for adrenal crisis should keep an emergency injection kit and a standardised European emergency card and receive life-saving doses of glucocorticoids in emergency situations as quickly as possible.

Corticosteroids are indispensable in the management of inflammatory, autoimmune, and respiratory disease, yet prolonged or unsupervised systemic use can produce iatrogenic Cushing's syndrome, and abrupt withdrawal risks life-threatening adrenal crisis. We report five male patients, aged 12 to 65 years, who developed Cushingoid features following systemic corticosteroid exposure for type two diabetes-associated dermatosis, bronchial asthma, epileptic encephalopathy, rheumatoid arthritis, and osteoarthritis. All five presented with moon facies; additional findings included purple striae, cutaneous thinning, abdominal hyperpigmentation, and impaired wound healing. Where measured, serum cortisol was low or low-normal, consistent with hypothalamic-pituitary-adrenal (HPA) axis suppression by exogenous steroid and thereby confirming an iatrogenic rather than endogenous origin. Opportunistic fungal infection masked by corticosteroid-mediated immunosuppression was a recurring complication. In one patient, abrupt discontinuation of dexamethasone precipitated adrenal crisis, multi-organ failure, and death. The remaining four patients recovered fully following structured tapering or physiological corticosteroid replacement. This report illustrates the clinical spectrum of iatrogenic hypercortisolism, emphasises the diagnostic significance of a suppressed endogenous cortisol, and underscores the imperative of gradual steroid withdrawal. It highlights the essential role of clinical pharmacists in rational prescribing, early adverse-effect recognition, and safe steroid tapering within a multidisciplinary care framework.

Primary adrenal insufficiency (Addison's disease) is a potentially life-threatening disorder most commonly caused by autoimmune adrenalitis, though rare etiologies such as infiltrative malignancies must be considered, particularly when bilateral adrenal involvement leads to clinical manifestations. Diffuse large B-cell lymphoma (DLBCL), an aggressive subtype of non-Hodgkin lymphoma, may rarely involve the adrenal glands and precipitate adrenal crisis. We report a 58-year-old male patient who presented with giddiness, vomiting, fatigability, hyperpigmentation, weight loss, and hypotension. Laboratory evaluation revealed hyponatremia, bicytopenia, and markedly elevated adrenocorticotropic hormone (ACTH) levels, consistent with primary adrenal insufficiency. Imaging demonstrated bilateral adrenal masses with intra-abdominal lymphadenopathy, and histopathological examination of adrenal biopsy confirmed DLBCL. The patient was promptly treated with intravenous corticosteroids, resulting in hemodynamic stabilization while undergoing regular antidiabetic therapy. The patient was later referred to oncology for further management. This case highlights a rare presentation of DLBCL manifesting as Addisonian crisis due to bilateral adrenal infiltration. Given the nonspecific clinical features that often delay diagnosis, clinicians should maintain a high index of suspicion for malignant causes in patients presenting with adrenal insufficiency and bilateral adrenal masses, as early recognition and timely corticosteroid therapy are critical for improving outcomes.

100 years ago in the U.S., tuberculosis was the most common cause of primary adrenal insufficiency (AI) (Addison's disease). Autoimmune adrenalitis is now responsible for 80-90% of AI in this country and Europe; nevertheless today, in the U.S. and certainly abroad, diverse infections can involve the adrenals in both the immunocompetent and immunocompromised and potentially produce AI. Such infections range widely: bacterial (e.g., Mycobacterium tuberculosis, in particular), fungal (e.g., histoplasmosis), viral and even protozoal (e.g., severe Plasmodium falciparum malaria). Suspecting AI, especially if chronic, is not straightforward, delays in AI diagnosis may reach > 6 months in 50%, and 50-75% of patients initially present in overt adrenal crisis. Diagnosing adrenal involvement by an infection may be drawn out, typically requires careful imaging, a thorough infectious disease evaluation, and may require adrenal biopsy.

Perioperative dexamethasone is commonly used in enhanced recovery protocols, yet its safety in adrenalectomy remains underevaluated. We report a 33-year-old woman who developed postoperative adrenal crisis-like deterioration 54 hours after right adrenalectomy for a radiologically and biochemically non-functioning adrenal tumor on basal preoperative testing. A single 5 mg intravenous dose of dexamethasone was administered intraoperatively for antiemetic prophylaxis. During clinical deterioration, the patient exhibited marked suppression of ACTH and cortisol, consistent with pharmacological glucocorticoid effects in the perioperative period. However, the clinical presentation was non-specific and alternative postoperative complications, including infection, thromboembolic disease, and metabolic disturbances, could not be fully excluded. The patient improved following combined supportive therapy and stress-dose hydrocortisone. Preoperative endocrine evaluation did not include a 1 mg overnight dexamethasone suppression test, and mild autonomous cortisol secretion could not be excluded. Dynamic assessment of adrenal reserve was not performed preoperatively. This case highlights that perioperative dexamethasone may be temporally associated with postoperative endocrine perturbations that mimic adrenal crisis in susceptible patients. However, causality cannot be established, and careful differential diagnosis is essential in the postoperative setting following adrenal surgery.

An adrenal crisis is a potentially life-threatening medical emergency, which requires rapid treatment with glucocorticoids. Guidelines advise immediate self-administration of hydrocortisone by intramuscular injection using an emergency management kit in case an adrenal crisis is suspected. However, self-injection is often not performed due to administration complexity or patient anxiety. Pulmonary administration of glucocorticoids may be a more patient-friendly and suitable alternative, especially when administered using a dry powder inhaler. Before advancing to the development of a dry powder inhaler, we aimed to evaluate whether the pharmacokinetics of inhaled prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis. Twelve healthy participants (aged 23-31 years, 50% females) received two separate doses of prednisolone sodium succinate, equivalent to 56.1 and 112.2 mg prednisolone on separate occasions, administered via a nebulizer. The primary outcome was the time to reach a target plasma concentration of 200 nmol/L. The median times to achieve this plasma concentration (excluding the nebulization time of approximately 10 minutes) were 17 (13 - 23) minutes and 9 (5-11) minutes for the 56.1 and 112.2 mg doses, respectively. Furthermore, pulmonary administered prednisolone sodium succinate was well tolerated. The results of this study, particularly the short time to the target plasma concentration, indicate that prednisolone sodium succinate is rapidly absorbed via the lungs and that the pharmacokinetics of inhaled nebulized prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis.

Primary adrenal lymphoma (PAL) is an uncommon extranodal non‑Hodgkin lymphoma that typically presents with bilateral adrenal masses and carries a poor prognosis, especially when complicated by adrenal insufficiency; primary bilateral adrenal lymphoma is a rare but important cause of adrenal insufficiency and adrenal crisis, particularly when large bilateral adrenal masses are detected on imaging. A 50‑year‑old man presented with several months of constitutional symptoms, including night sweats, vomiting, weight loss, diarrhoea and myalgia, and was initially treated conservatively with symptom resolution, but four months later he was readmitted with anorexia, further weight loss, fever and left upper quadrant pain; imaging revealed bilateral adrenal masses (6.7 cm right, 4.5 cm left) with high non‑contrast attenuation (>20 Hounsfield units) and splenomegaly, and MRI confirmed progression of the right adrenal lesion to 8.5 cm. Biopsy demonstrated diffuse large B‑cell lymphoma consistent with PAL, and he was commenced on hydrocortisone and fludrocortisone replacement together with eight cycles of R‑CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisolone) and intrathecal methotrexate, achieving complete radiological remission sustained to 2016, with remission maintained until his death from sepsis and multi‑organ failure in 2023. This case illustrates the broad symptom spectrum of PAL, from B-symptoms to adrenal crisis, and underscores the importance of considering PAL in the differential diagnosis of bilateral adrenal masses with high attenuation. Early recognition of adrenal insufficiency and adrenal biopsy are critical to guide timely initiation of life-saving glucocorticoid replacement and lymphoma-directed therapy.

The utilization of immunotherapy and targeted therapies in advanced malignancies is rapidly increasing due to advancing technologies. While highly effective, the unintended toxicities and immune-related adverse events (irAEs) associated with these treatments require vigilant monitoring. Autoimmune hypophysitis and subsequent pituitary dysfunction represent critical complications of immune checkpoint inhibitors (ICIs), particularly pembrolizumab. Hypopituitarism can manifest as panhypopituitarism leading to a life-threatening secondary adrenal crisis or as selective anterior pituitary hormone deficiencies, such as isolated adrenocorticotropic hormone (ACTH) or gonadotropin deficiency. We report the case of a 73-year-old man with recurrent melanoma who presented with pituitary dysfunction secondary to pembrolizumab therapy. This case highlights the necessity of investigating, screening, and promptly treating new constitutional symptoms in patients undergoing ICI therapy, as these endocrine complications can be fatal if left unrecognized.