Misinformation in healthcare is at crisis level worldwide, with the internet as primary source of prevarication. Topical corticosteroids (TCS) are a safe and effective treatment used in multiple dermatological conditions. Nonadherence to prescribed TCS can be due to phobia secondary to misinformation. TCS phobia is a complex multifaceted phenomenon that exploits patients with skin disease, creates cognitive dissonance and can obstruct successful treatment. This study aimed to examine the content of TCS-related misinformation available online. A formal review of PubMed was performed using the terms 'topical corticosteroids' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory, along with an informal Google search using combinations of these terms and further targeted searches on social media applications including Facebook™, Twitter™, Instagram™ and TikTok™. 'Topical steroid withdrawal', 'red skin syndrome' or 'TCS addiction' is a particularly prevalent myth currently being propagated on social media, with most content suggesting that eczema is due to a 'leaky gut' or food intolerance and not to skin inflammation. The risks of potential adverse effects such as skin thinning and stunted growth/development are often exaggerated. Multiple websites promoting misinformation were frequently endorsed by companies advertising consultations or testing to identify 'underlying causes', or 'natural' products as alternative treatments, including 'herbal' remedies, which can contain significant quantities of corticosteroids or other potent ingredients. The dermatology community should be vigilant of the type of TCS-related misinformation online and be active in attempts to counteract it with evidence-based advice.

Pheochromocytomas and paragangliomas (PGLs) are rare non-epithelial neuroendocrine neoplasms of the adrenal medulla and extra-adrenal paraganglia respectively. Duodenal PGL is quite rare and there are only two previous reports. Herein, we report a case of multiple catecholamines (CAs)-producing PGLs in the middle ear, retroperitoneum, and duodenum, and review the literature of duodenal PGLs. A 40-year-old man complained right-ear hearing loss, and an intracranial tumor was suspected. Magnetic resonance imaging of the head revealed a 3-cm mass at the right transvenous foramen, which was surgically resected following preoperative embolization. The pathological diagnosis was a sympathetic PGL of the right middle ear. Six years later, family history of PGL with germline mutation of succinate dehydrogenase complex iron sulfur subunit B, SDHB: c.268C>T (p.Arg90Ter) was clarified. The patient had elevated levels of plasma and urine CAs again. Abdominal computed tomography scanning revealed two retroperitoneal tumors measuring 30-mm at the anterior left renal vein and 13-mm at near the ligament of Treitz. The larger tumor was laparoscopically resected, but the smaller tumor was not identified by laparoscopy. After the operation, the patient remained hypertensive, and additional imaging tests suggested a tumor localized in the duodenum. The surgically resected tumor was confirmed to be a duodenal PGL. After that, the patient remained hypertension free, and urinary levels of noradrenaline and normetanephrine decreased to normal values. No recurrence or metastasis has been found at 1 year after the second operation. CAs secretion from PGLs in unexpected location, like the duodenum of our patient, may be overlooked and leads to a hypertensive crisis. In such cases, comprehensive evaluation including genetic testing, fluorodeoxyglucose-positron emission tomography scanning, and measurement of CAs will be useful for detecting PGLs. Most previous reports on duodenal PGL were gangliocytic PGL which has been renamed composite gangliocytoma/neuroma and neuroendocrine tumor, and defined the different tumor from duodenal PGL. We reviewed and discussed duodenal PGLs in addition to multiple PGLs associated with SDHB mutation.

Acute ST-segment elevation myocardial infarction (STEMI) can typically complicate with the development of cardiogenic shock; nevertheless, other less frequent types of shock may occur, including adrenal crisis (AC). We describe a case of STEMI complicated by AC and, for the first time, AC-induced focal takotsubo syndrome.

Adrenal crisis continues to be an important cause of death despite being a preventable condition. Significant deficits in patient education in the prevention of adrenal crisis have been identified as a contributor to adrenal crisis risk despite the importance of patient education being highlighted in international guidelines. Deficits in clinician education have also been identified as risk factors for adrenal crisis though have not been addressed. We use three clinical cases to highlight the role of both patient and clinician education in the prevention of adrenal crisis, review what is known about education related to adrenal insufficiency and provide a possible approach to addressing education deficits with the aim of reducing the risk of adrenal crisis through both patient and clinician education.

The etiology, presentation and mortality of patients with primary adrenal insufficiency (PAI) in developing countries may differ from economically developed nations. However, information in this regard is scanty. The aim of this study was to determine the etiology and compare the clinical characteristics and mortality in infectious and autoimmune causes of PAI in Indian patients. All eligible (n=89) patients (ages 15-83 years) diagnosed with PAI in between 2006-2019 were studied. Patients were followed for a median duration of 5.9 (range 0.1-15.7) years. Eighty-six subjects underwent an abdominal CT scan or ultrasonography and adrenal biopsy was performed in 60 patients. The most frequent aetiologies of PAI were histoplasmosis (AH, 45%), tuberculosis (AT, 15%), autoimmunity (AI, 25%) and primary lymphoma (6%). Forty two percent of patients presented in an acute adrenal crisis. AH and AT could not be differentiated on the basis of clinical features, except for a greater frequency of hepatomegaly-splenomegaly and type 2 diabetes mellitus (63% vs. 15%, p<0.01) in the former. Patients with an autoimmune etiology had a higher frequency of 21-hydroxylase antibodies (41% vs. 3%) and autoimmune thyroid disease (46% vs. 5%) versus those with infectious aetiologies. Mortality was significantly higher in AH (45%) compared with AT (8%) or AI (5%) (p=0.001). Causes of death included adrenal crises, progressive histoplasmosis and unexplained acute events occurring at home. In conclusion, infections, especially AH, were the most frequent cause of PAI in north India. Despite appropriate therapy, AH had very high mortality as compared with AT and AI.

Myriad questions regarding perioperative management of patients on glucocorticoids (GCs) continue to be debated including which patients are at risk for adrenal insufficiency (AI), what is the correct dose and duration of supplemental GCs, or are they necessary for everyone? These questions remain partly unanswered due to the heterogeneity and low quality of data, studies with small sample sizes, and the limited number of randomized trials. To date, we know that although all routes of GC administration can result in hypothalamic-pituitary-adrenal (HPA) axis suppression, perioperative adrenal crisis is rare. Correlation between biochemical testing for AI and clinical events is lacking. Some of the current perioperative management recommendations based on daily GC dose and duration of therapy may be difficult to follow in clinical practice. The prospective and retrospective studies consistently report that continuing the daily dose of GCs perioperatively is not associated with a higher risk for adrenal crises in patients with GC-induced AI. Considering that oral GC intake may be unreliable in the early postoperative period, providing the daily GC plus a short course of IV hydrocortisone 25 to 100 mg per day based on the degree of surgical stress seems reasonable. In patients who have stopped GC therapy before surgery, careful assessment of the HPA axis is necessary to avoid an adrenal crisis. In conclusion, our literature review indicates that lower doses and shorter duration of supplemental GCs perioperatively are sufficient to maintain homeostasis. We emphasize the need for well-designed randomized studies on this frequently encountered clinical scenario.

The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion.

Autoimmune polyglandular syndromes (APS) are polyendocrinopathies characterized by autoimmune dysfunction of multiple endocrine organs. We present the case of a 23-year-old male with a past medical history of autoimmune thyroiditis diagnosed seven months prior who presented with a chief complaint of six months of fatigue, shortness of breath, and weight loss. Physical exam was remarkable for global hyperpigmentation, notably of his palmar creases and gingiva. The patient was also tachycardic and hypotensive. He initially received two liters of 0.9% NaCl and 10 mg of intravenous dexamethasone. Random cortisol was <0.5 g. A cosyntropin test showed an insufficient increase in cortisol in response to adrenocorticotropin hormone (ACTH), confirming the diagnosis of primary adrenal insufficiency (AI). A computed tomography (CT) scan of the abdomen was negative for adrenal hemorrhage. A sexually transmitted disease (STD) panel was obtained to rule out the infectious cause and was negative. The patient was given glucocorticoids and his symptoms improved with fluid and electrolyte supplementation. This case report highlights the importance of close monitoring of patients with autoimmune endocrine abnormalities. These patients should be followed by an endocrinologist every six months for prompt diagnosis and risk mitigation. .

Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism.

Congenital adrenal hyperplasia associated to 11-beta-hydroxylase deficiency is a rare cause of secondary hypertension, usually discovered during childhood; however, a late diagnosis in adults has also been reported. Despite low cortisol levels, accumulated adrenal steroid precursors can activate the glucocorticoid receptor and thus protect the patient against adrenal crisis.

Immune checkpoint inhibitors (ICI) are cancer therapies that are approved in at least 19 different cancers. They function by stimulating immune cell responses against cancer, and their toxicities comprise a host of autoinflammatory syndromes that may impact any organ system. Endocrine toxicities occur in as high as 25-50% of ICI recipients, depending on the treatment regimen used. These toxicities vary in severity from mild, asymptomatic cases of subclinical hypothyroidism to severe, fatal cases of adrenal crisis, thyroid dysfunction, or diabetic ketoacidosis. Thus, timely recognition and treatment is critical. Herein, we present clinical cases of ICI-induced thyroid dysfunction, hypophysitis, and insulin-dependent diabetes mellitus. We use these cases to discuss the screening, diagnosis, and management of ICI-associated endocrine dysfunction.

Pheochromocytomas are rare adrenal tumors that are often diagnosed in workup for endocrine causes of refractory hypertension, as an incidental imaging finding, or in patients with classic symptoms of headache, palpitations, and/or diaphoresis. We describe a case of pheochromocytoma presenting in a 63-year-old woman with spontaneous and multifocal subarachnoid and intracerebral hemorrhage without underlying vasculopathy. The patient previously had no documented episodes of hypertension and took no regular medications. She experienced sudden-onset severe headache and presented with hypertensive crisis. Cranial imaging showed bifrontal and right temporal convexal subarachnoid and intracerebral hemorrhage of unknown etiology. Cranial arterial catheterization showed no vascular malformation underlying the site of hemorrhage. Given concern for potential malignant etiology, cross-sectional body imaging was performed that revealed a 7-cm right adrenal heterogeneous mass. Biochemical workup demonstrated markedly elevated plasma metanephrine and normetanephrine levels, diagnostic of pheochromocytoma. She underwent α- and β-blockade, and evaluation with a multidisciplinary team including repeat intracranial imaging to ensure resolution of the intracranial bleeding before definitive surgical management. She then underwent successful laparoscopic adrenalectomy. This case demonstrates that the workup of cryptogenic intracranial hemorrhage and hypertensive crisis should include evaluation for catecholamine-secreting tumors.

A 6-year-old castrated male Labradoodle was referred in uncompensated hypovolemic shock, with a 72-h history of lethargy, vomiting and diarrhea that had acutely worsened with subsequent development of profuse hemorrhagic diarrhea in the last 24 h after a visit to the groomer. In most respects this case was classic for a patient with a primary hypoadrenocortical crisis. After initial attempts to address hypovolemia and refractory hypotension, no clinical improvement was seen, and the respiratory rate had increased acutely to 80 bpm with crackles detected on thoracic auscultation and serosanguineous fluid began draining from the nose and mouth. An arterial blood gas sample while breathing room air revealed moderate hypoxemia (PaO2 59.9: RI 95-100 mmHg), an elevated alveolar-arterial (A-a) gradient at 54.7 (RI < 15 mmHg) and a PaO2:FiO2 ratio of 285 mmHg. Thoracic radiographs revealed severe bilateral alveolar lung pattern largely limited to the perihilar and caudodorsal lung fields. The radiographic findings, along with signs of ongoing hypovolemia, the lack of evidence of typical long-standing acquired cardiac disease, and the rapid resolution of the pulmonary edema without the need for diuretics or long-term cardiac medications supported non-cardiogenic pulmonary edema. The proposed cause of the non-cardiogenic pulmonary edema was speculated to be neurogenically mediated. Oxygen supplementation along with mineralocorticoid and glucocorticoid replacement therapy was sufficient for the management of the non-cardiogenic pulmonary edema in this case.

A 43-year-old man developed headache, dizziness, abdominal pain, and vomiting. His blood pressure was 203/121 mmHg, heart rate 122 beats/min, body temperature 39.1 °C, and respiratory rate 24/min. He had elevated levels of creatinine at 2.95 mg/dL and lipase at 1,364 U/L as well as an extremely low calcium level at 5.2 mg/dL. Hypertriglyceridemia and hyperglycemia were seen. Chest and abdominal computed tomography showed interstitial pneumonia, severe pancreatitis, and a right adrenal tumor. The patient also developed vertebral artery dissection and medullary infarction. After right adrenalectomy, the patient was diagnosed with pheochromocytoma multisystem crisis (PMC). Acute pancreatitis might augment numerous life-threatening manifestations of PMC.

Adrenal hemorrhage is an uncommon underrecognized condition that can be encountered in several clinical contexts. Diagnosing adrenal hemorrhage is challenging due to the non-specific clinical features. Therefore, it remains a diagnosis that is made serendipitously on imaging of acutely unwell patients rather than with prospective clinical suspicion. Adrenal hemorrhage can follow abdominal trauma or on a background of predisposing conditions such as adrenal tumors, sepsis, or coagulopathy. Adrenal hemorrhage is also increasingly reported in patients with COVID-19 infection and in the context of vaccine-induced immune thrombocytopenia and thrombosis, in both cases likely as a consequence of adrenal vein thrombosis. Unexplained abdominal pain with hemodynamic instability in a patient with a predisposing condition should alert the physician to the possibility of adrenal hemorrhage. Bilateral adrenal hemorrhage can lead to adrenal insufficiency and potentially fatal adrenal crisis without timely recognition and treatment. In this article, we highlight the clinical circumstances that are associated with higher risk of adrenal hemorrhage, encouraging clinicians to prospectively consider the diagnosis, and share a diagnostic and management strategy.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency caused by mutations in the CYP21A2 gene. Although women with CAH have decreased fecundity, they are able to conceive; thus, if pregnancy is not desired, contraception options should be offered. If fertility is desired, women with classic CAH should first optimize glucocorticoid treatment, followed by ovulation induction medications and gonadotropins if needed. Due to the possible pregnancy complications and implications on the offspring, preconception genetic testing and counseling with a high-risk obstetrics specialist is recommended. For couples trying to avoid having a child with CAH, care with a reproductive endocrinology and infertility specialist to utilize in vitro fertilization can be offered, with or without preimplantation genetic testing for monogenic disorders. Prenatal screening and diagnosis options during pregnancy include maternal serum cell free-DNA for sex of the baby, and chorionic villus sampling and amniocentesis for diagnosis of CAH. Pregnant women with classic CAH need glucocorticoids to be adjusted during the pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis. Maternal and fetal risks may include chorioamnionitis, maternal hypertension, gestational diabetes, cesarean section, and small for gestational age infants. This review on CAH due to 21-hydroxylase deficiency highlights reproductive health including genetic transmission, contraception options, glucocorticoid management, fertility treatments, as well as testing, antenatal monitoring, and management during pregnancy, delivery, and postpartum.

Pheochromocytoma is a rare but life-threatening condition due to catecholamine release induced by drug treatments such as β-blockers or glucocorticoids. We present a case of hypertensive crisis due to pheochromocytoma, induced after the initiation of dexamethasone and landiolol during intensive care for severe coronavirus disease 2019 (COVID-19). Based on a detailed medical history review, the patient was previously diagnosed with primary aldosteronism by confirmatory tests, moreover, an abdominal computed tomography scan identified an adrenal tumor 2 years before current admission. We tentatively diagnosed the patient with pheochromocytoma and initiated α-blockers without conducting a catecholamine report, leading to stable hemodynamics. We present a successfully managed case of pheochromocytoma concomitant with COVID-19, which has become a global crisis.

Deaths due to hypertensive crisis can be unexplained because of the impossibility to identify-before the decease-the specific cause of the crisis. In these cases, autopsy and microscopic examinations are needed. It can happen that the request to conduct these examinations can be submitted to forensic pathologists by prosecutors to ascertain medical malpractice claims. Indeed, we report the case of a 36-year-old woman who died after a minimally invasive medical procedure because of the occurrence of a severe hypertensive crisis. After death, the woman's relatives raised formal complaint for medical malpractice. For this reason, the prosecutor ordered to perform an autopsy. Examining the abdominal cavity, the forensic pathologists identified the left adrenal gland as expanded; in correspondence with organ's medulla, there was a gray and noncapsulated mass. Immunohistochemistry was performed: the microscopic samples were diffusely positive for chromogranin A, suggesting the diagnosis of a subclinical pheochromocytoma. In light of the above, medical malpractice was excluded. This case highlights that forensic pathologists should be aware that, in case of unexpected deaths due to hypertensive crisis, adrenal glands should be always accurately evaluated, performing specific immunohistochemistry study to exclude the presence of a pheochromocytoma.