Bilateral adrenal haemorrhage in antiphospholipid syndrome and a short review of the literature.

Antiphospholipid syndrome (APS) is an uncommon autoantibody-mediated condition characterised by acquired thrombophilia resulting in recurrent arterial and venous thrombosis. An inciting factor allows for the exposure of endothelial phospholipids, causing antigen formation and subsequent creation of antibodies. A woman in her 70s presented after vehicular trauma, suffering broken ribs, pneumothorax and incidentally discovered left adrenal haemorrhage. Two weeks later she presented with acute-onset abdominal pain and was found to have a right adrenal gland haemorrhage on CT imaging without interval trauma occurring. The patient had antiphospholipid antibody laboratory studies drawn and was given intravenous heparin with a bridge to warfarin at discharge. Laboratory results returned positive for lupus anticoagulant, beta-2 glycoprotein and anticardiolipin antibodies indicating triple positivity, with repeated laboratory tests positive in 12 weeks' time, confirming the diagnosis. Bilateral adrenal haemorrhage, rather than traditional venous thromboembolism, was the presenting pathology in this patient's diagnosis of APS.

Can evaluating adrenal glands in computed tomography contribute to predicting the prognosis of hospitalized COVID-19 patients?

OBJECTIVE: The novel coronavirus disease 2019 (COVID-19) may affect the adrenal glands. Therefore, it is important to evaluate the morphologic appearance of the adrenal glands by thorax computed tomography (CT). On CT scans, stranding in peripheral fatty tissue with enlarged adrenal glands may indicate signs of adrenal infarction (SAI). The present study aimed to evaluate the incidence of SAI and determine whether this finding may contribute to predictions of the prognosis of COVID-19. PATIENTS AND METHODS: A total of 343 patients who had been hospitalized at Malatya Training and Research Hospital between September 1 and 30, 2020, with a diagnosis of COVID-19 were enrolled in this study. All patients underwent thorax CT scans that included their adrenal glands. RESULTS: Of the enrolled patients, 16.0% had SAI. Moreover, 41.8% of patients with SAI and 15.3% of patients without SAI were treated in the Intensive Care Unit (ICU). Patients with SAI had a significantly higher rate of ICU admission (p < 0.001). Mortality rates were also significantly higher among patients with SAI than those without p < 0.001). CONCLUSIONS: In this study, it was found that COVID-19 patients with SAI may have a poorer prognosis. More comprehensive studies are needed on this subject, but the present study may provide helpful preliminary information in terms of prognosis.

[Bilateral adrenal hemorrhage after severe COVID-19 infection. Report of one case]. / Hemorragia adrenal bilateral en paciente recuperado de neumonía COVID-19 Grave. Caso Radiológico.

We report a 47-year-old male with a severe disease caused by COVID-19, who required mechanical ventilation for 18 ays. During the hospital stay he received dexamethasone and anticoagulation with heparin. After discharge a new chest CT scan showed homogeneous hypo vascular enlargement of both adrenal glands, not present in the initial imaging studies. It was interpreted as a subacute bilateral adrenal hemorrhage. The patient remained stable and without any complaint.

Characterisation of the onset and severity of adrenal and thyroid dysfunction associated with CTLA4-related hypophysitis.

CONTEXT: The use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in the treatment of melanoma, renal carcinoma and non-small cell lung cancer; however, it is associated with frequent immune-related adverse events (irAE). Ipilimumab-induced hypophysitis (IIH) is a well-recognised and not infrequent endocrine irAE. OBJECTIVE: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma. DESIGN: Aretrospective review of hormone levels in consecutive adult patients treated with ipilimumab (3 mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor. RESULTS: Of 189 patients, 24 (13%; 13 males; 60.5 ± 12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At the presentation of IIH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/L (≤3 µg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free thyroxine (fT4) levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with the recovery of thyroid hormone levels by 12 weeks after the presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH. CONCLUSION: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/L at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

Hemorragia adrenal bilateral en paciente recuperado de neumonía COVID-19 Grave: caso Radiológico / Bilateral adrenal hemorrhage after severe COVID-19 infection: report of one case

We report a 47-year-old male with a severe disease caused by COVID-19, who required mechanical ventilation for 18 ays. During the hospital stay he received dexamethasone and anticoagulation with heparin. After discharge a new chest CT scan showed homogeneous hypo vascular enlargement of both adrenal glands, not present in the initial imaging studies. It was interpreted as a subacute bilateral adrenal hemorrhage. The patient remained stable and without any complaint.

Haemorrhagic shock from solid tumours of the adrenal gland: a case of bleeding primary adrenal lymphoma.

Suprarenal or adrenal gland haemorrhage is an uncommon but potentially lethal condition if unrecognised. Adrenal masses rarely present with haemorrhage, but they remain an important differential aetiology for adrenal bleeding. We present a novel case of primary adrenal lymphoma with adrenal haemorrhage in a middle-aged woman who presented with right-sided abdominal pain and class 1 haemorrhagic shock. She was found to have spontaneous unilateral adrenal gland haemorrhage in the absence of any underlying previous pathology. Presenting features, diagnosis and subsequent oncological management are reported.

Acute adrenal infarction as an incidental CT finding and a potential prognosis factor in severe SARS-CoV-2 infection: a retrospective cohort analysis on 219 patients.

OBJECTIVES: To retrospectively investigate the incidence of acute adrenal infarction (AAI) in patients who underwent chest CT for severe SARS-CoV-2 infection and to correlate findings with prognosis. METHODS: The local ethics committee approved this retrospective study and waived the need of informed consent. From March 9 to April 10, 2020, all patients referred to our institution for a clinical suspicion of COVID-19 with moderate to severe symptoms underwent a chest CT for triage. Patients with a/parenchymal lesion characteristics of COVID-19 involving at least 50% of lung parenchyma and b/positive RT-PCR for SARS-CoV-2 were retrospectively included. Adrenal glands were reviewed by two independent readers to look for AAI. Additional demographics and potential biological markers of adrenal insufficiency were obtained. Correlations with ICU stay and mortality were sought. RESULTS: Out of the 219 patients with critical (n = 52) and severe lung (n = 167) parenchyma lesions, 51 (23%) had CT scan signs of AAI, which was bilateral in 45 patients (88%). Four patients had an acute biological adrenal gland insufficiency (8%). Univariate analysis in AAI+ patients demonstrated a higher rate of ICU stay (67% vs. 45%, p < 0.05) and a longer stay (more than 15 days for 31% for AAI+ vs. 19%, p < 0.05) compared with AAI- patients. Mortality rate was similar (27%, p = 0.92). CONCLUSIONS: Acute adrenal infarction on initial chest evaluation of severe COVID-19 is frequent (51/219, 23%) and might be a sign of poorer prognosis. KEY POINTS: • Acute adrenal infarction on initial chest CT evaluation of severe COVID-19 is frequent (51/219). • AAI might be a factor of poorer prognosis, with increased rate of ICU hospitalization and length of stay.

Imaging spectrum of adverse events of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, are increasingly used for a variety of malignancies and have been linked to numerous treatment-related side effects known as immune-related adverse events (irAEs). IrAEs can affect multiple organ systems and are important to recognise in order to avoid misinterpretation as progressive tumour and to ensure appropriate management. In this pictorial review, we will briefly discuss radiological response criteria of immunotherapy and describe the imaging appearances of the wide spectrum of these ICI-associated toxicities.

Adrenal haemorrhage as a complication of COVID-19 infection.

We report an unusual complication of COVID-19 infection in a 53-year-old Caucasian man. He presented with shortness of breath, fever and pleuritic chest pain. A CT pulmonary angiogram (CTPA) demonstrated acute bilateral pulmonary embolism and bilateral multifocal parenchymal ground glass change consistent with COVID-19 (SARS-CoV-2) infection. Right adrenal haemorrhage was suspected on the CTPA which was confirmed on triple-phase abdominal CT imaging. A short Synacthen test revealed normal adrenal function. He was treated initially with an intravenous heparin infusion, which was changed to apixaban with a planned outpatient review in 3 months' time. He made an uncomplicated recovery and was discharged. Follow-up imaging nearly 5 months later showed near complete resolution of the right adrenal haemorrhage with no CT evidence of an underlying adrenal lesion.

Hormonal dysfunction in adult patients affected with inherited metabolic disorders.

Inherited metabolic disorders (IMDs ) are a rare and diverse group of metabolic conditions mainly caused by enzyme deficiencies, and in some of these, hormonal dysfunction is a relatively common complication. It may present in childhood and subsequently hormonal replacement is required throughout their life. Endocrinopathies can be a presenting symptom of an IMD in adulthood, which should be suspected when associated with multiorgan involvement (neurological, musculoskeletal or liver, etc.). A single IMD can affect any gland with hypogonadism, adrenal insufficiency, diabetes mellitus and thyroid dysfunction being the most common. In some cases, however, it is diagnosed later in their adult life as a secondary complication of previous therapies such as chemotherapy used during Haematopoietic Stem Cell Transplantation (HSCT) in childhood.The mechanisms of endocrine dysfunction in this group of conditions are not well understood. Regardless, patients require ongoing clinical support from the endocrine, metabolic, bone metabolism and fertility specialists throughout their life.Hormonal profiling should be part of the routine blood test panel to diagnose asymptomatic endocrine disorders with delayed manifestations. It is also worth considering screening for common hormonal dysfunction when patients exhibit atypical non-IMD related symptoms. In some adult-onset cases presenting with multiple endocrinopathies, the diagnosis of an IMD should be suspected.Given that new therapies are in development (e.g. gene therapies, stem cell therapies, pharmacological chaperone and substrate reduction therapies), clinicians should be aware of their potential long-term effect on the endocrine system.

Neonatal Adrenal Hemorrhage: A Case Series.

Neonatal adrenal hemorrhage (NAH) in newborn infants is a rare event that is associated with specific anatomical and vascular characteristics. It is more common in term infants and occurs more often in neonates who feature perinatal asphyxia. Symptoms that more frequently prompt to diagnosis are prolonged jaundice, detection of an abdominal mass, anemia, scrotal discoloration and/or swelling, hypotonia, lethargy, and hypertension. However, NAH may also occur without symptoms with its detection being occasional. Imaging through ultrasound scans is the cornerstone of diagnosis and follow-up monitoring over time. Here we report on a small NAH case series comprising three full-term, macrosomic infants who were born by vaginal delivery. The first and second ones showed clear signs of birth asphyxia, whereas the third was completely asymptomatic. In all three patients, only the right adrenal gland was involved, in line with what happens in 70% of cases. NAH is usually self-limiting and prone to a progressive resolution in a time ranging between 3 weeks and 6 months and so did in our three patients. KEY POINTS: · NAH is caused by perinatal asphyxia.. · It is diagnosed with addominal ultrasound.. · It is usually self-limiting..

Bilateral Adrenal Hemorrhage in Coronavirus Disease 2019 Patient: A Case Report.

CONTEXT: Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences such as acute adrenal insufficiency. Early adrenal axis testing, as well as directed imaging, is crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy and thromboembolic events. CASE DESCRIPTION: A 66-year-old woman presented with acute COVID-19 infection and primary adrenal insufficiency due to bilateral adrenal hemorrhage (BAH). She also had a renal vein thrombosis. Her past medical history revealed primary antiphospholipid syndrome (APLS). Four weeks after discharge she had no signs of COVID-19 infection and her polymerase chain reaction test for COVID-19 was negative, but she still needed glucocorticoid and mineralocorticoid replacement therapy. The combination of APLS and COVID-19 was probably responsible of the adrenal event as a "two-hit" mechanism. CONCLUSIONS: COVID-19 infection is associated with coagulopathy and thromboembolic events, including BAH. Adrenal insufficiency is life threatening; therefore, we suggest that early adrenal axis testing for COVID-19 patients with clinical suspicion of adrenal insufficiency should be carried out.

Stem cells, evolutionary aspects and pathology of the adrenal medulla: A new developmental paradigm.

The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation.

Case Report: COVID-19 with Bilateral Adrenal Hemorrhage.

A 70-year-old Dominican Republic man presented with lower back pain for 10 days. Fifteen days before pain onset, he had low-grade fever, chills, and asthenia, and 4 days before admission, he had constipation, malaise, generalized weakness, anorexia, nausea, and vomiting. On admission, the patient was afebrile and hypotensive, with a heart rate of 105 and an oxyhemoglobin saturation on room air of 95%. Hyponatremia, lymphopenia, elevated C-reactive protein, and ferritin were observed in complementary tests. Computed tomography (CT) scan showed findings consistent with COVID-19 bilateral bronchopneumonia, and an increase in size and blurring (loss of the Y shape) of both adrenals indicative of acute bilateral adrenal hemorrhage. The patient tested negative by reverse transcription polymerase chain reaction (RT-PCR) of nasopharyngeal swab, yet positive for IgG and IgM by ELISA, suggesting COVID-19 diagnosis.

Bilateral adrenal haemorrhage secondary to rivaroxaban in a patient with antiphospholipid syndrome.

A 46-year-old man with antiphospholipid syndrome (APS) and previous pulmonary embolism on anticoagulation with rivaroxaban was brought in to the hospital after a syncopal episode. He was found to be hypotensive and tachycardic and later admitted to the intensive care unit. Clinical presentation and laboratory findings were consistent with adrenal insufficiency. MRI revealed bilateral adrenal haemorrhage and he received appropriate steroid replacement therapy. Symptoms slowly subsided and anticoagulation regimen was changed to warfarin. Adrenal haemorrhage was likely caused by APS and rivaroxaban, which brings into question whether novel oral anticoagulants are safe in this patient population.

A pictorial review of non-traumatic adrenergic crisis.

Non-traumatic adrenal crisis is a rare but critical diagnosis to make in emergency settings due to grave consequences. Various pathologies can present as acute crisis, such as spectrum of endocrine imbalance, ranging from catecholamine excess in pheochromocytomas to acute adrenal insufficiency related to glandular dysfunction. Critical manifestations may be due to structural causes related to adrenal hemorrhage, especially when they are bilateral. Oncological complications such as vascular invasion, tumoral bleed, rupture, and hormonal dysfunction can occur. Due to non-specific clinical presentation, these conditions may come as a surprise on imaging performed for other reasons. Recognition of these imaging findings is critical for appropriate patient management. Although there are few articles discussing non-traumatic emergencies in literature, this review is inclusive of all possible etiologies, thus provides a holistic approach and insight into each situation. Specific imaging approach is needed to tailor the diagnosis. This article will also discuss about the advanced imaging techniques that will complement diagnosis.