Adrenal Hemorrhage

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Adrenal Hemorrhage

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Adrenal hemorrhage is a relatively uncommon condition with a variable and nonspecific presentation that may lead to acute adrenal crisis, shock, and death unless it is recognized promptly and treated appropriately. [1, 2] Several risk factors have been associated with adrenal hemorrhage, based on case reports. Its pathologic characteristics typically include bilateral gland involvement with extensive necrosis of all 3 cortical layers and of medullary adrenal cells. Retrograde migration of medullary cells into the zona fasciculata, widespread hemorrhage into the adrenal gland that may extend into the perirenal fat, and, frequently, adrenal vein thrombosis may occur.

CT scan appearance is shown in the image below.

Although the precise mechanisms leading to adrenal hemorrhage are unclear in nontraumatic cases, available evidence has implicated adrenocorticotropic hormone (ACTH), adrenal vein spasm and thrombosis, and the normally limited venous drainage of the adrenal in the pathogenesis of this condition.

The adrenal gland has a rich arterial supply, in contrast to its limited venous drainage, which is critically dependent on a single vein. Furthermore, in stressful situations, ACTH secretion increases, which stimulates adrenal arterial blood flow that may exceed the limited venous drainage capacity of the organ and lead to hemorrhage.

In addition, adrenal vein spasm induced by high catecholamine levels secreted in stressful situations and by adrenal vein thrombosis induced by coagulopathies may lead to venous stasis and hemorrhage. Adrenal vein thrombosis has been found in several patients with adrenal hemorrhage, and it may occur in association with sepsis, heparin-induced thrombocytopenia, [3] primary antiphospholipid antibody syndrome, or disseminated intravascular coagulation (DIC).

Regardless of the precise mechanisms, extensive, bilateral adrenal hemorrhage commonly leads to acute adrenal insufficiency and adrenal crisis, unless it is recognized and treated promptly.

United States

Adrenal hemorrhage has been reported in 0.3-1.8% of unselected cases in autopsy studies, although extensive bilateral adrenal hemorrhage may be present in 15% of individuals who die of shock.

Acute adrenal insufficiency (adrenal crisis) may occur in association with extensive, bilateral adrenal hemorrhage, and it is uniformly fatal if unrecognized and untreated. In contrast, unilateral adrenal hemorrhage is not associated with acute adrenal insufficiency.

Patients with adrenal hemorrhage may die because of underlying disease or diseases associated with adrenal hemorrhage, despite treatment with stress-dose glucocorticoids. Overall, adrenal hemorrhage is associated with a 15% mortality rate, which varies according to the severity of the underlying illness predisposing to adrenal hemorrhage. For example, patients with Waterhouse-Friderichsen syndrome (adrenal hemorrhage occurring in sepsis, most frequently meningococcal) have a 55-60% mortality rate. [4]

Chronic adrenal insufficiency occurs in most patients who survive extensive, bilateral adrenal hemorrhage, necessitating long-term glucocorticoid replacement. In contrast, the need for mineralocorticoid replacement is variable. Androgen replacement therapy may also be beneficial in women with chronic adrenal insufficiency. Rare case reports exist of patients who had complete recovery of adrenal function after an episode of extensive, bilateral adrenal hemorrhage and acute adrenal insufficiency.

Extensive, bilateral adrenal hemorrhage is more common in males (male-to-female ratio of 2:1), probably reflecting a male predilection for several of the underlying conditions associated with adrenal hemorrhage.

Although adrenal hemorrhage may occur in people of any age, most patients with nontraumatic, extensive, bilateral adrenal hemorrhage are aged 40-80 years at the time of the acute event. In contrast, patients with traumatic adrenal hemorrhage typically are in the second to third decade of life.

Most patients with Waterhouse-Friderichsen syndrome are in the pediatric age group, although adults have infrequently been affected.

Adrenal hemorrhage in neonates is a well-described entity and has even been diagnosed in utero. A full discussion of this entity is beyond the scope of this review.

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Nicholas A Tritos, MD, DSc, MMSc, FACP, FACE Associate Professor of Medicine, Harvard Medical School; Associate in Medicine, Neuroendocrine Clinical Center, Massachusetts General Hospital

Nicholas A Tritos, MD, DSc, MMSc, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Medical Association, Endocrine Society, Massachusetts Medical Society, Pituitary Society

Disclosure: Received research grant from: Ipsen; Pfizer; Novo Nordisk; Novartis.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Dimitris A Papanicolaou, MD 

Dimitris A Papanicolaou, MD is a member of the following medical societies: American College of Physicians, Endocrine Society, Royal Society of Medicine

Disclosure: Nothing to disclose.

Adrenal Hemorrhage

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