A 35-year-old woman is evaluated for a 3-month history of appetite loss, fatigue, weight loss, and abdominal pain. She has no chronic medical conditions and takes no medications. While undergoing upper gastrointestinal endoscopy, the patient develops cardiovascular collapse and dies, despite aggressive resuscitative measures. On autopsy, increased pigmentation is noted around the nipple areola and anal and vaginal mucous membranes. Which of the following additional findings are most likely to be seen on autopsy?
Primary adrenal insufficiency | |
Etiology |
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Clinical features |
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Laboratory findings |
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This patient with a three month history of weight loss, abdominal pain, and fatigue developed cardiovascular collapse during a medical procedure (endoscopy), which suggests chronic adrenal insufficiency complicated by acute adrenal crisis. Severe physiologic stress (eg, infection, medical procedures) normally induces increased glucocorticoid production; however, patients with adrenal insufficiency are unable to increase production. Adrenal crisis (eg, hypotension, shock) is rapidly fatal if unrecognized.
Adrenal insufficiency can be caused by dysfunction of either the adrenal glands (primary) or pituitary (secondary). This patient's concomitant skin hyperpigmentation is highly suggestive of chronic primary adrenal insufficiency (PAI), as the resulting cortisol deficiency leads to increased ACTH secretion. ACTH is derived from proopiomelanocortin (POMC), the same prohormone from which melanocyte-stimulating hormone (MSH) is derived. Increased ACTH also leads to increased MSH secretion, which results in hyperpigmentation.
Autoimmune adrenalitis is the most common cause (>90%) of chronic PAI and occurs due to autoantibody formation, resulting in atrophy of the bilateral adrenal glands. It can occur as an isolated disorder or in association with other autoimmune syndromes (eg, hypothyroidism, vitiligo).
(Choice B) Bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome [WFS]) can cause PAI and adrenal crisis but is typically seen acutely in the setting of bacterial sepsis (eg, Neisseria meningitidis). However, hyperpigmentation occurs in chronic adrenal insufficiency and therefore would not be expected with WFS.
(Choices C and D) Ischemic necrosis of the pituitary (Sheehan syndrome) most commonly occurs due to hypoperfusion of the enlarged pituitary gland during childbirth. Acute pituitary hemorrhage (pituitary apoplexy) typically occurs in patients with pituitary adenomas. These conditions can cause central (secondary) adrenal insufficiency; however, hyperpigmentation is not seen because ACTH levels are low, and POMC levels are not increased.
(Choice E) A cortisol-producing adrenal tumor can cause contralateral adrenal atrophy due to suppression of ACTH secretion; however, it would not be associated with hyperpigmentation and would manifest as hypercortisolism rather than adrenal insufficiency.
Educational objective:
Primary adrenal insufficiency (PAI) is characterized by weight loss, abdominal pain, fatigue, and hyperpigmentation. Physiologic stress in patients with PAI can trigger acute adrenal crisis (eg, fever, shock, mental status changes). Autoimmune adrenalitis is the most common cause of PAI and leads to bilateral adrenal atrophy.