Adrenal Insufficiency as the First Manifestation of AA Amyloidosis in a Patient with Familial Mediterranean Fever: A Case Report

Background: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease, and AA amyloidosis is its most severe complication. While AA amyloidosis predominantly affects the kidneys, adrenal involvement is exceptionally rare and infrequently reported.

Case Presentation: A 32-year-old man on chronic hemodialysis for end-stage renal failure due to amyloid nephropathy was referred for chronic abdominal pain, hypercalcemia (> 115 mg/L), hyponatremia (130 mmol/L), and severe intradialytic hypotension. He reported that his typical FMF attacks had ceased after starting hemodialysis; however, he had recently developed new, continuous symptoms, including intense asthenia and chronic abdominal pain. Physical examination revealed progressive hyperpigmentation on sun-exposed areas. Endocrinological work-up confirmed primary adrenal insufficiency (very high ACTH with low cortisol). An abdominal CT scan showed bilateral adrenal calcifications. The patient's history included recurrent febrile episodes since childhood and a family history suggestive of FMF. AA amyloidosis was confirmed via salivary gland biopsy, and genetic testing revealed a homozygous M694I mutation in the MEFV gene. The patient was started on hydrocortisone replacement therapy. Despite initial improvement, he died one year later from complications related to advanced AA amyloidosis, including severe diarrhea and malnutrition.

Conclusions: This case illustrates the rare occurrence of adrenal insufficiency due to AA amyloidosis in FMF. It highlights the need to screen for adrenal insufficiency in dialysis patients presenting with chronic abdominal pain, unexplained hypercalcemia, or intradialytic hypotension. The presence of adrenal calcifications on abdominal CT should raise suspicion for this diagnosis. Most importantly, this case underscores that FMF is prevalent in Algeria and that AA amyloidosis and its devastating complications can be prevented by early initiation of colchicine therapy in childhood. Increased awareness and early diagnosis are crucial to avert such tragic outcomes.