A 48-year-old previously healthy black man presented with lightheadedness, painful bilateral neck swelling and 40-pound weight loss over two months, along with multiple fainting spells. On exam, he had severe orthostatic hypotension and tender cervical lymphadenopathy. He appeared to be euvolemic and rest of the physical examination was normal. His serum sodium was 119 mmol/L, serum osmolality 256 mOsm/kg and urine osmolality 817 mOsm/kg, which were indicative of a high anti-diuretic hormone state. Magnetic resonance imaging of head and neck was significant for bilateral enlarged cervical lymph nodes. Computed tomography of chest, abdomen, and pelvis did not reveal malignancy, but did, however, have prominent cardiophrenic, retroperitoneal and mediastinal lymph nodes. Urinalysis revealed nephrotic range proteinuria.
He was treated with free water restriction and salt tablets which led to gradual resolution of hyponatremia. Orthostatic hypotension was refractory despite treatment with fludrocortisone. Serum protein electrophoresis revealed a small M-spike which was consistent with IgG lambda on immunofixation. Excisional biopsy of an inguinal lymph node revealed amyloid deposition. Bone marrow biopsy showed amorphous proteinaceous waxy material consistent with amyloid which stained strongly with Congo red stain. There were 8% plasma cells. Mass spectrometry of the lymph node confirmed AL type of amyloid. Peripheral blood smear revealed normocytic, normochromic anemia with Howell-Jolly bodies leading to inference that he had functional asplenia due to splenic amyloid deposition. Transthoracic echocardiogram was significant for mild concentric hypertrophy of the left ventricle with a preserved ejection fraction. He continues to be severely orthostatic resulting in multiple syncopal episodes. Currently, he is being evaluated for autologous hematopoietic stem cell transplantation.
Amyloidosis is the deposition of abnormal protein fibrils in tissues and organs. These mutated fibrils undergo conformational change that renders them misfolded and insoluble. Types include primary (AL), secondary (AA) or hereditary (ATTR). The most common variant is AL amyloid, which arises from a monoclonal B-cell disorder and consists of amyloidogenic immunoglobulin light chains. Amyloidosis is a devastating, multi-system disorder affecting mainly the kidneys, heart and the nervous system. Nephrotic range proteinuria, congestive heart failure, sensorimotor neuropathy are common manifestations of this disease. Orthostatic hypotension and syncope are rare, but have been reported in association with amyloidosis, for which the mechanism is unclear. It has been postulated that compression neuropathy due to amyloid deposits within the nerve and ischemia due to amyloid deposition in the blood vessel wall supplying the nerve lead to autonomic neuropathy which causes orthostatic hypotension. In addition, cardiac involvement may also contribute to it.
Amyloidosis is a great mimic and manifests in multiple organ systems. Amyloidosis should be considered in the differential diagnosis in cases with the unusual constellation of refractory orthostatic hypotension, lymphadenopathy and hyponatremia.