Abnormalities in iron metabolism clouded the final diagnosis in a patient with autoimmune polyglandular syndrome. A 20-year-old man presented with a 1-week history of fatigue, sore throat, vomiting, and constipation. He also reported subacute constitutional weakness and darkening of the palmar creases and the nape of his neck in the 9 months prior to presentation. After an episode of presyncope in the setting of worsening nausea and vomiting, he presented to an acute care center and was found to be profoundly hypoglycemic (glucose, 37 mg/dL) and hypotensive (88/46 mmHg). Laboratory results revealed hyponatremia (106 mEq/L) and hyperkalemia (4.7 mEq/L)
At 13-years-old, our patient had an episode of Bell’s palsy that was attributed to Lyme disease. He denied use of medications, drug allergies, and sexual activity, and his travel history was limited to the Midwest and East Coast of the United States. His mother and sister had Hashimoto’s thyroiditis, and a maternal uncle had type I diabetes.
Assessment
On physical examination, the patient was a thin young man with mild diffuse hyperpigmentation and dry mucous membranes. His serum cortisol level was undetectable and his adrenocorticotrophin level was elevated. A cosyntropin stimulation test failed to increase cortisol levels into the detectable range at 30 or 60 minutes. He also had an elevated thyroid-stimulating hormone level of 124 mcIU/mL and a low free thyroxine level of 0.2 ng/dL. Abdominal computed tomography (CT) with contrast demonstrated abnormally small adrenal glands (between 1-2Â gm each; normal, 5 gm) without evidence of hemorrhage, calcification, or masses
Antithyroid antibodies (antithyroglobulin and antithyroid microsomal antibodies) were markedly positive, although antiadrenal antibodies were negative. Plasma renin activity was high, and aldosterone was undetectable, consistent with mineralocorticoid deficiency. Histoplasmosis, HIV infection, hepatitis, and syphilis were ruled out with serologic testing. Very long fatty acid chain levels were negative, excluding adrenoleukodystrophy. The patient had no evidence of diabetes mellitus, with a normal hemoglobin A1c percentage and a negative test result for anti-islet cell antibodies. No clinical or biochemical evidence of hypogonadism was identified.
Other unusual findings arose in the course of our evaluation. On CT, the liver demonstrated increased attenuation (75-80 Hounsfield units; normal, 60 HU), suggesting iron deposition. Serum testing showed an elevated ferritin, iron, and percent transferrin saturation with a normal transferrin and total iron-binding capacity. Ceruloplasmin and copper levels were within normal limits. Cardiac magnetic resonance imaging (MRI) showed no evidence of excess iron, but a hepatic FerriScan (Resonance Health, Claremont, Western Australia), which uses MRI to gauge liver iron concentration, displayed a diffuse signal at the upper limit of the reference range, a finding consistent with possible iron deposition (1.8 mg/g dry tissue; normal range, 0.17-1.8). Concurrently, a blood smear disclosed dysplastic neutrophils, erythroid precursors, and otherwise normochromic/normo-cytic anemia with occasional teardrops. Other test results—lactate dehydrogenase, B12, folate, methylmalonic acid, lead, homocysteine, haptoglobin, and a hemoglobin-opathy analysis—were within the reference range.
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-Bridget P. Keenan, MD, PhD, Swaytha Yalamanchi, MD, Steven Hsu, MD, Kelly Norsworthy, MD, Todd T. Brown, MD, PhD
This article originally appeared in the January 2016 issue of The American Journal of Medicine.
