Hypoparathyroidism and Subclinical Hypothyroidism with Secondary Hemochromatosis
A 29-year-old female admitted to our hospital for evaluation of asymptomatic hypocalcemia. Fifteen years ago she was diagnosed with aplastic anemia, treated with antilymphocyte globulin and antithymocyte globulin, and had routine transfusions of RBCs of 2 units per week (about 1,400 units over 15 years). In addition, starting 10 years ago, selective iron-chelating agent (deferasirox 1,500 mg/day) was administered due to increased serum ferritin levels. Continued hypocalcaemia was detected in blood tests at regular follow-up visits and the patient visited the endocrinologic department as an outpatient for additional examinations and treatment. She has no histories of cervical irradiation, thyroid disease or related family history. She had a blood pressure of 120/80 mm Hg, pulse rate of 78 beats per minute, temperature of 36.8℃, and a respiratory rate of 20 breaths per minute. Her skin was unusually dark in color with conjunctiva pallor. Chest examination showed that breathing was clear, heartbeat was regular and no unusual sounds were detected. Her abdomen was flat and soft with no unusual sounds, and the liver and spleen were not palpated. Neither leg had pitting edema. Neurological tests showed no local neurological symptoms, Chvostek sign or Trousseau sign.\nIn the laboratory findings, peripheral blood test indicated a white blood cell count of 700/mm3 (neutrophil 150), hemoglobin level of 8.0 g/dL, and platelet count of 37,000/mm3. A serum biochemical test reported blood urea nitrogen levels of 10.1 mg/dL, serum creatinine of 0.7 mg/dL, albumin levels of 3.9 g/dL, aspartate aminotransferase levels of 53 IU/L, alanine aminotransferase levels of 60 IU/L, alkaline phosphatase of 94 IU/L, and total bilirubin of 0.5 mg/dL. In a serum electrolyte test, sodium level was 140 mEq/L and potassium level was 4.3 mEq/L, both of which are in the normal range. However, total calcium was 6.7 mEq/dL (albumin corrected calcium 6.78 mEq/dL; normal range, 8.4 to 10.2), and ionized calcium was 1.78 mEq/L (normal range, 2.2 to 2.6). Serum ferritin levels were 27,583.03 ng/mL (normal range, 4.63 to 274.6), iron levels were 291 µg/dL (normal range, 65 to 157), and total iron binding capacity was 389 µg/dL (normal range, 256 to 426) which showed an increase. The transferrin saturation level was high to 74.8% (normal range, 22% to 46%).\nShe was diagnosed with hypocalcaemia induced by hypoparathyroidism based on test results showing intact parathyroid hormone (iPTH) levels of 31 pg/mL (normal range, 9 to 55), 25(OH)VitD of 7.03 ng/mL (normal range, 4.8 to 52.8), and 1,25(OH)2VitD levels of 36.2 pg/mL (normal range, 25.1 to 66.1). Although 1,000 mg of calcium carbonate and 0.5 µg of alfacalcidol were given twice a day, hypocalcaemia continued with increased levels of 24 hours urine calcium (700 mg/day) and 24 hours urine creatinine (0.99 g/day); thiazide 12.5 mg was also administered to maintain the total calcium at 7.5 to 8.0 mEq/dL and ionized calcium at 1.9 to 2.2 mEq/L. Tests were performed to determine if the hemochromatosis had spread to other organs; chest X-rays showed no signs of cardiomegaly, but computed tomography (CT) before contrast enhancement showed thyroid (Hounsfield unit 157.0) and liver (Hounsfield unit 136.0), as well as a increased signal intensity associated with the cardiac muscle and enlarged inferior vena cava and hepatic veins (). The T2-weighted magnetic resonance imaging (MRI) of the abdomen revealed a dark signal intensity in the liver, spleen, bone marrow, and pancreas, leading to the secondary diagnosis of hemochromatosis (). Organs showing signs of iron impregnation were tested for function; the thyroid function test showed elevated levels of thyroid stimulating hormone (TSH, 17.18 µIU/mL; normal range, 0.4 to 4.8) with free thyroxine levels of 1.28 ng/dL (normal range, 0.8 to 1.71), and triiodothyronine levels of 1.43 ng/mL (normal range, 0.6 to 1.6). Thyroid peroxidase antibody and thyroglobulin antibody were both negative which resulted in apparent hypothyroidism caused by hemochromatosis. The patient was receiving low-dose of thyroid hormone (levothyroxine 50 µg/day), but her TSH levels were still over 10 µIU/mL at follow-up. Therefore the dose of the hormone was gradually increased. The most recent test result showed TSH levels of 8.12 µIU/mL, and the dose of thyroid hormone was increased to 150 µg/day for follow-up observation. Echocardiography revealed dilated left ventricular chamber size (left ventricular end diastolic diameter 54 mm) with global hypokinesia, and a moderate to severe left ventricular systolic dysfunction (ejection fraction 23%), which suggests congestive heart failure with dilated cardiomyopathy and restrictive diastolic dysfunction induced by hemochromatosis. The patient is medicated with digoxin 0.1875 mg, candesartan 8 mg, bisoprolol 2.5 mg, and spiractone 25 mg without any significant symptoms and is on follow-up observation as an outpatient.