Lactose Intolerance Revealed by Severe Resistance to Treatment with Levothyroxine Manuel Mun ˜ oz-Torres, Mariela Varsavsky, and Guillermo Alonso The most common cause of apparent ineffectiveness or resistance to treatment with oral levothyroxine (LT 4 ) is the result of noncompliance, known as pseudomalabsorption. However, an abnormality in the bioavailability of LT 4 should also be considered in patients requiring large doses of LT 4 to achieve euthyroidism. The incidence of lactose intolerance in Caucasian adult patients is 7%–20%, but the association with resistance to treatment with oral LT 4 is unusual. We report a 55-year-old woman in whom treatment LT 4 for hypothyroidism was found related to a previously undiagnosed oligo-symptomatic lactose intolerance, an unusual association. Although rare, intolerance to lactose should be considered in the differential diagnosis of gastrointestinal diseases that can cause malabsorption of LT 4 . The possibility of correcting this disorder with simple dietary measures justifies its consideration. Introduction A dequate absorption of levothyroxine (LT 4 ) provides the basis of oral replacement therapy of hypothyroid- ism. When serum thyroid-stimulating hormone (TSH) levels remain increased despite an adequate dose of LT 4 , failure to take the drug seems to be a likely explanation. However, the possibility of true malabsorption of LT 4 , as well as other disorders that might cause increased LT 4 requirements should be taken into account before considering the patient as noncompliant. We describe an unusual case of LT 4 mal- absorption in a patient with previously overlooked lactose intolerance. Case Report A 55-year-old woman was referred to our clinic for com- plaints including cold intolerance, fatigue, dry skin, in- creasing weight, husky voice, hair loss, slow speech, and mental and physical lethargy. The patient had been di- agnosed as having primary hypothyroidism (autoimmune thyroiditis) approximately 1 year prior to the referral. Her serum TSH was greater than 75 mUI=mL (normal range, 0.4– 4 mUI=mL) and her free thyroxine (FT 4 ) 0.2 ng=dL (normal range, 0.8–1.9 ng=dL). Oral thyroid hormone replacement was initiated with a daily dose of 100 mg LT 4 (LevothroidÒ, Forest Pharmaceuticals, Inc., St. Louis, MO). No decrease in serum TSH was observed in the 6-month follow-up. Subse- quently, the LT 4 dosage was raised stepwise up to 900 mg daily in a period of 8 months and a challenge with triio- dothyronine alone and in combination with LT 4 was still unable to normalize the serum TSH. The patient also had a history of essential hypertension (enalapril, 20 mg plus dox- azosin 10 mg) and stable angina pectoris. She also had spo- radic episodes of watery diarrhea that had started 7–8 years before, however no specific diagnostic tests had been per- formed. There was no family history of thyroid or other relevant diseases. She had no other concomitant medication that could interfere with LT 4 absorption or metabolism. LT 4 pseudo-malabsorption or malabsorption was suspected and therefore the patient was hospitalized for further testing. Physical examination on admission showed body mass index 31 kg=m 2 , blood pressure 150=90 mm Hg, and bradycardia (58 beats per minute); palpation of thyroid gland revealed no abnormalities. Initial ancillary test results were electro- cardiogram (ECG) with sinus bradycardia and chest x-rays showing cardiomegaly. Laboratory tests revealing serum TSH greater than 75 mU=mL; FT 4, 0.10 ng=dL, and free triio- dothyronine (FT 3 ) 0.6 pg=mL (normal range, 1.4–4.4 pg= mL); the antithyroid peroxidase antibodies were positive (6000 IU=mL; normal range, < 150). Anti-TSH receptor anti- bodies and antithyroglobulin antibodies were negative. Se- rum total cholesterol levels were 268 mg=dL, high-density lipoprotein-cholesteraol (HDL-c), 36 mg=dL; low-density lipoprotein-choloesterol (LDL-c), 176 mg=dL; creatine kinase, 471 IU=l (normal range, 96–140 IU=L); aldolase, 15 IU=L (normal range, 1.5–12 IU=L); lactate dehydrogenase (LDH), 579 IU=L (normal range, 210–420 IU=L). Other hematologic, biochemical, and hormonal parameters were normal. The patient denied that she was noncompliant with the LT 4 therapy. We confirmed the ingestion of tablets (300 mg daily) under direct observation for 10 days. There was no serum FT 4 increase after that period. Then intestinal malabsorption Department of Endocrinology, Hospital Universitario San Cecilio de Granada, Granada, Spain. THYROID Volume 16, Number 11, 2006 ª Mary Ann Liebert, Inc. 1171