Refractory hypothyroidism due to enteral malabsorption of levothyroxine after cholecystectomy

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Management of hypothyroidism may be challenging due to malabsorption or non-adherence. Replacement of enteral dose is 1.6-1.8mcg/kg with intestinal absorption of 70-80%. Some patients require higher doses of levothyroxine (LT4 > 1.9mcg/kg). Various gastrointestinal disorders that lead to malabsorption or loss of intestinal secretions may result in higher requirement. We present a case of refractory hypothyroidism despite large doses of oral levothyroxine due to malabsorption of oral LT4. A 60-year old, 130 kg female presented with fatigue and intermittent diarrhea, with TSH 206 uIU/ml (0.45-5.33 uIU/ml) and FT4 < 0.25 ng/dl (0.61-1.44 ng/dl). She had had total thyroidectomy and radioiodine treatment at outside institution for papillary thyroid microcarcinoma and had normal thyroid function tests on standard doses of LT4 until she underwent cholecystectomy. She reported intermittent diarrhea and abnormal thyroid function tests (TSH 206 uIU/ml) following cholecystectomy. Her doses were increased gradually and she was taking LT4 1200 mcg and lliothyronine 25mcg orally daily on an empty stomach without missed doses when she presented. Extensive gastrointestinal evaluation failed to reveal any evidence of malabsorption. She was hospitalized multiple times for severe symptomatic hypothyroidism. LT4 absorption tests revealed poor enteral absorption. Subcutaneously administered LT4 did not result in a rise in FT4 or TT4. She responded to twice weekly intravenous 300mcg LT4 and daily 600 mcg LT4 soft gel capsules, with TSH improving to 18uIU/ml and FT4 0.68ng/dl. Hypothyroidism in our patient was refractory to large doses of oral LT4 and responded to intravenous but not subcutaneous LT4. Studies indicate possible hypotheses including intestinal malabsorption of LT4 due reduction in bile salts after cholecystectomy, type 3-deiodinase overexpression and altered intestinal microbiota. About 10-20% of hypothyroid patients require greater than weight based amounts of LT4 for unknown reasons. We recommend early initiation of parenteral LT4 therapy to reduce morbidity. More studies are needed to evaluate mechanism of enteral LT4 malabsorption in such refractory cases.



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