SUN-535 Direct Observational Treatment (DOT) With Levothyroxine Absorption Test in Persistently Elevated TSH levels—Refractory Hypothyroidism: Experience With Three Cases

Abstract F.T. Masood: None. Z. Kiran: None. A. Baloch: None. M. Khan: None. Direct Observational Treatment (DOT) With Levothyroxine Absorption Test in Persistently Elevated TSH levels—Refractory Hypothyroidism: Experience With Three Cases. Background: Hypothyroid individuals require lifelong Levothyroxine (LT4) therapy. Persistently elevated TSH is a common clinical problem in patients treated with LT4, some of them fail to attain normal biochemical Euthyroid status despite LT4 dose titration in excess of weight-based calculations.LT4 absorption test is utilized to distinguish LT4 malabsorption from pseudo-malabsorption like intentional non-adherence, taking sub-therapeutic dose or interaction with certain foods and drugs. Clinical Cases: We observed three outpatient cases (two females and one male) ages between 31 to 61 years with hypothyroidism and no obvious cause of malabsorption, drug interaction or use of calcium or iron supplements. They were receiving doses of LT4 which varied from 500 mcg to 850 mcg and had TSH levels between 19.4 and 50 uIU/ml (N=0.4-4.2 uIU/ml). They all underwent an observed administration of 1000 μg of LT4 (standard weekly dose worked out on the basis of BMI<40 kg/m2, age=18-65yrs) with blood tests at baseline and 4 hours after LT4 ingestion on same day. In all three patients we continued the weekly therapy for four weeks and measurement of TSH and T4 levels at four weekly intervals. Percentage absorption was calculated using the following formula, with normal absorption being ≥60%:% Absorbed = Increment T4 (mcg/dl) x 10 (dl/L)/T4(mcg) x Vd(L) x 100 Increment T4 = peak T4 - baseline T4Volume of distribution Vd (L) = 0.442 x BMIAll patients had a peak two-fold increase from baseline of their T4 after administration of 1000 μg of LT4. The subsequent results over the course of four weeks supervised dosing showed TSH stabilized within normal limits or showed improved results. The rapid rise in the T4 level and showing percentage absorption ranging from 71-80% after taking LT4 essentially ruled out its malabsorption. Directly Observed Therapy has the advantage of close monitoring that may improve adherence to treatment and achieving targeted TSH levels. One out of three patients showed persistent clinical follow-up for two years. Clinical Lessons: Simple and cost effective DOT can be used as tool to detect patients’ noncompliance as one of the causes of poor control of hypothyroidism. Using DOT will make patients compliant as inconvenience of taking the medication daily in a fasting state and a forced delayed breakfast are no longer required and patients can take other medications without fear of drug interaction. DOT for 4 to 6 weeks improves control of hypothyroidism and also help differentiating between malabsorption and patients’ noncompliance. Once-weekly LT4 with doses 1000 ug have been shown to be a safe treatment alternative to standard daily LT4 therapy for treating refractory hypothyroid patients. Sunday, June 2, 2024