Background: Cystic fibrosis (CF), a monogenic disease from mutations in the CFTR gene on chromosome 7, causes pancreatic insufficiency and impaired nutrients absorption. Unlike other malabsorption disorders, no data are available in literature on L-T4 absorption in CF. This study analyzed L-T4 absorption and requirement in hypothyroid CF patients.
Methods: Ten CF patients (7 F, 3 M; mean age 37 yr), with autoimmune (n=6) or post-thyroidectomy (n=4) hypothyroidism, were administered L-T4 tablets. None took medications known to alter L-T4 absorption or metabolism. Fifty age- and sex-matched subjects (43 F, 7 M; mean age 40 yr), with either autoimmune (n=25) or post-operative (n=25) hypothyroidism, served as internal reference group. All patients were advised to take oral L-T4 (starting dose 1.6 μg/kg/daily) at morning under fasting, at least 1 h before breakfast. Target serum TSH values were 0.53.0 μIU/ml, according to patients age. In each patient, serum TSH and FT4 were measured at enrolment, 8 weeks after starting L-T4 and 4 weeks after every dose adjustment. Two CF patients (1F and 1 M) volunteered for an acute loading test of 600 μg L-T4.
Results: At enrolment, the 6 CF patients with HT had subclinical hypothyroidism (median TSH 6.1 uIU/ml; range 5.210) and the 4 patients who had undergone thyroidectomy were overt hypothyroid (median TSH 26.5 μIU/ml; range 1161, on discharge). L-T4 was started as described. After 8 weeks, all CF patients had inappropriately high serum TSH (median 5.2 μIU/ml vs 2.0 μIU/ml in controls) despite an adequate L-T4 daily dosage, indicating T4 malabsorption. In such patients L-T4 dose has been increased by 25% to 50% or more (2.0 to 5 μg/kg/d) depending on the aetiology (autoimmune/post-operative) compared to controls (median dose 1.68 μg/kg/d; P=0.001). Also, target serum TSH (median 2.95 μIU/ml) was reached in 10±3 months compared to 4±2 months in controls (P=0.001). In the two patients participating to the acute loading test, T4 pharmacokinetic indices (total T4 at 0=4.38 μg/dl, normal values 5.114.1; Cmax =5.62 μg/dl, AUC 04 h=21.97 μg/dl) were compatible with malabsorption.
Conclusions: These preliminary observations provide the first evidence of increased need for T4 in CF patients. CF should be included among the digestive diseases causing intestinal malabsorption of L-T4, likely due to the combination of pancreatic insufficiency, chronic intestinal inflammation and reduced production of biliary salts.
18 - 21 May 2019
European Society of Endocrinology