Lean body mass based levothyroxine supplement lessens deterioration of cardiac function and exercise capacity in radioiodine ablated differentiated thyroid carcinoma patients

Abstract

Conventional supplement therapy of levothyroxine (LT4) for differentiated thyroid carcinoma (DTC) keeps the patient in subclinical hyperthyroid state, which affects the heart activity and lowers exercise capacity. Lean body mass (LBM) has been recently suggested as best determinant of LT4 supplement dosing in patients with DTC. The present study was done to optimize the dose of LT4 in low risk group (T1, N0, M0) of patients with DTC and thereby preventing the adverse cardiac effects and improve exercise capacity. The importance of dose adjustment of LT4 based on lean body mass has not been properly addressed before. Sixty patients with differentiated (papillary) thyroid carcinoma (young age group) without any signs of metastases, previous cardiac problems and chronic disease were consecutively enrolled in the study. They were referred to Institute of Nuclear Medicine and Ultrasound, Dhaka during the year 2007-2009 from different district Hospitals of Bangladesh. All patients had undergone total thyroidectomy and then received about 100 m ci radioiodine ablative therapy and subsequently 200 μ gm LT4 daily for initial 2 months. Age, weight, height, body surface area, body mass index and life style matched 23 healthy euthyroid volunteers were also selected. All clinical, biochemical, echocardiographic and Exercise Tolerance Test (ETT) data of healthy adults control were obtained for comparison with patients at baseline study after two months of radioiodine ablative therapy and on LT4 replacement on conventional 200 μ gm/day at first follow up visit. Then 60 patients were grouped as Group-I and Group-II, each group consisted of 30 patients. Thirty patients of Group-I had undergone dual energy X-ray absortiometry (DXA) investigation to estimate lean body mass and received optimized LT4 dose depending on lean body mass (about 131± 23 μ gm/day, 3.5-4 μ gm/kg/ LBM/day). In Group-II, 30 patients continued the conventional fixed dose of LT4 (200 μ gm/day). Patients of both groups were followed up clinically and hormone assay were done at 3 months interval. At 6-12 months of LT4 supplement (conventional and LBM based) all study parameters (Symptom Rating Score, hormone data, echocardiographic data and ETT) were reevaluated. Serum FT3 (Group-I, 5.5±1.3 p mol/L; Group-II,10.1±1.3 p mol/L, *p < 0.001), FT4 (Group-I,17.9 ±1.9 p mol/L; Group-II, 27.4±0.94 p mol/L; *p < 0.001) were higher and TSH (Group-I, 0.1±0.01 mIU/L; Group-II, 0.09±0.05 mIU/L; *p < 0.001) was suppressed in patients with DTC at conventional LT4 dose (200 μ gm/day) compared to healthy control and patients with optimized dose of LT4 (mean±SD, 131± 23 μgm/day) of Group-I at second visit. Symptom Rating Scale score (SRS, Group–I, 2±1, Group-II, 8±1, at second visit; *p < 0.001), heart rate (Group-I, 87±14 beats/min, Group-II, 100±20 bpm, at second visit; *p < 0.003). SBP (Group-I, 114±7 mm Hg, Group-II, 119±8 mm Hg, at second visit), DBP (Group-I, 75±7 mm Hg, Group-II, 78±4 mm Hg, at second visit) were slightly higher in patients (Group-II) after receiving conventional LT4 suppressive dose but were not statistically significant. Left ventricular mass (LVM) (*p<0.05), left ventricular mass index (LVMi) (*p<0.01), fraction shortening (FS%) (*p<0.001) and heart rate adjusted mean velocity of circumferential fiber shortening (mVCFc) (*p<0.001) were increased in patients of Group-II after exposure of conventional LT4 dose compared to patients received optimized dose (Group-I) at second visit. Ejection time was also decreased in patients of Group-II at second visit compared to patients of Group-I at first visit *P<0.01. Mild degree of diastolic function abnormalities were also noted in Group-II patients at second visit compared to Group-I patients. Early (E) diastolic velocity of Group-II was significantly low at second visit compared to that of Group-I at first visit (*p<0.005) and late (A) was comparatively high in group II compared to Group-I at second visit (A, Group-I, 51±8 cm /sec, Group-II, 58±8 cm /sec; *p<0.01). Deceleration time (Dct) was significantly low in Group-II compared to patients in Group-I at two visits and patients of Group-II at first visit (Dct, Group-I, 155±16 m sec, Group-II, 127±18 m sec; *p<0.001). Similarly in tissue Doppler imaging technique, late diastolic mitral annular velocity (Am) was higher in Group-II compared to Group-I at second visit (Am, Group-I, 15±3 cm /sec, Group-II, 19±6 cm /sec; *p<0.003). Significantly high modified Tei index was also noted in patients of Group-II at second visit compared to their first visit value and patients of Group-I at different visits (Group-I, 0.34±0.08; Group-II, 0.48±0.06 at second visit *p<0.001). Exercise capacity as evaluated by exercise tolerance test (ETT), showed significant difference (*p<0.05) in metabolic equivalent (MET) between healthy volunteers and patients groups at first visit but no difference was found between two patient groups at different time points. It is concluded that optimization of dose of LT4 based on lean body mass can avoid chronic exposure of mild excess of thyroid hormone in the body and improve quality of life in patients with low risk DTC by preventing and minimizing adverse cardiac effects.