Central hypothyroidism: a cross-sectional study evaluating cognitive and metabolic effects of thyroxin replacement therapy

Optimising thyroid replacement therapy in patients with hypopituitarism is difficult since dose titration is mainly depending on clinical information. We investigated whether tests impaired in primary hypothyroidism, i.e. cognitive function and lipid parameters, can be used to predict substitution quality in central hypothyroidism (CH). 33 patients with CH (15 females, 18 males) and failure of 3 pituitary axis receiving thyroxin replacement (1.17µg/kg body weight) and 25 normal subjects (NS; 15 females, 10 males) were included in a cross-sectional study. Biochemical parameters – such as lipid electrophoresis, Achilles’ reflex time (ART), Wechsler Memory Scale and attention testing were assessed. FT3 and fT4 levels (mean±SEM) were similar in CH and NS (fT3 5.3±0.12 vs. 5.0±0.14; fT4 11.8±0.5 vs. 12.0±0.4 pmol/l; ns), whereas TSH was lower in CH as expected (0.4±0.01 vs. 1.4±0.4µIU/ml; P<0.001). Compared to NS, patients with CH have unfavourable lipid parameters: higher LDL (131±5 vs. 115±6; P<0.04) and lower HDL (48±3 vs. 58±4; P<0.05). ART was prolonged in CH (0.441±0.1 vs. 0.378±0.01 ms; P<0.001). Evaluating cognitive function only one test detected lower T values in CH (44±2 vs. 49±2; P<0.05). Patients (CH) were analysed by grouping into 3 tertiles (I, II, III) depending on fT3 or fT4 levels. Persons with low (I) compared to high (III) fT4 had an impaired cognitive function (P<0.02) and tendency to unfavourable lipid parameters (P<0.1). However, results in respective fT3 tertiles were equal. In summary, patients with CH during routine T4 substitution have lower TSH, but similar fT3 and fT4 levels compared to NS. Unfavourable lipid values, prolonged ART and slight cognitive impairment are evident in CH in comparison to NS and might reflect subclinical central hypothyroidism in a subset of patients. Low fT4 levels in CH were associated with unfavourable metabolic effects. Therefore, fT4 in contrast to fT3 concentration might give assistance to optimise replacement therapy.