Endocrine Abstracts

Diagnosis of Central Hypothyroidism (CeH) is commonly given when FT4 concentrations are below the lower limit of normal range. A reduction in FT4 concentrations greater than 20% was proposed in ETA 2018 Guidelines as an unphysiological fluctuation indicating the onset of milder forms of CeH with FT4 still within the normal range. Similarly, TSH-index was proposed to quantify thyrotrope reserve, hence as a tool to detect patients at risk of CeH. Here we verified the performance of these parameters for the diagnosis of CeH in 221 patients with pituitary lesions – 127 adenomas and 94 empty sellas – and at least three evaluations of Thyroid Function Tests (TFTs, i.e. paired detection of TSH and FT4) during a median follow-up of 4 years. We also studied TFTs of 42 matched controls, selected from a cohort of euthyroid patients (TSH 0.5-4.5 mU/l) with multinodular goiter and negative thyroid autoimmunity followed up during the same period. We evaluated FT4 concentrations, TSH, TSH-index and defined two derived parameters, FT4var and ΔTSH-index, which were respectively the greatest reduction of FT4 and TSH-index compared to their median value for each patient (FT4var=FT4 nadir – median FT4; ΔTSH-index = TSH-index nadir – median TSH-index). The diagnosis of CeH+ was made according to ETA 2018 Guidelines. In CeH- patients, FT4var did not differ statistically in patients with adenomas, empty sellas and controls (varying from 15 to 25%; P=n.s.). Consistently, in patients diagnosed with CeH+, FT4var (and its percentage value FT4var%) was able to distinguish patients harbouring adenomas or empty sellas with and without CeH [CeH+ vs CeH-: FT4var -3.1±1.9 vs -1.4 pmol/l (IQR-2.1; -0.7), P=0.03; FT4var% -28%±15 vs -8% (IQR -14; -5), P<0.001]. Moreover, in our cohort, TSH-index allowed in distinguishing patients harbouring a pituitary lesion CeH+ vs CeH-, at baseline [CeH+ vs CeH– 1.8 (IQR 0.8; 2.2) vs 2.5 (IQR 2; 2.9); P<0.001]) and during follow-up [CeH+ vs CeH–: 1.3±1.3 vs 2.5±0.7, P<0.001]. In conclusion, both patients with pituitary lesions and controls show fluctuations of TFTs around an individual set-point. In patients with pituitary lesions such as adenomas and empty sellas, FT4var, FT4var% and TSH-index are useful tools able to highlight milder forms of CeH. We found that a fluctuation of FT4 value (FT4var) or FT4var% respectively greater than 3.1 pmol/l or 28% indicated the onset of mild CeH. The coexistence of a TSH-index lower than 1.3 may be useful to support this challenging diagnosis.