Endocrine Abstracts

Introduction: Milder forms of central hypothyroidism (CeH) are still challenging to diagnose due to absence of gold standards, wide variability of fT4 values and aspecificity of symptoms. We aimed to find diagnostic clues at diagnosis (pituitary lesion dimensions, other hormonal deficit) and during long-term follow-up, guiding the clinician to a precocious diagnosis of CeH.

Study: 142 patients harbouring a pituitary adenoma with complete pituitary assessment at diagnosis (hormonal/imaging) were studied between 2000 and 2020. Median age was 47.5 years (SD 16.5). Lesions were 45% microadenomas (55% macroadenomas)., 62% were functioning and 30% incidentalomas. At diagnosis, 67% of patients with CeH suffered from at least another hormonal deficit, especially gonadotropins failure (OR 6.9, P= 0.0001) and corticotrope failure (OR 7.6, P= 0.001). No correlation was found between CeH and having a functional adenoma (P= NS). Radiological measures were available in 102/142 patients. Patients with CeH at diagnosis had bigger adenomas (P=0.054). Given a maximum adenoma diameter > 12 mm, the probability of carrying CeH was statistically significant (OR 3.53, P= 0.03, sensitivity 68.7%, specificity 61.6%).

Mean follow-up was 7.64 years (2-53-9.73) and follow-up data were available for 69 patients, with at least one evaluation of paired TSH and fT4 per year. Only 4/69 developed overt CeH defined by inappropriately normal or low TSH with fT4 values beyond the lower limit of normal. In those patients mean fT4 variability (defined by the difference between the median value of fT4 and the lowest fT4 value detected over follow-up) was -18% (SD ± 10) and median TSH index (TSH_i) was +1.7 (IQR 0.36-2.18) with a mean decrease of -47% (SD ± 50). Among the other 65/69 patients with a normal thyrotrope reserve, mean ft4 variability was -2% (SD ± 9) displaying a -2 SD as low as -20% and mean TSH_i was +2.51 (SD ± 0.522) with a median decrease of – 7% (IQR -16; -3) displaying a 2.5° percentile as low as -38%. The difference in intra-individual ft4 variations and TSH_i decrease was statistically different in these two cohorts (P=0.04, P=0.048 respectively).

Conclusions: In patients carrying pituitary adenomas, the presence of mild CeH could we inferred at diagnosis if adenoma diameter is > 12 mm and gonadotropin or corticotrope deficiency coexist. During follow-up, if intra-individual variation of fT4 from baseline exceed -20% and TSH index decreases by more than -38%, the development of CeH could be suspected.