Diagnosing Thyrotropin-Secreting Pituitary Adenomas by Short-Term Somatostatin Analogue Test

Diagnosis of thyrotropin (TSH)-secreting pituitary adenomas (TSHoma) before surgery remains a challenge, especially for microadenomas. We aimed to establish a short-term somatostatin analogue (SSA) test to differentiate TSHomas from other causes of syndromes of inappropriate secretion of TSH (IST), mainly resistance to thyroid hormone β (RTHβ). We first evaluated the sensitivity and specificity of SSA test in a training cohort (TSHoma, n = 32; RTHβ, n = 20). The test was then validated in an independent cohort (TSHoma, n = 9; RTHβ, n = 2). We finally applied the SSA test in 12 perceptively enrolled IST cases with negative imaging findings and absent thyroid hormone receptor beta (THRB) mutations or mixed hormone imbalances. Both TSHoma and RTHβ patients showed a decrease of TSH at the start of the SSA test, but the velocity of the TSH suppression slowly decreased in RTHβ patients after 2 hours. The suppression ratio of TSH at 24 hours versus 2 and 0 hours was significantly greater in TSHoma patients compared with RTHβ patients (70.58% ± 18.6% vs. 6.01% ± 25.41%, p < 0.0001, 79.83% ± 12.79% vs. 51.16% ± 13.62%, p < 0.0001, respectively). The 24- versus 2-hour suppression ratio showed the best diagnostic accuracy at a cut point of 44.46% in the training cohort, with a sensitivity of 95.00%, a specificity of 93.75%, and a positive predictive value (PPV) of 88.89%. The accuracy was confirmed in the validation cohort. Three out of 12 patients in the prospective cohort showed a TSH suppression ratio greater than 44.46% and all developed microadenomas during follow-up. A short-term SSA test provides an alternative diagnostic approach for TSHomas. A positive SSA test result is suggestive for a TSHoma even before positive findings become apparent on pituitary imaging. However, studies including larger number of patients, especially those with RTHβ, are needed to confirm our findings.