Tandem Mass Spectrometry as a Novel Tool for Elucidating Pituitary–Thyroid Relationships

Background: Our objective was to determine the performance of liquid chromatography–tandem mass spectrometry (LC-MS/MS) in documenting both group and individual relationships between thyroid hormone and thyroid-stimulating hormone (TSH) concentrations.

Methods: This was a prospective analysis of 50 euthyroid patients undergoing thyroidectomy. Thyroxine (T₄), triiodothyronine (T₃), free T₄ (FT₄), and TSH levels were documented on two occasions before thyroidectomy. After thyroidectomy, patients were treated with levothyroxine (LT₄) to achieve either a normal or low serum TSH concentration. All laboratory evaluations were repeated twice while patients were taking LT₄. Thyroid hormone concentrations were documented by both immunoassay and LC-MS/MS, and their relationship with TSH was studied both in the entire group and in individual patients pre- and postthyroidectomy.

Results: FT₄ and total T₃ correlated better with the log-transformed TSH when measured by LC-MS/MS. Postthyroidectomy the closest correlation was between log TSH and FT₄ (r = 0.86, p < 0.001). The next best correlation was between log TSH and total T₃ (r = 0.71, p < 0.001). When all data points were combined, the slope of the relationship between log TSH and total T₃ was relatively blunted compared with the log TSH–FT₄ slope (slope − 0.39 vs. − 1.38; p < 0.001), perhaps suggesting autoregulation of T₃ in response to the altered conditions postthyroidectomy.

Conclusion: LC-MS/MS is an excellent tool for documenting the known physiological phenomenon of a log–linear relationship between TSH and thyroid hormone concentrations. In a group of patients studied pre- and postthyroidectomy, both FT₄ and total T₃ measured by tandem mass spectrometry correlate well with TSH. However, T₃ correlates slightly less well and has a relatively blunted relationship with the log-transformed TSH. These paired data suggest that in LT₄-replaced patients T₃ concentrations are held stable in the face of fluctuating T₄ concentrations.