Context: It has been claimed that with the use of the TRH test and knowledge of the nocturnal TSH surge, the diagnosis of so-called "hidden" central hypothyroidism might be uncovered, in a substantial proportion of euthyroid cranially irradiated children.

Study Subjects: We conducted 24-hour TSH profiles and TRH tests in 37 euthyroid adult cancer survivors 2-29 (median, 11.5) yrs. after irradiation (18-64 Gy) and 33 matched normal controls.

Results: Basal and stimulated TSH levels (during the TRH test) were significantly (P < 0.05) higher in the patients who had received cranio-spinal irradiation, and more so in those with severe GH deficiency. Six patients (16%) had a hypothalamic TSH response to TRH. The maximum TSH surge calculated from the highest peak (average of the highest 3 sequential samples) and the smallest nadir (average of the smallest 3 sequential samples) in the whole 24-hour profile period was above the cut-off value of 50% in all except one control subject and two patients. However, the nocturnal TSH surge was greatly reduced or absent in 8 normals (24%) and 6 patients (16%), not due to genuine loss of diurnal rhythm, but simply due to a shift in the timing of the peak TSH and/or the nadir TSH to outside the recommended sampling times (for the nocturnal surge) of 2200-0400 h and 1400-1800 h, respectively; thereby potentially leading to an erroneous diagnosis of "hidden" central hypothyroidism. Overall, the maximum TSH surge was significantly (P = 0.01) reduced in the GH deficient patients only (100.7 ± 11%) compared with normals (154.9 ± 18.2%). Free T4 levels did not correlate with TSH surge results.

Conclusions: The normality of free T4 levels and the wide discrepancy between the high rate of these TSH abnormalities and the very low rate of overt secondary hypothyroidism (3-6%) after prolonged periods of post-irradiation follow-up strongly suggest that, in the vast majority of patients, these abnormalities in TSH dynamics represent subtle functional disturbances in the h-p axis rather than genuine pathology that may progress with time. We suggest that, in this context, the use of the term "hidden" central hypothyroidism is inappropriate, as these subtle changes may not have any clinical significance.