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Circadian and Stimulated Thyrotropin Secretion in Cranially Irradiated Adult Cancer Survivors

Department of Endocrinology, Christie Hospital, Manchester M20 4BX, United Kingdom

Address all correspondence and requests for reprints to: Dr. Stephen M. Shalet, Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. E-mail: stephen.m.shalet{at}man.ac.uk.

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-h TSH profiles and TRH tests in 37 euthyroid adult cancer survivors 2–29 yr (median, 11.5) after irradiation (18–64 Gy) and in 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 craniospinal irradiation, 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 three sequential samples) and the smallest nadir (average of the smallest three sequential samples) in the whole 24-h profile period was above the cutoff value of 50% in all except one control subject and two patients. However, the nocturnal TSH surge was greatly reduced or absent in eight normal subjects (24%) and six patients (16%), not due to a genuine loss of diurnal rhythm, but simply 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 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 only in the GH-deficient patients (100.7 ± 11%) compared with normal subjects (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 postirradiation follow-up strongly suggest that in the vast majority of patients, these abnormalities in TSH dynamics represent subtle functional disturbances in the hypothalamic-pituitary axis rather than genuine pathology that may progress with time. We suggest that in this context, use of the term hidden central hypothyroidism is inappropriate, because these subtle changes may not have any clinical significance.

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