Diagnosis of hidden central hypothyroidism in survivors of childhood cancer

To determine how often central hypothyroidism remains undetected by routine out-patient tests of thyroid hormone, we studied 208 pediatric cancer surv ivors referred for evaluation because of signs of subtle hypothyroidism or hypopituitarism. Of the 208 (68 females and 140 males), 110 had brain tumor s, 14 had other head/neck tumors, 11 had solid tumors remote from head and neck, and 73 had leukemia. Patients mere evaluated 1-16 yr (mean, 6.1 +/- 4 .1 yr) after tumor diagnosis. The nocturnal TSH surge and response to TRH w ere measured. Of 160 patients with free T-4 in lowest third of normal, 34% had central hypothyroidism (blunted TSH surge or low/delayed TSH peak or de layed TSH decline after TRH); 9% had central hypothyroidism with mild TSH e levation (mixed hypothyroidism). Another 16% had mild primary hypothyroidis m (TSH, 5-15 mU/L. Of 48 with free T-4 in the upper two thirds of normal, 1 4% had central hypothyroidism; 17% had mild primary hypothyroidism. Inciden ce of central, mixed, and mild primary hypothyroidism 10 yr after tumor dia gnosis was significantly related to total cranial radiation dose (P < 0.000 1). Of 62 patients with central hypothyroidism, 34% had not developed GH de ficiency. TSH surge identified 71%, and response to TRH identified 60% of t hose with central hypothyroidism. More than half of the slowly growing pati ents who have received cranial or craniospinal radiation for childhood canc er develop subtle hypothyroidism. In our study group, 92% of patients with central hypothyroidism and 27% with mixed hypothyroidism would have remaine d undiagnosed using baseline thyroid function tests alone, Both TSH surge a nd response to TRH must be evaluated to identify all of these patients.