Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children

OBJECTIVE The effects of GH therapy on thyroid function among previous repo rts have shown remarkable discrepancies, probably due to differences in hor mone assay methods, degree of purification of former pituitary-derived GH p reparations, dosage schedules, diagnostic criteria, patient selection, dura tion of treatment and study design. These considerations motivated us to in vestigate whether and how GH replacement therapy changes serum thyroid horm one levels, including the much less studied rT3 levels, in a group of unequ ivocally GH-deficient children receiving long-term recombinant human GH the rapy. PATIENTS AND DESIGN Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for a t least 6 months and without GH replacement, either before GH was started o r after GH was withdrawn for 30-60 days. Eight patients were on thyroxine r eplacement treatment and thyroxine doses were kept constant during the stud y. Blood was collected before and after 15, 20 and 60 minutes of TRH admini stration in both therapeutic conditions (with GH and without GH). MEASUREMENTS Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured b y immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS Patients were classified into two groups, according to basal TSH re vels: group I (TSH > 0.4 mU/l, n = 12) and group It ton thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17.0 +/- 1. 1 vs. 14.3 +/- 0.9 mU/l, P<0.001, and 18.0 +/- 1.7 vs. 14.2 +/- 1.7 mU/l, P <0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0. 2 nmol/l, P<0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P<0.05, respecti vely), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol /l, P<0.01, and 0.48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P<0.01, respectivel y). Basal (3.2 +/- 0.50 vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TR H-stimulated peak TSH levels (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated TSH secretion, expressed as area under t he curve (609 +/- 97 vs. 499 +/- 53 mU/l.minutes(-1), P=0.15, paired t-test ), remained unchanged during GH replacement in group I patients. Low serum FT4 and high serum T3 levels were observed in only one patient each, but lo w serum rT3 revels were found in six patients (four in group I and two in g roup II) during GH replacement. CONCLUSIONS These results show that long-term GH replacement therapy in chi ldren with unequivocal GHD significantly decreases serum FT4 and rT3 levels and increases serum T3 levels; that these changes are independent of TSH a nd result from increased peripheral conversion of T4 to T3 and that GH repl acement therapy in GH deficient children does not induce hypothyroidism, bu t simply reveals previously unrecognized cases whose serum FT4 values fall in the low range during GH replacement.