Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients.
OBJECTIVE
Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion.


METHODS
Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.).


METHODS
Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years.


METHODS
GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method.


RESULTS
Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly higher on day 15 (24.4 +/- 3.8) than those observed on days 0 (14.2 +/- 1.6), 4 (15.2 +/- 3.0) and 7 (19.6 +/- 5.0). There was a 79% increase in this response on day 15 compared with the pre-treatment period. Hyperthyroid patients had a blunted GH response to GHRH on days 0, 4 and 7 in comparison with control subjects. However, on day 15, no differences were observed between the area under the curve (mean +/- SE mU/l.120 min) in thyrotoxic patients (1770 +/- 306) and in the control group (3300 +/- 816). IGF-I and albumin levels did not change during iopanoic acid administration.


CONCLUSIONS
The results show that an acute reduction in serum T3 levels elicits an increase in GH responsiveness to GHRH in hyperthyroidism. Although the mechanisms involved in this process are still unknown, it is possible that T3 influences GH responsiveness to GHRH via hypothalamic somatostatin release. Alternatively, T3 could have a direct effect at the pituitary somatotroph, modulating GHRH intracellular pathways.
Ramos-Dias
J C
JC
Division of Endocrinology, Universidade Federal de São Paulo, São Paulo, Brazil.
Lengyel
A M
AM
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D007480:Iopanoic Acid / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011441:Propylthiouracil / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood*
D013956:Antithyroid Agents; D014284:Triiodothyronine; D011441:Propylthiouracil; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D007480:Iopanoic Acid; D013974:Thyroxine