TY - JOUR
T1 - Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone
T2 - The value of changes after short term triiodothyronine administration
AU - Sarne, David H.
AU - Refetoff, Samuel
AU - Rosenfield, Robert L.
AU - Farriaux, Jean Paul
PY - 1988/4
Y1 - 1988/4
N2 - Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal infjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P < 0.0001). Mean SHBG levels in the patients with GRTH [37.6 ± 16.2 (± Sd) nmol/L] were not significantly different from those in the normal infjects (35.1 ± 19.3 nmol/L) or hypothyroid patients (26.3 ± 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 ± 19.2 nmol/L; P < 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 μg daily to 7 normal infjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (ΔSHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (nonresistant infjects). After administration of 50 ng T3 daily, the mean ΔSHBG level was decreased [−2.9 ± 5.3 (±SD) nmol/L] in the resistant patients and increased (4.0 ± 4.9 nmol/L; P < 0.005) in the nonresistant infjects. After administration of 100 μg T3 daily, the mean ASHBG was −4.5 ± 6.8 nmol/L in the resistant patients and 8.6 ± 5.1 nmol/L (P < 0.0001) in the nonresistant infjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant infject. After administration of 200 μg T3 daily, the mean ΔSHBG increase was 0.7 ± 7.3 nmol/L in the resistant patients and 16.6 ± 7.3 nmol/L (P < 0.0001) in the nonresistant infjects. Neither the combination of a normal basal serum SHBG value and elevated serum thyroid hormone values nor the relationship between serum SHBG and FT4I values was sufficient t o separate all GRTH patients from those with thyrotoxicosis. The combination of elevated serum thyroid hormone values and failure of serum SHBG to increase above the basal value after the administration of T3 for 6 days was found in 9 of 10 patients with GRTH but in none of the thyrotoxic infjects. The response of SHBG to T3 administration is useful in the demonstration of peripheral tissue resistance to thyroid hormone.
AB - Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal infjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P < 0.0001). Mean SHBG levels in the patients with GRTH [37.6 ± 16.2 (± Sd) nmol/L] were not significantly different from those in the normal infjects (35.1 ± 19.3 nmol/L) or hypothyroid patients (26.3 ± 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 ± 19.2 nmol/L; P < 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 μg daily to 7 normal infjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (ΔSHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (nonresistant infjects). After administration of 50 ng T3 daily, the mean ΔSHBG level was decreased [−2.9 ± 5.3 (±SD) nmol/L] in the resistant patients and increased (4.0 ± 4.9 nmol/L; P < 0.005) in the nonresistant infjects. After administration of 100 μg T3 daily, the mean ASHBG was −4.5 ± 6.8 nmol/L in the resistant patients and 8.6 ± 5.1 nmol/L (P < 0.0001) in the nonresistant infjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant infject. After administration of 200 μg T3 daily, the mean ΔSHBG increase was 0.7 ± 7.3 nmol/L in the resistant patients and 16.6 ± 7.3 nmol/L (P < 0.0001) in the nonresistant infjects. Neither the combination of a normal basal serum SHBG value and elevated serum thyroid hormone values nor the relationship between serum SHBG and FT4I values was sufficient t o separate all GRTH patients from those with thyrotoxicosis. The combination of elevated serum thyroid hormone values and failure of serum SHBG to increase above the basal value after the administration of T3 for 6 days was found in 9 of 10 patients with GRTH but in none of the thyrotoxic infjects. The response of SHBG to T3 administration is useful in the demonstration of peripheral tissue resistance to thyroid hormone.
UR - http://www.scopus.com/inward/record.url?scp=0023941459&partnerID=8YFLogxK
U2 - 10.1210/jcem-66-4-740
DO - 10.1210/jcem-66-4-740
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C2 - 3346353
AN - SCOPUS:0023941459
SN - 0021-972X
VL - 66
SP - 740
EP - 746
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -