Effect of androgen deprivation therapy in the thyroid function test of patients with prostate cancer

Abstract

We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid function test in prostate cancer patients. Serum levels of tri-iodothyronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined in a cross-sectional study that included 279 patients diagnosed with prostate cancer. A subset of 96 patients free of prostate-specific antigen relapse after radical prostatectomy became a control group and 183 patients under continuous ADT formed the study group. Sixty-four patients out of the study group were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119 with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3-218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively, p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58), respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80-1.90), respectively, p=0.018. No statistically significant differences between the T3, T4, TSH and FT4 serum levels were detected according to the modality of ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%); however, all cases had a normal FT4 serum level. This mild hypothyroidism was detected in two of the 96 patients of the control group (2.1%) and in four of the 183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function test. A statistically significant increase in TSH serum level and a decrease in FT4 serum level were detected in patients under ADT. However, only a mild hypothyroidism was detected in about 2% of the patients with prostate cancer, independently of ADT.

Effect of Testosterone on Thyroid Weight and Function in Iodine Deficient Castrated Rats

“…These fi ndings are similar to those of androgen deprived men [9] . Testosterone defi ciency in iodine defi cient rats enhanced increase in serum TSH and thyroid enlargement and caused further decrease in serum-free T 4 induced by iodine defi ciency.…”

“…Morote et al considered the eff ect of androgen deprivation therapy (ADT) in the thyroid function tests of patients with prostatic cancer, and demonstrated that ADT alters thyroid function tests. A statistically signifi cant increase in serum TSH level and a decrease in free T 4 were found in patients under ADT [9] . Changes observed in thyroid volume and serum T4, FT4, T3 and TSH concentrations in iodine defi cient as compared to normal rats are similar to previous reports [2,12] .…”

Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: A systematic literature review

“…A small but statistically significant increase in TSH levels (1.81 mU/L in ADT cases, 1.58 mU/L in controls, p = 0.007) and decrease in free thyroxine levels (1.18 ng/dL versus 1.24 ng/dL, respectively, p = 0.018) were noted. Although Salminen et al hypothesized that LHRH agonists may have some previously uncharacterized activity upon the TSH receptor [114], Morote et al correctly pointed out that the clinical significance of a small increase in TSH levels is dubious [115]. The limited available data do not suggest routine monitoring of thyroid function tests is warranted in men undergoing ADT, although further studies are needed.…”

“…A preliminary report of ten men with advanced prostate cancer found declines in free triiodothyronine (T3) levels but not free thyroxine (T4) levels over a 12-month period [113]. Two groups more recently explored this issue using case-control designs [114,115]. Salminen et al prospectively measured levels of thyroid stimulating hormone (TSH), free thyroxine, and thyroid binding globulin (TBG) in 35 men on ADT and compared it to 36 men undergoing radiotherapy alone [114].…”

“…Although the decline in free thyroxine was greater than among controls, it is of doubtful clinical significance given the lack of change in TSH and TBG. Morote et al compared TSH and free thyroxine levels in 183 patients undergoing ADT (LHRH agonist therapy or combined androgen blockade) and 96 controls who had undergone radical prostatectomy but were not taking ADT [115]. A small but statistically significant increase in TSH levels (1.81 mU/L in ADT cases, 1.58 mU/L in controls, p = 0.007) and decrease in free thyroxine levels (1.18 ng/dL versus 1.24 ng/dL, respectively, p = 0.018) were noted.…”