Edward J. Diamond

Re: Insulin-Like Growth Factor-I (IGF-I) and IGF Binding Protein-3 as Predictors of Advanced-Stage Prostate Cancer

A recent study (1) suggested that elevated plasma levels of insulin-like growth factor-I (IGF-I) were a predictor of advanced-stage prostate cancer. We have studied IGF-I in prostate cancer and have found no relationship to disease stage. We studied IGF-I in a group of 126 men with prostate cancer and benign prostatic hypertrophy (BPH). Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All cancer patients had initially been diagnosed on the basis of levels of prostate-specific antigen (PSA) or abnormal physical examination. All men with BPH had had negative prostate biopsy examinations. Histologic confirmation of cancer diagnosis was also obtained for all subjects. All participants gave written informed consent. All staging of cancer cases was clinical, because almost all of the patients were to receive I seed implant therapy. Serum IGF-I was measured by use of the Nichols Advantage, an automated chemiluminescent immunoassay analyzer (Nichols Institute Diagnostics, San Juan Capistrano, CA). There was no statistically significant difference in the IGF-I levels in men with BPH compared with those in men with prostate cancer, nor was there statistically significant variation of IGF-I level among men with stages T1, T2, or T3 prostate cancer (P .323, one-way analysis of variance; Fig. 1). Multivariable linear regression revealed no statistically significant effect of PSA level, Gleason score, or T stage on IGF-I level (P .277) in men with prostate cancer. Shariat et al. (2) have shown that systemic levels of IGF-I are not associated with metastasis, established markers of biologically aggressive disease, or disease progression in patients with clinically localized prostate cancer. Our results agree with those of Shariat et al. and suggest that serum IGF-I levels are not related to advanced-stage prostate cancer.

Serum Triiodothyronine is Increased in Men With Prostate Cancer and Benign Prostatic Hyperplasia

UNLABELLED Triiodothyronine is the active thyroid hormone produced by de-iodination of the precursor thyroxine that is necessary for the growth of prostate cancer cells in vitro. For this reason we assessed serum triiodothyronine levels in men with localized prostate cancer, benign prostatic hyperplasia (BPH) and controls in the same age group. MATERIALS AND METHODS We studied 161 men referred for treatment of localized prostate cancer, 20 with BPH and 27 controls. Serum triiodothyronine was determined by fluorometric immunoassay and a commercially available instrument. RESULTS Men with BPH had the highest triiodothyronine levels, followed by those with prostate cancer. Controls had the lowest triiodothyronine. There was significant triiodothyronine variation among the 3 groups (1-way ANOVA p = 0.001). In men with BPH serum triiodothyronine was significantly different from that in men with prostate cancer (Tukeys multiple range test p = 0.013). Men with prostate cancer had serum triiodothyronine that was significantly different than in controls (p = 0.048), as did those with BPH (p <0.001). Because serum triiodothyronine normally decreases with age, we performed multivariate analysis of variance controlling for age. There was a significant decrease in serum triiodothyronine with age (p = 0.020). There was also significant triiodothyronine variation among the 3 subject groups independent of age (p <0.001). CONCLUSIONS Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem but it is impossible to identify such tumors with certainty. With more and better biomarkers many older men with prostate cancer may be spared the rigors of radiation therapy and/or surgery as well as complications. Triiodothyronine may be such a biomarker. Also, new prostate cancer and BPH therapies may be directed toward inhibiting the mitogenic effects of triiodothyronine.

Elevated serum triiodothyronine (t3) in Ashkenazi Jewish prostate cancer patients carrying the i1307k allele of the APC(adenopolyposis coli) gene

PURPOSE The risk of developing any cancer in carriers of the I1307K mutation of the adenopolyposis coli (APC) gene is significantly increased (odds ratio 1.5, P = 0.01). One of the cancers associated with the I1307K mutation is prostate cancer (odds ratio 2.0, P = 0.14). Also, there is an association of APC mutations with thyroid cancer. In this study, we measured triiodothyronine (t3) levels in Ashkenazi Jewish prostate cancer patients, with and without the I1307K mutation of the APC gene. MATERIALS AND METHODS Participants in our study were found through urology and radiation oncology clinics in 1999 and 2000. All eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. The I1307K allele of the APC gene was detected by amplification of DNA isolated from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Serum t3 level was determined by fluorescent immunoassay with a standard, commercially available instrument. RESULTS We studied 77 patients. The youngest patient was 46, the oldest 88, average age 67 +/- 7.2 (mean +/- SD). Eleven males carrying the APCI 1307K allele had significantly higher serum t3 levels than 66 males carrying the wild type allele. There were no homozygotes for the I1307K allele. None of the males had a t3 level that was above the normal range for our laboratory (137 ng/dl). CONCLUSIONS Our findings of increased serum t3 level with the APC I1307K allele in prostate cancer patients is not surprising, given the mitogenic potential of t3. Further studies may clarify whether t3 elevation is the mechanism whereby APC gene mutations increase the risk of prostate cancer, or whether other pathophysiologic abnormalities are involved.

Serum thyroid-stimulating hormone is elevated in men with Gleason 8 prostate cancer

To measure the levels of serum thyroid‐ stimulating hormone (TSH) in men with prostate cancer, as those with a Gleason score of ≥ 8 are at high risk of skeletal metastases (and should be considered for bone scintigraphy at diagnosis), and because the structural integrity of the skeleton depends on constant remodelling controlled by many local and systemic factors, including TSH, an important regulator of this process.

Measurement of Thyroid Hormones and Related Molecules

Publisher Summary Laboratory evaluation of thyroid status centers around chemical measurements of thyroid gland secretory products present in the circulation, assessment of the hypothalamic–pituitary–thyroid axis, and measurement of related molecules that affect thyroid gland function, such as thyroid binding proteins and auto antibodies. Biologically active free hormone concentrations would appear to be the best way to assess thyroid status. A sensitive thyroid stimulating hormone (TSH) measurement is all that is needed to monitor thyroid function in most ambulatory individuals. Measurements of thyroid gland-related molecules such as anti-Tg, anti-TPO (thyroid peroxidase), and TSH-receptor autoantibodies give information concerning the cause of thyroid malfunction and can also be used to follow progression of disease. This chapter historically reviews the methods in use for measuring thyroid hormones and relatedsubstances in humans, and focuses on the merits and limitations of each approach. Serum thyroglobulin measurements are used to follow patients being treated for differentiated thyroid carcinoma, to monitor thyroid activity during treatment for hyperthyroidism, and help to determine the defect in neonatal hypothyroidism. The literature references cited are representative for the topics covered but are not all-inclusive.