Evaluation of the serum testosterone to prostate-specific antigen ratio as a predictor of prostate cancer risk.

OBJECTIVE: To analyse the ratio of serum testosterone (sT) to prostate-specific antigen (PSA) as a predictor of prostate cancer risk, as low levels of sT have been related to a greater risk of prostate cancer, and its ratio with serum PSA level was recently proposed as a new tool to increase the specificity of PSA. PATIENTS AND METHODS: In all, 439 consecutive men with a normal digital rectal examination and a serum PSA level of 4.1-20 ng/mL had a transrectal ultrasonography-guided biopsy using a 10-core scheme, with an additional 1-8 cores according to prostate volume and patient age. The sT level was determined before the procedure using a chemiluminescent assay, and the ratio of sT to PSA (sT/PSA) was calculated after transforming sT measurements from ng/dL to ng/mL. The percentage free PSA (%fPSA) and PSA density were also included in this analysis. RESULTS: The overall cancer detection rate was 42.1%. The median sT level was 469 ng/dL in men with cancer and 499 ng/dL in those without (P = 0.521). The median sT/PSA was 0.68 and 0.74, respectively (P = 0.215). However, the median %fPSA was 14 in men with cancer and 17 in men without (P < 0.001) and the median PSA density was 0.22 and 0.16, respectively (P < 0.001). The multivariate analysis confirmed the independent predictive value only for %fPSA (odds ratio 0.94, 95% confidence interval 0.91-0.98) and PSA density (5.8, 3.42-19.8). CONCLUSION: These results do not support the use of sT/PSA for predicting the risk of prostate cancer and to increase the specificity of PSA.

Lipoprotein lipase expression in livers of morbidly obese patients could be responsible for liver steatosis.

BACKGROUND: Most patients with morbid obesity develop non-alcoholic fatty liver disease (NAFLD). The origins of lipid deposition in the liver and the effects of bariatric surgery in the obese with NAFLD are controversial. METHODS: We analyzed lipids and lipoprotein lipase (LPL) in both plasma and liver biopsies performed before and 12-18 months after Roux-en-Y gastric bypass surgery in 26 patients. RESULTS: In the livers of morbidly obese patients, the levels of LPL messenger RNA (mRNA) were higher (4.5-fold) before surgery than afterwards than control livers. In these patients, LPL activity was also significantly higher (91 +/- 7 mU/g) than in controls (51 +/- 3 mU/g, p = 0.0026) and correlated with the severity of the liver damage. All hepatic lipids were significantly increased in obese patients; however, after bariatric surgery, these lipids, with the exception of NEFA, tended to recover to normal levels. CONCLUSIONS: The liver of obese patients presented higher LPL activity than controls, and unlike the controls, this enzyme could be synthesized in the liver because it also present LPL mRNA. The presence of the LPL activity could enable the liver to capture circulating triacylglycerides, thus favoring the typical steatosis observed in these patients.

Increased expression and activity of hepatic lipase in the liver of morbidly obese adult patients in relation to lipid content.

BACKGROUND: The types and sources of lipid deposition in the liver of most patients with morbid obesity, as well as the effects of bariatric surgery, are discussed. METHODS: In 26 patients with morbid obesity who underwent bariatric surgery, we analyzed different kinds of lipids and hepatic lipase (HL) from both plasma and liver biopsies performed 12-18 months after surgery. RESULTS: The HL activity and HL-mRNA in morbidly obese (MO) livers were high (258 +/- 17 mU/g, and 4.5-fold, respectively); after surgery, the activity decreased (137 +/- 15 mU/g, p < 0.001) but not the levels of HL-mRNA (4.3-fold). Plasma HL activity was also high (4.31 +/- 0.94 mU/mL plasma), and it decreased during weight loss (2.01 +/- 0.29 mU/mL, p < 0.01); moreover, it correlated (r = 0.3694, p < 0.05) with decreased liver HL activity. Adrenocorticotropic hormone in MO was higher (27 +/- 3 pg/mL) than after surgery (13 +/- 1 pg/mL, p < 0.001). All hepatic and plasma lipids were significantly increased in MO patients, but, after bariatric surgery, most of those parameters recovered or normalized. Liver HL activity correlated with total and esterified cholesterol (r = 0.4399, p < 0.001 and r = 0.4395, p < 0.01, respectively). CONCLUSION: High HL in MO patients could allow for liver intake of cholesterol that could be re-exported to steroidogenic organs to synthesize steroidal hormones. A decrease of plasma HL during weight loss could be a good index for improvement of liver disease.

Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapy.

OBJECTIVE: To analyse individual variations in serum testosterone level, the cumulative rate of 'breakthrough' increases over castrate levels, and to evaluate whether the increases can be predicted. PATIENTS AND METHODS: Serum testosterone levels were determined every 6 months over 3 years in 73 consecutive patients with prostate cancer who were medically castrated, prospectively enrolled in a single tertiary academic centre. Patients recruited for this study were being treated with a 3-monthly depot of luteinizing hormone-releasing hormone agonist over 6-48 months. Serum testosterone was measured using a chemiluminescent assay with a lower sensitivity level of 15 ng/dL and interassay coefficient of variation of 25% at low testosterone concentrations. RESULTS: Individual variations could not be explained by the interassay variation coefficient in 26% of the patients. The rate of breakthrough increases >50 ng/dL increased from 12.3% at the first determination to 24.7% at the third, then remaining stable. The rate of breakthrough increases of 20-50 ng/dL increased from 27.4% at the first determination to 31.5% at the second, and then remained stable. A first determination of <20 ng/dL provided an 11.4% probability for future increases of >50 ng/dL, with a 5.7% probability if two consecutive determinations were <20 ng/dL and a null probability when three consecutive determinations were <20 ng/dL. CONCLUSIONS: Individual variations in serum testosterone level cannot be explained by the coefficient of variation of the assay in a quarter of patients who are medically castrated. Breakthrough increases over castrate levels increase over time and those of >50 ng/dL can be predicted from the previous levels.

The relationship between total and free serum testosterone and the risk of prostate cancer and tumour aggressiveness.

OBJECTIVE: To analyse the relationship between the levels of total and free serum testosterone and the risk of prostate cancer and tumour aggressiveness. PATIENTS AND METHODS: Total and free serum testosterone were determined in 478 patients consecutively assessed by transrectal ultrasonography-guided prostate biopsy because of an abnormal digital rectal examination and/or serum prostate-specific antigen (PSA) level of >4.0 ng/mL. Tumour aggressiveness was assessed according to serum PSA level, biopsy Gleason score and clinical stage in the subset of 216 patients with cancer (45.2%). We also compared prostate cancer risk and tumour aggressiveness in 80 hypogonadal patients (16.7%) and 398 eugonadal patients (83.3%). RESULTS: The median total serum testosterone level in patients without and with prostate cancer was 466.0 and 466.5 ng/dL, respectively (P > 0.05); the median levels of free serum testosterone were 9.9 and 10.0 pg/mL, respectively (P > 0.05). The cancer detection rate in hypogonadal patients was 41.3% (33/80) and 46.0% in eugonadal patients (183/398) (P > 0.05). The median level of total testosterone was 433 ng/dL in patients with low-risk prostate cancer, 467 ng/dL in those with intermediate-risk tumours and 468 ng/dL in those with high-risk tumours (P > 0.05); the median levels of free testosterone were 9.4, 9.8 and 10.3 pg/mL, respectively (P > 0.05). CONCLUSIONS: Prostate cancer risk and tumour aggressiveness are not related to serum levels of total and free testosterone, but hypogonadal patients do not have a greater risk of prostate cancer and tumour aggressiveness.

Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema.

OBJECTIVE: Erythropoietin has been recently found to be increased in the vitreous fluid from ischemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aims of the present study were 1) to measure erythropoietin levels in the vitreous fluid from patients with diabetic macular edema (DME), a condition in which the ischemia is not a predominant event, and 2) to compare erythropoietin mRNA expression between human retinas from nondiabetic and diabetic donors without retinopathy. RESEARCH DESIGN AND METHODS: Vitreous samples from 12 type 2 diabetic patients with DME without significant retinal ischemia and 12 PDR patients were prospectively analyzed. Ten nondiabetic patients with macular holes served as the control group. Erythropoietin was assessed by radioimmunoassay (milliunits per milliliter). Erythropoietin mRNA expression was measured by quantitative real-time RT-PCR analysis in the retina from eight nondiabetic and eight age-matched diabetic donors without diabetic retinopathy RESULTS: Intravitreal erythropoietin concentration was higher in both PDR and DME patients than in nondiabetic control subjects (PDR vs. control subjects: median 302 [range 117-1,850] vs. 30 mU/ml [10-75], P < 0.01; DME vs. control subjects: 430 [41-3,000] vs. 30 mU/ml [10-75], P < 0.01). However, no significant differences were found between DME and PDR patients. Erythropoietin mRNA expression was detected in the human retina, and it was higher in the retina from diabetic than from nondiabetic donors. CONCLUSIONS: As occurs in PDR, intravitreous erythropoietin concentrations are strikingly higher in DME. Erythropoietin is expressed in the human retina, and it is upregulated in diabetic patients even without retinopathy. These findings suggest that other factors apart from ischemia are involved in the overexpression of erythropoietin in diabetic retinopathy.

Twelve-Month Estrogen Levels in Premenopausal Women With Hormone Receptor-Positive Breast Cancer Receiving Adjuvant Triptorelin Plus Exemestane or Tamoxifen in the Suppression of Ovarian Function Trial (SOFT): The SOFT-EST Substudy.

PURPOSE: To describe estradiol (E2), estrone (E1), and estrone sulfate (E1S) levels during the first year of monthly triptorelin plus exemestane or tamoxifen and to assess possible suboptimal suppression while receiving exemestane plus triptorelin. PATIENTS AND METHODS: Premenopausal patients with early breast cancer on the Suppression of Ovarian Function Trial who selected triptorelin as the ovarian suppression method and were randomly assigned to exemestane plus triptorelin or tamoxifen plus triptorelin were enrolled until the target population of 120 patients was reached. Blood sampling time points were 0, 3, 6, 12, 18, 24, 36, and 48 months. Serum estrogens were measured with a highly sensitive and specific assay. This preplanned 12-month analysis evaluated E2, E1, E1S, follicle-stimulating hormone, and luteinizing hormone levels in all patients and the proportion of patients with E2 levels greater than 2.72 pg/mL at any time point during treatment with exemestane plus triptorelin. RESULTS: One hundred sixteen patients (exemestane, n = 86; tamoxifen, n = 30; median age, 44 years; median E2, 51 pg/mL; 55% prior chemotherapy) started triptorelin and had one or more samples drawn. With exemestane plus triptorelin, median reductions from baseline E2, E1, and E1S levels were consistently ≥ 95%, resulting in significantly lower levels than with tamoxifen plus triptorelin at all time points. Among patients on exemestane plus triptorelin, 25%, 24%, and 17% had an E2 level greater than 2.72 pg/mL at 3, 6, and 12 months, respectively. Baseline factors related to on-treatment E2 level greater than 2.72 pg/mL were no prior chemotherapy (P = .06), higher body mass index (P = .05), and lower follicle-stimulating hormone and luteinizing hormone (each P < .01). CONCLUSION: During the first year, most patients on exemestane plus triptorelin had E2 levels below the defined threshold of 2.72 pg/mL, consistent with levels reported in postmenopausal patients on aromatase inhibitors, but at each time point, at least 17% of patients had levels greater than the threshold.

Plasma corticotropin-releasing factor in depressed patients before and after the dexamethasone suppression test.

BACKGROUND: Plasma cortisol, beta-endorphin, corticotropin, corticotropin-releasing factor, and salivary cortisol concentrations, resting and after ingestion of 1 mg of dexamethasone, were investigated in depressed patients and controls. METHODS: Fourteen outpatients from the psychiatric department diagnosed with depressive disorder (ICD-10 Classification) participated in the study. The comparison group consisted of 12 healthy volunteers from the hospital staff. All hormones were measured using direct iodine-125 radioimmunoassay, except corticotropin-releasing factor, which included a sample preextraction and concentration step. RESULTS: The basal plasma cortisol and corticotropin-releasing factor levels in depressive disorder were significantly higher than in the healthy group. After dexamethasone administration, corticotropin-releasing factor plasma values decreased significantly in the depressed group, but showed no significant changes in the controls. In depressive disorder baseline values correlated significantly for salivary cortisol and plasma cortisol, salivary cortisol and plasma corticotropin-releasing factor and plasma corticotropin and beta-endorphin. Similar correlations were found in the healthy subjects, except for salivary cortisol and plasma corticotropin-releasing factor. CONCLUSIONS: These findings indicate that the increased corticotropin-releasing factor plasma concentrations demonstrated in depressive disorder reflect the hypothalamic corticotropin-releasing factor hypersecretion evidenced in this illness. Therefore, measurements of plasma corticotropin-releasing factor levels can be considered a reliable tool for investigating the role of this peptide in the pathophysiology of depression.

[Usefullness of intraoperatory parathyroid hormone measurement in surgical management of primary hyperparathyroidism due to a parathyroid adenoma]. / Utilidad de la determinación intraoperatoria de parathormona en el tratamiento quirúrgico del hiperparatiroidismo primario por adenoma de paratiroides.

BACKGROUND AND OBJECTIVE: Surgical neck exploration of the 4 parathyroid glands is quite an aggressive procedure for most patients with primary hyperparathyroidism (PHPT) due to a parathyroid adenoma. Intraoperatory measurement of parathyroid hormone (PTH) seems to be a useful tool for the management of these cases, allowing the use of minimally invasive surgical techniques with a lower morbidity. Our aims was to assess the usefulness of PTH intraoperatory measurement for the surgical management of PHPT. PATIENTS AND METHOD: We studied 27 consecutive patients, diagnosed with PHPT secondary to parathyroid adenoma. Localization studies included neck ultrasonography and Tc-MIBI scintigraphy. PTH at the stage of anesthesia induction as well as 5 and 10 minutes after the removal of the adenoma was determined. A PTH decrement greater than 50% at 10 minutes was considered as curative. PTH was measured by an immunoluminometric method (Advantage, Nichols). RESULTS: In all cases, calcium levels were normal 24 hours after the operation, and therefore all them were considered as cured. PTH levels decreased more than 50% in all patients. In one case, PTH levels remained high after the exeresis of a preoperatively localized lesion. The pathologic study confirmed that it was a normal parathyroid gland. We then continued the surgical exploration which eventually allowed us to find a contralateral adenoma. A further PTH measurement showed an over 50% decrease. Therefore, PTH was predictive of surgical success in all 28 measurements. CONCLUSIONS: Intraoperatory determination of PTH is useful for the surgical management of PHPT and it could allow the use of minimally invasive surgical techniques.

Soluble CD40 ligand in morbidly obese patients: effect of body mass index on recovery to normal levels after gastric bypass surgery.

IMPORTANCE: In recent years, the CD40/CD40L system has been implicated in the pathophysiology of severe chronic inflammatory diseases. Recently, obesity has been described as a low chronic inflammatory disease, so this system could also be involved in the inflammatory process. OBJECTIVE: To study soluble CD40 ligand (sCD40L) and other factors implicated in coagulation (plasminogen activator inhibitor 1, antithrombin III, and fibrinogen) and inflammation (C-reactive protein) in patients with morbid obesity and different body mass indexes (BMIs) (calculated as weight in kilograms divided by height in meters squared), before and after weight loss induced by bariatric surgery. DESIGN: Plasma samples were obtained before and after a bariatric surgery intervention. Several inflammatory markers were then studied (sCD40L, plasminogen activator inhibitor 1, antithrombin III, and C-reactive protein). The values obtained were compared with a control group of nonobese persons. PARTICIPANTS: Thirty-four morbidly obese patients undergoing gastric bypass surgery and 22 normal-weight controls matched for age and sex. INTERVENTIONS: A Roux-en-Y gastric bypass was performed in morbidly obese patients. MAIN OUTCOME MEASURES: Levels of sCD40L, plasminogen activator inhibitor 1, antithrombin III, fibrinogen, and C-reactive protein 12 months after bariatric surgery. RESULTS: Obese men showed a tendency for decreased plasma sCD40L levels 1 year after surgery (mean [SEM], 246.5 [70.4] pg/mL before vs 82.2 [23.2] pg/mL after surgery; P < .05), whereas there were not any significant changes in obese women (285.9 [67.5] pg/mL before vs 287.0 [56.9] pg/mL after surgery). Levels of the other markers studied decreased significantly with weight loss in both sexes. However, all other studied markers tend to have higher concentrations in patients with higher BMIs, except for sCD40L, which tended to have lower concentrations in patients with BMIs higher than 55. The decreases with weight loss were lower with higher BMIs for all measurements, except for antithrombin III. CONCLUSIONS AND RELEVANCE: Increased BMI, but not sex, influences recovery to normal levels for the markers studied, possibly indicating a worse prognosis.

Alterations in the common pathway of coagulation during weight loss induced by gastric bypass in severely obese patients.

The objective of this study was to establish the relationship between the plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (ATIII), fibrinogen, and white blood cell (WBC) levels in severely obese patients. We analyzed various plasma parameters implicated in the intrinsic and extrinsic coagulation pathway from 34 severely obese patients before and 1, 6, and 12 months after gastric bypass. In obese people, ATIII, fibrinogen, and WBC levels were in the upper limit of the normal range, and all were higher and significantly different from nonobese people. After bariatric surgery, the ATIII level continued to be high during the first month and increased until 12 months, while fibrinogen decreased only at that time. PAI-1 plasma protein and PAI-1 mRNA levels in liver and adipose tissue show similar profiles and had a strong positive correlation (r = 0.576, P = 0.0003 in liver; r = 0.433, P = 0.0004 in adipose tissue). They were higher in obese patients compared with nonobese control, but tended to recover normal values 1 month after surgery. Thus, the liver and adipose tissue could be an important source of PAI-1 protein in plasma. Gastric bypass surgery leads to a normalization of the hematological profile and a decrease in PAI-1 levels, which entails a decrease of risk for thromboembolism in severely obese.

Only C-reactive protein, but not TNF-α or IL6, reflects the improvement in inflammation after bariatric surgery.

BACKGROUND: Increased C-reactive protein (CRP) levels strongly predict inflammatory diseases such as obesity and tissue damage. We wanted to study the CRP in plasma and tissue in morbidly obese patients before and after surgery and relate it with the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues. METHODS: We analyzed CRP concentration in plasma, adipose and liver, and the expression of IL-6 and TNF-α, in those tissues, in 34 morbidly obese patients before and 1, 6 and 12 months after gastric bypass. RESULTS: Morbidly obese had a greater amount of CRP in plasma (3 times) and tissues (21, 5 and 7 times more in liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively) than control subjects. The expression of IL-6 in SAT showed a similar profile to plasma and SAT CRP in both obese patients and after weight loss, despite no significant correlation was found. We were only able to detect IL-6 in the liver of a subset of patients. The expression of TNF-α after surgery showed a no significant slight tendency to decrease in SAT with weight loss, but in the liver, we did not observe any change. CONCLUSION: IL-6 in SAT, but not in liver, seems to be more closely related to plasma and tissue CRP than TNF-α in both obese patients and after weight loss. Plasma CRP protein perfectly reflects the decrease in inflammation and improves with weight loss in the tissues.

Surgically induced weight loss by gastric bypass improves non alcoholic fatty liver disease in morbid obese patients.

AIM: To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients. METHODS: A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index > 40 kg/m(2) who underwent open surgical weight loss operations had paired liver biopsies, the first at surgery and the second after 16 ± 3 mo of weight loss. Biopsies were evaluated and compared in a blinded fashion. The presence of metabolic syndrome, anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy. RESULTS: Percentage of excess weight loss was 72.1% ± 6.6%. There was a reduction in prevalence of metabolic syndrome from 57.7% (15 patients) to 7.7% (2 patients) (P < 0.001). Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery. There were improvements in steatosis (P < 0.001), lobular (P < 0.001) and portal (P < 0.05) inflammation and fibrosis (P < 0.001) at the second biopsy. There were 25 (96.1%) patients with non alcoholic steatohepatitis (NASH) in their index biopsy and only four (15.3%) of the repeat biopsies fulfilled the criteria for NASH. The persistence of fibrosis (F > 1) was present in five patients at second biopsy. Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery. CONCLUSION: Restrictive mildly malabsorptive surgery provides significant weight loss, resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.

The relationships between IGF-1 and CRP, NO, leptin, and adiponectin during weight loss in the morbidly obese.

BACKGROUND: The relationship between C-reactive protein (CRP), nitric oxide (NO), leptin, adiponectin, and insulin growth factor 1 (IGF-1) is poorly defined in morbidly obese patients before and after gastric bypass and, in some cases, is controversial. METHODS: We examined the plasma of 34 morbidly obese patients before and 1, 6, and 12 months after Roux-en-Y gastric bypass surgery. RESULTS: Obese people had more CRP (21.3 +/- 1.8 microg/ml) and leptin (36.9 +/- 4.0 ng/ml) than those in the control group (nonobese people: CRP = 6.9 +/- 0.9 microg/ml, p < 0.0001; leptin = 7.5 +/- 0.4 ng/ml, p < 0.0001). However, they had less NO (30.4 +/- 2.7 nmol/ml), IGF-1 (77.5 +/- 6.6 ng/ml), and adiponectin (11.1 +/- 1.0 microg/ml) than those in the control group (NO = 45.8 +/- 3.9 nmol/ml, p = 0.0059; IGF-1 = 202.0 +/- 12.0 ng/ml, p < 0.0001; adiponectin = 18.0 +/- 2.0 microg/ml, p < 0.0001). During weight loss, the amount of CRP and leptin decreased until they reached the nonobese values, but the level of NO remained lower than in nonobese people, even 1 year after surgery. The linear regression slopes were negative and very significant for leptin (p = 0.0005) and CRP (p = 0.0018) but were less significant for NO (p = 0.0221). IGF-1 displayed a very good linear regression (both negative and significant) with some anthropometric parameters, including body mass index (p = 0.0025), total fat (p = 0.0177), and the percentage of fat (p < 0.0001). CONCLUSION: For the first time, we report the relationship between IGF-1 and CRP, NO, leptin, and adiponectin. For all these parameters, the best and most widely demonstrated improvements in comorbidities before and during weight loss in morbid obesity were associated with CRP and leptin.

Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy.

PURPOSE: We determined the testosterone castration level with clinical relevance in patients with prostate cancer on continuous androgen deprivation therapy. Secondary objectives were to analyze the role of associated bicalutamide in breakthrough increases of serum testosterone in these patients and the possible benefit of maximal androgen blockade. MATERIALS AND METHODS: Serum testosterone was determined 3 times (in 6 months) in 73 patients with nonmetastatic prostate cancer treated with medical castration, 28 (38.4%) of whom also received bicalutamide (maximal androgen blockade). During a mean followup of 51 months (range 12 to 240) 41 (67.1%) events of androgen independent progression were identified, and correlated with breakthrough testosterone increases of 50 ng/dl (classic level) and 20 ng/dl (surgical castration level). RESULTS: Testosterone was less than 20 ng/dl in all determinations in 32 patients (43.6%). Breakthrough increases between 20 and 50 ng/dl were observed in 23 patients (31.5%), and increases greater than 50 ng/dl were observed in the remaining 18 (24.7%). The lowest testosterone level with a significant impact on survival free of androgen independent progression was 32 ng/dl. Mean survival free of androgen independent progression in patients with breakthrough increases greater than 32 ng/dl was 88 months (95% CI 55-121) while it was 137 months (95% CI 104-170) in those without breakthrough increases (p <0.03). Patients on maximal androgen blockade had an incidence of testosterone increase similar to those receiving monotherapy. However, maximal androgen blockade provided a significantly longer survival free of androgen independent progression in those with breakthrough increases greater than 50 ng/dl. CONCLUSIONS: In the current report the lowest testosterone castration level with clinical relevance in medically castrated patients with prostate cancer was 32 ng/dl. Breakthrough increases greater than this threshold predicted a lower survival free of androgen independent progression. Maximal androgen blockade might benefit medically castrated cases of prostate cancer with breakthrough increases of more than 50 ng/dl.

Failure to maintain a suppressed level of serum testosterone during long-acting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer.

OBJECTIVES: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. METHODS: Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. RESULTS: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. CONCLUSIONS: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

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

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.