Domenico Canale

Androgen receptor polymorphism (CAG repeats) and androgenicity

Objective  Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism.

Free l-carnitine in human semen: its variability in different andrologic pathologies

Free L-carnitine was assayed in semen from patients with various andrologic diseases by an enzymatic-spectrophotometric method. Extremely low concentrations were found in semen from patients with agenesis of the vas deferens (31.8 +/- 18.8 nm/ml). Semen from men with vasectomies contains a higher concentration of free carnitine (105.0 +/- 8.1 nm/ml). When comparing these data with those of ten fertile control subjects (817.0 +/- 200 nm/ml), we assume that seminal free L-carnitine mainly originates from the epididymis. Semen from patients with azoospermia caused by testicular failure also contains a low carnitine concentration. In hypogonadotropic eunuchoids the gonadotropin treatment increased the low basal concentration. A correlation between semen carnitine content and sperm motility and number was also tested in 124 infertile patients. The results show a positive correlation between free L-carnitine and sperm count (r = 0.617; P less than 0.01), between free L-carnitine and sperm motility (r = 0.614; P less than 0.01), and between free L-carnitine and the number of motile spermatozoa per milliliter (r = 0.646; P less than 0.01).

Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis.

Summary. Nimesulide, a novel non‐steroidal anti‐inflammatory drug, was used in cases of abacterial prostato‐vesiculitis. Thirty patients with a mean age of 33.7 years (range 18–58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration‐time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH‐NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value ± SD of 0.58 ± 0.13 μg ml−1) and at the fourth hour for OH‐NIM (2.98 ± 0.38 μg ml−1). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 ± 2.34% for NIM; 31.87 ± 8.66% for OH‐NIM.

Testicular function after 131I therapy for hyperthyroidism

Objective  Radioiodine‐131 is commonly used for treatment of hyperthyroidism but there are few available data on the effects of this treatment on male gonadal function. The untoward effects of 131I have been mainly studied in male patients treated with high doses for thyroid cancer. In the present work we studied the absorbed radiation dose to the testes and testicular function in hyperthyroid men after 131I treatment.

Ultrasound monitoring of testis and prostate maturation in hypogonadotropic hypogonadic males during gonadotropin-releasing hormone treatment *

The effects of the administration of gonadotropin-releasing hormone (GnRH) on the increase of testis and prostate volume was monitored by ultrasound in six patients affected by idiopathic hypogonadotropic hypogonadism. A significant increase of testis volume was observed after 90 and 180 days (6.65 versus 3.32 mL, 99.1% net increase and 8.47 mL, 176.8% increase, respectively) of pulsatile GnRH treatment. A similar increase of prostate volume was observed at day 90 (12.67 versus 7.78 mL, 70.3% net increase) and day 180 (14.70 mL, 97.7% increase). The ultrasound monitoring of the modifications of testis and prostate volume may represent a biological assay of the effects of GnRH treatment and offer additional data on the response of target organs to the hormonal treatment.

Results of Vardenafil Mediated Power Doppler Ultrasound, Contrast Enhanced Ultrasound and Systematic Random Biopsies to Detect Prostate Cancer

PURPOSE We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. MATERIALS AND METHODS Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. RESULTS Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p <0.005 and <0.001, respectively). The detection rate of standard plus contrast or vardenafil enhanced power Doppler ultrasound was 10% and 11.7% (p not significant). CONCLUSIONS Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique.

Serum PSA levels are not affected by the menstrual cycle or the menopause, but are increased in subjects with polycystic ovary syndrome

Background/aims: Prostatic specific antigen (PSA) is the most specific prostatic tumor marker in man. Recently, PSA has been detected in a variety of tissues and fluids in women, and its determination suggested as a marker of hyperandrogenism. However, precise information about the physiology of PSA in females is not available. The goal of this study was to assess serum concentrations of PSA in healthy pre-menopausal women (healthy pre-menopausal group), menopausal women (menopause group) and patients with polycystic ovary syndrome (PCOS group). Methods: PSA, androgens, LH, FSH, 17-β-estradiol (E2), progesterone (Pg) were assessed in 40 post-menopausal women, 35 fertile controls and 35 women with PCOS. Results: No significant difference in PSA concentrations could be demonstrated in different phases of the menstrual cycle in healthy pre-menopausal group and between pre- and post-menopausal groups. No correlations could be demonstrated between serum PSA levels and the following parameters: age, body mass index (BMI), LH, FSH, E2, testosterone (T), DHEAS, and SHBG, both in pre- and post-menopausal women. Significantly higher PSA levels (median=14 pg/ml) were found in the PCOS group compared to both pre-menopausal (median=5 pg/ml) and menopausal (median= 5 pg/ml) groups (p<0.05). Conclusions: only minor fluctuations of serum PSA concentrations are observed in healthy pre- and post-menopausal women, while serum level is higher in PCOS, and therefore PSA can be considered a suitable marker of female hyperandrogenism.

Detection of a new de novo mutation at codon 251 of exon 8 of thyroid hormone receptor β gene in an Italian kindred with resistance to thyroid hormone

Resistance to thyroid hormone (RTH) is almost invariably associated with mutations of the thyroid hormone (TH) receptor β (hTRβ) gene and is inherited as an autosomal dominant disease. Mutations of hTRβ identified in patients affected by RTH cluster generally at two spots of the ligand binding domain. We investigated whether an Italian kindred with RTH had a mutation in the thyroid hormone (TH) receptor β gene. Blood samples were obtained from the available family members for biochemical and genetic analyses. Thyroid function tests in basal conditions, and in the case of the propositus also following incremental doses of T3, were performed. Exon 4 to 10 of hTRβ gene were amplified using the polymerase chain reaction (PCR) and the mutation was identified by direct sequence analysis. The affinity constant of this mutated receptor for T3 was measured by in vitro transcription-translation and was then compared with that of wild type. We identified a heterozygous G to A transition at nucleotide 1037 of exon 8 at codon 251, resulting in a glycine (G) to glutamic acid (E) substitution (G251E) in the patient affected by RTH and in his affected offspring, but not in the normal family members. This novel mutation represents a de novo mutation since both parents of the index case were unaffected and did not have this genomic mutation. When expressed in vitro, the mutant protein (G251E) showed a marked decrease of the affinity for T3, suggesting an impaired ligand-dependent transactivation activity of this mutant receptor. In vivo studies with incremental doses of L-T3 demonstrated a reduced sensitivity to TH in the index case, in particular at the pituitary level where the thyrotrophs’ activity was not completely inhibited even by 200 µg/day of L-T3. G251E mutation represents the fourth mutation described up to now in exon 8 of hTRβ among the subjects affected by RTH. A third cluster of mutations of the c-erbA β gene located proximally with respect to the other two so far described begins to emerge in RTH patients.

Effects of radioiodine treatment for differentiated thyroid cancer on testis function

To evaluate the effects of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on testis function.

Follow-Up of Patients After Male-to-Female (Mtf) Sex Reassignment Surgery (SRS)

Following surgery and legalization of the gender reassignment, long-term physical, sexual, hormonal, and psychological follow-up is necessary to establish and maintain the success of the procedure. Since persistent regret after sex reassignment surgery must be considered, along with suicide, as the worst conceivable outcome of SRS [1], it is crucial to know the opinion of patients when evaluating the cosmetic and functional results of the surgery [2].