D. Esposito

Female sexual dysfunction in women with thyroid disorders.

Background: Few data exist on the prevalence of female sexual dysfunction (FSD) in thyroid disorders. Aim: We evaluated FSD in women with thyroid diseases and in control age-matched healthy women to investigate the relationship between sexual function and thyroid hormones. Methods: One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group 1), 22 hypothyroidism (Group 2), 45 Hashimoto’s thyroiditis (Group 3), 19 nodular goiter (Group 4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function. Results: The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group 4, the prevalence (68.4%) was significantly higher than in controls (p<0.005). The mean total FSFI score was 20.1±7.1 in women with thyroid diseases and 25.6±4.7 in the controls (p<0.001). Compared with controls, there was a significant decrease of desire in Group 2; desire, arousal and lubrication in Group 3; desire, arousal, lubrication, orgasm and satisfaction in Group 4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r=−0.7, p=0.01) in Group 4, which showed the lowest FSFI score (17.8±5.7) and the highest body mass index (28.4±7.1 kg/m2). Conclusions: Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group 4 and a role for TSH in FSD, further researches are needed.

Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism

BACKGROUND In adult men, anti-Müllerian hormone (AMH) levels are higher in semen than in serum, but the significance and control of its seminal secretion are still unknown. This study evaluated seminal and serum AMH levels during long-term gonadotropin therapy in men with hypogonadotropic hypogonadism (HH). METHODS A total of 20 men with never treated prepubertal-onset HH received i.m. hCG to normalize testosterone (T) and induce puberty. Afterwards, 11 of them, requiring fertility, were treated with HCG plus recombinant FSH (rFSH) (75 IU) twice a week, whereas 9 continued to receive hCG alone for 12 months. Before and during therapy, serum AMH, inhibin B and T levels were assessed. Semen samples were also collected during therapy for sperm count and seminal AMH assay. RESULTS HCG alone decreased basal high serum AMH and stimulated T and inhibin B levels. rFSH plus hCG increased seminal AMH levels, which were consequently significantly higher than with hCG alone, and positively correlated to sperm densities and testicular volumes at 3 and 12 months (P < 0.001). CONCLUSIONS Our data demonstrate that rFSH, added to hCG, stimulates seminal AMH and spermatogenesis in HH. Thus, seminal AMH levels are under T and FSH control and are closely related to progression of spermatogenesis. Our results also suggest that an early seminal AMH increase may be a marker of good future response to gonadotropin therapy in HH.

ANTISPERM ANTIBODIES IN CRYPTORCHIDISM BEFORE AND AFTER SURGERY

PURPOSE We verified the prevalence of serum antisperm antibodies at diagnosis in a large group of cryptorchid boys, and determined whether it may be influenced by orchiopexy. MATERIALS AND METHODS We prospectively evaluated serum antisperm antibodies in 186 and 23 boys 0.67 to 14.25 years old with unilateral and bilateral cryptorchidism, respectively, before, and 3, 12 and 24 months after surgery. At diagnosis Tanner stage was 1 and 2 or 3 in 188 and 21 cases, respectively. During the 2-year followup 23 boys entered puberty. A total of 111 normal prepubertal (Tanner stage 1) and 54 pubertal (Tanner stage 2 or 3) boys served as controls. Antisperm antibodies were detected using the tray agglutination and indirect immunobead tests. RESULTS At diagnosis 29 cryptorchid boys (13.8%) were antisperm antibody positive, including 21 of the 188 prepubertal (11.1%) and 8 of the 21 pubertal (38%) boys (significantly different, chi-square test p <0.001). In 27 cases the tray agglutination test was positive with titers between 1:16 and 1:512, in 18 the indirect immunobead test was positive for IgG with titers between 1:10 and 1:100, and in 16 both tests were positive. There was no statistical difference when antisperm antibody results were analyzed for unilateral and bilateral cryptorchidism or testis location. All normal boys were antisperm antibody negative. During the 2-year followup antisperm antibodies appeared in 1 previously negative case, and the antibody titer increased to 128 to 512 in the tray agglutination and to 1:100 in the indirect immunobead tests in 4 positive cases. In all of these cases pubertal changes were also observed. CONCLUSIONS Our study indicates that cryptorchidism may elicit an autoimmune response against sperm antigen in childhood independent of testis location and orchiopexy. Moreover, patients of pubertal age appear to be at higher risk for antisperm antibody development.

Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism

Background: Recombinant-FSH (rFSH) added to hCG at dose of 450 IU weekly is effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism (HH), but there are no data on the use of lower doses. Aim: This observational retrospective study evaluated whether 150–225 IU of rFSH weekly were able to induce spermatogenesis in HH men who failed to start it with hCG alone. Subjects and methods: Thirty-four patients with pre-pubertal onset HH (20–44 yr old) without adverse fertility factors were considered for this study. After hCG pre-treatment they received also either rFSH (Group 1) or highly purified urinary FSH (hpFSH) (Group 2) 75 IU sc 2 or 3 times weekly. Semen analysis was performed every 3 months during pre-treatment and the 1st yr of combined therapy. Patients were also invited to refer pregnancies in their partners during the subsequent 12 months. Results: Total sperm count/ejaculate did not show significant difference between 2 groups, while a significantly higher forward motility was observed in Group 1 (p<0.05). The median times to achieve sperm output thresholds (first sperm appearance, sperm concentration >1.5 or >5 mil/ml) were significantly lower in Group 1 (p<0.04, 0.03, and 0.001, respectively). A tendency to a shorter time to pregnancy was shown in partners of Group 1. Conclusions: Our data indicate that lower rFSH week dose than that so far used was able to induce potentially fertilizing sperm output in HH men previously treated with hCG. The rFSH effects are comparable to those of hpFSH but with a trend to a faster outcome achievement.

Twenty-four hour melatonin pattern in acromegaly: Effect of acute octreotide administration

We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F; 23–52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 μg sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26–50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson’s correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p< 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p<:0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions

Hashimoto's thyroiditis and entero-chromaffin-like cell hyperplasia: Early detection and somatostatin analogue Treatment

Type IIIb polyglandular autoimmune disease comprises autoimmune thyroid disease (HT) and chronic atrophic gastritis (AIG). Hypergastrinemia, secondary to AIG, predisposes to gastric enterochromaffin-like cell (ECL) hyperplasia, a preneoplastic condition. We evaluated the prevalence of AIG, hypergastrinemia and ECL hyperplasia in HT patients. A secondary end-point was to assess the efficacy of treatment with a somatostatin analogue in HT patient with ECL hyperplasia. From 2009 to 2011, 146 HT patients were enrolled in a prospective study. All cases underwent hormonal profile, and parietal cell antibody (PCA), gastrin, and chromogranin A (CgA) serum level assays. Selected patients with elevated gastrin and CgA levels underwent gastro esophageal endoscopy (EGDS). Patients positive for ECL hyperplasia received Octreotide LAR 30 mg/28 days for 12 months. Gastrin and CgA assays were repeated every three months and EGDS after one year. The results show that gastrin and CgA were significantly higher than normal in 17/115 (14.7%) patients. Seven more HT had isolated PCA positivity and in the 17 PCA positive patients histology diagnosed AIG, corpus prevalent, with mild to moderate atrophy. Diffuse ECL hyperplasia of the gastric body was present in three subjects, one of them presenting a type-1 carcinoid. Gastrin and CgA levels were significantly reduced (p<0.01) after 3 months of therapy with a somatostatin analogue and returned to normal after 1 year. ECL hyperplasia regressed in all three patients. We suggest that selected HT patients may need a more accurate surveillance for early signs of gastric EC risk. In the case of altered values of gastrin and in the presence of PCA positivity, EGDS and histology should be performed for an early diagnosis of AIG and treatment of ECL hyperplasia.