ABSTRACT
BACKGROUND: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify. OBJECTIVE: We describe KS clinical presentation in a large Italian cohort. DESIGN: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution. METHODS: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients. RESULTS: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis. CONCLUSIONS: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.
Subject(s)
Hypogonadism , Klinefelter Syndrome , Metabolic Syndrome , Follicle Stimulating Hormone/therapeutic use , Humans , Hypogonadism/drug therapy , Klinefelter Syndrome/complications , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/epidemiology , Male , Metabolic Syndrome/complications , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Testis , Testosterone/therapeutic useABSTRACT
BACKGROUND: The familial nonmedullary thyroid cancer (FNMTC) is suspected to be a Mendelian condition in up to 3-8% of thyroid cancers. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. The inheritance of FNMTC appears to be autosomal dominant with incomplete penetrance and variable expressivity. The finding of the causative gene of FNMTC and the identification of patients at risk that need genetic testing were our aim. METHODS: We analyzed by whole-exome sequencing patients and non-affected relatives of five families with at least two family members affected by papillary thyroid cancer, selecting for new or extremely rare variants with predicted pathogenic value. RESULTS: A family showed, in all three affected members, a new loss-of-function variant (frameshift deletion) in BROX gene at 1q41 that was absent from all internal and external databases. In a second family with three affected relatives, we found an additional new BROX variant. The smaller families presented no variants in BROX or in the other causative genes studied. CONCLUSIONS: BROX could be a new causative gene for FNMTC. Variants in BROX may result in the haploinsufficiency of a key gene involved in the morphogenesis of MVBs, in the endosomal sorting of cargo proteins, and in EGFR. Functional studies are needed to support this result. The thorough genomic analysis by NGS in all families with three or more affected members should become a routine approach to obtain a comprehensive genetic view and find confirmative second cases.
Subject(s)
Endosomal Sorting Complexes Required for Transport/genetics , Genetic Predisposition to Disease , Germ-Line Mutation , Haploinsufficiency , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Adult , Female , Genetic Testing , Humans , Male , Middle Aged , Prognosis , Thyroid Cancer, Papillary/etiology , Thyroid Cancer, Papillary/metabolism , Thyroid Neoplasms/etiology , Thyroid Neoplasms/metabolismABSTRACT
PURPOSE: We aimed to verify if 1 year-testosterone-replacement therapy could produce a psychopathological recovery and a satisfactory quality of life in Klinefelter syndrome (KS) patients compared to matched healthy controls. Further, we analyzed personality traits and coping strategies, an issue not yet examined in androgen-treated KS patients. We also enquired whether any of the sociodemographic and psychological variables might predict a patient's general and sexual life satisfaction. METHODS: The Quality of Life Enjoyment and Satisfaction Questionnaire and the Temperament and Character Inventory-Revised were administered to both 23 KS patients and matched healthy subjects. Psychopathology was investigated by the Symptom Checklist-90-Revised (SCL-90-R) and the Mini-mental State Examination. The COPE Inventory was used to identify cognitive and behavioral strategies to manage disease-related distress. RESULTS: In testosterone-treated KS patients, when compared with controls, SCL-90-R subscales analysis evidenced high psychological distress, mainly presented as obsessive thoughts, hanger-hostility, phobias, and psychoticism. Self-directedness and self-transcendence, along with the prevalent use of emotion-focused coping strategies, outlined the personality of our KS patients. Depression and somatization proved to be predictors of general life dissatisfaction. Depression, anger-hostility, and paranoid ideation, instead, emerged as predictors of sexual life dissatisfaction. CONCLUSION: Endocrinologists should cooperate with mental health providers to foster a better outcome of the disease in KS patients.
Subject(s)
Adaptation, Psychological/physiology , Cognition , Hormone Replacement Therapy , Klinefelter Syndrome , Quality of Life , Testosterone/therapeutic use , Adult , Hormone Replacement Therapy/methods , Hormone Replacement Therapy/psychology , Humans , Italy/epidemiology , Klinefelter Syndrome/epidemiology , Klinefelter Syndrome/psychology , Klinefelter Syndrome/therapy , Male , Mental Health , Mental Status and Dementia Tests , Personality Assessment , Psychological Distress , Sexual BehaviorABSTRACT
PURPOSE: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. METHODS: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. RESULTS: High IGF-I levels (ULN 1.01-1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma. CONCLUSION: The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.
Subject(s)
Acromegaly/epidemiology , Prolactinoma/physiopathology , Acromegaly/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Prevalence , Prognosis , Prospective Studies , Young AdultABSTRACT
PURPOSE: Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. METHODS: We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. RESULTS: Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. CONCLUSION: TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.
Subject(s)
Klinefelter Syndrome/drug therapy , Testosterone/therapeutic use , Adult , Body Composition/drug effects , Body Mass Index , Bone Density/drug effects , Humans , Hypogonadism/blood , Hypogonadism/drug therapy , Hypogonadism/epidemiology , Hypogonadism/etiology , Klinefelter Syndrome/blood , Klinefelter Syndrome/complications , Klinefelter Syndrome/epidemiology , Male , Middle Aged , Testosterone/bloodABSTRACT
PURPOSE: Serum-negative-chronic-autoimmune-thyroiditis (SN-CAT) is considered a milder variant of classic Hashimoto's thyroiditis (CHT). However, its prevalence remains unknown and it is still unclear whether SN-CAT behaves differently in terms of L-thyroxine (LT4) substitution treatment of hypothyroidism. Aims of this study were to estimate the prevalence of SN-CAT in a large series of hypothyroid patients and to compare LT4 requirements in hypothyroid patients with SN-CAT and CHT. METHODS: Five-hundred-eighty-one consecutive patients with primary-autoimmune-hypothyroidism were enrolled in a cross-sectional study. LT4 requirements and thyroid-volume changes were longitudinally evaluated in 49 hypothyroid patients with SN-CAT and in 98 sex and age-matched hypothyroid patients with CHT. RESULTS: In our series the prevalence of SN-CAT was 20.8%. At diagnosis, patients in the CHT and SN-CAT groups had similar male/female ratio, age and BMI, while serum TSH and thyroid-volume were significantly greater in the CHT group. In the longitudinal study, during a follow-up of 8.9 ± 4.6 years, 8 out of 49 (16.3%) SN-CAT patients developed positive tests for of circulating TPO-Ab and/or Tg-Ab. Thyroid-volume significantly decreased in CHT patients, but not in those with SN-CAT. The maximum daily substitution dose of LT4 was smaller in SN-CAT patients as compared with the CHT ones. Multivariate analysis showed that age, BMI, basal TSH and thyroid antibody status independently and significantly predicted the maximum daily substitution dose of LT4. CONCLUSIONS: SN-CAT accounts for a significant proportion of patients with autoimmune hypothyroidism. Compared with hypothyroid patients diagnosed with CHT, the SN-CAT ones require smaller doses of LT4 to correct their hypothyroidism.
Subject(s)
Hashimoto Disease/drug therapy , Thyroiditis, Autoimmune/drug therapy , Thyroxine/administration & dosage , Adult , Aged , Autoantibodies/blood , Case-Control Studies , Chronic Disease , Cross-Sectional Studies , Dose-Response Relationship, Drug , Female , Hashimoto Disease/blood , Hashimoto Disease/diagnosis , Hashimoto Disease/epidemiology , Hormone Replacement Therapy/methods , Humans , Hypothyroidism/blood , Hypothyroidism/diagnosis , Hypothyroidism/drug therapy , Hypothyroidism/epidemiology , Longitudinal Studies , Male , Middle Aged , Thyroid Hormones/blood , Thyroiditis/blood , Thyroiditis/diagnosis , Thyroiditis/drug therapy , Thyroiditis/epidemiology , Thyroiditis, Autoimmune/blood , Thyroiditis, Autoimmune/diagnosis , Thyroiditis, Autoimmune/epidemiology , Thyrotropin/blood , UltrasonographyABSTRACT
PURPOSE: The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between patients with KS and hypogonadism due to other causes (Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, iatrogenic hypogonadism and acquired hypogonadotropic hypogonadism after surgical removal of pituitary adenomas) called non-KS. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. METHODS: This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred and seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and Chi-square test. RESULTS: FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. CONCLUSIONS: We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.
Subject(s)
Klinefelter Syndrome/physiopathology , Thyroid Gland/physiology , Academic Medical Centers , Adolescent , Adult , Aged , Case-Control Studies , Female , Hashimoto Disease/blood , Hashimoto Disease/physiopathology , Humans , Hypogonadism/blood , Hypogonadism/physiopathology , Italy , Klinefelter Syndrome/blood , Male , Middle Aged , Thyroid Diseases/blood , Thyroid Diseases/physiopathology , Thyroid Function Tests , Thyroid Hormones/blood , Thyrotropin/blood , Young AdultABSTRACT
Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.
Subject(s)
Cardiovascular Abnormalities/etiology , Klinefelter Syndrome/complications , Metabolic Syndrome/etiology , Humans , Risk FactorsABSTRACT
Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients' interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.
Subject(s)
Hypogonadism/genetics , Hypogonadism/pathology , Klinefelter Syndrome/genetics , Klinefelter Syndrome/pathology , Humans , PhenotypeABSTRACT
BACKGROUND: The real efficacy of selenium supplementation in Hashimoto's thyroiditis (HT) is still an unresolved issue. OBJECTIVES: We studied the short-term effect of L-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of L-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. METHODS: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive L-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. RESULTS: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. CONCLUSION: The short-term L-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term L-selenomethionine supplementation in HT.
Subject(s)
Biomarkers/blood , Hashimoto Disease/drug therapy , Selenium/administration & dosage , Adolescent , Adult , Dietary Supplements , Female , Humans , Immunoassay , Middle Aged , Prognosis , Prospective Studies , Selenium/blood , Thyroid Hormones/blood , Young AdultABSTRACT
Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B2[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4 mm arachidonic acid (AA). A ≥ 50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ = -0.548, p < 0.001) and with 11-dehydro-TXB2 (ρ = -0.523, p < 0.001). In a linear regression model, KS independently predicted a lower AC-50% (ß = -0.597, p < 0.001) and higher levels of 8-iso-PGF2α (ß = 0.709, p < 0.001) and 11-dehydro-TXB2 (ß = 0.605, p < 0.001). In contrast, no correlation has been found between max-A%, testosterone and estradiol levels in KS. We observed increased platelet reactivity in KS. This might, at least in part, explain the increased thrombotic risk associated with this disease.
Subject(s)
Blood Platelets/metabolism , Klinefelter Syndrome/blood , Platelet Activation/immunology , Platelet Aggregation/physiology , Adult , Cardiovascular Diseases , Creatinine/metabolism , Cross-Sectional Studies , Dinoprost/analogs & derivatives , Dinoprost/metabolism , Estradiol/blood , Humans , Male , Risk Factors , Testosterone/blood , Testosterone/therapeutic use , Thromboxane B2/analogs & derivatives , Thromboxane B2/metabolismABSTRACT
AIM: Routine central neck dissection for differentiated thyroid cancer (DTC) to prevent a future recurrence is still a matter of discussion, due to the increased risk of injury to parathyroid glands, without a clear demonstrable benefits in terms of long-term survival. Aim of this study was to investigate if, treating patients with total thyroidectomy (TT) without prophylactic central lymphadenectomy can minimize the risk of hypocalcemia by routine administration of oral calcium and vitamin D supplements, providing at the same time a low recurrence rate. METHODS: In the set of a retrospective study, 221 patients affected by DTC were enrolled. All of them underwent to TT without prophylactic central lymphadenectomy. In the early postoperative period, oral calcium 2g/d taken twice (1 g every 12 hours) and vitamin D 1 g/d taken twice (0.5 g every 12 hours) were administered; changes in serum calcium and hypocalcemia-related symptoms were recorded. Follow-up was based on neck ultrasound and monitoring of serum Tg and Tg-antibodies levels every 6 months during suppressive l-tiroxine treatment. RESULTS: Symptomatic hypocalcemia developed only in 6.3% of patients, whereas laboratory hypocalcemia developed in 10%. Hypocalcemic symptoms were minimal in 4 patients. Intravenous calcium was administered to 6 patients with severe hypocalcemic symptoms. Permanent hypocalcemia developed in two patients. CONCLUSION: Until a conclusive evidence of the actual benefit of prophylactic central lymphadenectomy in the treatment of DTC, it may be avoided. The oral calcium and vitamin D supplements can take a role in the prevention of postoperative hypocalcemia and for increasing the likelihood of a safe and early discharge from the hospital.
Subject(s)
Calcium/administration & dosage , Hypocalcemia/prevention & control , Neoplasm Recurrence, Local/prevention & control , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Vitamin D/administration & dosage , Vitamins/administration & dosage , Administration, Oral , Adult , Combined Modality Therapy , Female , Humans , Lymph Node Excision , Male , Neck Dissection , Neoplasm Recurrence, Local/epidemiology , Retrospective StudiesABSTRACT
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/m(2)). 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.
Subject(s)
Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunctions, Psychological/epidemiology , Thyroid Diseases/epidemiology , Adult , Body Mass Index , Female , Goiter, Nodular/complications , Goiter, Nodular/epidemiology , Humans , Italy/epidemiology , Menopause , Middle Aged , Premenopause , Prevalence , Sexual Dysfunction, Physiological/etiology , Sexual Dysfunctions, Psychological/etiology , Thyroid Diseases/complications , Thyrotropin/bloodABSTRACT
Multiple endocrine neoplasia syndromes have since been classified as types 1 and 2, each with specific phenotypic patterns. MEN1 is usually associated with pituitary, parathyroid and paraneoplastic neuroendocrine tumours. The hallmark of MEN2 is a very high lifetime risk of developing medullary thyroid carcinoma (MTC) more than 95% in untreated patients. Three clinical subtypesdMEN2A, MEN2B, and familial MTC (FMTC) have been defined based on the risk of pheochromocytoma, hyperparathyroidism, and the presence or absence of characteristic physical features). MEN2 occurs as a result of germline activating missense mutations of the RET (REarranged during Transfection) proto-oncogene. MEN2-associated mutations are almost always located in exons 10, 11, or 13 through 16. Strong genotype-phenotype correlations exist with respect to clinical subtype, age at onset, and aggressiveness of MTC in MEN2. These are used to determine the age at which prophylactic thyroidectomy should occur and whether screening for pheochromocytoma or hyperparathyroidism is necessary. Specific RET mutations can also impact management in patients presenting with apparently sporadic MTC. Therefore, genetic testing should be performed before surgical intervention in all patients diagnosed with MTC. Recently, Pellegata et al. have reported that germline mutations in CDKN1B can predispose to the development of multiple endocrine tumours in both rats and humans and this new MEN syndrome is named MENX and MEN4, respectively. CDKN1B. A recent report showed that in sporadic MTC, CDKN1B V109G polymorphism correlates with a more favorable disease progression than the wild-type allele and might be considered a new promising prognostic marker. New insights on MEN syndrome pathogenesis and related inherited endocrine disorders are of particular interest for an adequate surgical and therapeutic approach.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p27/genetics , Multiple Endocrine Neoplasia/genetics , Polymorphism, Genetic , Protein Kinase Inhibitors/metabolism , Adrenal Gland Neoplasms/genetics , Alleles , Animals , Biomarkers/blood , Disease Progression , Exons , Genotype , Humans , Hyperparathyroidism/genetics , Multiple Endocrine Neoplasia/diagnosis , Multiple Endocrine Neoplasia/surgery , Multiple Endocrine Neoplasia Type 1/genetics , Multiple Endocrine Neoplasia Type 2a/genetics , Multiple Endocrine Neoplasia Type 2b/genetics , Mutation, Missense , Phenotype , Pheochromocytoma/genetics , Proto-Oncogene Mas , Risk Assessment , Risk Factors , Syndrome , Thyroid Neoplasms/genetics , Thyroidectomy , Treatment OutcomeABSTRACT
AIM: to evaluate the role of pre and post-operative oral calcium and vitamin D supplements in prevention of hypocalcemia after total thyroidectomy. PATIENTS AND METHODS: 50 consecutive patients, undergoing total thyroidectomy, were enrolled. Oral calcium and vitamin D were administered in the pre and post-operative time. The data concerning symptomatic and laboratoristic hypocalcemia were collected. RESULTS: Incidence of symptomatic hypocalcemia was very low (6%); incidence of laboratoristic hypocalcemia was 10%. No permanent hypocalcemia developed. CONCLUSIONS: Implementing oral calcium and vitamin D both before and after total thyroidectomy can reduce the incidence of hypocalcemia related to surgery.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Calcium/administration & dosage , Hypocalcemia/etiology , Hypocalcemia/prevention & control , Thyroidectomy/adverse effects , Vitamin D/administration & dosage , Administration, Oral , Adult , Female , Humans , Hypocalcemia/epidemiology , Incidence , Italy/epidemiology , Male , Middle Aged , Postoperative Period , Preoperative Period , Thyroidectomy/methods , Treatment OutcomeABSTRACT
BACKGROUND: Pubertal gynecomastia is a common problem occurring in up to 65% of adolescent boys. Gynecomastia comes at a time when self-image awareness is at its greatest and psychologically could be a psychologically disabling condition. Surgery is considered the mainstay of treatment for severe or persistent cases. A medical management aimed at altering the effective androgen/estrogen ratio has been suggested with inconstant results. Some promising results have been obtained by using anti-estrogens. Surprisingly there are no data on the estrogen receptor (ER) α and ß RNA expression in gynecomastia. AIM: We studied ER RNA subtypes in pubertal gynecomastia. METHODS: ERα and ß RNA were determined by real time RT-PCR in 50 mammary samples from pubertal boys with idiopathic gynecomastia subjected to reductive mammoplasty. To study ERα and ß pattern of expression, epithelial and stromal primary cell cultures were set up from fresh tissues. RESULTS: These analyses indicated that in all stromal cells ERß was expressed at higher level than ERα and in epithelial cells both ERα and ERß were barely detectable. CONCLUSIONS: Our data suggest that also stromal cells are involved in the pathophysiology of pubertal gynecomastia. The high level of expression of ERß seen in pubertal gynecomastia adds new insight on validation of ERß as a target for candidate diseases and exploration of ERß as a marker for clinical decision-making and treatment in pubertal gynecomastia. This could drive to search for new and selective anti-estrogen drugs for medical treatment of pubertal gynecomastia with a particular attention to the ERß-selective ligand.
Subject(s)
Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Gynecomastia/genetics , Puberty , Adolescent , Cells, Cultured , Child , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Gene Expression Regulation , Gynecomastia/metabolism , Gynecomastia/pathology , Humans , Male , Primary Cell Culture , Puberty/genetics , Puberty/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Tissue DistributionABSTRACT
Nearly 70 years after its description, Klinefelter syndrome (KS) remains a largely undiagnosed condition. As its clinical presentation may be subtle, many of those affected may be unaware or diagnosed only during evaluation for hypogonadism and/or infertility. In February 2010 an interdisciplinary panel of specialists met in Abano Terme (Padua, Italy) in a workshop on "Klinefelter Syndrome: diagnosis and clinical management". The main aim of this meeting was to discuss several aspects related to the epidemiology, pathogenesis, and evaluation of KS and to develop a consensus defining its early diagnosis and treatment. In the present consensus we have highlighted the features that may prompt the physicians to look after patients with KS both for the syndrome and correlated diseases. We have provided evidences that, during the different phases of life, there might be some advantages in establishing the diagnosis and starting proper follow-up and treatment. The workshop was carried out under the auspices of the Italian Society of andrology and Sexual Medicine (SIAMS).
Subject(s)
Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/therapy , Adolescent , Adult , Child , Cognition , Diabetes Mellitus/etiology , Gonadal Steroid Hormones/blood , Humans , Infant, Newborn , Klinefelter Syndrome/complications , Male , Metabolic Syndrome/etiology , Osteoporosis/etiology , Puberty/physiologyABSTRACT
OBJECTIVE: The occurrence of antipituitary antibodies (APA) in patients with idiopathic hyperprolactinaemia (IH) and the effects of dopamine agonists on these antibodies and long-term pituitary function outcome have been so far not evaluated. This longitudinal study was aimed at investigating, in patients with IH the occurrence of APA and the effect of cabergoline on the pituitary function and behaviour of APA. DESIGN: Sixty-six patients with IH were studied. APA (by indirect immunofluorescence) and pituitary function were investigated every year for 3 years. RESULTS: Seventeen patients resulted APA positive (Group 1) and 49 APA negative (Group 2). Eight patients of Group 1 (Group 1a) and 24 of Group 2 (Group 2a) were asymptomatic and then not treated; instead, nine patients in Group 1 (Group 1b) and 25 in Group 2 (Group 2b), showing symptoms of hyperprolactinaemia, were treated with cabergoline for 2 years. Among the untreated patients, during the follow-up, those with APA positive (Group 1a) showed an increase of APA titres and PRL levels with partial pituitary impairment in some of them; instead those with APA negative (Group 2a) persisted negative with normal pituitary function despite persistent hyperprolactinaemia. Among the treated patients, those with APA positive (Group 1b) showed normalization of PRL levels, APA disappearance and recovery of pituitary function (when initially impaired) during cabergoline treatment, persisting also at last observation (off-therapy). Instead all patients of Group 2b persisted with APA negative during the follow-up with normalization of PRL levels and stable normal pituitary function during cabergoline therapy but showing a further increase of PRL at the last observation. CONCLUSIONS: The presence of APA in some patients with IH suggests a possible occurrence of autoimmune hypophysitis at potential/subclinical stage; an early and prolonged cabergoline therapy could interrupt the progression to an overt clinical stage of the disease. However, the small amount of patients investigated suggests caution against generalization of our assumption and prompts to further controlled studies on a more numerous population to verify these conclusions.
Subject(s)
Autoantibodies/blood , Ergolines/pharmacology , Ergolines/therapeutic use , Hyperprolactinemia/drug therapy , Hyperprolactinemia/immunology , Pituitary Gland/drug effects , Adult , Autoimmune Diseases/chemically induced , Autoimmune Diseases/epidemiology , Cabergoline , Cohort Studies , Dopamine Agonists/adverse effects , Dopamine Agonists/pharmacology , Dopamine Agonists/therapeutic use , Ergolines/adverse effects , Female , Hormone Antagonists/adverse effects , Hormone Antagonists/pharmacology , Hormone Antagonists/therapeutic use , Humans , Hyperprolactinemia/blood , Hyperprolactinemia/epidemiology , Longitudinal Studies , Male , Pituitary Diseases/chemically induced , Pituitary Diseases/epidemiology , Pituitary Function Tests , Pituitary Gland/immunology , Pituitary Gland/physiopathology , Seroepidemiologic Studies , Thyroid Hormones/blood , Thyrotropin/blood , Time FactorsABSTRACT
Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied class of chemopreventive drugs for PCa. Retinoids play a key role in several vital functions as vision and development, and also exert anti-proliferative actions. Anti-proliferative effects of retinoids rely on the regulation of many biological processes, including differentiation, cell proliferation, and apoptosis. Retinoid actions are mediated by two classes of nuclear proteins called retinoic acid (RARalpha,beta and gamma and retinoic alpha,beta and gamma receptors, which are ligand-regulated transcription factors. Effects of both all-trans-retinoic acid (RA), the natural active derivative of vitamin A, and its synthetic derivatives, on prostate gland or prostate cell lines implicate retinoids in the regulation of prostate growth and suppression of PCa development. Deficient retinoid availability and action at the cellular level because of either decreased content or altered metabolism in PCa cells can play a key role in abnormal cellular differentiation pathways, and the loss of anti-proliferative effects. Here we review the in vitro and in vivo effects of retinoids in PCa.
Subject(s)
Prostatic Neoplasms/prevention & control , Retinoids/pharmacology , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Humans , Male , Molecular Structure , Prostate/drug effects , Prostate/pathology , Prostate/physiopathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Retinoids/chemistry , Retinoids/therapeutic useABSTRACT
A high percentage of men aged 60 or older have satisfactory sexual activity, even if reduced sexual desire, frequency of intercourses and erections, impaired satisfaction with sex and difficulty with orgasm, and decreased semen volume frequently occur. The present report analyses the following issues: erectile dysfunction, fertility, the role of hormones in influencing libido and erection mechanisms, and the therapeutic strategies suggested.