Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship?

OBJECTIVE: A high prevalence of insulin resistance (IR) has proven to manifest in patients with adrenal incidentalomas (AI). It has been demonstrated that an increase in IR is related to the size of tumourous masses; additionally, luteinizing hormone (LH)-dependent adrenal pathologies are well documented in patients with LH-responsive adrenal tumours occurring under conditions of physiologically elevated LH. We hypothesized that an association between LH and insulin might play a role in adrenal tumourigenesis and steroidogenesis. DESIGN: The aim of our study was to investigate the association between LH and IR; adrenal tumour size (ATS) and IR; LH and cortisol after the 1 mg overnight dexamethasone test (1 mg DST); and ATS and 1 mg DST cortisol in AI patients. This was a case-control study conducted in the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Belgrade, Serbia. The total study group consisted of 105 menopausal women: 75 AI patients [27 with nonfunctional AI (NAI) and 48 with (possible) autonomous cortisol secretion ((P)ACS)] and 30 age-, BMI-, LH- and menopause duration-matched healthy control (HC) women. To estimate IR, we used homeostasis model assessment (HOMA-IR). RESULTS: Luteinizing hormone and ATS are in a significant positive correlation with HOMA-IR and 1 mg DST cortisol in menopausal patients with AI and (P)ACS. CONCLUSIONS: Our data point to a possible cause-effect relationship between LH and insulin in patients with AI and (P)ACS adding to the body of evidence of their involvement in adrenal tumourigenesis and steroidogenesis.

Influence of obesity and hormone disturbances on sexuality of women in the menopause.

OBJECTIVE: To assess influence of obesity and hormone disturbances on sexuality in the menopause. METHODS: The study included 73 menopausal women, who were divided into groups according to body mass index (BMI) ≥ 26.7 kg/m2. Anthropometric characteristics and blood pressure were measured. Blood was taken at 08:00 for hormones. All the participants filled in McCoy Female Sexual Questionnaire for the assessment of sexual life. STATISTICS: Student's t-test, correlation, analysis of variance (ANOVA). RESULTS: Follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) were very significantly lower in obese compared to controls. E2 and systolic blood pressure were very significantly, while diastolic blood pressure significantly higher in obese compared to controls. Obese women had significantly decreased frequency of pain during sexual intercourse (3.48 ± 2.64 vs. 4.09 ± 2.81). Influence of age on frequency of sexual intercourse was very significant. Significant influence in interaction between BMI and age on frequency of sexual fantasies as well as significant influence of BMI on satisfaction with partner as lover is also found. CONCLUSION: Obesity has influence on different aspects of sexuality in the postmenopausal women. Our results suggest the need of awareness toward obesity and its impact on sexuality in the menopause.

Obstructive Sleep Apnea Is Associated With Low Testosterone Levels in Severely Obese Men.

Background: Disrupted sleep affects cardio-metabolic and reproductive health. Obstructive sleep apnea syndrome represents a major complication of obesity and has been associated with gonadal axis activity changes and lower serum testosterone concentration in men. However, there is no consistent opinion on the effect of obstructive sleep apnea on testosterone levels in men. Objective: The aim of this study was to determine the influence of obstructive sleep apnea on total and free testosterone levels in severely obese men. Materials and methods: The study included 104 severely obese (Body Mass Index (BMI) ≥ 35 kg/m2) men, aged 20 to 60, who underwent anthropometric, blood pressure, fasting plasma glucose, lipid profile, and sex hormone measurements. All participants were subjected to polysomnography. According to apnea-hypopnea index (AHI) patients were divided into 3 groups: <15 (n = 20), 15 - 29.9 (n = 17) and ≥ 30 (n = 67). Results: There was a significant difference between AHI groups in age (29.1 ± 7.2, 43.2 ± 13.2, 45.2 ± 10.2 years; p < 0.001), BMI (42.8 ± 5.9, 43.2 ± 5.9, 47.1 ± 7.8 kg/m2; p = 0.023), the prevalence of metabolic syndrome (MetS) (55%, 82.4%, 83.6%, p = 0.017), continuous metabolic syndrome score (siMS) (4.01 ± 1.21, 3.42 ± 0.80, 3.94 ± 1.81, 4.20 ± 1.07; p = 0.038), total testosterone (TT) (16.6 ± 6.1, 15.2 ± 5.3, 11.3 ± 4.44 nmol/l; p < 0.001) and free testosterone (FT) levels (440.4 ± 160.8, 389.6 ± 162.5, 294.5 ± 107.0 pmol/l; p < 0.001). TT level was in a significant negative correlation with AHI, oxygen desaturation index (ODI), BMI, MetS and siMS. Also, FT was in a significant negative correlation with AHI, ODI, BMI, age, MetS and siMS. The multiple regression analysis revealed that both AHI and ODI were in significant correlation with TT and FT after adjustment for age, BMI, siMS score and MetS components. Conclusion: Obstructive sleep apnea is associated with low TT and FT levels in severely obese men.

Approach to the Patient with Subclinical Cushing's Syndrome.

A growing number of patients with adrenal incidentalomas and subclinical Cushing's syndrome (SCS) led to an increasing number of different guidelines, and diagnostic and treatment recommendations. Excess cortisol secretion in patients with SCS is associated with several comorbidities, such as hypertension, dyslipidemia, type 2 diabetes mellitus, and obesity, which in the long-term increase mortality of these patients. Subtle cortisol secretion affects bone health, quality of life and causes depression, but due to the unapparent clinical features, patients with SCS are often at risk between over and under treatment. This narrative review aimed to summarize the latest recommendations on the approach to the patient with subclinical Cushing's syndrome.

[Complete androgen insensitivity syndrome].

SUMMARY INTRODUCTION: Androgen insensitivity syndrome (AIS) belongs to disorders of sex development, resulting from complete or partial resistance to the biological actions of androgens in persons who are genetically males (XY) with normally developed testes and age-appropriate for males of serum testosterone concentration. CASE OUTLINE: A 21-year-old female patient was admitted at our Clinic further evaluation and treatment of testicular feminization syndrome, which was diagnosed at the age of 16 years.The patient had never menstruated. On physical examination, her external genitalia and breast development appeared as completely normal feminine structures but pubic and axillary hair was absent. Cytogenetic analysis showed a 46 XY karyotype. The values of sex hormones were as in adult males. The multi-sliced computed tomography (MSCT) showed structures on both sides of the pelvic region, suggestive of testes. Bilateral orchiectomy was performed. Hormone replacement therapy was prescribed after gonadectomy. Vaginal dilatation was advised to avoid dyspareunia. CONCLUSION: The diagnosis of complete androgen insensitivity is based on clinical findigs, hormonal analysis karyotype, visualization methods and genetic analysis. Bilateral gonadectomy is generally recommended in early adulthood to avoid the risk of testicular malignancy. Vaginal length may be short requiring dilatation in an effort to avoid dyspareunia. Vaginal surgery is rarely indicated for the creation of a functional vagina.

Premature ovarian failure.

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone), karyotype (<30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.