Bone: A Neglected Endocrine Organ?

Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects.

The impact of water pollution on the health of older people.

Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature onset of age-related health problems. Water pollutants can in general be classified as chemical (both organic and inorganic), physical, and biological agents. Certain chemical pollutants have been found to disrupt hormonal balance by blocking, mimicking, or disrupting functions within the intricate homeostasis of the human body. Moreover, certain water pollutants, including specific pesticides and industrial chemicals, have been associated with neurological and psychiatric disorders, such as mood swings, depression, cognitive decline, and anxiety, impacting both women and men. Water pollution is also associated with physical ailments, such as diarrhea, skin diseases, malnutrition, and cancer. Exposure to specific pollutants may promote premature menopause and vasomotor symptoms, elevate the risk of cardiovascular disease, and reduce bone density. In men, exposure to water pollution has been shown to reduce LH, FSH, and testosterone serum levels. The oxidative stress induced by pollutants prompts apoptosis of Sertoli and germ cells, inhibiting spermatogenesis and altering the normal morphology and concentration of sperm. Environmental estrogens further contribute to reduced sperm counts, reproductive system disruptions, and the feminization of male traits. Studies affirm that men generally exhibit a lower susceptibility than women to hormonal changes and health issues attributed to water pollutants. This discrepancy may be attributed to the varied water-related activities which have traditionally been undertaken by women, as well as differences in immune responses between genders. The implementation of effective measures to control water pollution and interventions aimed at safeguarding and enhancing the well-being of the aging population is imperative. The improvement of drinking water quality has emerged as a potential public health effort with the capacity to curtail the onset of cognitive impairment and dementia in an aging population.

Association of Obesity and Bariatric Surgery on Hair Health.

Obesity and obesity-related conditions today constitute a public health problem worldwide. Obesity is an "epidemic" chronic disorder, which is defined by the WHO as normal or excessive fat accumulation that may impair health. It is also defined for adults as a BMI that is greater than or equal to 30. The most common obesity-related diseases are type 2 diabetes mellitus, cardiovascular diseases, metabolic syndrome, chronic kidney disease, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, and certain types of cancer. It has been also proven that obesity can have a negative effect on hair. It can lead to hair thinning. Patients with obesity can undergo bariatric surgery if they meet the inclusion criteria. The four common types of weight loss surgery include a duodenal switch with biliopancreatic diversion, laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, and sleeve gastrectomy. Bariatric surgery can affect skin and hair and is associated with telogen effluvium due to weight loss, microelement deficiency, anesthesia, low calorie intake, and low protein intake. Patients who undergo bariatric surgery can experience post-bariatric surgery depression. Hair loss can have a major impact on self-esteem, negatively affecting one's self-image. The purpose of this narrative review is to critically review how obesity, obesity-related diseases, and bariatric surgery affect hair health in general and the hair development cycle, and how they influence hair loss.

Analysis of the Polymorphisms and Expression Levels of the BCL2, BAX and c-MYC Genes in Patients with Ovarian Cancer.

Ovarian cancer (OC) is one of the biggest problems in gynecological oncology and is one of the most lethal cancers in women worldwide. Most patients with OC are diagnosed at an advanced stage; therefore, there is an urgent need to find new biomarkers for this disease. Gene expression profiling is proving to be a very effective tool for exploring new molecular markers for OC patients, although the relationship between such markers and patient survival and clinical outcomes is still elusive. Moreover, polymorphisms in genes encoding both apoptosis-associated proteins and oncoproteins may serve as key markers of cancer susceptibility. The aim of our study was to analyze the polymorphisms and expressions of the BCL2, BAX and c-MYC genes in a group of 198 women, including 98 with OC. The polymorphisms and mRNA expressions of the BCL2, BAX and c-MYC genes were analyzed using real-time PCR. The analysis of the BAX (rs4645878; G>A) and c-MYC (rs4645943; C>T) polymorphisms showed no association with ovarian cancer risk. The BCL2 polymorphism (rs2279115; C>A) showed a significant difference in the frequency of genotypes between the studied groups (CC: 23.47% vs. 16.00%, AA: 25.51% vs. 37.00%; p = 0.046; OR = 1.61). Furthermore, the expression levels of the BCL2 and c-MYC genes showed a decrease at the transcript level for OC patients compared to the control group (BCL2: 17.46% ± 3.26 vs. 100% ± 8.32; p < 0.05; c-MYC: 37.56% ± 8.16 vs. 100% ± 9.12; p < 0.05). No significant changes in the mRNA level were observed for the BAX gene (104.36% ± 9.26 vs. 100% ± 9.44; p > 0.05). A similar relationship was demonstrated in the case of the protein expressions of the studied genes. These findings suggest that the CC genotype and C allele of the BCL2 polymorphism could be genetic risk factors for OC development. A gene expression analysis indicated that BCL2 and c-MYC are associated with OC risk.

Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new addition to the therapeutic arsenal for the metabolic management of PCOS. GLP-1 receptor agonists cause insulin release in a glucose-dependent manner, yielding clinical benefits such as heightened satiety, reduced appetite, and appetite regulation. GLP-1RAs have demonstrated efficacy in reducing glycated hemoglobin levels and promoting weight loss while ameliorating hyperlipidemia. Prior to initiating GLP-1RA therapy, patients should undergo screening for contraindications, including history of pancreatitis, diabetic retinopathy, or thyroid cancer. The effects of treatment should be monitored using laboratory testing and body weight measurements. Effective communication between clinician and patient should be maintained with regular check-in for a period of 6 to 12 months.

Managing Early Onset Osteoporosis: The Impact of Premature Ovarian Insufficiency on Bone Health.

Premature ovarian insufficiency is a reproductive endocrine disorder characterized by the cessation of ovarian function before the age of 40 years. Although the etiopathology of POI remains largely unknown, certain causative factors have been identified. Individuals affected by POI are at an increased risk of experiencing bone mineral density (BMD) loss. Hormonal replacement therapy (HRT) is recommended for patients with POI to mitigate the risk of decreased BMD, starting from the time of diagnosis until reaching the average age of natural menopause. Various studies have compared the dose-effect relationship of estradiol supplementation, as well as different HRT formulations on BMD. The impact of oral contraception on reduced BMD or the potential benefits of adding testosterone to estrogen replacement therapy are still subjects of ongoing discussion. This review provides an overview of the latest advancements in the diagnosis, evaluation, and treatment of POI as it relates to BMD loss.

Decreased neurokinin B as a risk factor of functional hypothalamic amenorrhea.

BACKGROUND: Neurokinin B (NKB) belongs to the tachykinin family of proteins who's regulation is essential for proper function of the reproductive system. It has been shown that patients with functional hypothalamic amenorrhea (FHA) exhibit decreased levels of serum kisspeptin. As kisspeptin secretion is regulated by NKB signaling, it is reasonable to suspect that patients with FHA will also have abnormal NKB secretion. AIM: To assess NKB levels in patients with FHA and to determine whether NKB signaling is affected in these patients. We hypothesized that decreased NKB signaling is a factor contributing to the development of the FHA. MATERIALS AND METHODS: A total of 147 patients with FHA and 88 healthy age-matched controls were enrolled. Baseline blood samples were drawn from both groups to measure serum concentrations of NKB, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (fT4), cortisol, dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), glucose, and insulin. RESULTS: Mean serum NKB levels were found to be decreased significantly in the FHA group when compared with the control group (628.35 ± 324.92 vs. 721.41 ± 337.57 ng/L, respectively p = 0.002). No statistical difference was observed in NKB-1 levels within the FHA group when selecting for normal and decreased body mass index. CONCLUSIONS: Patients with FHA were found to have decreased serum NKB concentrations when compared to healthy controls. Abnormal NKB secretion is likely a key factor contributing to development of FHA.

PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. A diagnosis of PCOS is established when a patient exhibits two of three Rotterdam criteria: oligoovulation or anovulation, excess androgen activity, and polycystic ovarian morphology. The pathogenesis of PCOS, as it affects adolescents, is often discussed in terms of a "two-hit" theory. This refers to a stepwise process in which the first "hit" is an inborn congenitally programmed predisposition, while the second "hit" arises from a provocative factor such as insulin resistance. The dynamic physiological and anatomical changes which occur in puberty make for a challenging diagnosis in this group of patients. It is important to be mindful of the physiological particularities in adolescence which often mimic the symptoms of PCOS. In their first-year post-menarche, approximately 75% of menstruating adolescents report their cycle to last between 21-45 days. Recent studies have shown that regular menstrual cyclicity is only achieved within 2-3 years post-menarche. Anovulation, as a crucial diagnostic element for PCOS, features in about half of early-post-menarchal adolescents. Hirsutism and acne are the most common clinical manifestations of hyperandrogenism, and mild features are developed by most adolescents as a result of elevated androgen levels. Distinguishing between a pathological sign and normal features of maturation is often difficult. A polycystic ovarian morphology (PCOM) through ultrasound has been found in up to 40%, 35%, and 33.3% of patients when assessed at 2, 3, and 4 years, respectively, after menarche. PCOM in adolescence is not associated with future abnormalities in ovulatory rate or menstrual cycle duration. For this reason, international guidelines recommend against the use of pelvic ultrasound until 8 years post-menarche. The primary aim of management is focused mainly on improving hormonal and metabolic status, the prevention of future comorbid complications, and generally improving the overall quality of life in young women with PCOS. Considerable controversy surrounds the choice of optimal pharmacological treatment to address PCOS in adolescents. Reliable studies, which include this sub-section of the population, are very limited. There is a lack of robust and reliable trials in the literature addressing the use of combined oral contraceptives. Further work needs to be undertaken in order to provide safe and effective care to the adolescent population in this regard.

Cognitive decline and dementia in women after menopause: Prevention strategies.

Worldwide, cognitive decline and dementia are becoming one of the biggest challenges for public health. The decline in cognition and the development of dementia may be caused by predisposing or trigger factors. There is no consensus over whether the drop in estrogen levels after menopause is a risk factor for cognitive decline and dementia. This article discusses the prevention of cognitive decline and dementia in women after menopause, both primary prevention (essentially pharmacological intervention) and secondary prevention (chiefly diet and weight reduction). Further study is required to clarify whether menopausal hormone therapy (MHT) has a role in dementia.

Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea.

OBJECTIVE: Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the "circumstances of" nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). MATERIALS AND METHODS: One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. RESULTS: Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-ß-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. CONCLUSIONS: This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

The influence of estro-progestin therapy on neurohormonal activity in functional hypothalamic amenorrhea.

Background: Functional hypothalamic amenorrhea (FHA) is a chronic endocrine disorder caused by the abnormal pulsatile secretion of neurohormones in the hypothalamus. Secretion of GnRH is regulated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons produce, among other neurohormones, neurokinin B (NKB) which regulates the coordinated stimulation or inhibition of GnRH secreting neurons. Aim of the study: Assessment and comparison of serum NKB in patients with FHA at baseline, and following 6 months of estrogen-progestagen therapy. Materials and methods: Fifty-five patients with functional hypothalamic amenorrhea were included in the study group. Serum concentrations of neurokinin B (NKB), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-ß-estradiol (E2), prolactin (PRL), cortisol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), fasting glucose and insulin, as well as lipid profile were measured at baseline. At the time of diagnosis, patients with FHA were prescribed a course of 2 mg 17-ß-estradiol and 10 mg dydrogesterone for duration of 6 months. Serum NKB was then reassessed following treatment at 6 months. Results: At baseline, the FHA group was found to have a decreased serum NKB concentration when compared to a healthy control group. Following 6 months of sequential estrogen-progestogen hormone therapy, this study did not find any statistically significant difference in serum NKB concentration in the treatment arm compared to baseline. Conclusions: For the first time, NKB secretion has been studied in patients with FHA. A significantly lower level of serum NKB was observed in these patients at baseline, when compared to a control group. After 6 months of combination estrogen-progesterone therapy, no significant changes in NKB levels were observed in these patients. These findings, for the first time in the literature, provide insight into the perceived benefit of HRT, calling into question its benefit in addressing the underlying etiopathogenetic contributors of FHA. These new findings may contribute to more targeted and appropriate treatment of such patients in the future.

Stress, kisspeptin, and functional hypothalamic amenorrhea.

Functional hypothalamic amenorrhea (FHA) is the most common cause of secondary amenorrhea in women of reproductive age. FHA is predominantly caused by stress, decreased caloric intake, excessive exercise, or a combination thereof. These physical, psychological, and metabolic stressors cause aberration in the pulsatile release of gonadotropin-releasing hormone (GnRH) and subsequently impair function of the hypothalamic-pituitary-ovarian (HPO) axis. Various neurotransmitters acting in the central nervous system are involved in control of the HPO axis and of these, kisspeptin is one of the most important. Corticotropin-releasing hormone (CRH), also inhibits the pulsatile secretion of GnRH and also acts as an intermediary between stress factors and the reproductive system. One of the main ongoing concerns in patients with FHA is chronic hypoestrogenism, a condition, which is associated with sexual dysfunction and infertility. It may also lead to osteoporosis, and predispose to neurodegenerative and cardiovascular diseases. Treatment of FHA requires the elimination of causative factors, however, making the necessary lifestyle changes is not always easy to initiate and maintain. Broadening our knowledge of the complex neural mechanisms regulating reproductive function in which kisspeptin plays a key role can help in the development of new treatment options such as the potential of kisspeptin receptor agonists for patients with FHA.

Neuroendocrine Determinants of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background.

The Genetic Backdrop of Hypogonadotropic Hypogonadism.

The pituitary is an organ of dual provenance: the anterior lobe is epithelial in origin, whereas the posterior lobe derives from the neural ectoderm. The pituitary gland is a pivotal element of the axis regulating reproductive function in mammals. It collects signals from the hypothalamus, and by secreting gonadotropins (FSH and LH) it stimulates the ovary into cyclic activity resulting in a menstrual cycle and in ovulation. Pituitary organogenesis is comprised of three main stages controlled by different signaling molecules: first, the initiation of pituitary organogenesis and subsequent formation of Rathke's pouch; second, the migration of Rathke's pouch cells and their proliferation; and third, lineage determination and cellular differentiation. Any disruption of this sequence, e.g., gene mutation, can lead to numerous developmental disorders. Gene mutations contributing to disordered pituitary development can themselves be classified: mutations affecting transcriptional determinants of pituitary development, mutations related to gonadotropin deficiency, mutations concerning the beta subunit of FSH and LH, and mutations in the DAX-1 gene as a cause of adrenal hypoplasia and disturbed responsiveness of the pituitary to GnRH. All these mutations lead to disruption in the hypothalamic-pituitary-ovarian axis and contribute to the development of primary amenorrhea.

Menopause in women with schizophrenia, schizoaffective disorder and bipolar disorder.

The transition to menopause, usually occurring between the ages of 40 and 55, is a time when women are particularly vulnerable. When preexisting mental illness is present, symptoms are often amplified during this period. Moreover, women with mental illnesses experience menopausal symptoms similarly to healthy women. In this narrative review we summarize the current data regarding menopause in women with schizophrenia, schizoaffective disorder, and bipolar disorder, as well as current standards of management and care. The management of chronic disease in women suffering from severe mental illness is also considered.

Hyperthyroidism associated with struma ovarii - a case report and review of literature.

BACKGROUND: Hyperthyroidism is a state characterized by elevated serum level of thyroid hormones: thyroxine (T4) and triiodothyronine (T3). This is mainly related to the condition and functioning of the thyroid gland. In 60-80% of cases elevation of these hormones are caused by Grave's disease. Thyrotoxicosis is an extreme presentation of hyperthyroidism which can, in rare cases, be caused by excessive synthesis of thyroxine by tumor cells. Struma ovarii is a rare ovarian teratoma composed of thyroid tissue in more than 50%. OBJECTIVE AND METHOD: To present a case of a 30-year-old female patient with a past history of Grave's disease treated by strumectomy 7 years prior; now presenting for the assessment of secondary amenorrhea. Pelvic ultrasound revealed bilateral solid tumors on the left and right ovary, respectively measuring 5 cm and 6 cm in diameter. Her clinical presentation was suggestive of overt hyperthyroidism, and she presented with a significantly elevated CA-125 (152.7 U/mL). RESULTS: The patient subsequently underwent a bilateral oophorectomy in which both masses were excised and histopathological examination confirmed teratoma maturum cysticum. Struma ovarii was noted as a component of the left ovary teratoma. CONCLUSION: Establishing a proper diagnosis of hyperthyroidism and elucidating its origin is often challenging. Struma ovarii is a rare cause of hyperthyroidism but should always be considered in case of treatment resistant hyperthyroidism. This case-report lends itself as an example of the value in maintaining gynecological-endocrinological knowledge in the setting if clinical gynecology.

Autoimmune Diseases in Patients with Premature Ovarian Insufficiency-Our Current State of Knowledge.

Premature ovarian insufficiency (POI), previously known as premature ovarian failure or premature menopause, is defined as loss of ovarian function before the age of 40 years. The risk of POI before the age of 40 is 1%. Clinical symptoms develop as a result of estrogen deficiency and may include amenorrhea, oligomenorrhea, vasomotor instability (hot flushes, night sweats), sleep disturbances, vulvovaginal atrophy, altered urinary frequency, dyspareunia, low libido, and lack of energy. Most causes of POI remain undefined, however, it is estimated that anywhere from 4-30% of cases are autoimmune in origin. As the ovaries are a common target for autoimmune attacks, an autoimmune etiology of POI should always be considered, especially in the presence of anti-oocyte antibodies (AOAs), autoimmune diseases, or lymphocytic oophoritis in biopsy. POI can occur in isolation, but is often associated with other autoimmune conditions. Concordant thyroid disorders such as hypothyroidism, Hashimoto thyroiditis, and Grave's disease are most commonly seen. Adrenal autoimmune disorders are the second most common disorders associated with POI. Among women with diabetes mellitus, POI develops in roughly 2.5%. Additionally, autoimmune-related POI can also present as part of autoimmune polyglandular syndrome (APS), a condition in which autoimmune activity causes specific endocrine organ damage. In its most common presentation (type-3), APS is associated with Hashomoto's type thyroid antibodies and has a prevalence of 10-40%. 21OH-Antibodies in Addison's disease (AD) can develop in association to APS-2.

Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism.

Hyperthecosis is defined as the presence of nests of luteinized theca cells in the ovarian stroma. Persistent testosterone released by ovarian theca cells is unmasked postmenopausally through the loss of granulosa cell-mediated aromatization of testosterone to estradiol. Ovarian hyperthecosis (OH) usually presents with symptoms of hyperandrogenism and is often described as a severe or extreme form of Polycystic Ovary Syndrome (PCOS). Serum testosterone levels in excess of 150 ng/dl (>5.2 nmol/l) are seen in affected patients and this threshold is used to confirm a diagnosis. Treatment of hyperthecosis is multi-faceted. It addresses the attendant hyperandrogenism (hirsutism and virilization) as well as metabolic complications such as obesity and insulin resistance. Ultimately, laparoscopic bilateral salpingo-oophorectomy is definitive treatment. This remains the treatment of choice in postmenopausal women whereas treatment using GnRH agonists may be used in women of reproductive age, especially younger women. Nevertheless, if serum testosterone remains elevated despite several months of therapy with a GnRH agonist, surgery is often required for biopsy sample collection and further definitive therapy. In order to mitigate the common clinical manifestations of hyperandrogenism, anti-androgen therapy (either cyproterone acetate or spironolactone) may be used to suppress the actions of testosterone on tissues. In patients with impaired glucose metabolism and insulin resistance, Metformin should also be considered as part of treatment. Combined, such a treatment regimen will often lead to decreased ovarian androgen secretion.

Impact of Hormonal Replacement Therapy on Bone Mineral Density in Premature Ovarian Insufficiency Patients.

Premature ovarian insufficiency (POI) is a type of hypergonadotropic hypogonadism caused by impaired ovarian function before the age of 40. Due to the hypoestrogenism, women with POI experience a variety of health complications, including an increased risk of bone mineral density loss and developing osteopenia and osteoporosis, which poses an important problem for public health. Purpose: The aim of this study was to evaluate and compare the values of bone mineral density (BMD), T-score and Z-score within the lumbar spine (L1-L4) using the dual energy X-ray absorptiometry method. The dual-energy X-ray absorptiometry (DXA) scans described in this original prospective article were performed at the time of POI diagnosis and after treatment with sequential hormone replacement therapy (HRT). Materials and methods: This study included 132 patients with a mean age of 31.86 ± 7.75 years who had been diagnosed with idiopathic POI. The control group consisted of 17 healthy women with regular menstrual cycles, with a mean age of 23.21 ± 5.86 years. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), insulin, and fasting serum glucose were measured. Lumbar spine (L1-L4) BMD was assessed by means of dual-energy X-ray absorptiometry. DXA scans were performed at the time of diagnosis and following treatment with sequential hormone replacement therapy (HRT) comprised of daily oral 2 mg 17-ß-estradiol and 10 mg dydrogesterone. The mean time of observation was 3 ± 2 years. Results: Patients in the POI group presented with characteristic hypergonadotropic hypogonadism. They had a significantly decreased mean lumbar spine BMD when compared to healthy controls (1.088 ± 0.14 g/cm2) vs. 1.150 ± 0.30 g/cm2) (p = 0.04) as well as a decreased T-score (0.75 ± 1.167 vs. -0.144 ± 0.82) (p = 003). There was a significant increase in BMD (1.088 ± 0.14 vs. 1.109 ± 0.14; p < 0.001), T-score (-0.75 ± 1.17 vs. -0.59 ± 1.22; p < 0.001), and Z-score (-0.75 ± 1.12 vs. -0.49 ± 1.11; p < 0.001) after the implementation of HRT when compared to pre-treatment results. Conclusions: In conclusion, this study has demonstrated that patients with POI often have decreased bone mineral density and that the implementation of HRT has a significant and positive influence on bone mass. The implementation of full-dose HRT and monitoring of bone status is particularly important in these patients.

CHEK2 Mutation in Patient with Multiple Endocrine Glands Tumors. Case Report.

BACKGROUND: Many studies show the occurrence of several multiple endocrine neoplasia syndromes caused by different mutations, for example, in MEN1 and RET genes. Nevertheless, there are less common mutations causing multiple endocrine glands tumors. Examples of such mutations are CHEK2 gene mutations, causing breast, kidney, gastric, colorectal, prostate, lung, ovarian, and thyroid cancers. CASE DESCRIPTION: In 2005, a 30-year-old woman was admitted to the hospital due to uncontrolled hypertension and obesity. Performed tests have shown ACTH (adrenocorticotropic hormone)-independent micronodular adrenal hyperplasia (AIMAH) as a cause. In 2010, the further diagnostic analysis revealed Cushing's disease caused by ACTH-secreting pituitary microadenoma. Additionally, in 2011, the patient underwent the strumectomy of multinodular struma. Papillary thyroid carcinoma was found in the excised tissue. In 2018, transvaginal ultrasonography revealed a tumor of the right ovary. After a performed hysterectomy with bilateral salpingo-oophorectomy, the histopathology result has shown female adnexal tumors of probable Wolffian origin (FATWO) located in the broad ligament of the uterus. Due to the history of multiglandular diseases, the patient was referred to genetic testing. We found a positive pathogenic mutation in CHEK2-suppressor gene involved in DNA repair, cell cycle arrest, and apoptosis in response to DNA damage. CONCLUSION: CHEK2 variants may predispose to a range of endocrine glands tumors, including those identified in our patient. Multiple endocrine glands tumors, as in the presented patient, are a serious problem of public health, due to numerous hospitalizations and necessary repeated surgical treatments. Moreover, the association between CHEK2 and ovarian cancer can be a serious problem with reproductive health.