Endocrines, Volume 2, Issue 3 (September 2021) – 17 articles

Despite the improvements in diagnostic and therapeutic approaches, breast cancer still remains one of the world’s leading causes of death among women. Particularly, triple negative breast cancer (TNBC) is characterized by aggressiveness, metastatic spreading, drug resistance and a very high percentage of death in patients. Nowadays, identification of new targets in TNBC appears very compelling. TNBC are considered negative for the estrogen receptor alpha (ERα) expression. Nevertheless, they often express ERβ and its variants. As such, this TNBC subtype still responds to estrogens. While the ERβ1 variant seems to act as a tumor-suppressor, the two variants ERβ2 and 5 exhibit pro-oncogenic activities in TNBC. Thus, ERβ1 activation might be used to limit the growth and spreading as well as to increase the drug sensitivity of TNBC. In contrast, the pro-oncogenic properties of ERβ2 and ERβ5 suggest the possible development and clinical use of specific antagonists in TNBC treatment. Furthermore, the role of ERβ might be regarded in the context of the androgen receptor (AR) expression, which represents another key marker in TNBC. The relationship between AR and ERβ as well as the ability to modulate the receptor-mediated effects through agonists/antagonists represent a challenge to develop more appropriate therapies in clinical management of TNBC patients. In this review, we will discuss the most recent data in the field. Therapeutic implications of these findings are also presented in the light of the discovery of specific ERβ modulators. Full article

Adenomyosis is commonly treated by total hysterectomy. Adenomyomectomy is considered for women of reproductive age who wish to preserve their fertility. However, a high recurrence rate following adenomyomectomy has been reported because complete removal of the lesion is difficult, and uterine rupture during pregnancy remains a complication. We previously reported that laparoscopic adenomyomectomy using a cold knife prevented thermal damage to the myometrium and elastography to avoid residual lesions. Here, we report the case of a patient who underwent complete resection of a subtype II adenomyosis and resection of deep endometriosis (DE) with the closure of the pouch of Douglas. The patient was 31 years old, had severe dysmenorrhea, and had left ureteral stenosis and subtype II adenomyosis associated with the closure of the pouch of Douglas by the DE. After resection of the DE posterior wall adenomyosis, residual lesions were confirmed by laparoscopic real-time elastography. Eight weeks after surgery, postoperative transvaginal ultrasound showed that the myometrium had shrunk from 28 to 22.7 mm, and the hydronephrosis had disappeared, although a stent remained necessary. In this study, we report the complete resection of subtype II adenomyosis and DE, combined with elastography to visualize the lesions during resection. Full article

The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress. Prolonged stress and/or inadequate regulation of the stress system can lead to a condition of chronic hypercortisolism or, in some cases, a blunted cortisol response to stress, contributing to insulin resistance, increased adiposity and type 2 diabetes mellitus. Moreover, acute and chronic stress can exacerbate or worsen metabolic conditions by supporting an inflammatory state and a tight relationship between stress, inflammation and adipose tissue has been reported and has been a growing subject of interest in recent years. We reviewed and summarized the evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus. Furthermore, we emphasized the possible role of infectious-related stress such as SarsCov2 infection in adrenal axis dysregulation, insulin resistance and diabetes in a bidirectional link. Understanding and better defining the links between stress and obesity or diabetes could contribute to further definition of the pathogenesis and the management of stress-related complications, in which the HPA axis dysregulation has a primary role. Full article

Adequate serum vitamin D and iron levels are thought to influence physical training adaptations and mood positively. The primary purpose of this prospective, observational study was to investigate relationships between serum 25-OH vitamin D/25(OH)D and serum ferritin levels with body composition and athlete burnout symptoms. Seventy-three collegiate athletes (female: n = 49; male: n = 24) from indoor (swimming, basketball) and outdoor (soccer, cross-country) sports were tested pre-season and post-season for serum 25(OH)D and serum ferritin (nutrient biomarkers) via venipuncture; body composition (total lean mass, bone mineral density/BMD, and % body fat) via dual energy X-ray absorptiometry (DXA) scans; and athlete burnout symptoms (post-season) via the athlete burnout questionnaire (ABQ). When male and female cohorts were combined, significant correlations (Pearson’s r) were noted between pre-season serum 25(OH)D versus the change (∆: post-season minus pre-season) in both BMD (r = −0.34; p = 0.0003) and % body fat (r = −0.28; p = 0.015). Serum ferritin ∆ was significantly associated with lean mass ∆ (r = −0.34; p = 0.003). For burnout symptoms, serum 25(OH)D ∆ significantly explained 20.6% of the variance for devaluation of the sport in the male cohort only. Across time, serum 25(OH)D levels decreased while serum ferritin levels increased, non-significantly, in both males and females. Relationships between nutrient biomarkers and body composition were opposite of physiological expectations. Full article

The Italian SIAPEC-AIT 2014 classification, the 2017 Bethesda System for Reporting Thyroid Cytology (TBSRTC), the 2016 UK Royal College of Pathologists (RCPath) thyroid reporting system, and the 2019 Japanese reporting system for thyroid aspiration cytology (JRSTAC2019) represent the most widely used reporting systems among clinicians and pathologists for the purpose of cytologically diagnosing, estimating the potential risk of malignancy (ROM), and defining the most appropriate treatment for a patient with a thyroid nodule. Although all the systems use overlapping diagnostic categories and morphologic criteria, they differ on the basis of the criteria for inclusion in the cytologic categories, which may, in turn, affect the ROM of a given category and the clinical management of the patient, particularly with regard to the “indeterminate” categories. The aim of this review is to analyze the main differences that emerge between the systems and to propose possible solutions for a comprehensive reporting system that integrates and harmonizes all the criteria of the Italian classification and the Bethesda system, also taking into account the impact that the new tumor entity NIFTP (non-invasive follicular tumor with papillary-like nuclear features) that has, in many instances, replaced the non-invasive form of the follicular variant of papillary carcinoma, has had on the modification of malignancy risks. Full article

Early diagnosis and long-term management of endometriosis is important in adolescent girls considering their potential for future pregnancy and need for preventing disease progression. However, symptoms and clinical findings of adolescent endometriosis may differ from those of typical adult endometriosis, making diagnosis difficult. In adolescents, menstrual pain may present as acyclic and unresponsive to commonly used medication. Typical imaging findings in adult endometriosis, such as ovarian endometriotic cysts and fibrotic scars, are less common in adolescents. Peritoneal lesions, characteristic of early-stage endometriosis, are commonly found in this age group. It should be noted that endometriosis may also be found in adolescents before menarche, because of premenarcheal endometriosis or congenital uterine anomaly and outflow obstruction; the latter requiring surgical correction. Although surgery is reported to be effective for pain, postsurgical recurrence rate is high, and the effect of hormonal treatment is controversial. The optimal timing for surgical intervention also remains to be determined. Here, we aim to identify the unique characteristics of endometriosis in adolescents to achieve early diagnosis and optimal management for this group of patients. Full article

A low dose of dienogest (DNG) 1 mg/day is useful for treating dysmenorrhea in young women. However, the effect of DNG on bone turnover during bone growth and formation, rather than at maturity, is currently unknown even at low doses. We investigated change in bone turnover after 3 months of DNG 1 mg/day. This retrospective cohort study included young women aged 10–24 years with dysmenorrhea and irregular menstruation. Gonadotropins and the bone metabolism markers TRACP-5b and BAP were compared before and at 3 months after administration of DNG 1 mg/day. There were no significant changes in TRACP-5b (before, 455.6 ± 323.6 mU/dL; 3 months after, 462.1 ± 346.1 mU/dL), BAP (before, 24.7 ± 19.0 μg/L; 3 months after, 25.2 ± 22.3 μg/L), or the TRACP-5b/BAP ratio (before, 22.1 ± 7.0; 3 months after, 21.5 ± 6.3). Administration of DNG 1 mg/day had no significant effect on bone turnover after 3 months during the bone-growth phase in young women. Full article

Background: Juvenile cystic adenomyosis (JCA) is a rare uterine lesion. We present the case of a young woman who was diagnosed with JCA and subsequently managed with laparoscopic cyst removal with sharp and blunt dissection. Moreover, we provide a literature review and a surgical video. Case: A 22-year-old nulliparous woman presented with severe dysmenorrhea and was assessed using contrast-enhanced abdominal computed tomography, transvaginal ultrasonography and pelvic magnetic resonance imaging, and diagnosed with a cystic lesion on the left side of the myometrium. She underwent laparoscopic cyst excision and uterine reconstruction. Histology was suggestive of JCA. The dysmenorrhea resolved postoperatively. Conclusion: Surgical resection is the first choice of treatment for cystic adenomyosis, and a laparoscopic approach using scissor forceps is effective. Full article

Irisin is a myokine that primarily targets adipose tissue, where it increases energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissue. As our knowledge has deepened in recent years, muscle has been found to be a major target organ for irisin as well. Several studies have attempted to characterize the role of irisin in muscle to improve glucose metabolism through mechanisms such as reducing insulin resistance. Although they are very intriguing reports, some contradictory results make it difficult to grasp the whole picture of the action of irisin on muscle. In this review, we attempted to organize the current knowledge of the role of irisin in muscle glucose metabolism. We discussed the direct effects of irisin on glucose metabolism in three types of muscle, that is, skeletal muscle, smooth muscle, and the myocardium. We also describe irisin’s effects on mitochondria and its interactions with other hormones. Furthermore, to consider the relationship between the irisin-induced improvement of glucose metabolism in muscle and systemic disorders of glucose metabolism, we reviewed the results from animal interventional studies and human clinical studies. Full article

Endometriosis-associated ovarian malignancies have been well documented. Although these malignancies also occur as extraovarian lesions, little is known about them. Thus, this literature review aimed to further explore these rarely experienced tumors. A total of 257 published cases between April 1990 and April 2020 were found using PubMed, and 212 cases were included in the analysis considering Sampson’s criteria and the history of endometriosis. We classified these cases as follows: intestine, abdominal scar, vagina and vulva, peritoneum and deep endometriosis, urinary tract, uterine cervix, and others. Age of patients, history of endometriosis, types of past hormonal therapy, symptoms, histological types, and treatment were identified. The most common tumor site was the intestine. Endometrioid carcinoma was the dominant histological type. Contrary to the ovary, clear cell carcinoma was rare in extraovarian sites. On the other hand, clear cell carcinoma represented the largest number of abdominal scars. This difference may help us to understand the development of endometriosis-related malignancies. Hormonal treatment was mentioned in 67 cases and estrogen replacement therapy in 33 cases. Although risks of estrogen therapy are still controversial, the highly differentiated histological types and hormone-dependent characteristics of endometriosis-associated malignancy should be considered. Physicians should be careful about estrogen monotherapy after hysterectomy and long-term hormone replacement therapy in patients with a history of endometriosis. Full article

Purpose: to determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: most patients, 83.3% (n = 40), harbored macroadenomas and 31.3% (n = 15) invasive pituitary adenomas. In this case, 14 patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60–120] and 20 [range 20–30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and untreated patients (p > 0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanreotide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR = 4.64, p = 0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR = 0.65, p = 0.570), independently of the doses and the duration of SSA treatment (p > 0.05). Conclusions: the dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses. Full article

Psychoneuroendocrineimmunology (PNEI) brings together knowledge acquired since the 1930s from endocrinology, immunology, neuroscience, and psychology. With PNEI, a model of research and interpretation of health and disease is emerging, which sees the human body as a structured and interconnected unit, where the psychological and biological systems are mutually coordinated. In the PNEI view, many factors could influence mental health, with the endocrine system involved in mediating the effects of environmental stress on mental health and inflammation in the onset and course of psychiatric disorders as a result of individual and collective conditions and behaviors. Among these, nutrition is one way by which the environment impacts physiology: indeed, many pieces of research showed that several elements (e.g., probiotics, fish oil, zinc) have a positive effect on mental disorders thus being potentially augmentation agents in treatment. Still, physical activity can moderate depressive symptoms, while prolonged stress increases the risk of psychopathology. Taken together, the PNEI-based approach may inform prevention and treatment strategies, also in the field of mental health care. Full article

Endocrine axes (prolactin, thyroid and adrenal axes) directly and indirectly modulate and drive human female central functions, mainly behavior and reproduction. Though having distinct abilities, they greatly act both at peripheral as well as at neuroendocrine levels, so as to participate in the control of reproduction. Any event that changes these balanced activities produces specific peripheral signals that induce abnormal functions centrally, thus triggering menstrual disorders such as oligomenorrhea or amenorrhea. It is clear that the knowledge of the relationships that exist between the different endocrine axes becomes essential for the choice of therapeutical approach. This review aims to focus on the main aspects of the physiopathology of the endocrine diseases that might be at the basis of that interference with female reproductive capacity. Full article

The aim of the study is to present the problem of functional hypothalamic amenorrhea, taking into account any disease and treatment, diagnosis, and consequences of this disease. We searched PubMed (MEDLINE) and included 38 original and review articles concerning functional hypothalamic amenorrhea. Functional hypothalamic amenorrhea is the most common cause of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences. The basis of functional hypothalamic amenorrhea is hormonal, based on impaired pulsatile GnRH secretion in the hypothalamus, then decreased secretion of gonadotropins, and, consequently, impaired hormonal function of the ovaries. This disorder leads to hypoestrogenism, manifested by a disturbance of the menstrual cycle in the form of amenorrhea, leading to anovulation. Prolonged state of hypoestrogenism can be very detrimental to general health, leading to many harmful short- and long-term consequences. Treatment of functional hypothalamic amenorrhea should be started as soon as possible, and it should primarily involve lifestyle modification. Only then should pharmacological treatment be applied. Importantly, treatment is most often long-term, but it results in recovery for the majority of patients. Effective therapy, based on multidirectional action, can protect patients from numerous negative impacts on fertility, cardiovascular system and bone health, as well as reducing mental morbidity. Full article

Kidney pathophysiology is influenced by gender. Evidence suggests that kidney damage is more severe in males than in females and that sexual hormones contribute to this. Elevated prolactin concentration is common in renal impairment patients and is associated with an unfavorable prognosis. However, PRL is involved in the osmoregulatory process and promotes endothelial proliferation, dilatation, and permeability in blood vessels. Several proteinases cleavage its structure, forming vasoinhibins. These fragments have antagonistic PRL effects on endothelium and might be associated with renal endothelial dysfunction, but its role in the kidneys has not been enough investigated. Therefore, the purpose of this review is to describe the influence of sexual dimorphism and gonadal hormones on kidney damage, emphasizing the role of the hormone prolactin and its cleavage products, the vasoinhibins. Full article

Autoimmune rheumatological diseases’ incidence and prevalence have risen over the last decades and they are becoming increasingly important worldwide. Thyroid autoimmune diseases share with them an imbalance in the immune system that lead to a pro-inflammatory environment. Usually this is the result of a multi-factorial process. In fact, it includes not only a possible genetic predisposition, but also environmental causes like microbiota dysbiosis, diet rich in processed foods, exposure to toxicants and infections. However, many aspects are currently under study. This paper aims to examine the factors that participate in the developing of rheumatological and thyroid autoimmune diseases. Moreover, as glucocorticoids still represent a leading treatment for systemic autoimmune rheumatological diseases, our secondary aim is to summarize the main effects of glucocorticoids treatment focusing on iatrogenic Cushing’s syndrome and glucocorticoids’ withdrawal syndrome. Full article