Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 23, Issue 12, 2023

Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as “critical” and “important” have been considered in the systematic review of evidence and only those classified as “critical” have been considered in the formulation of recommendations. Results: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. Conclusion: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Hypertension is the most important risk factor for cardiovascular disease worldwide. Although the pathogenesis of hypertension is complex and multifactorial, obesity-related hypertension has become a major focus of attention because of the continued increase in the prevalence of overweight and obesity. Several mechanisms have been suggested to underlie obesity-related hypertension, including an increase in sympathetic nervous system activity, an upregulation of the renin-angiotensinaldosterone system, alterations in adipose-derived cytokines, and an augmentation of insulin resistance. Emerging evidence from observational studies (including those using Mendelian randomization) suggests that the presence of high triglycerides, which is a common comorbidity in obesity, is an independent risk factor for new-onset hypertension. However, little is known about the mechanisms underlying triglyceride-associated hypertension. We summarize the existing clinical evidence that has demonstrated the adverse effect of triglycerides on blood pressure, and we then discuss possible underlying mechanisms based on the evidence from animal and human studies, with a particular focus on the roles of endothelial function, white blood cells, i.e., lymphocytes, and pulse rate.

Background: Metabolic syndrome, also referred to as Syndrome X or obesity syndrome is a cluster of diseases prevalent worldwide in both developed and developing countries. According to WHO, it is referred to as a pathological condition wherein multiple disorders are manifested in the same individual. These include hypertension, hyperglycemia, dyslipidemia and abdominal obesity. Aims: Metabolic syndrome is one of the most serious non-communicable health hazards that have gained pivotal importance in the present scenario. The increasing prevalence affecting around 25 % of the world populace, mainly attributes to the acceptance of western culture, i.e. the intake of highcalorie food along with a substantial decrease in manual labor and adoption of sedentary lifestyles. Therefore, its timely prevention and management are the dire need in the present scenario. Methods: For successful accomplishment of the present review, an exhaustive analysis was performed utilizing a pool of previous related literature. The terms used during the search included ‘metabolic syndrome, prevalence, etiology, current pharmacotherapy for metabolic syndrome, etc. PUBMED, Medline and SCOPUS were explored for the study of abstracts, research and review papers in the quest for related data. The articles were downloaded and utilized for a meta-analysis study approach. Conclusion: In this review, an attempt was made to apprehend and summarize the epidemiology and treatment strategies for metabolic syndrome with a better understanding of its pathogenesis. It was postulated that an early diagnostic approach and subsequent line of treatment is required to prevent the deterioration of an individual’s health and life.

Viruses significantly impact global health because they are the leading cause of death everywhere they are found. Despite the rapid development of human healthcare, more effective viricidal or antiviral therapies must be developed. The need to find safe, novel, and effective alternatives against viral diseases is heightened by the rapid emergence of resistance to, and the high cost of, synthetic antiviral drug(s). The development of novel multi-target antiviral compounds that affect multiple steps of the viral life cycle and host proteins has benefited tremendously from looking to nature for guidance and inspiration. Hundreds of natural molecules are preferred over synthetic drugs because of concerns regarding efficacy and safety and a high resistance rate to conventional therapies. In addition, naturally occurring antiviral agents have demonstrated reasonable antiviral value in both animal and human studies. Therefore, finding new antiviral drugs is crucial, and natural products provide an excellent opportunity. This brief review examines the evidence of antiviral effects exhibited by various plants and herbs.

Background: The progression of Type 2 Diabetes Mellitus (T2DM) can lead to various complications. Compounds derived from natural products have been found to be effective in combatting T2DM. This study aimed to investigate the effects of Astragaloside IV (AS-IV) on insulin resistance and the inflammatory response of adipocytes. The study also aimed to determine the downstream signaling pathways involved. Materials and Methods: The glucose consumption of adipocytes was assessed using a glucose assay kit. qRT-PCR, Western blot, and ELISA assays were used to measure mRNA and protein levels. The interaction between miR-21 and PTEN was assessed using a Dual-luciferase reporter assay. Results: The results showed that AS-IV increased glucose consumption and the expression of GLUT-4 in adipocytes with insulin resistance in a concentration-dependent manner. However, ASIV decreased the protein levels of TNF-α and IL-6 in these cells. Additionally, AS-IV up-regulated miR-21 expression in adipocytes with insulin resistance in a concentration-dependent manner. Furthermore, miR-21 overexpression increased glucose consumption and GLUT-4 expression but decreased TNF-α and IL-6 protein levels in adipocytes. Conversely, miR-21 inhibition attenuated the AS-IV-induced increase in glucose consumption and GLUT-4 expression and the decrease in TNF- α and IL-6 protein levels in adipocytes. MiR-21 also inversely regulated PTEN in adipocytes, and PTEN overexpression had effects similar to miR-21 inhibition in AS-IV-treated adipocytes. Finally, AS-IV up-regulated p-PI3K and p-AKT protein expression in adipocytes, which was attenuated by miR-21 inhibition. Conclusion: The study concluded that AS-IV attenuated insulin resistance and the inflammatory response in adipocytes. The mechanistic studies indicated that AS-IV modulated the miR- 21/PTEN/PI3K/AKT signaling in adipocytes to exert these effects.

Background: Wernicke's encephalopathy, resulting from thiamine deficiency, is a rare but serious neurological complication of bariatric procedures. A clinical and radiologic diagnosis is often difficult, and thiamine blood tests are not broadly available. Only a few cases of Wernicke’s encephalopathy after sleeve gastrectomy have been reported in the literature, nonetheless, subjects can be underdiagnosed, and their cases can be underreported. Case Presentation: We present the case of a 20-year-old female patient who developed Wernicke’s encephalopathy after sleeve gastrectomy for grade II obesity with metabolic complications. She was presented to the Emergency Department showing confusion, gait ataxia and horizontal nystagmus two months after surgery. Persistent vomiting and lack of compliance with vitamin intake were reported. Cerebral MRI showed acute bilateral lesions in the periaqueductal and periventricular regions. Parenteral thiamine supplementation was administered, obtaining a progressive resolution of altered mental status, motor ataxia, and nystagmus. She was discharged on oral thiamine supplementation and underwent a multidisciplinary rehabilitation program, since anterograde, retrograde, and working memory impairment persisted. After a 2-year follow-up, she was compliant with a balanced fractionated diet and vitamin supplementation. A new cerebral MRI showed regression of the neuroradiological findings, but minimal memory impairment remained. Conclusion: Wernicke’s encephalopathy is a concrete possibility after sleeve gastrectomy and should always be suspected in patients with recurrent vomiting, poor nutritional intake, and non-compliance to vitamin supplementation. Immediate and aggressive thiamine supplementation is mandatory to prevent patients from irreversible neurological impairment, even though full recovery is not always achieved.

Background: Ketosis-prone diabetes (KPD) is an emerging entity, sharing features of both type 1 diabetes mellitus and type 2 diabetes mellitus. Patients with KPD usually present with diabetic ketoacidosis without the classic phenotype of autoimmune type 1 diabetes. In most cases, they are Afro-American adults, who require insulin therapy for the management of acute decompensation, then usually encountering insulin-free remission for prolonged periods of time with diet or with non-insulin agents. Meanwhile, hypogonadism is a known condition that could be associated with higher risk of developing both type 1 and type 2 diabetes and could be a risk factor for decompensated diabetes. The association of KPD and hypogonadism is reported for the first time in literature. Case Presentation: Here we report two peculiar cases of young African patients, affected by KPD and hypergonadotropic hypogonadism, respectively Klinefelter’s syndrome and primary ovarian failure. Both patients were treated promptly for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. After the correct clinical evaluation, oral antidiabetic drugs were added. Conclusion: KPD remains an under-recognized and under-diagnosed type of diabetes. As hypogonadism is strongly linked to dysmetabolic disorders, the evaluation of sex hormones should be performed at the onset of diabetes. Further studies should investigate the hypothalamic-pituitary-gonadal axis and its role in the development of KDP and its manifestations and complications.

Background: Differential diagnosis of primary and secondary hyperthyroidism can be challenging. Moreover, although extremely rare, the two conditions can coexist. Case Presentation: A 58-year-old woman presented with symptoms of thyrotoxicosis, gradual changes in face shape, headache and progressive enlargement of hands and feet in the last year. When she was 46 years old, she was diagnosed with Graves’ disease, and treated with 4-year methimazole therapy. Since 2016, a progressive increase of free-T4 and free-T3 with normal-TSH and positive TrAb was noticed. Results: At biochemical examination, fT3 was 5.3pg/ml (n. v. 2.5 - 3.9 pg/ml), fT4 was 20.6 pg/ml (n.v 6-12 pg/ml), IGF1 was 698 ng/ml (57 – 240 ng/ml*), GH (basally and after OGTT), and prolactin were significantly increased; while TSH was 1.8 (n.v. 0.35-4.0 mcUI/ml). A pituitary MRI demonstrated a large sellar tumor with suprasellar extension. The patient underwent endoscopic transsphenoidal surgery. Histological examination revealed a plurihormonal (GH-PRLTSH- secreting) PIT-1-positive pituitary adenoma/pituitary neuroendocrine tumor (PitNET). At 3- month follow-up, the pituitary function was normal, and no residual tumor was detected at the MRI. Conclusion: We report a rare case of Graves’ disease coexisting with a plurihormonal PIT-1-positive pituitary adenoma/PitNET.

Background: Doege-Potter syndrome is a rare paraneoplastic entity that is often diagnosed incidentally during the work-up of hypoglycemia of unclear etiology. It is characterized by a non-islet cell tumor hypoglycemia mostly associated with solitary fibrous tumors. These uncommon tumors have been reported in <5% of solitary fibrous tumors. Although not unique in its kind, this case is extremely important as this syndrome often conceals unrecognized tumors that can be surgically resolved. Case Presentation: We present the case of a 59-year-old non-diabetic man with a 2-month history of severe and recurrent fasting hypoglycaemia presenting with severe dyspnea and sweating. Further workup revealed low insulin, C-peptide, and IGF-1 levels and a large right in-trathoracic solitary fibrous tumor. Unfortunately, bioassays for IGF-2 were unavailable at our hos-pital. Nevertheless, as hypoglycemia completely resolved after resection of the mass, Doege-Potter syndrome was highly suspected. Conclusion: Doege-Potter syndrome is a complication of rare tumors. If hy-poglycemia is unexplained, this syndrome should always be suspected, and the presence of un-known masses should be investigated.