Treatment Of Endocrine Diseases Research Articles

Evaluation of potentially inappropriate medication in older patients with cardiovascular diseases-STOPP/START-based study.

This study aims to evaluate the use of STOPP/START criteria in the identification of Potentially inappropriate medication and potential prescribing omissions in older patients with cardiovascular diseases in Bulgaria. Excessive morbidity and mortality has been linked to drug-related problems and increased use of healthcare services and is an understudied problem for Bulgaria. A prospective, questionnaire-based study was conducted among 543 older patients across 25 pharmacies in Bulgaria. Socio-demographic characteristic, disease profile, symptoms, and medication data were collected. The questionnaire was developed for the purposes of the EUROAGEISM project. Out of all 543 patients, only those with documented cardio-vascular diseases were extracted and the medication profile per patient was evaluated for Potentially inappropriate medication (PIMs) and potentially prescribing omissions (PPOs) using STOPP/START criteria version 2. In addition, several risks for potentially inappropriate prescribing (PIPs), PPOs and PIMs were calculated with the focus being on the Odds and Risks to develop a PIP. Four hundred and twenty eight from 531 patients with known therapy for cardiovascular diseases (CVDs) were included in the analysis of PIP (40.52% aged 65-69 years, 61.88% female, 64% had up to 6 comorbidities, and 21.72% presenting with polypharmacy). A total of 71 PIMs in 64 patients with polypharmacy were identified during applying STOPP criteria. 56% of patients taking above five medicines daily had PIMs. The majority of PIMs (31%) were related to CVDs treatment, followed by PIMs in the treatment of endocrine diseases (22.54%), duplication of medicines (8.46%) and prolonged treatment with benzodiazepines (8.46%). Forty four PPOs were identified with START criteria. 22.72% were related to lack of proton pump inhibitors (PPI) in the presence of gastroesophageal disorders, and the same percentage was for lack of Calcium-vitamin D supplementation in osteoporosis. Applying the methodology of risks calculation the sample risk for PPO was 2.1% and for PIM 3.4%. At sample level the relative risk for PPO was 62% out of the risk for PIM and at population level varied between 42.8 and 89.8% and it is statistically significant. The number needed to treat for the event to happen is 77.5, meaning that at every 78 prescriptions there is a chance to appear PIP. Application of methodologies for detection of potentially inappropriate prescribing is not part of routine clinical practice in Bulgaria. Our study demonstrates a high percentage of potentially inappropriate medication among older patients with polypharmacy. Along with the aging population in Bulgaria, economic burden of polypharmacy and the prevalence of cardiovascular diseases, it is especially important to address potentially inappropriate medication use in cardiovascular patients. There is a considerable necessity for implementation of measures for early detection of potentially inappropriate medication and potentially prescribing omission as a part of de-prescribing strategies in older patients.

Overview of PROTACs Targeting the Estrogen Receptor: Achievements for Biological and Drug Discovery.

Estrogen receptors (ERs) are steroid hormone receptors, which belong to a large nuclear receptor family. Endocrine diseases correlate strongly with dysregulated ER signaling. Traditional therapies continue to rely on small molecule inhibitors, including aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), all of which permit acquired resistance to endocrine therapy. Proteolytic targeting chimeras (PROTACs) offer unprecedented potential for solving acquired endocrine resistance. ARV-471, an ER-targeting PROTAC developed by Arvinas, was designated as an Investigational New Drug by the US FDA in 2019, and a phase I trial in patients suffering from locally advanced or metastatic ER-positive/HER2- negative breast cancer was initiated. In this review, we will focus on progress in developing ER-targeting PROTACs from publications and patents aimed at the treatment of endocrine diseases.

Вплив ендокринних захворювань на функціонування репродуктивної системи

У лекції розглядаються питання впливу ендокринних захворювань на функціонування репродуктивної системи. Репродуктивна система жінки подається як сукупність взаємозв’язаних структурних елементів: гіпоталамуса, гіпофіза, яєчників, органів-мішеней та інших ендокринних залоз, що забезпечують реалізацію генеративної функції. Під час вагітності змінюється метаболізм гормонів, що є важливим чинником при діагностиці та лікуванні ендокринної патології у вагітних і жінок, які планують вагітність. Підкреслюється, що наявність субклінічних розладів органів ендокринної системи є чинником, що знижує нормальну функціональну відповідь, необхідну для адекватного розвитку індукованої вагітності. Тому при будь-яких порушеннях репродуктивної функції (безплідність, невиношування вагітності) необхідна оцінка функції органів ендокринної системи, а настання вагітності в жінок з ендокринною патологією потребує суттєвої корекції проваджуваної терапії.

Iatrogenic Osteoporosis

The literature review provides information on the major calcium-regulating hormones and their role in the regulation of bone remodeling. These processes are also influenced by sex steroids, growth hormone, insulin, cortisol, thyroid hormones and various local growth factors. In this regard, osteopenia and osteoporosis are closely linked to a number of endocrine diseases, some of which are common (diabetes mellitus, hyperthyroidism), others — quite rare (endogenous hypercortisolism). Osteoporosis associated with diabetes, steroid osteoporosis, osteoporosis in thyroid function abnormality are considered in detail. It is emphasized that timely diagnosis and adequate treatment of endocrine diseases associated with a decrease in bone mineral density, contribute to slowing or stopping bone loss, normalization of bone remodeling, enables to reduce the incidence of fractures and to improve the quality of life of the patient.

PHYSIOLOGICAL EFFICIENCY OF DRINKS FROM FENUGREEK SEEDS

Background. Today, diabetes is one of the most common diseases with a steady upward trend. In particular in Ukraine it ranks 2nd among endocrine diseases in the number of patients. The annual growth of such patients averages 9.8–11 %. In the treatment of endocrine diseases, dietary nutrition aimed at normalizing metabolismis of great importance. It is recommended to add to the diet special, func­tionally-oriented foods based on biologically valuable raw materials. The aim of the workis to determine the physiological efficiency of drinks from fenugreek seeds. Materials and methods. The physiological effects of fenugreek seed drinks were determined from clinical trials involving 54 patients with type II diabetes and 40 patients diagnosed with pre-diabetes. Two groups of 32 patients who did not consume the product were also selected. Biochemical methods were used to assess the effect of the product on the correction of condition of patients according to the indicators of the general condition of patients, the indicator of the level of glucose and cholesterol in the blood.The assessment of physical and psycho-emotional states was conducted by a survey. Drink is a plant-based milk analogue from the fenugreek seeds is presented in a ready-to-drink form.Depending on the disease and the condition of the body, participants in clinical trials drank the developed drink daily at 200–400 cm3/day (1–2 times a day at 200 cm3) for 30–60 days together with an individually prescribed treatment package. Results. It was found that patients who consumed a drink of fenugreek seeds in addition to the main diet had a faster normalization of blood glucose levels, more pronounced improvement in physical condition, as well as a reduction in the overall duration of treatment than patients in the control group. There was an improvement in lipid metabolism in patients of both study groups who drank a plant-based milk analogue from fenugreek seeds, and patients have noted that consumption of the developed drink helped to improve the condition of the gastrointestinal tract.This can be explained by the large number of galactomannans in the fenugreek seeds, which promote the secretion of mucous substances during the production of the drink. Conclusion. The new plant-based milk analogue from fenugreek seeds helps to normalize blood sugar and cholesterol levels, and therefore can be recommended for use in dietary and therapeutic diets of people with diabetes and atherosclerosis during treatment and recovery. Taking into accountthe properties of fenugreek seeds, the developed product can be recommended to protect the organs of the gastrointestinal tract in these diseases and in general to normalize metabolism.

Heterogeneous toroidal spiral particles for islet encapsulation.

Transplantable cell encapsulation systems present a promising approach to deliver a therapeutic solution from hormone-producing cells for the treatment of endocrine diseases like type 1 diabetes. However, the development of a broadly effective and safe transplantation system has been challenging. While some current micro-sized capsules have been optimized for adequate nutrient and metabolic transport, they lack the robustness and retrievability for the clinical safety translation that macro-devices may offer. An existing challenge to be addressed in the current macro-devices is their configuration which may lead to unsatisfactory mass transfer. Here, we design and characterize a millimeter-size particle system of poly-ethylene glycol (PEG) featuring internal toroidal spiral channels, called toroidal spiral particles (TSPs). The characteristic internal structure of the TSPs allows for large encapsulation capacity and large surface area available to all the encapsulated cell mass for effective molecular diffusion. The polymeric matrix renders the particle flexible yet robust for safe transplantation and retrieval. We demonstrate the feasibility of fabricating these particles with various polymer compositions, while optimizing their mechanical properties as well as glucose and insulin permeability. Encapsulation of islets of Langerhans is achieved with high loading capacity (∼160 IEQ per TSP) and excellent cell viability. TSP-encapsulated islets showed similar glucose-stimulated insulin secretion to the naked islets. Preliminary biocompatibility of the TSPs on naïve C57BL/6 mice shows minimal inflammatory response after 4-week transplantation into the intraperitoneal (IP) space. Long-term therapeutic efficacy of encapsulated islets needs to be confirmed in diabetic rodent models in the future, while determining minimal mass required to reverse diabetes. However, we believe from the in vitro favorable results and the TSPs' unique design that TSPs may provide a safe, effective method to transplant and retrieve therapeutic cells for type 1 diabetes treatment and may also be applicable for other cell therapies.

Establishment of reference ranges of sex hormones for healthy children in Shenzhen, China based on chemiluminescence

To study the reference ranges of six sex hormones, i.e., luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone, for healthy children aged 0-18 years in Shenzhen, China. Stratified cluster sampling was performed to select 2 178 healthy children aged 0-18 years in the districts of Futian, Luohu, Nanshan, Bao'an, and Longgang in Shenzhen between September 2015 and September 2016. There were 1 219 boys and 959 girls, including 81 neonates, 335 infants, 346 young children, 469 preschool children, 419 school-aged children, and 528 adolescents. The American Beckman DXI800 chemiluminescence meter was used to measure the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone. There were significant differences in the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone between different age groups (P<0.05). There were also significant differences in the levels of these sex hormones between boys and girls in the same age group (P<0.05). The reference ranges of six sex hormones were established for healthy children aged 0-18 years in Shenzhen based on the levels of these hormones in different age groups. There are significant differences in sex hormones between different age groups or sex groups. The reference ranges of six sex hormones established for different sexes or ages have great significance in the diagnosis and treatment of endocrine diseases in children.

Endocrine problems during pregnancy

Endocrine disorders may have an important influence on fertility, the course of a pregnancy and fetal development. For example, fertility is decreased and the risk of miscarriage is increased in women with autoimmune disorders, such as Addison's disease or autoimmune thyroiditis. Treatment of endocrine diseases in many cases has to be adapted during the course of a pregnancy. In patients with Addison's disease the dosage of hydrocortisone necessarily has to be increased. This is also valid for the time of delivery. Disorders of the thyroid gland are of great importance during pregnancy. If hypothyroidism is diagnosed in early pregnancy, immediate treatment with levothyroxine should be initiated. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Treatment of Graves's disease will be performed during the first trimenon with propylthiouracile, afterwards with methimazole (thiamazole). In contrast, thyrotoxicosis due to hCG should not be treated with methimazole. In this paper, we present an overview on the most important endocrine disorders during pregnancy.

Editorial: Neurological and Psychiatric Disorders in Endocrine Diseases

In the last few decades, a number of reciprocal associations between endocrine system dysfunctions and neurological or psychiatric manifestations have appeared, and only in the minority of the cases this link has been fully elucidated (1). Unfortunately, the complexity, and sometimes also the severity, of the clinical issues and the limited availability of reliable experimental models for the study of the endocrine system–nervous system cross-interactions do not help the fast achievement of scientific progresses. Isolated neurological or psychiatric symptoms as well as more complex disorders can occur in the setting of most endocrine diseases. Such manifestations can be the direct result of hyper- or hyposecretion of hormones from the endocrine glands or may occur as events secondary to the pathogenic mechanisms of the endocrinopathy, like in the case of autoimmunity affecting both endocrine glands and the brain (2). Moreover, the medical or surgical treatment of endocrine diseases can sometimes determine the occurrence of neurological or psychiatric syndromes. Some genetic aberrations can also lead to conditions affecting both the endocrine and the nervous system with a variety of possible manifestations. On the other side, many psychiatric or neurological diseases, including but not limiting to conditions, which affect the hypothalamus or the pituitary gland, may impair the physiological endocrine functions and demonstrate once again the intricate complexity of the psychoneuroendocrine connection. Covering all basic, translational, and clinical aspects in a single Research Topic on the “Neurological and psychiatric disorders in endocrine diseases” cannot be realistically feasible. The scope is simply raising a number of interesting points from experts in the field to bring a contribution to the knowledge and maybe direct future research in this very intriguing area. Thus, we have collected reviews and original research articles, which may speak to a wide audience, including neurologists, psychiatrists, endocrinologists, and basic scientists in neuroscience, endocrinology, and metabolism. In the clinical area, an interesting study assesses the plasma levels of the muscle-derived hormone irisin in anorexic women, without finding any significant correlation between irisin level and physical exercise (3). Another fascinating study analyzes the complexity of psychiatric and personality disorders in women with polycystic ovary syndrome, highlighting the issue of psychological distress in this patient group (4). A comprehensive picture of gender dysphoria, a psychiatric condition, which requires endocrine management, in Ireland is presented (5). In a short review, the most relevant reproductive, neurodevelopmental, and genetic aspects of hypogonadotropic hypogonadal syndromes are outlined (6). A German study indicates that psychopathology significantly predicts quality of life in patients with acromegaly and suggests that depressive symptoms and anxiety, being modifiable factors, may represent relevant targets for a broad treatment intervention in acromegalic patients (7). In a concise review, the psychiatric alterations, the neurocognitive impairment, and the altered quality of life affecting at some extent the majority of the patients with Cushing’s syndrome are summarized, and the authors highlight that resolution of hypercortisolism, a challenging and non-granted achievement, does not always lead to the complete remission of the neuropsychiatric changes or restore the quality of life (8). With an incursion in the surgical field, the complications potentially affecting the laryngeal nerves during thyroid surgery are extensively reviewed, suggesting that still the incidence of laryngeal nerves damage secondary to thyroid surgery cannot be suppressed but may be maintained in a low range with thorough surgical techniques and the use of intraoperative neuromonitoring (9). Three articles address the complex interactions between metabolism and neuropsychiatric symptoms. The first one focuses on biological differences between restrictive anorexia nervosa and constitutional thinness, a controversial concept to describe young girls who follow a normal diet and differ from restrictive anorexia nervosa on a number of endocrine parameters (10). At the opposite of the spectrum, the second one reviews the role of inflammatory processes in the neuropsychiatric comorbidity associated with obesity (11). Finally, the last one summarizes the fascinating link through ghrelin peptides between appetite/reward/growth hormone axis and psychiatric disorders (12).

Charity Program «Alfa-Endo» for children with endocrine disease

Charity program to help children with endocrine diseases «Alpha-Endo” is aiming to improve quality of medical care for children with endocrine pathology. The main directions of the Program include: molecular-genetic and immunological testing of hereditary endocrine diseases; improvement of health and social care for children; and obesity prevention. The best evidence-based Russian and international managerial strategies, and clinical practices of diagnostics, prevention and treatment of endocrine diseases are reviewed by experts and implemented within the Program. The synergistic cooperation involving the highly qualified Endocrinology Research Centre staff, significant financial resources “Alfa Group” and organizational support of CAF Foundation helps to solve difficult problems in pediatric endocrinology and improve welfare of children with endocrine diseases.

MANAGEMENT OF ENDOCRINE DISEASE: Management of pregnant patients with Cushing's syndrome.

Progress in the diagnosis and treatment of endocrine diseases has turned pregnancy into a possibility for women with such medical disorders, including Cushing's syndrome (CS). Nevertheless, despite its rarity, pregnancy in patients with CS can be troublesome because of the risk of maternal-fetal complications. Therefore, hypercortisolism, if present, should be surgically or medically controlled in most cases. Moreover, changes in the hypothalamic-pituitary-adrenal axis during normal pregnancy may mislead the diagnosis of CS during this period, because many laboratory assessments suggestive of CS may be present in normal pregnancy, with clinical features mimicking those seen in patients with CS. The aim of the present review is to update the diagnostic approach to this medical condition, mainly for pregnant women without previous diagnosis of CS, and to describe the therapeutic strategies for CS during pregnancy in order to minimize complications for both mother and fetus.

Continuing the JCEM Mission With Its New Editorial Team

Assuming the Editorship of The Journal of Clinical Endocrinology & Metabolism is an awesome and personally humbling proposition. A host of wonderful and invaluable insights into the diagnosis and treatment of endocrine diseases has been published in the JCEM since its birth in 1941. Many people—authors, reviewers, editors—have worked together to disseminate new basic and clinical knowledge for our collective and increasingly complex endocrine subspecialties. As has been the trend in general internal medicine, we are now witnessing general endocrinologists who are very comfortable within their own areas of expertise but are not so certain when it comes to diagnosing and treating certain endocrine diseases outside their comfort zones. This is understandable, given the glut of information, peer-reviewed or not, both in print and on the internet, that bombards us on a daily basis. Nonetheless, we all want to be more holistic than reductionist. This state of affairs precisely leads me to my overall vision and mission for the JCEM. I want the JCEM to provide you with a broad spectrum of information that is up to date, and at the same time inclusive of our scientific history. We can do this because it is our good fortune to have countless authors who want to publish in the JCEM, a huge number of able reviewers who critically read thousands of manuscript submissions a year, and a group of Associate Editors with overlapping areas of expertise who ensure completion of our mission to publish only the very best for you to read and use to further your own research and/or practice. We should all be excited and humbled to be part of this awesome enterprise. We will make some changes in the Journal over the next few months and perhaps years, most of which I will not divulge now but will encourage you to discover. One sustained effort will be to reduce the bulk of the printed version of the JCEM and to be reasonably more selective of what we publish. The JCEM content will also live on our new online platform, Literatum by Atypon, so you’ll be able to access articles wherever you are. You’ll witness firsthand a more dramatic innovation during the upcoming ENDO 2015 meeting in March in San Diego, California. The JCEM is inaugurating a session called “The Best of JCEM 2014.” Its purpose is to invite authors of manuscripts that were the most highly scored by our Editors and reviewers in 2014. During this session, you will hear original research presentations from 10 speakers, each representing a different subspecialty area, who will describe their published work as well as more recent unpublished information. The goals of this session are to help all of us keep up with all of endocrinology, maintain our intellectual breadth, provide a great opportunity for fellows and other younger scientists to gain the bully pulpit, and celebrate the creative process we have that fuels the JCEM’s unique educational enterprise. Our overall goal is to retain the best of the JCEM and at the same time build on the excellent performances provided by prior Editors-In-Chief. Among these dedicated people I want to single out my immediate predecessor, Len Wartofsky. He has been a superb role model of unfailing service, tough integrity, and quiet intellectualism. It is upon his shoulders we will stand as we follow our vision to extend the excellence of the JCEM to even greater heights. I am excited about working with our new set of Associate Editors, who represent the whole of endocrinology, from bench to bedside, and will ensure that we publish the best clinical work and research: Alvin Matsumoto, MD, FACP; Anthony Heaney, MD, PhD; Anuja Dokras, MD; Dianne Figlewicz Lattemann, PhD; Robert Eckel, MD; Ele Ferrannini, MD; Matthew Rin-

Endocrine Myopathies: Clinical Review

Endocrinopathy is generally associated with hormonally-mediated systemic disorders. Myopathy is a result of this association and sometimes can be the first manifestation of endocrine diseases. This condition generally misdiagnosed as weakness and diagnosis and treatment of endocrine diseases are delayed. Especially cushing’s disease, exogen glucocorticoid use, hypothyroidism, hyperaldesteronism and osteomalacia can mimic inflammatory myopathies clinically. Endocrine myopathies are group of disease which must be part of differential diagnosis who has proximal muscle weakness. Statin and glucocorticoid use come to the knowledge of physician because these are the most common cause of drug related proximal myopathy. While evaluating patient with proximal myopathy, thyroid function tests, vitamin D levels, parathyroid hormone must be measured and primary hyperaldesteronism work up when clinically suspicion occurs. Treatment of endocrine myopathies are based on correction of endocrine disorder

Female hormone release of microencapsulated Xenopus laevis ovarian cells

Cell microencapsulation has potential for the treatment of endocrine diseases. This study aims to probe the feasibility of Xenopus laevis as an animal model for cell microencapsulation and transplantation and to evaluate the female hormone release of microencapsulated X. laevis ovarian cells. The cells were harvested, cultured and microencapsulated into alginate-chitosan-alginate microcapsules with an electrostatic generator. The estradiol and progesterone releases of the microencapsulated X. laevis ovarian cells were investigated both in vitro and in vivo. The results showed that the microencapsulated cells kept secreting estradiol and progesterone in vitro for 60 days. After transplantation, serum estradiol and progesterone levels in ovariectomized X. laevis remained elevated for 60 days. X. laevis has been proved to be a suitable animal model for cell microencapsulation and transplantation. Microencapsulated ovarian cells may be considered as a promising endogenous drug delivery system for the treatment of deficiency of female hormones.

Abstract P6-02-02: Altered matrix homeostasis regulates estrogen biosynthesis in adipose tissue

Abstract Several estrogen-dependent pathological conditions including breast cancer, uterine fibroids, and endometriosis are associated with local overexpression of aromatase, a key enzyme in estrogen biosynthesis and important therapeutic target for postmenopausal ER+ breast cancer. In addition, excessive aromatase expression in adipose tissue at least partially accounts for obesity-associated breast cancer risk among postmenopausal women. While altered matrix homeostasis is associated with these aromatase-overexpressing tissues, little is known as to whether it can directly impact local steroidogenic gene expression and estrogen biosynthesis. A paucity of knowledge in this area is partly due to the lack of proper model systems that can recapitulate the mechanical properties of a cell's microenvironment. Our data indicate that matrix alone can significantly stimulate aromatase transcription in breast stromal cells (BSCs) via distinct signaling pathways. With the help of a repertoire of molecular and biophysical tools, such as micropost, micropattern and polyacrylamide gel and 3-dimensional matrix culture, we determined that matrix rigidity and cellular shape play important role in the regulation of aromatase transcription in the BSCs. We further discovered that cytoskeleton dynamics can significantly alter the ECM-stimulated aromatase transcription in BSCs. Following careful and elaborate studies with the help of siRNA-mediated knockdown and over-expression of the individual factors, we found that a non-canonical collagen receptor member of discoidin domain receptor (DDR) family, DDR1, transduce the external signal inside the cells to facilitate the aromatase transcription. Further studies with siRNA-mediated knockdown and specific inhibitors revealed that DDR1 activates a signaling cascade, which promotes activation of the cJun kinase (JNK-1) by phosphorylation and subsequently the activation of Activation Protein-1 family member JunB. Activated JunB physically binds at the cancer-specific promoters of aromatase and induce transcription in stromal cells. To determine the consequence of the altered matrix generated aromatase on the growth of estrogen receptor (ER)-positive breast cancer cell lines we set up in vitro co-culture system. Proliferation of ZR75-1 and its ability to produce estrogen-stimulated genes were enhanced in multiple fold, when the cells were co-cultured physically with BSCs inside collagen or fed with BSC conditioned media in the presence of testosterone. The link between matrix homeostasis and hormone metabolism is a vastly under-explored topic. Results from our work has bridged a major gap of knowledge in this field. Findings from the study also identified new factors that are key for the tissue-specific activation of estrogen biosynthesis and provide novel prognostic tools and markers, as well as new therapeutic targets for reducing local estrogen production, thus overcoming the side effects often associated with systemic inhibition of aromatase. The proposed work promises to establish a novel paradigm for regulation of steroidogenic gene expression and estrogen production and may have a far-reaching impact on the etiology and treatment of endocrine diseases that are associated with altered matrix homeostasis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-02-02.

The role of molecular genetics in diagnostics and treatment of endocrine diseases. Brief characteristic of monogenic forms of hereditary endocrinopathies diagnosed in Endocrinological Research Centre during the 15 year period (1996-2010)

Recent years have witnessed great progress in molecular genetics leading to impressive breakthroughs in medical sciences at large and in endocrinology in particular. The objective of the present article is to summarize information on the cases of monogenic hereditary endocrinopathies verified in the Endocrinological Research Centre during the 15 year period (1996-2010). These data are based on the analysis of 36 different genes associated with endocrine pathologies, such as hereditary forms of hypopytuitarism, disturbances of steroid hormone biosynthesis, abnormal gender formation, monogenic forms of diabetes mellitus, endocrine tumours, etc. The importance of molecular-genetic investigations for the treatment and prevention of endocrine diseases is discussed.

Mechanisms of insulin secretion in malnutrition: modulation by amino acids in rodent models

Protein restriction at early stages of life reduces β-cell volume, number of insulin-containing granules, insulin content and release by pancreatic islets in response to glucose and other secretagogues, abnormalities similar to those seen in type 2 diabetes. Amino acids are capable to directly modulate insulin secretion and/or contribute to the maintenance of β-cell function, resulting in an improvement of insulin release. Animal models of protein malnutrition have provided important insights into the adaptive mechanisms involved in insulin secretion in malnutrition. In this review, we discuss studies focusing on the modulation of insulin secretion by amino acids, specially leucine and taurine, in rodent models of protein malnutrition. Leucine supplementation increases insulin secretion by pancreatic islets in malnourished mice. This effect is at least in part due to increase in the expression of proteins involved in the secretion process, and the activation of the PI3K/PKB/mTOR pathway seems also to contribute. Mice supplemented with taurine have increased insulin content and secretion as well as increased expression of genes essential for β-cell functionality. The knowledge of the mechanisms through which amino acids act on pancreatic β-cells to stimulate insulin secretion is of interest for clinical medicine. It can reveal new targets for the development of drugs toward the treatment of endocrine diseases, in special type 2 diabetes.

Diagnosis and treatment of endocrine diseases in children: a new challenge to pediatricians

Diagnosis and treatment of endocrine diseases in children: a new challenge to pediatricians

Endoscopic thyroidectomy and parathyroidectomy by the axillary approach. A preliminary report.

The use of endoscopic procedures leads to a reduction in the size of the surgical scar, making it more inconspicuous. In this paper, we evaluated the merits and limits of endoscopic neck surgery. Between August 1999 and July 2000, 102 patients underwent neck surgery in our department for thyroid or parathyroid disease. Twenty-eight of them were treated by the axillary. A 12-mm and two 5-mm trocars were inserted through the skin of the axilla. Carbon dioxide was then insufflated up to 4 mmHg, and the endoscopic surgery was performed. Endoscopic procedures were performed successfully in 26 cases (19 thyroidectomies and seven parathyroidectomies). There were two conversions to open procedures. The mean operating times for the thyroidectomies and parathyroidectomies were 212 and 171 min, respectively. No evidence of injury to the recurrent laryngeal nerve was observed in any of the cases. The postoperative cosmetic status of the patients was excellent. We believe that endoscopic thyroidectomy and parathyroidectomy by the axillary approach will find a role in the treatment of endocrine diseases in the neck.

Radiopharmaceuticals for nuclear endocrinology at the University of Michigan.

The historical background at the University of Michigan laid a foundation for the innovative development of radionuclides in diagnosis and treatment of endocrine diseases. From that background, Dr. William Beierwaltes, the chief of Nuclear Medicine, inspired two talented young chemists to synthesize unique radiopharmaceuticals that transformed diagnostic approaches to certain endocrine disorders. Dr. Raymond Counsell's 131-I-radiocholesterol, enabled imaging that defined function in the adrenal cortex, and thereby distinguished the different forms of Cushing's syndrome and of primary aldosteronism; in addition, this new technique differentiated benign adrenal cortical adenomas from other adrenal cortical tumors. Dr. Donald Wieland created metaiodobenzlylguanidine (MIBG), a compound that can be tagged with either 131-I or 123-I, and led to the scintigraphic depiction of adrenergic tumors, particularly pheochromocytomas and neuroblastoma, anywhere in the body of a patient. Treatments with large doses of MIBG have reduced the malignant forms of pheochromocytomas and brought remissions to children with neuroblastomas. MIBG also concentrated in the autonomic neurons and so the nerves of the heart were also portrayed. Subsequent novel syntheses included positron-emitting nuclides that, through positron emission tomography, have revealed the physiology and altered physiology of the human heart. These men and their discoveries exemplify the creative endeavors that compel us to seek further the wonders of nuclear science.