Endocrinopathies in beta thalassemia: a narrative review.

Beta thalassemia is the most common genetic blood disorder, characterized by reduced production or complete absence of beta-globin chains. The combination of systematic red blood cell transfusion and iron chelation therapy is the most readily available supportive treatment and one that has considerably prolonged the survival of thalassemia patients. Despite this, the development of endocrine abnormalities correlated with beta thalassemia still exists and is mostly associated with iron overload, chronic anemia, and hypoxia. A multifactorial approach has been employed to investigate other factors involved in the pathogenesis of endocrinopathies, including genotype, liver disease, HCV, splenectomy, socioeconomic factors, chelation therapy, and deficiency of elements. The development of specific biomarkers for predicting endocrinopathy risk has been the subject of extensive discussion. The objective of the present narrative review is to present recent data on endocrinopathies in beta thalassemia patients, including the prevalence, the proposed pathogenetic mechanisms, the risk factors, the diagnostic methods applied, and finally the recommended treatment options.

Endocrine disorders in Prader-Willi syndrome: a model to understand and treat hypothalamic dysfunction.

Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal chromosomal region, 15q11-13. Impaired hypothalamic development and function is the cause of most of the phenotypes comprising the developmental trajectory of Prader-Willi syndrome: from anorexia at birth to excessive weight gain preceding hyperphagia, and early severe obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine dysfunctions observed. Additionally, as a result of hypothalamic dysfunction, oxytocin and ghrelin systems are impaired in most patients. Standard pituitary and gonadal hormone replacement therapies are required. In this Review, we discuss Prader-Willi syndrome as a model of hypothalamic dysfunction, and provide a comprehensive description of the accumulated knowledge on genetics, pathophysiology, and treatment approaches of this rare disorder.

Acupuncture Medical Therapy and its Underlying Mechanisms: A Systematic Review.

As a traditional Chinese alternative health care approach, acupuncture is gaining increasing attention and reputation in China and overseas. While becoming increasingly popular globally, some consumers and professionals still know little about the therapy and underlying mechanisms of acupuncture. Due to local superiority, there are large numbers of both clinical applications and mechanistic studies performed in China compared to countries overseas. Herein, this review attempts to give a comprehensive profile of the development, application, and mechanisms of acupuncture in treating major diseases. The number of clinical publications concerning acupuncture-treated neurological diseases, endocrine and metabolic diseases, circulatory diseases, respiratory diseases, etc. is first counted, and then, the application and therapeutic mechanisms of acupuncture on the predominant diseases in each category, including obesity, facial paralysis, sciatica, depression, hypertension, asthma, etc., are specifically discussed in this paper. The evolution of acupuncture tools and the rationality of acupoints are also discussed. This review not only summarizes the mechanisms of acupuncture but also provides useful information, such as specific acupoints and acupuncture procedures, for treating common diseases. Therefore, the current study provides useful information for both investigators and acupuncturists.

Vitamin D effects and endocrine diseases.

A lack of vitamin D has been linked to autoimmune diseases including type 1 diabetes, autoimmune thyroiditis and to obesity. The prevalence of vitamin D deficiency is higher in diabetic or obese children and patients with thyroiditis compared to healthy controls. Moreover, low vitamin D values seem to be associated with major complications and poor glycemic control, in particular in obese children. Supplementation with vitamin D, which has immune-regulatory properties, may support our therapies and improve the outcomes in different diseases. Although some studies suggest a possible role of vitamin D in the etiology of autoimmune diseases and obesity, data on supplementation benefits are inconclusive and further studies are needed. In this paper, we focus on the current evidence regarding vitamin D function in endocrine diseases and possible benefits of its supplementation in pediatric age.

Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis.

Human microbiota seems to play a key role in endocrine and reproductive systems. Fortunately, microbiota reproductive dysbiosis start to be treated by probiotics using typical species from genus Lactobacillus. This work presents the compiled and analysed results from the most up-to-date information from clinical trials regarding microbiota, fertility, probiotics and oral route administration, reviewing open access scientific documents. These studies analyse the clinical impact of probiotics administered on several endocrine disorders' manifestations in women: mastitis; vaginal dysbiosis; pregnancy complication disorders; and polycystic ovary syndrome. In all cases, the clinical modulation achieved by probiotics was evaluated positively through the improvement of specific disease outcomes with the exception of the pregnancy disorders studies, where the sample sizes results were statistically insufficient. High amounts of studies were discarded because no data were provided on specific probiotic strains, doses, impact on the individual autochthon microbiota, or data regarding specific hormonal values modifications and endocrine regulation effects. However, most of the selected studies with probiotics contained no protocolised administration. Therefore, we consider that intervention studies with probiotics might allocate the focus, not only in obtaining a final outcome, but in how to personalise the administration according to the disorder to be palliated.

Depression in Cancer Care.

Depression is common among cancer patients and their families, and may lead to substantial clinical consequences. Clinicians should routinely screen cancer patients for comorbid depression and should provide appropriate care at both primary and specialized care levels. Good quality care is beneficial not only for cancer patients themselves but also for their family members. It includes good communication between patients and health providers, and addressing of unmet needs of cancer patients. Specialized care comprises pharmacotherapy and psychotherapy. The advancement of psychotherapy for cancer patients parallels the advancement of general psychotherapy. Among the many types of psychotherapies, mindfulness-based interventions have been attracting growing attention. Some relevant studies that have been conducted in Keio University Hospital are described herein.

Hypothalamic hamartoma with epilepsy: Review of endocrine comorbidity.

The most common, and usually the only, endocrine disturbance in patients with hypothalamic hamartoma (HH) and epilepsy is central precocious puberty (CPP). The mechanism for CPP associated with HH may relate to ectopic generation and pulsatile release of gonadotropin-releasing hormone (GnRH) from the HH, but this remains an unproven hypothesis. Possible regulators of GnRH release that are intrinsic to HH tissue include the following: (1) glial factors (such as transforming growth factor α[TGFα) and (2) γ-aminobutyric acid (GABA)-mediated excitation. Both are known to be present in surgically-resected HH tissue, but are present in patients with and without a history of CPP, suggesting the possibility that symptoms related to HH are directly associated with the region of anatomic attachment of the HH to the hypothalamus, which determines functional network connections, rather than to differences in HH tissue expression or pathophysiology. CPP associated with HH presents with isosexual development prior to the age of 8 years in girls and 9 years in boys. It is not uncommon for CPP with HH to present in children at an earlier age in comparison to other causes of CPP, including in infancy. Surgical resection of the HH can be effective for treating CPP, but is reserved for patients with intractable epilepsy, since GnRH agonists are widely available and effective treatment. Other endocrine disturbances with HH are rare, but can include growth hormone deficiency, hypothyroidism, and adrenal insufficiency. Diabetes insipidus is commonly encountered postoperatively, but is not observed with HH prior to surgical intervention.

[The Choosing Wisely Initiative of the German Society of Internal Medicine : Recommendations of the German Society for Endocrinology and the German Society for Geriatrics]. / Die Klug-entscheiden-Initiative der Deutschen Gesellschaft für Innere Medizin : Empfehlungen der Deutschen Gesellschaft für Endokrinologie und der Deutschen Gesellschaft für Geriatrie.

POSITIVE RECOMMENDATIONS: A. After osteoporotic fractures in the elderly, as a rule specific antiosteoporotic therapy should be initiated. a. Osteoporosis as a disease of the elderly should be diagnosed and treated (recommendation of the German Society for Geriatrics). B. All patients with diabetes mellitus should complete a specific diabetes training program when antidiabetic drug medication is initiated. C. In Germany, all pregnant women should be advised to undertake iodine supplementation. D. Endocrine causes of hypertension should be ruled out in younger patients and in patients on multiple antihypertensive drugs. E. All unclear cases of hypercalcemia should be clarified. NEGATIVE RECOMMENDATIONS: A. Testosterone substitution therapy should not be initiated on the basis of only one measurement of a reduced testosterone level without clinical signs and clarification of the underlying cause. B. Imaging procedures should only be used after the existence of hormonal disease has been confirmed. C. Sonographic screening for thyroid disease is not advised in the elderly. D. Long-term therapy with levothyroxine for nodular goiter should be avoided. E. In relevant stress situations hydrocortisone replacement therapy should not be continued without dose adjustment in patients with adrenal or pituitary insufficiency.

Acupuncture in endocrine disorders: a critical appraisal.

Acupuncture is an integral part of ancient Chinese medical practice. The technique has been used extensively in pain relief and is being tried for many other chronic conditions. Industrial development and affluence lead to the increase in the prevalence of many endocrine disorders such as diabetes, obesity, and polycystic ovarian disease. The rising prevalence of the endocrine morbidity is observed in both the developing and developed nations. The management of these disorders involves major lifestyle modification coupled with a long-term drug intake. In such situations, patients often look at alternative therapeutic options existing in complementary and alternative medicine. The globalization of the world medical practice has led to the spread of acupuncture beyond China to other parts of the world. Acupuncture has been tried extensively in the management of various endocrine disorders with inconsistent results. In this review, we highlight the principles of acupuncture and its role in the management of various endocrine disorders.

Selected highlights of the VIII International Symposium of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) on Growth, Puberty and Endocrine Complications in Thalassaemia. Auditorium of the Sultan Qaboos University (SQU) Muscat (Sultanate of Oman), 20th of December 2014.

The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on the 20th of December, 2014. The symposium included four sessions on a wide range of topics covering growth disorders and endocrine complications in thalassaemia. Despite the fact that endocrine complications are very common in multi-transfused thalassaemia patients a recent survey conducted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported by hematologists or pediatricians experienced in thalassaemias or thalassaemia syndromes in following endocrine complications included: Lack of familiarity with medical treatment of endocrine complications, interpretation of endocrine tests, lack of collaboration and on-time consultation between thalassaemic centres supervised by haematologists and endocrinologists. Endocrine monitoring of growth, pubertal development, reproductive ability and endocrine function in general are essential to achieve a good quality of life as well as controlling the pain which results from the defects of bone structure, all of which increase with the age of patients. Such comprehensive care is best provided by coordinated, multidisciplinary teams working in expert centres. The multidisciplinary team must include an endocrinologist, preferably someone experienced in the management of hormonal deficiencies caused early in life by transfusion-induced iron overload.

[Update of recommendations for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology]. / Actualización de las recomendaciones para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales. Grupo de trabajo de osteoporosis y metabolismo mineral de la SEEN.

OBJECTIVE: To update previous recommendations developed by the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition for the evaluation and treatment of osteoporosis associated to different endocrine and nutritional diseases. PARTICIPANTS: Members of the Working Group on Osteoporosis and Mineral Metabolism of the Spanish Society of Endocrinology and Nutrition. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date between 18 October 2011 and 30 October 2014 were included. The recommendations were discussed and approved by all members of the Working Group. CONCLUSIONS: This update summarizes the new data regarding evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions.

Endocrine disorders in Fanconi anemia: recommendations for screening and treatment.

CONTEXT: Endocrine problems are common in patients with Fanconi anemia (FA). About 80% of children and adults with FA have at least one endocrine abnormality, including short stature, GH deficiency, abnormal glucose or insulin metabolism, dyslipidemia, hypothyroidism, pubertal delay, hypogonadism, or impaired fertility. The goal of this report is to provide an overview of endocrine abnormalities and guidelines for routine screening and treatment to allow early diagnosis and timely intervention. EVIDENCE ACQUISITION: This work is based on a comprehensive literature review, including relevant articles published between 1971 and 2014, and proceedings of a Consensus Conference held by the Fanconi Anemia Research Fund in 2013. EVIDENCE SYNTHESIS: The panel of experts collected published evidence and discussed its relevance to reflect current information about the endocrine care of children and adults with FA before the Consensus Conference and through subsequent deliberations that led to the consensus. CONCLUSIONS: Individuals with FA should be routinely screened for endocrine abnormalities, including evaluation of growth; glucose, insulin, and lipid metabolism; thyroid function; puberty; gonadal function; and bone mineral metabolism. Inclusion of an endocrinologist as part of the multidisciplinary patient care team is key to providing comprehensive care for patients with FA.

[Management of endocrine dysfunctions after allogeneic hematopoietic stem cell transplantation: a report of the SFGM-TC on adrenal insufficiency and osteoporosis]. / Suivi et prise en charge des troubles endocriniens en post-greffe de cellules souches hématopoïétiques: insuffisance corticotrope et ostéoporose.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on secondary adrenal insufficiency and osteoporosis post-transplant.

Morbidities and mortality in transfusion-dependent Beta-thalassemia patients (single-center experience).

BACKGROUND: The improvement of quality and duration of life of transfusion-dependent B thalassemia patients over the last years discloses several complications due to the underling disorder, iron overload and the treatment with iron chelators. Our Aim was to assess the morbidity patterns and mortality rate of transfusion-dependent thalassemia patients, and compare the outcomes in relation to age of onset, type, duration, and compliance to iron chelation therapy and frequency of blood transfusion. PROCEDURE: This retrospective study included 447 transfusion-dependent ß-thalassemia patients who attended the Thalassemia Center, Ain Shams University Children's Hospital over the last 10 years in the period between January 2000 and January 2010. Data were collected from the patients or their caregivers, as well as by reviewing follow up sheets for examinations and investigations done to detect morbidities as well as iron chelation therapies given. Determination of mortality rate and the causes of death were also done. RESULTS: Results revealed that the most common morbidities were endocrinologic (44.7%) followed by cardiovascular (41.3%) and hepatic (40.5%), then renal (4%). The different iron chelation therapy groups showed a comparable prevalence of different morbidities. The mortality rate was 1.5% and infection was the most common cause of death. The 5, 10, 20 years' survival rate among the studied patients was 80%, 50%, 20%, respectively. CONCLUSION: In the past 10 years, the survival and morbidity rates in our center have markedly improved as a result of regular blood transfusion, new iron chelators, and better compliance of the patients.

[Transcranial physical methods for correction of neuroendocrine and cerebral disorders in adolescent girls with obesity].

AIM: To evaluate the efficiency of combined central and local physiotherapeutic procedures in correcting neuroendocrine and menstrual disorders in pubertal girls (PG) with obesity. SUBJECTS AND METHODS: Eighty-seven PGs, including 67 with different levels of obesity and 20 healthy non-obese girls, were examined. The hormonal profile, lipidogram, and fasting insulin and glucose levels were studied. Body mass index (BMI) and waist and hip circumferences were estimated. The functional state of the central nervous system was studied by electroencephalography. The parameters of the autonomic nervous system were estimated by cardiointervalography. The PGs with obesity were divided into 2 groups: a study group (SG) (n = 40) and a control group (CG) (n = 27). The healthy PGs (n = 20) formed a comparison group. The SG patients received bitemporal transcranial magnetic therapy in combination with frontomastoid transcranial electrostimulation, as well as myoelectrostimulation of the anterior abdominal wall, by transferring the area of stimulation from right to left hypochondrium. A course consisted of 10-15 daily sessions. CG had placebo physioprocedures (with disconnected electrodes). RESULTS: After 6-month treatment, SG and CG showed average reductions in BMI by 5.9 and 2.5 kg/m2, respectively. Lipidograms normalized in 70%; menstrual cycles were restored in 25 of 30 patients with impaired cycles in SG and in 1 of 22 in CG. Hormonal profiles were significantly improved in 62.5% of the patients in SG and unchanged in CG. CONCLUSION: The high efficiency of combined (central and local) physiotherapeutic procedures is likely to be dueto the normalization of pituitary-ovarian relationships and enables one to recommend the proposed procedure in a rehabilitation program for PGs with obesity and reproductive system disorders.

Vitamin D endocrine system and the immune response in rheumatic diseases.

Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders.

Critical appraisal of growth retardation and pubertal disturbances in thalassemia.

Growth and pubertal disturbances are the commonest endocrinopathies in homozygous thalassemia, accounting for significant morbidity in 70-80% children and adolescents globally. This review focuses on the pathophysiology of the endocrinopathy from a historical perspective and altered natural history induced by better care due to transfusion and chelation therapy. We have also discussed clinical features, diagnosis, and management strategies of growth retardation, sexual infantilism, pubertal aberrations, and scope of growth hormone, sex steroids, and other endocrine therapies. The article also emphasizes current and future strategies for screening, monitoring of growth and pubertal disturbances, and early intervention for the restoration of fertility potential and bone mass in the affected individuals.