Endocrine manifestations in adults with 22q11.2 deletion syndrome: a retrospective single-center cohort study.

INTRODUCTION AND OBJECTIVE: Patients with the 22q11.2 deletion syndrome (22q11DS) frequently display cardiological and psychiatric diseases, but are also at increased risk for endocrine manifestations. The aim of this study was to evaluate the screening, prevalence, and management of hypoparathyroidism and thyroid disease in patients with 22q11DS, to evaluate the metabolic profile, and to compare these results with current literature and guidelines. DESIGN: We performed a retrospective study of patients with genetically confirmed 22q11DS, followed at the center for human genetics of the University Hospitals Leuven, resulting in a cohort of 75 patients. Medical history, medication, and laboratory results concerning hypoparathyroidism, thyroid dysfunction, and the metabolic profile were collected. RESULTS: Of the total cohort, 26 patients (35%) had at least one hypocalcaemic episode. During hypocalcaemia, parathyroid hormone (PTH) was measured in only 12 patients with 11 having normal or low PTH, confirming a diagnosis of hypoparathyroidism. Recurrent episodes of hypocalcaemia occurred in seventeen patients (23%). Adherence to the guidelines was low, with 13% of patients having a yearly serum calcium evaluation, 12% receiving daily calcium supplements, and 20% receiving non-active vitamin D. Hypothyroidism was present in 31 patients (44%) and hyperthyroidism in 6 patients (8%). Information on body mass index (BMI) was available in 52 patients (69%), of which 38% were obese (BMI ≥ 30 kg/m2). CONCLUSION: Hypoparathyroidism, hypothyroidism, and obesity are common endocrine manifestations in patients with 22q11DS but are probably underdiagnosed and undertreated, indicating the need for multidisciplinary follow-up including an endocrinologist.

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.

[Justification of the need to normalize vitamin D status for immunoprophylaxis].

Currently, there is an increase in the resistance of microorganisms to the available arsenal of antimicrobial drugs, which makes it necessary to maintain and stimulate the body's own immune-protective properties. The main extraskeletal effect of vitamin D activity is associated with the homeostasis of the immune system. The role of vitamin D in reducing the risk of infection with infectious agents has been studied for a long time. Literature search on the effective use of vitamin D for immunoprophylaxis was carried out in Scopus, Web of Science, PubMed, clinicaltrials.gov databases over the past 10 years for related keywords: vitamin D, immunoprophylaxis. Vitamin D stimulates the synthesis of antimicrobial peptides, cathelicidins and defensins, which exhibit broad-spectrum activity against viruses, bacteria and fungal infections; reduces the concentration of pro-inflammatory cytokines; increases the concentration of anti-inflammatory cytokines. Vitamin D is also involved in cell differentiation, maturation and proliferation of immune cells. The article presents the literature review in order to justify additional intake of vitamin D in case of diagnosis of its deficiency and insufficiency for the purpose of immunoprophylaxis in children and adults, especially in risk groups (elderly age, pregnant women, patients with chronic diseases of respiratory, endocrine and urinary systems, gastrointestinal tract, and infectious diseases). Inclusion of vitamin D in the diet as a dietary supplement, as well as fortification of products with it, can be an effective measure to reduce the risk of both morbidity and mortality, especially during the period of quarantine measures.

Rate of gestational weight gain and adverse pregnancy outcomes in rural nulliparous women: a prospective cohort analysis from China.

Both inadequate and excessive gestational weight gain (GWG) have been shown to increase the risk of adverse pregnancy outcomes, but the risk profiles of GWG rate are unclear. We aimed to examine the associations between GWG rate in the second/third trimester and a spectrum of pregnancy outcomes. This study consisted of 14 219 Chinese rural nulliparous women who participated in a randomised controlled trial of prenatal micronutrient supplementation during 2006-2009. The outcomes included stillbirth, neonatal and infant death, preterm birth, macrosomia, low birth weight (LBW) and large and small for gestational age (LGA and SGA, respectively). GWG rate was divided into quintiles within each BMI category. Compared with women in the middle quintile, those in the lowest quintile had higher risks of neonatal death (adjusted OR 2·27; 95 % CI 1·03, 5·02), infant death (adjusted OR 1·85; 95 % CI 1·02, 3·37) and early preterm birth (adjusted OR 2·33; 95 % CI 1·13, 4·77), while those in the highest quintile had higher risks of overall preterm birth (adjusted OR 1·28; 95 % CI 1·04, 1·59), late preterm birth (adjusted OR 1·25; 95 % CI 1·00, 1·56), LBW (adjusted OR 1·48; 95 % CI 1·02, 2·15), macrosomia (adjusted OR 1·89; 95 % CI 1·46, 2·45) and LGA (adjusted OR 1·56; 95 % CI 1·31, 1·85). In conclusion, very low and very high GWG rates in the second/third trimester appear to be associated with adverse pregnancy outcomes in Chinese nulliparous women, indicating that an appropriate GWG rate during pregnancy is necessary for neonatal health.

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.

Neonatal Endocrine Labomas - Pitfalls and Challenges in Reporting Neonatal Hormonal Reports.

This review highlights pitfalls and challenges in interpreting neonatal hormone reports. Pre-analytical errors contribute to nearly 50% of all errors. Modern chemiluminescence assay are more accurate, have lower risk of Hook's effect, but continue to have problems of assay interference. Liquid chromatography mass spectroscopy is gold standard for most hormone assays. Neonatal hypoglycemia diagnostic cut-offs are lower than adults. Random growth hormone testing is of value in diagnosing growth hormone deficiency in neonates. 17-hydroxy-progesterone testing in first three days of life for congenital adrenal hyperplasia (CAH) remains a challenge due to cross-reactivity with maternal circulating steroids, prematurity and lack of adrenal maturation. Both T4 and TSH testing is encouraged after 48 hours of delivery for diagnosing neonatal hypothyroidism; repeat testing should be done immediately for confirmation of diagnosis. There is an urgent need to develop age- sex- and ethnicity-based normative data for different hormone parameters in neonates. Laboratory should develop their own neonatal references and avoid using ranges from manufacturers. In neonatal endocrinopathies, the clinical scenario should primarily dictate the treatment formulation with hormonal assay to supplement treatment.

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.

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.

Uncertainties in endocrine substitution therapy for central endocrine insufficiencies: growth hormone deficiency.

The growth hormone deficiency (GHD) syndrome is associated with several metabolic abnormalities and it has been postulated that the increased cardiovascular disease (CVD) morbidity and mortality in GHD patients may be related to the missing metabolic effects of GH. Many CVD risk factors show improvements after GH therapy. Reduced bone mineral density (BMD) has been recorded both in patients with isolated GHD and in those with multiple pituitary deficiencies, indicating that GHD per se is responsible for the low BMD in both types of patients. These matters are, however, more complicated, as hypopituitary patients with GHD may have different phenotypes due to differences in underlying diagnoses. These phenotypes may not be clear-cut in individual patients. Moreover, patients may transit between different phenotypes over time due to extension of the pathology in the pituitary and/or the consequences of the treatment (surgery and/or radiotherapy). Three different phenotypes of hypopituitary patients will be discussed, with a focus on CVD risk and bone health: (1) patients with isolated GHD, e.g. due to prophylactic cranial radiotherapy for lymphoblastic leukaemia in childhood; (2) patients with GHD and multiple hormone deficiencies due to pituitary macroadenomas treated by surgery; (3) patients with GHD caused by craniopharyngiomas with multiple hormone deficiencies and hypothalamic involvement, where hypothalamic damage frequently dominates the positive metabolic effects of GH therapy. These phenotypes illustrate the differential impact of various pituitary pathologies on the phenotype of patients with GHD.

Traumatic brain injury and neuro-endocrine disruption: medical and psychosocial rehabilitation.

INTRODUCTION: Traumatic Brain Injury (TBI) initiates a cascade of neuromodulatory damage that blurs the distinctions between physical and psychological medicine. Monitoring endocrine function through labs is not part of the medical care algorithm for treatment of TBI, but the clinical symptoms are easily misidentified as they include: depression, fatigue, poor concentration, irritability and a decline in overall cognitive functioning. The reciprocal flow of change between neuroendocrine health and psychosocial health is well established within the field of neuroscience, social psychology, endocrinology and behavioral neurology, but has not translated into patient care. OBJECTIVES: This paper outlines common neuroendocrine disruptions secondary to TBI and their clinical implications for treating mental health professionals. CONCLUSION: Wider adoption of the consensus guidelines on the detection and monitoring of endocrine abnormalities post-TBI may diminish the severity of functional impairment and improve quality of life.

Hypothalamic-pituitary lesions in pediatric patients: endocrine symptoms often precede neuro-ophthalmic presenting symptoms.

OBJECTIVE: To evaluate whether analyses of clinical and endocrine presenting symptoms could help to shorten the time to diagnosis of hypothalamic-pituitary lesions in children. STUDY DESIGN: A retrospective, single-center, cohort study of 176 patients (93 boys), aged 6 years (range, 0.2-18 years), with hypothalamic-pituitary lesions was performed. RESULTS: The lesions were craniopharyngioma (n = 56), optic pathway glioma (n = 54), suprasellar arachnoid cyst (n = 25), hamartoma (n = 22), germ cell tumor (n = 12), and hypothalamic-pituitary astrocytoma (n = 7). The most common presenting symptoms were neurologic (50%) and/or visual complaints (38%), followed by solitary endocrine symptoms (28%). Precocious puberty led to diagnosis in 19% of prepubertal patients (n = 131), occurring earlier in patients with hamartoma than in patients with optic-pathway glioma (P < .02). Isolated diabetes insipidus led to diagnosis for all germ-cell tumors. For 122 patients with neuro-ophthalmic presenting symptoms, the mean symptom interval was 0.5 year (95% CI, 0.4-0.6 year), although 66% of patients had abnormal body mass index or growth velocity, which preceded the presenting symptom interval onset by 1.9 years (95% CI, 1.5-2.4 years) (P < .0001) and 1.4 years (95% CI, 1-1.8 years) (P < .0001), respectively. Among them, 41 patients were obese before diagnosis (median 2.2 years [IQR, 1-3 years] prior to diagnosis) and 35 of them had normal growth velocity at the onset of obesity. The sensitivity of current guidelines for management of childhood obesity failed to identify 61%-85% of obese children with an underlying hypothalamic-pituitary lesion in our series. CONCLUSIONS: Endocrine disorders occurred in two-thirds of patients prior to the onset of the neuro-ophthalmic presenting symptom but were missed. Identifying them may help to diagnose hypothalamic-pituitary lesions earlier.

Endocrine health problems detected in 519 patients evaluated in a pediatric cancer survivor program.

CONTEXT: Many pediatric cancer survivors have endocrine conditions. Surveillance for late effects is recommended by national guidelines. Endocrine surveillance is recommended after alkylating agents, steroids, methotrexate, and radiation. OBJECTIVE: The objective of the study was to describe the endocrine outcomes in patients followed up in a program that uses national screening guidelines. DESIGN: The design of the study was a medical records review. SETTING: The study was conducted in the Comprehensive Cancer Survivor Program, an academic pediatric oncology program. PARTICIPANTS: The study included 519 pediatric and young adult survivors of noncentral nervous system childhood malignancies between January 1, 2001, and December 15, 2005. INTERVENTION: Patients were evaluated with history, physical examinations, and evaluations recommended in the Children's Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. OUTCOME MEASURES: The frequency and types of endocrine conditions were measured. RESULTS: Four hundred eighty endocrine conditions were observed in 299 survivors (57.6% of survivors). The most common types of endocrine conditions were problems with weight and gonadal function. In a Cox regression model, stem cell transplant, radiation, and older age at cancer diagnosis were associated with higher hazard of an endocrine condition. Radiation, stem cell transplant, and sarcoma diagnosis were associated with growth problems. CONCLUSIONS: Endocrine disorders were common after pediatric cancers. Endocrinologists should be aware of national guidelines, anticipate referral of pediatric cancer survivors, and participate in further research to optimize screening for and treatment of endocrine effects of cancer therapy.

A psychoneuroendocrinology service.

BACKGROUND: Research evidence has highlighted the relevance of endocrine/metabolic abnormalities in psychiatry and of psychosocial implications in endocrinology. However, the value of interdisciplinary expertise has not been implemented in clinical practice. We have therefore designed a new outpatient clinic, called the Psychoneuroendocrinology Service, to apply the principles of current psychosomatic medicine and report here on the first 100 referrals. METHODS AND RESULTS: Of the first 100 patients (74 females/26 males; mean age 44 +/- 13.8 years), the sources of referral were the Mental Health Center (n = 41), specialists (n = 37) and primary care physicians (n = 22). The main reasons for referral were endocrine assessment (n = 40), unexplained medical symptoms (n = 18) and poor response to treatment (n = 17). The most frequent medical diagnoses were obesity/overweight (n = 22), hypertension (n = 20) and hypothyroidism (n = 11). The most frequent psychiatric diagnoses were major depression (n = 15), schizophrenia/schizoaffective disorder (n = 13) and bipolar disorder (n = 12). Subclinical symptoms (Diagnostic Criteria for Psychosomatic Research) found were persistent somatization (n = 18), demoralization (n = 14) and irritable mood (n = 7). Therapeutic strategies included lifestyle modifications (n = 45), explanatory therapy (n = 30), low-dose clonazepam (n = 23) and modifications of existing treatment with psychotropic drugs (n = 16). CONCLUSIONS: In this highly selected population, several difficult patients could be appropriately managed by virtue of a holistic view. Such an approach must involve experienced clinicians with a broad-spectrum training in psychoneuroendocrinology and psychosomatic medicine. If confirmed in its efficacy and cost-effectiveness, this model might be further expanded.

Gynaecomastia in a man and hyperoestrogenism in a woman due to ingestion of nettle (Urtica dioica).

Nettle (Urtica dioica) is commonly sold as a herbal tea in Turkey. We report a case of gynaecomastia in a man (in which the only aetiologic factor identified was nettle tea consumption) and a case of galactorrhoea in a woman (in which the only aetiologic factor identified was also nettle tea ingestion).

Holiday review. Duty of care to the undiagnosed patient: ethical imperative, or just a load of Hogwarts?

With the restoration of You-Know-Who to full corporeal form, the practice of the dark arts may lead to multitudes being charmed, befuddled and confounded. At present, muggle ethics dictate that aid may be rendered in a life-or limb-threatening situation, but the margins are blurred when neither is at stake. Muggle and wizard healers, fearful of being labelled ambulance chasers, may shy away from approaching those who remain blissfully unaware of their illnesses. We describe 4 case studies in which we intervened as muggle healers, to salutary effect. The afflicted were healed or helped, without bringing the weight of the Ministries of Magic or Magical Healing upon us. We advocate a spirit of cooperation between muggle and magical folk, mindful of the strengths that the healing arts from each community have to offer. As long as the intent is beneficent, healers or even the wizard or muggle on the street may intervene and render aid to the afflicted.

Endocrinopatía autoinmune múltiple / Multiple autoimmune endocrinopathy

Se presenta una niña de tres años y ocho meses, con antecedentes familiares de endocrinopatía autoinmune que consulta por síndrome malabsortivo y candidiasis mucocutánea con onicomicosis crónica. Evoluciona presentando una crisis de tetania generalizada secundaria a hipoparatiroidismo y luego un hipertiroidismo clínico. Con pruebas de laboratorio positivas para enfermedades autoinmune. (AU)

Endocrinopatía autoinmune múltiple / Multiple autoimmune endocrinopathy

Se presenta una niña de tres años y ocho meses, con antecedentes familiares de endocrinopatía autoinmune que consulta por síndrome malabsortivo y candidiasis mucocutánea con onicomicosis crónica. Evoluciona presentando una crisis de tetania generalizada secundaria a hipoparatiroidismo y luego un hipertiroidismo clínico. Con pruebas de laboratorio positivas para enfermedades autoinmune.

Síndrome del nevo basocelular: presentación de dos casos y revisión de la literatura / Nevoid basal cell carcinoma syndrome: report of two cases and review of the literature

Los autores presentan dos casos de síndrome del nevo basocelular (SNBC), un raro desorden genético caracterizado por múltiples carcinomas basocelulares (CB), queratoquistes odontogénicos (QQO) mandíbulo-maxilares, alteraciones neurológicas y otras alteraciones menos frecuentes. Se describen dos casos. Un niño de 12 años, quien presentaba QQO en los maxilares, CB múltiples, alteraciones esqueléticas y otros trastornos, y una mujer de 27 años con QQO y CB múltiples. Se destaca la importancia del diagnóstico temprano en la consulta odontológica (AU)

Thyroid disease and other endocrine disorders in pregnancy.

Endocrine disorders, in particular, thyroid disorders, are common in pregnancy. The endocrine adaptation to pregnancy, need for adequate iodine supplementation, and thyroxine replacement are presented. In addition, autoimmune diseases of the thyroid and pituitary that may occur subsequent to the immune changes of pregnancy and the postpartum period are discussed. A brief account of the presentation of other endocrine disorders (ie, pituitary,parathyroid, calcium, adrenal and gonadal disorders) also is given, along with their evaluation and management.