Complicaciones endocrinológicas del síndrome de down en pediatría: revisión de la literatura / Endocrine complications of Down syndrome in pediatrics: a review of the literature

El síndrome de Down constituye la cromosopatía más frecuente a nivel mundial y afecta 6,03 a 7,86 de cada 10.000 nacidos vivos en Colombia. Los pacientes pediátricos de este grupo poblacional presentan una mayor incidencia de complicaciones endocrinológicas comparados con la población general. El objetivo de este artículo es revisar las complicaciones endocrinológicas prevalentes en el paciente pediátrico con síndrome de Down, relacionadas con el hipocrecimiento, desarrollo puberal, patología tiroidea, diabetes mellitus, dislipidemias y obesidad; así como describir su seguimiento y tratamiento. Se realizó una búsqueda en la literatura desde agosto de 2020 hasta diciembre de 2021, en las bases de datos PubMed y Google Scholar; incluyendo un total de 44 publicaciones para la presente revisión. Se concluye que el paciente pediátrico con síndrome de Down evidencia un patrón de hipocrecimiento junto a un mayor riesgo de obesidad y sobrepeso. Adicionalmente, presenta con mayor frecuencia patología tiroidea y diabetes mellitus.

Down syndrome is the most common chromosomal disorder worldwide, affecting 6,03 to 7,86 per 10.000 live births in Colombia. Pediatric patients with Down syndrome have a higher incidence of endocrine disorders compared to the general population. The aim of this paper was to review the endocrinological manifestations prevalent in pediatric patients with Down syndrome related to small stature, pubertal development, thyroid dysfunction, diabetes mellitus, dyslipidemia, and obesity. Additionally, their follow-up and adequate treatment are described. A literature search was carried out from August 2020 to December 2021 in the PubMed and Google Scholar databases. A total of 44 publications were included for this review. It is concluded that pediatric patients with Down syndrome are more likely to have short stature and have a higher risk of obesity and overweight. In addition, thyroid dysfunction and diabetes mellitus are frequent complications.

Síndrome POEMS: desafios no diagnóstico de um caso atípico / POEMS syndrome: challenges in the diagnosis of an atypical case

Introdução: Síndrome POEMS trata de um raro evento paraneoplásico, sem relato atual na literatura sobre sua real prevalência. A maior parte dos casos ocorre em homens de meia idade; Relato do Caso: Relatamos o caso de um paciente masculino, 65 anos, admitido com queixa edema e parestesia em pernas que evoluiu para plegia, associada a hiporexia e fadiga. Investigação ambulatorial inicial evidenciou polirradiculoneuropatia inflamatória desmielinizante crônica (PIDC) de etiologia indefinida. Excluídos secundarismos para polirradiculoneuropatia inflamatória desmielinizante crônica, o paciente foi a seguir diagnosticado com hipotireoidismo primário, hipogonadismo severo, lesões hipercrômicas em pele, ascite, derrame pleural e trombocitose, além de gamopatia monoclonal IgA Lambda por imunofixação sérica. Sorologias para HIV, Sífilis e Hepatites todas negativas. Excluída a possibilidade de Mieloma Múltiplo e outras gamopatias, foi aventada a hipótese de Síndrome POEMS, sendo realizada dosagem de Fator de Crescimento Endotelial Vascular (VEGF) plasmática (425 pg/mL; VR = <96.2). O paciente passou então a preencher os critérios obrigatórios para diagnóstico, além de um maior (VEGF elevada) e vários outros menores. Trata-se de um caso atípico na medida em que, lesões ósseas, presentes em até 97% dos casos, não foram evidenciadas no paciente em questão, tornando desafiador o diagnóstico e sendo então necessário recorrer à dosagem de VEGF. O diagnóstico de síndromes raras, embora desafiante, traz ao clínico um olhar mais amplo do paciente na medida em que incrementa o raciocínio clínico. Difundir e explorar esse universo é cada vez mais necessário

Introduction: POEMS syndrome is a rare paraneoplastic event, with no current report in the literature about its real prevalence. Most cases occur in middle-aged men; Case Report: We report the case of a male patient, 65 years old, admitted with complaints of edema and paresthesia in the legs that progressed to plegia, associated with hyporexia and fatigue. Initial outpatient investigation revealed Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) of undefined etiology. Excluding secondaries for chronic inflammatory demyelinating polyradiculoneuropathy, the patient was subsequently diagnosed with primary hypothyroidism, severe hypogonadism, hyperchromic skin lesions, ascites, pleural effusion and thrombocytosis, in addition to monoclonal IgA Lambda gammopathy by serum immunofixation. All serologies for HIV, Hepatitis and syphilis were negative. Excluding the possibility of Multiple Myeloma and other gammopathies, the hypothesis of POEMS Syndrome was raised, and plasma Vascular Endotelial Growth Factor (VEGF) measurement was performed (425 pg/mL; RV = <96.2). The patient then started to fulfill the mandatory criteria for diagnosis, in addition to a major (elevated VEGF) and several other minors. This is an atypical case in that bone lesions, present in up to 97% of the cases, were not evidenced in the patient in question, making the diagnosis challenging and therefore requiring the use of VEGF dosage. The diagnosis of rare syndromes, although challenging, brings the clinician a broader view of the patient as it increases clinical reasoning. Spreading and exploring this universe is increasingly necessary

Nanocurcumin Modulates miR-223-3p and NF-κB Levels in the Pancreas of Rat Model of Polycystic Ovary Syndrome to Attenuate Autophagy Flare, Insulin Resistance and Improve ß Cell Mass.

PURPOSE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine disorder. 50-70% of PCOS patients suffer from glucose intolerance, insulin and ß cell impairments. Updated studies reveal the crucial regulatory role of inflammation modulators in various diseases, by manipulating autophagy and oxidative stress. However, the data available about autophagy in PCOS pancreas, especially in relation to inflammation key players are little. This study investigated pancreatic autophagy status in PCOS rat model, with miR-223-3p and NF-κB levels as pivotal regulators of oxidative stress-autophagy axis, insulin, and ß cell integrity. We then analyzed nanocurcumin effects as a putative anti-inflammatory nutraceutical on the disrupted parameters. METHODS: Nanocurcumin was characterized using transmission electron microscopy (TEM) and Fourier-transform IR (FT-IR) spectroscopy. Adult virgin Wistar rats were selected, and PCOS was induced using letrozole (1mg/kg). Nanocurcumin was ingested following letrozole. Sex hormones and insulin resistance were determined. miR-223-3p expression was determined using real-time PCR. Immunohistochemistry and Western blotting determined ß cells, NF-κB, and autophagy markers p62 and LC3II. RESULTS: PCOS group showed significant disruptions in sex hormones and a double fold increase in glucose and insulin levels, exhibiting insulin resistance. Immunostaining confirmed around 46% deterioration of ß cell mass. Real-time PCR showed significant downregulation of miR-223-3p. Immunohistochemistry and Western blotting revealed a drastic upsurge of NF-κB, and autophagy markers p62 and LC3II, confirming bioinformatics target analysis. Interestingly, compared to PCOS group, nanocurcumin (200mg/kg) significantly upregulated miR-223-3p expression by 30%. It subsided NF-κB and autophagy eruption to restore ß cell mass and attenuate insulin resistance. CONCLUSION: To the best of our knowledge, this study is the first to highlight the vital contribution of miR-223-3p and NF-κB levels in aggravating PCOS pancreatic autophagy and consequent impairments. It spots nanocurcumin potential as an inflammation and autophagy modulator, for possible better management of PCOS complications.

Endocrine adverse effects of immune checkpoint inhibitors.

Immune checkpoint inhibitors are increasingly being utilised as an effective therapy for a variety of cancers. However, they have the potential to cause serious autoimmune toxicities in multiple organ systems termed 'immunotherapy-related adverse events'. Endocrine toxicities are common, can occur well after commencement of therapy and can result in significant morbidity and mortality if not recognised. This makes it important for all physicians, in addition to endocrinologists and oncologists, to understand the nature of these reactions and the general approach to their diagnosis and management. This review aims to provide an overview of the epidemiology, pathophysiology, clinical presentation and management of the endocrine adverse events.

Endocrine Complications in Children and Adolescents With Non-Central Nervous System Solid Tumors.

Background: Due to remarkable progress in cancer treatment, endocrine complications are now the major medical issues facing childhood cancer survivors. Although non-central nervous system solid tumors (NCSTs) account for approximately 40% of all pediatric cancers, there have been few studies on endocrine complications associated with NCSTs. This study investigated endocrinopathies following the treatment of pediatric NCSTs. Design and setting: Retrospective study in a single academic center. Methods: This study analyzed 253 survivors of childhood NCSTs who were diagnosed between January of 2000 and December of 2018. The medical charts were reviewed regarding the frequency of endocrinopathies and treatment modalities. The hazard ratios were assessed by multivariable Cox regression analysis. The final height-SDS were analyzed by multivariable linear regression analysis. Results: There were 76 patients (30%) that developed at least one endocrine complication. Forty-four patients (17.4%) experienced endocrine complications within five years of their cancer diagnosis. The most common endocrine complication was growth failure (n = 35), followed by obesity (n = 18), and primary gonadal failure (n = 16). High cumulative doses of alkylating agents increased the risk of developing at least one endocrine complication. Hematopoietic stem cell transplantation was an important risk factor for primary gonadal failure. Conclusions: This study described the comprehensive endocrine outcomes, including growth failure, obesity, primary gonadal failure, primary hypothyroidism, dyslipidemia, and osteoporosis, following the treatment of childhood NCSTs. As endocrinopathies occurred within five years of primary tumor diagnosis, surveillance for endocrine dysfunction is required for early intervention and management.

Missed diagnosis of POEMS syndrome with onset of progressive fatigue and numbness: a case report.

POEMS syndrome is a rare multisystem disease associated with an underlying plasma cell disorder. Its name is an acronym for peripheral neuropathy (P), endocrinopathy (E), organomegaly (O), monoclonal plasma cell proliferative disorder (M), and skin changes (S). This case report describes a patient with POEMS syndrome who presented with progressive fatigue and numbness in the lower extremities. Initially, the patient was erroneously diagnosed with diabetes and diabetic peripheral neuropathy because of the endocrinopathy associated with POEMS syndrome. After a second hospitalization, the patient was diagnosed with POEMS syndrome and recovered with alkylator therapy and a peripheral blood stem cell transplant. The patient's overall condition was improved at the 1-year follow-up. POEMS syndrome should be considered if a patient presents with endocrinopathy and unexplained peripheral neuropathy.

Prader-Willi syndrome: an update on obesity and endocrine problems.

Prader-Willi syndrome (PWS) is a rare complex genetic disorder that results from a lack of expression of the paternally inherited chromosome 15q11-q13. PWS is characterized by hypotonia and feeding difficulty in early infancy and development of morbid obesity aggravated by uncontrolled hyperphagia after childhood and adolescent. Dysmorphic facial features, delayed motor and language development, various degrees of cognitive impairment, and behavioral problems are common in PWS. Without early, intensive nutritional therapy along with behavioral modification, PWS patients develop severe obesity associated with type 2 diabetes, obstructive sleep apnea, right-side heart failure, and other obesity-related metabolic complications. Hypothalamic dysfunction in PWS can lead to several endocrine disorders, including short stature with growth hormone deficiency, hypothyroidism, central adrenal insufficiency, and hypogonadism. In this review, we discuss the natural history of PWS and the mechanisms of hyperphagia and obesity. We also provide an update on obesity treatments and recommendations for screening and monitoring of various endocrine problems that can occur in PWS.

Impact of Victoria's first dedicated endocrine hypertension service on the pattern of primary aldosteronism diagnoses.

BACKGROUND: Primary aldosteronism (PA) accounts for 3.2-12.7% of hypertension in primary care but is often diagnosed late, if at all. A delayed or missed diagnosis leads to poor blood pressure control and greater cardiovascular risk. AIMS: To analyse the impact of Victoria's first dedicated endocrine hypertension service (EHS) on the pattern of PA diagnosis. METHODS: Socio-demographic and clinical data from all patients who attended the EHS since July 2016 (n = 267) was collected prospectively. Patients were divided into Year 1 (Y1), Year 2 (Y2) and Year 3 (Y3), based on their first visit. RESULTS: The proportion of primary care referrals increased (20% in Y1, 47% in Y2, 52% in Y3) with more referrals being made for treatment-naive hypertension (3% in Y1, 14% in Y2, 19% in Y3). Among PA patients, the median duration of hypertension prior to their first visit decreased (11 years in Y1, 10 years in Y2, 7 years in Y3), and the prevalence of end-organ damage decreased (44% in Y1, 42% in Y2, 33% in Y3). Targeted management of PA improved clinical and biochemical outcomes. The average blood pressure reduction following targeted management increased from 16/12 mmHg in Y1 to 23/12 mmHg in Y3. CONCLUSION: The EHS, with its strong component of general practitioner engagement, led to increased primary care referrals and PA detection earlier in the course of hypertension. Referred patients were on fewer antihypertensives and had less end-organ damage which simplified the diagnostic process, allowing targeted treatment to be commenced earlier and patient outcomes optimised.

[Early endocrine complications in childhood cancer survivors]. / Complicaciones endocrinas precoces en supervivientes de neoplasias infantiles.

BACKGROUND AND OBJECTIVES: The treatment of childhood cancers has increased survival rates, but also the risk of sequelae, such as endocrine complications. The objective of this study is to evaluate the endocrine disorders in survivors of childhood malignant tumors within the first years after treatment and analyze the variables related to their appearance. SUBJECTS AND METHODS: A retrospective medical record review of patients referred to pediatric endocrinology after treatment of malignancy. Outcome measures were frequency and types of endocrine dysfunction and new-onset obesity. Clinical and laboratory evaluations were performed every 6 months. Statistics tests were: chi square and multiple logistic regression. RESULTS: Fifty five patients (26 women) were included with an age at diagnosis of tumour (mean±standard deviation) 6.0±4.4 years and followed up for 6.8±3.6 years. Thirty endocrine disorders were diagnosed in 26 patients (47.3%), 17 women (P=.01). Eleven adolescents had primary hypogonadism (26.2% to 0.6±0.5 years of follow-up) in relation to local irradiation (adjusted odds ratio [OR] 3.99, P=.005). Eleven patients had a pituitary disorder (20.0%) 5.2±2.4 years after diagnosis in relation to brain irradiation (OR 1.54, P=.039). Six children (10.9%) had primary hypothyroidism from 3.2±1.0 years of follow-up. Two children developed obesity. CONCLUSIONS: Endocrine disorders are frequently seen within the first years after diagnosis of a childhood cancer, so hormonal evaluation should start early and be repeated periodically.

Endocrine system disturb induced by antineoplastic agents / 中国癌症杂志

Effects of antineoplastic agents on endocrine system are common, but it is difficult to identify since clinical complaints are subtle, and even more difficult to relate a particular chemotherapeutic regimen to the induced endocrine disturb. This review was organized according to the pattern of endocrine system diseases induced by antineoplastic agents, such as disorders of glucose metabolism, free water clearance, mineral metabolism, lipid metabolism and GH secretion and growth, metabolic bone diseases, adrenal dysfunction, thyroid disorders and reproductive dysfunction. Early detection and treatment of endocrine deficiency may have a significant impact on the quality and duration of life in a cancer survivor.