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OBJECTIVE: We describe a rare case of functioning gonadotropins-producing pediatric adenoma immunostaining positively for FSH and focally for TSH causing central precocious puberty associated to central hypothyroidism in a 6 year-old girl. MATERIALS AND METHODS: Clinical evaluation revealed precocious puberty, as confirmed by hormonal determination with elevated FSH and estradiol, while central hypothyroidism was biochemically diagnosed by a low fT4 and normal TSH. Head MRI showed the presence of a hyperintense pituitary lesion. The patient successfully underwent transsphenoidal endoscopic resection of the pituitary macroadenoma. RESULTS: Pathologic evaluation of the tissue resected at surgery confirmed the diagnosis of pituitary adenoma with positive immunohistochemistry for FSH and focally for TSH in a mixed pattern. Ten months after surgery, there were no neurological signs and symptoms. Postoperative head MRI showed no abnormalities and no evidence of tumor regrowth. CONCLUSIONS: Early and accurate diagnosis, multidisciplinary approach and close follow up are crucial factors for the favorable outcome.
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Adenoma , Hipotireoidismo , Neoplasias Hipofisárias , Puberdade Precoce , Adenoma/complicações , Adenoma/patologia , Adenoma/cirurgia , Criança , Feminino , Hormônio Foliculoestimulante , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Puberdade Precoce/etiologia , TireotropinaRESUMO
Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.
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Sobreviventes de Câncer , Preservação da Fertilidade/tendências , Neoplasias/epidemiologia , Neoplasias/terapia , Adolescente , Adulto , Criança , Feminino , Guias como Assunto , Humanos , Neoplasias/complicações , Neoplasias/patologia , Medição de Risco , Adulto JovemRESUMO
Hyperkalaemia hypertension and metabolic acidosis in children can pose a challenge of both diagnosis and management. This case chronicles the diagnostic journey of a 2-year-old girl with hyperkalaemia associated with hypertension and metabolic acidosis accidentally detected during a viruses.
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Acidose , Hiperpotassemia , Acidose/diagnóstico , Acidose/etiologia , Pré-Escolar , Feminino , Humanos , Hiperpotassemia/complicações , Hiperpotassemia/diagnóstico , HipertensãoRESUMO
Congenital adrenal hyperplasia (CAH) consists of several autosomal recessive disorders that inhibit steroid biosynthesis. We describe a case report diagnosed with adrenal insufficiency due to low adrenal steroids and adrenocorticotropic hormone excess due to lack of cortisol negative feedback signaling to the pituary gland. Genetic work up revealed two missense variants, p.Thr204Arg and p.Leu260Arg in the STAR gene, inherited by both parents (non-consanguineous). The StAR protein supports CYP11A1 enzyme to cleave the side chain of cholesterol and synthesize pregnenolone which is metabolized to all steroid hormones. We used bioinformatics to predict the impact of the variants on StAR activity and then we performed functional tests to characterize the two novel variants. In a cell system we tested the ability of variants to support cholesterol conversion to pregnenolone and measured their mRNA and protein expression. For both variants, we observed loss of StAR function, reduced protein expression and categorized them as pathogenic variants according to guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. These results fit the phenotype of the girl during diagnosis. This study characterizes two novel variants and expands the list of missense variants that cause CAH.
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Hiperplasia Suprarrenal Congênita/genética , Transtorno 46,XY do Desenvolvimento Sexual/genética , Mutação de Sentido Incorreto , Fosfoproteínas/química , Fosfoproteínas/genética , Hiperplasia Suprarrenal Congênita/metabolismo , Animais , Células COS , Chlorocebus aethiops , Colesterol/metabolismo , Transtorno 46,XY do Desenvolvimento Sexual/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Modelos Moleculares , Linhagem , Pregnenolona/metabolismo , Conformação ProteicaRESUMO
In the published article [1], an error has been noticed in the author group section.
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OBJECTIVE: The diagnosis of growth hormone deficiency (GHD) is currently based on clinical, auxological, biochemical and neuro-radiological investigation. Provocative tests of GH secretion using physiological/pharmacological stimuli are required to confirm GHD. The clonidine test (CT) is widely used to assess GH secretory status. In this retrospective study, we analyzed the reliability of CT and the effect of puberty in a large number of children with short stature who had been evaluated for suspected GHD. DESIGN AND PATIENTS: Data were collected retrospectively from 327 children and adolescents with short stature (204 boys and 123 girls, median age 10.5 years (IQR 7.90-12.40) followed in four Italian Paediatric Endocrine Units (Cagliari, Genova, Napoli and Roma) between 2005 and 2013. MEASUREMENTS: All children underwent CT as the first GH stimulation test after exclusion of other known cause of their short stature. RESULTS: In 73 prepubertal children and 25 pubertal children, the GH peak after CT was <7 µg/L. GHD was confirmed in 87 (37 organic, 50 idiopathic). Six prepubertal and five pubertal patients showed false positive responses. The median BMI-SDS in these children was similar to that of children with GH peak ≥7 µg/L, and none were obese. Overall, the prevalence of false-positive responses was 3.3%. The median (IQR) peak GH after CT was similar between prepubertal and pubertal GHD (3.80 µg/L [1.7-6.00] vs 3.51 µg/L [0.76-5.74]) and non-GHD (13.70 µg/L [10.70-18.40] vs 12.40 µg/L [9.90-19.25]) children. CONCLUSIONS: Our results show that CT is a reliable and safe GH-releasing agent in both prepubertal and pubertal children.
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Nanismo Hipofisário/sangue , Nanismo Hipofisário/diagnóstico , Hormônio do Crescimento Humano/sangue , Índice de Massa Corporal , Criança , Clonidina/farmacologia , Feminino , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Puberdade/metabolismo , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the self-reported prevalence of poor adherence to recombinant human growth hormone (rhGH) therapy in a large, representative sample of Italian children and adolescents and to assess treatment and patient level correlates of poor adherence. METHODS: The study was conducted in 46 pediatric centers throughout Italy. A questionnaire was administered to consecutive children/adolescents treated with rhGH or their parents. Eligible patients were represented by subjects aged between 6 and 16 years, of both sexes, on rhGH treatment for at least 6 months. The questionnaire was administered to the person in charge of preparing the injection. Multivariable logistic regression analysis was performed to identify factors independently associated with adherence. RESULTS: Overall, 1,007 children/adolescents were involved, of whom 24.4% missed 1 or more injections during a typical week and were thus considered as nonadherent. The most frequently reported reasons for missing a dose were being away from home (33.3%), forgetfulness (24.7%), not feeling well (12.9%), and pain (10.3%). Multivariable analysis indicated association between poor adherence and adolescence, low level of parent education, longer duration of treatment, need to convince the child to inject, and low level of awareness of the consequences of not properly following treatment. The likelihood of adherence markedly increased with higher levels of perceived device convenience. CONCLUSION: Poor adherence is still a major problem in the treatment of growth disorders. Increasing awareness and reassessment of treatment adherence on an annual basis should be part of clinical practice of pediatric endocrinologists involved with rhGH treatment. ABBREVIATIONS: CI = confidence interval GH = growth hormone rhGH = recombinant human growth hormone.
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Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Criança , Feminino , Humanos , Itália , Modelos Logísticos , Masculino , Análise Multivariada , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Magnetic resonance imaging (MRI) has proved to be an essential tool in the assessment of pituitary stalk lesions including lymphocytic infundibulo-hypophysitis, Langerhans cell histiocytosis (LCH), germ cell tumours, nongerminomatous germ cell tumours, pituicytomas and other tumours, metastases from lymphoma or breast cancer, Wegener's hypophysitis, neurosarcoidosis and inflammatory infiltrations by infectious diseases. The diagnosis of lesions determining pituitary stalk thickness is challenging, and the identification of the underlying condition may require a long-term follow-up. Thus, clinicians should readily recognize that, when the diagnosis of central diabetes insipidus has been established, specific MRI sequences should be used in the assessment of the hypothalamic-pituitary region, and whole-brain evaluation is recommended. For clinical practice, a timely diagnosis is advisable to avoid central nervous system damage, pituitary defects and the risk of dissemination of germ cell tumours or organ involvement by LCH. Proper aetiological diagnosis can be achieved via a series of steps that start with careful observation of several neuroimaging predictors and endocrine dysfunction and then progress to more sophisticated and advanced imaging techniques.
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Imageamento por Ressonância Magnética/métodos , Hipófise/patologia , Humanos , Doenças da Hipófise/diagnóstico , Neoplasias Hipofisárias/diagnósticoRESUMO
The management of adrenal insufficiency is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in subjects with congenital adrenal hyperplasia (CAH) and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropic hormone. In order to personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of adrenal insufficiency include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present three illustrative cases of adrenal insufficiency with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with adrenal insufficiency.
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CONTEXT: The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. OBJECTIVE: Aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. PATIENTS AND METHODS: Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies-HDs) and 18 severe organic GHD (≥3 HDs). RESULTS: Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis-ROC- identified 7.3 µg/L as the optimal GH peak cutoff to GST (95% CI 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value-PPV-88.0%, negative predictive value-NPV-95.7%), able to correctly classify 91.8% of the entire cohort while 5.8 µg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3HDs showed a GH peak <5µg/L at ITT and <5.8µg/L at GST but one. The optimal cutoff for IGF1 was -1.4 SDS (95% CI -1.94-0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. CONCLUSIONS: A GH peak to GST <5.8 µg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pre-test probability of permanent GHD.
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Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.
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Endocrinologia , Raquitismo , Humanos , Raquitismo/diagnóstico , Raquitismo/terapia , Raquitismo/metabolismo , Endocrinologia/métodos , Endocrinologia/normas , Itália , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Criança , Sociedades Médicas/normas , Gerenciamento ClínicoRESUMO
OBJECTIVE: It is still not known whether fat mass excess could exert a positive effect on bone. The aim of our study was to evaluate bone strength and quality in a group of overweight and obese children and adolescents by assessing bone geometry at metacarpal bones and ultrasound at phalangeal level. DESIGN AND PATIENTS: This is a cross sectional observational study performed in 123 subjects, aged 11.2 ± 2.9 years. MEASUREMENTS: Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone for the determination of the outer (D) and inner (d) diameter, cortical area (CA), medullary endocortical area (EA), metacarpal index (MI) and bone strength (Bending Breaking Resistance Index; BBRI). A total of 98 subjects underwent amplitude dependent speed of sound (Ad-SOS) and bone transmission time (BTT) assessment by phalangeal ultrasonography. RESULTS: SDs for each measured parameter were as follows: Males: D = -0.71 ± 0.95, d = -0·29 ± 0.86, CA = -0.69 ± 0.69, EA = -0.32 ± 0.79, Ad-SOS = -1.14 ± 0.91, BTT = -1.17 ± 1.11 and BBRI (417 ± 151 vs 495 ± 174 mm(3) ) were all significantly lower than in controls (P < 0.05). Females: D = -1.03 ± 1.06, d = -0.38 ± 0.92, CA = -0.91 ± 0.72, EA = -0.46 ± 0.79, Ad-SOS = -1.08 ± 1.11, BTT = -0.97 ± 1.07 and BBRI (342 ± 117 vs 649 ± 318 mm(3) ) were all significantly lower than in controls (P < 0.05). CONCLUSIONS: Obese children show an unfavourable bone geometry and a bone of low quality and reduced strength compared to controls at a nonweight bearing skeletal site. This finding seems to support a detrimental effect of fat mass on bone and explain the frequent occurrence of wrist fractures in this group of children.
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Densidade Óssea/fisiologia , Ossos Metacarpais/patologia , Obesidade/metabolismo , Obesidade/patologia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: Survival after childhood cancer has significantly improved in recent decades. Nevertheless, an increased incidence of metabolic syndrome and cardiovascular disease among childhood cancer survivors (CCS) has been reported. The aim of this study was to evaluate whether fat-to-lean mass ratio (FLR) is associated with a dysmetabolic profile in CCS. METHODS: At least 2 years from completion of therapy, data from CCS aged 10 to 16 years at follow-up and without any concurrent steroid treatment were collected. Body mass index, waist circumference (WC), WC-to-height ratio, laboratory blood tests, and FLR calculated by dual-energy X-ray absorptiometry measurements were considered. Body mass index >85th percentile and >97th percentile, WC >90th percentile, and WC-to-height ratio > 0.5 were chosen as criteria of overweight and obesity, visceral obesity, and increased cardiovascular risk, respectively. RESULTS: We enrolled 205 CCS previously treated for hematologic cancer or solid or central nervous system tumor. The best cutoff of FLR was 0.6. CCS; those with FLR ≥0.6 (43%) were more frequently overweight and obese (P < 0.001), and presented with higher levels of triglycerides (P = 0.011), homeostatic model assessment for insulin resistance (P = 0.001), alanine transaminase (P = 0.004), and trunk fat (P < 0.001) and lower levels of insulin-like growth factor 1 (P < 0.001) and lean mass (P = 0.009). WC >90th percentile (P = 0.007), insulin-like growth factor 1 (P = 0.002), and trunk fat (P = 0.006) were independent predictors of FLR ≥0.6 in a model including all the previous variables. CONCLUSIONS: An increased FLR is suggestive of altered body composition phenotype, allowing identification of CCS at higher risk of metabolic syndrome. Diet and physical activity are needed from commencement of oncological treatments to preserve overall nutritional status and maintain it over the long term.
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Sobreviventes de Câncer , Síndrome Metabólica , Neoplasias , Humanos , Sobrepeso , Fator de Crescimento Insulin-Like I , Síndrome Metabólica/etiologia , Neoplasias/complicações , Neoplasias/terapia , Obesidade , Índice de Massa Corporal , Composição Corporal , Circunferência da CinturaRESUMO
[This corrects the article DOI: 10.3389/fendo.2022.975511.].
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Background: Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males. Methods: In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS. Conclusions: According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
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Criptorquidismo , Síndrome de Noonan , Masculino , Criança , Adulto , Feminino , Humanos , Síndrome de Noonan/genética , Gônadas , Puberdade/genética , Proteínas Quinases Ativadas por MitógenoRESUMO
Context: Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway. Objective: The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls. Methods: We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups. Results: Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03). Conclusion: Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.
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Objective: This Italian survey aims to evaluate real-life long-term efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. Design and methods: This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3 and T4) and at near-final height (nFH) (T5), when available. Results: One hundred and seventeen SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33 years (74% prepubertal), 99 completed the first year of treatment and 46 reached nFH. During rhGH therapy, growth velocity (GV), standard deviation score (SDS) and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14 ± 0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (ß = -0.31, P = 0.030) and the GV during the first year of rhGH treatment (ß = 0.45, P = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Conclusions: Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype. Significance Statement: Among children with idiopathic short stature, the prevalence of SHOX-D is near to 1/1000-2000 (1.1-15%) with a wide phenotypic spectrum. Current guidelines support rhGH therapy in SHOX-D children, but long-term data are still few. Our real-life data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless of the wide variety of genotypes. Moreover, rhGH therapy seems to blunt the SHOX-D phenotype. The response to rhGH in the first year of treatment and the age when rhGH was started significantly impact the height gain.
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OBJECTIVE: To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE). METHODS: Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied. RESULTS: There was a significant reduction in parent-adjusted height z score with time in females and males (p<0.0001), with a significant gender difference (p<0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p<0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age <12 years had a median parent-adjusted height z score of -0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than -0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose >426 mg/kg (OR: 3.6). CONCLUSIONS: The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with >400 mg/kg cumulative dose of corticosteroids.
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Transtornos do Crescimento/etiologia , Lúpus Eritematoso Sistêmico/complicações , Puberdade Tardia/etiologia , Adolescente , Idade de Início , Antropometria/métodos , Estatura/fisiologia , Índice de Massa Corporal , Criança , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Crescimento/fisiologia , Transtornos do Crescimento/fisiopatologia , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Estudos Prospectivos , Puberdade/fisiologia , Puberdade Tardia/fisiopatologia , Fatores SexuaisRESUMO
Magnetic resonance imaging (MRI) is the radiological examination method of choice for evaluating hypothalamo-pituitary-related endocrine disease and is considered essential in the assessment of patients with suspected hypothalamo-pituitary pathology. Physicians involved in the care of such patients have, in MRI, a valuable tool that can aid them in determining the pathogenesis of their patients' underlying pituitary conditions. Indeed, the use of MRI has led to an enormous increase in our knowledge of pituitary morphology, improving, in particular, the differential diagnosis of hypopituitarism. Specifically, MRI allows detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI recognition of pituitary hyperintensity in the posterior part of the sella, now considered a marker of neurohypophyseal functional integrity, has been the most striking finding in the diagnosis and understanding of certain forms of 'idiopathic' and permanent growth hormone deficiency (GHD). Published data show a number of correlations between pituitary abnormalities as observed on MRI and a patient's endocrine profile. Indeed, several trends have emerged and have been confirmed: (i) a normal MRI or anterior pituitary hypoplasia generally indicates isolated growth hormone deficiency that is mostly transient and resolves upon adult height achievement; (ii) patients with multiple pituitary hormone deficiencies (MPHD) seldom show a normal pituitary gland; and (iii) the classic triad of ectopic posterior pituitary, pituitary stalk hypoplasia/agenesis and anterior pituitary hypoplasia is more frequently reported in MPHD patients and is generally associated with permanent GHD. Pituitary abnormalities have also been reported in patients with hypopituitarism carrying mutations in several genes encoding transcription factors. Establishing endocrine and MRI phenotypes is extremely useful for the selection and management of patients with hypopituitarism, both in terms of possible genetic counselling and in the early diagnosis of evolving anterior pituitary hormone deficiencies. Going forward, neuroimaging techniques are expected to progressively expand and improve our knowledge and understanding of pituitary diseases.
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Hormônio do Crescimento/deficiência , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Doenças da Hipófise/diagnóstico , Animais , Diferenciação Celular , Humanos , Tamanho do Órgão , Hipófise/anatomia & histologia , Hipófise/embriologia , Diagnóstico Pré-NatalRESUMO
Central diabetes insipidus (CDI) is a complex disorder in which large volumes of dilute urine are excreted due to arginine-vasopressin deficiency, and it is caused by a variety of disorders affecting the hypothalamic-posterior pituitary network. The differential diagnosis is challenging and requires a detailed medical history, physical examination, biochemical approach, imaging studies, and, in some cases, histological confirmation. Magnetic resonance imaging is the gold standard method for evaluating congenital or acquired cerebral and pituitary stalk lesions. Pituitary stalk size at presentation could be normal, but it may change over time, depending on the underlying condition, while other brain areas or organs may become involved during follow-up. Early diagnosis and treatment are crucial to avoid central nervous system damage and germ cell tumor dissemination and to minimize complications of multiple pituitary hormone defects. We provide a practical update on the diagnosis and management of patients with CDI and highlight several pitfalls that may complicate the differential diagnosis of conditions presenting with polyuria and polydipsia. The need for a careful and close follow-up of patients with apparently idiopathic CDI is particularly emphasized because the underlying condition may be recognized over time. The clinical scenario that we outline at the beginning of this article represents the basis for the discussion about how the etiological diagnosis of CDI can be overlooked and demonstrates how a water intake and urine output improvement can be a sign of progressive damage of both hypothalamus and anterior pituitary gland with associated pituitary hormonal deficiencies.