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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 Congénita/genética , Trastorno del Desarrollo Sexual 46,XY/genética , Mutación Missense , Fosfoproteínas/química , Fosfoproteínas/genética , Hiperplasia Suprarrenal Congénita/metabolismo , Animales , Células COS , Chlorocebus aethiops , Colesterol/metabolismo , Trastorno del Desarrollo Sexual 46,XY/metabolismo , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Masculino , Modelos Moleculares , Linaje , Pregnenolona/metabolismo , Conformación ProteicaRESUMEN
INTRODUCTION: We aimed to describe the clinico-radiological findings of patients with disorders of diencephalic-mesencephalic junction (DMJ) formation and midbrain anteroposterior patterning. METHODS: We reviewed the DMJ anatomy of 445 patients with brain malformations. Associated supra/infratentorial abnormalities and clinical findings were noted. Craniocaudal and anteroposterior diameters of midbrain, pons, medulla, vermis, and transverse cerebellar diameter were compared with age-matched controls. Post hoc tests were corrected according to Bonferroni (p(B)). RESULTS: Two patterns of DMJ anomaly were identified in 12 patients (7 females, mean age 41 months). Type A was characterized by hypothalamic-mesencephalic fusion on axial plane, with possible midbrain ventral cleft (7 patients). Anteroposterior (p(B) = .006) and craniocaudal (p(B) = .027) diameters of the pons, craniocaudal diameter of the vermis (p(B) = .015), and transverse cerebellar diameter (p(B) = .011) were smaller than the controls. Corticospinal tract, basal ganglia, and commissural anomalies were also associated. Clinical findings included spastic-dystonic tetraparesis, hypothalamic dysfunction, epilepsy, and severe developmental delay. Type B was characterized by incomplete thalamic-mesencephalic cleavage on sagittal plane, with parenchymal bands connecting the interthalamic adhesion with the midbrain (five patients). Anteroposterior diameters of midbrain (p(B) = .002), pons (p(B) = .0004), and medulla (p(B) = .002) as well as the vermian anteroposterior (p(B) = .040) and craniocaudal diameters (p(B) = .014) were smaller than the controls. These patients were less neurologically impaired, most presenting mild developmental delay. CONCLUSIONS: The spectrum of DMJ patterning defects is wide and may be associated with several brain malformations. Infratentorial brain structures should be carefully evaluated to better define the type of associated midbrain-hindbrain anomalies.
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Anomalías Múltiples/diagnóstico , Diencéfalo/anomalías , Mesencéfalo/anomalías , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
In this report we present a case of a 14-year-old girl with type 1 diabetes mellitus (T1DM) who experienced glycemic instability and multiple hormonal deficits, including diabetes insipidus, central hypothyroidism, and central adrenal insufficiency. Brain and sellar magnetic resonance imaging revealed a mass in the suprasellar region, which was confirmed to be a pituitary abscess through transsphenoidal biopsy. T1DM is a chronic systemic disease that can lead to suboptimal glycemic control and increased susceptibility to infections. Pituitary abscess is a rare and serious infection that can manifest with nonspecific signs and symptoms, as well as pituitary hormonal deficiencies. Currently, after a 6-year follow-up the pituitary hormone deficiencies have resolved apart from persistent partial diabetes insipidus. Through a review of the current literature, we discuss the clinical characteristics of pituitary abscess, the challenges in diagnosing it, and speculate on the potential clinical and pathophysiological relationship between this uncommon infection and T1DM in our patient.
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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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[This corrects the article DOI: 10.3389/fendo.2022.975511.].
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The fecal microbiome of 55 obese children and adolescents (BMI-SDS 3.2 ± 0.7) and of 25 normal-weight subjects, matched both for age and sex (BMI-SDS - 0.3 ± 1.1) was analysed. Streptococcus, Acidaminococcus, Sutterella, Prevotella, Sutterella wadsworthensis, Streptococcus thermophilus, and Prevotella copri positively correlated with obesity. The inferred pathways strongly associated with obesity concern the biosynthesis pathways of tyrosine, phenylalanine, tryptophan and methionine pathways. Furthermore, polyamine biosynthesis virulence factors and pro-inflammatory lipopolysaccharide biosynthesis pathway showed higher abundances in obese samples, while the butanediol biosynthesis showed low abundance in obese subjects. Different taxa strongly linked with obesity have been related to an increased risk of multiple diseases involving metabolic pathways related to inflammation (polyamine and lipopolysaccharide biosynthesis). Cholesterol, LDL, and CRP positively correlated with specific clusters of microbial in obese patients. The Firmicutes/Bacteroidetes-ratio was lower in obese samples than in controls and differently from the literature we state that this ratio could not be a biomarker for obesity.
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Microbioma Gastrointestinal , Microbiota , Obesidad Infantil , Niño , Adolescente , Humanos , Lipopolisacáridos , AlgoritmosRESUMEN
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 , Niño , Adulto , Femenino , Humanos , Síndrome de Noonan/genética , Gónadas , Pubertad/genética , Proteínas Quinasas Activadas por MitógenosRESUMEN
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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Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased. Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years. Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP). Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence (P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values ââin group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81â hours per day using electronic devices; 88.5% of this group stopped any physical activity. Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors.
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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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Hormona del Crecimiento/deficiencia , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Enfermedades de la Hipófisis/diagnóstico , Animales , Diferenciación Celular , Humanos , Tamaño de los Órganos , Hipófisis/anatomía & histología , Hipófisis/embriología , Diagnóstico PrenatalRESUMEN
We report the case of a 13-year-old patient, female, born in Northern Italy, who presented with an acute episode of aphasia, lasting about 15 min, accompanied by left arm dysesthesia. The state of consciousness remained preserved throughout the episode. After a first clinical evaluation at second-level hospital, the patient was sent to our institute for further investigations. Brain MRI performed at admission showed no noteworthy structural alterations. Electroencephalogram was not significant, as was the echocardiographic examination. ECG was normal, except for a corrected-QT at the upper limits of the normal range for age and gender. The neurological examination was substantially normal for the entire duration of the hospital stay. The symptomatology initially described has never reappeared. Blood tests were substantially negative, in particular thrombophilic screening excluded hereditary-familial thrombophilic diseases. Color doppler ultrasound of the supra-aortic trunks, splanchnic vessels and lower limbs were also normal. Only positivity to SARS-CoV-2 serology is reported. In the recent clinical history there were no symptoms attributable to symptomatic coronavirus infection.
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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.
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Diabetes Insípida Neurogénica , Diabetes Insípida , Diabetes Mellitus , Neurohipófisis , Niño , Diabetes Insípida/diagnóstico , Diabetes Insípida/etiología , Diabetes Insípida/terapia , Diabetes Insípida Neurogénica/diagnóstico , Diabetes Insípida Neurogénica/etiología , Diabetes Insípida Neurogénica/terapia , Diabetes Mellitus/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , PolidipsiaRESUMEN
Diabetes mellitus (DM) has been frequently associated with an impaired immune response against infectious agents, making affected patients at risk for more severe disease and sometimes causing worse outcomes. The recent COVID-19 pandemic has seriously affected patients with both diabetes, in particular those carrying comorbidities or with poor glycemic control. As regards pediatric diabetes mellitus, the availability of more accurate and technological tools for glycemic management and the improved markers of metabolic control might mitigate the negative impact of infections. Notably, good metabolic control of diabetes since its diagnosis reduces not only the risk of microangiopathic complications but also of impaired immune response to infectious diseases. Therefore, vaccinations are strongly recommended. Our paper aims to provide the most updated evidence regarding infectious diseases in type 1 pediatric DM.
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COVID-19 , Enfermedades Transmisibles , Diabetes Mellitus Tipo 1 , Hiperglucemia , COVID-19/complicaciones , Niño , Diabetes Mellitus Tipo 1/complicaciones , Humanos , PandemiasRESUMEN
Craniopharyngiomas are rare brain tumors of the sellar region and are the most common non-neuroepithelial intracerebral neoplasm in children. Despite a low-grade histologic classification, craniopharyngiomas can have a severe clinical course due to hypothalamic involvement. The hypothalamus plays a crucial role in regulating vital functions, and it is a critical component of the sleep-wake regulatory system. This systematic review aims to provide an overview of the current knowledge on sleep disorders in patients with craniopharyngioma to unravel their underlying mechanisms and identify possible therapeutic strategies. A comprehensive electronic literature search of the PubMed/MEDLINE and Scopus databases was conducted in accordance with the PRISMA® statement. Extensively published, peer-reviewed articles involving patients with childhood craniopharyngioma and focused on this specific topic were considered eligible for inclusion. Thirty-two articles were included; a high prevalence of excessive daytime sleepiness was reported in CP patients, with wide variability (25-100%) depending on the diagnostic method of detection (25-43% by subjective measures, 50-100% by objective investigations). In particular, secondary narcolepsy was reported in 14-35%, sleep-disordered breathing in 4-46%. Moreover, sleep-wake rhythm dysregulation has been notified, although no prevalence data are available. Possible mechanisms underlying these disorders are discussed, including hypothalamic injury, damage to the suprachiasmatic nucleus, low melatonin levels, hypocretin deficiency, and hypothalamic obesity. The diagnosis and management of sleep disorders and associated comorbidities are challenging. This review summarizes the pathophysiology of sleep disorders in childhood-onset CP and the main treatment options. Finally, a possible diagnostic algorithm in order to accurately identify and treat sleep disorders in these patients is proposed.
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Context: Data on pubertal timing in Silver Russell syndrome (SRS) are limited. Design and methods: Retrospective observational study including twenty-three SRS patients [11p15 loss of methylation, (11p15 LOM, n=10) and maternal uniparental disomy of chromosome 7 (mUPD7, n=13)] and 21 small for gestational age (SGA). Clinical (thelarche in females; testis volume ≥ 4 ml in males; pubarche), BMI SD trend from the age of 5 to 9 years to the time of puberty, biochemical parameters of puberty onset [Luteinizing hormone (LH), 17-ß-estradiol, testosterone], and bone age progression were evaluated. Results: Pubertal onset and pubarche occurred significantly earlier in children with SRS than in SGA (p 0.03 and p 0.001, respectively) and clinical signs of puberty onset occurred earlier in mUPD7 than in 11p15LOM group (p 0.003). Five SRS children experienced central precocious puberty and LH, 17-ß-estradiol, testosterone were detected earlier in SRS than in SGA (p 0.01; p 0.0001). Bone age delay in SRS children was followed by rapid advancement; the delta between bone age and chronological age in SRS group became significantly higher than in SGA group at the age of 9-11 years (p 0.007). 11p15LOM patients were underweight at the age of 5 years and showed a progressive normalization of BMI that was significantly higher than in mUPD7 (p 0.04) and SGA groups (p 0.03) at puberty onset. Conclusion: Timing of puberty is affected in SRS and occurred earlier in mUPD7 compared to 11p15LOM. The impact of early puberty on adult height and metabolic status deserves long-term evaluation.
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Enfermedades del Recién Nacido , Pubertad Precoz , Síndrome de Silver-Russell , Adulto , Niño , Preescolar , Estradiol , Femenino , Retardo del Crecimiento Fetal , Edad Gestacional , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Hormona Luteinizante , Masculino , Síndrome de Silver-Russell/genética , TestosteronaRESUMEN
The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi-Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.A136V and p.R174G TREX1 variants, respectively. Genetic findings, obtained by a customized panel including 183 genes associated with monogenic stroke, were combined with interferon signature testing and biochemical assays to determine the mutations' effects in vitro. Our results for the p.A136V variant are inconsistent with prior biochemistry-pathology correlates for dominant AGS-causing TREX1 mutants. The p.R174G variant modestly altered exonuclease activity in a manner consistent with perturbation of substrate interaction rather than catalysis, which represents the first robust enzymological data for a TREX1 variant identified in a CADASIL-like patient. In conclusion, functional analysis allowed us to interpret the impact of TREX1 variants on patients' phenotypes. While the p.A136V variant is unlikely to be causative for AGS in Patient A, Patient B's phenotype is potentially related to the p.R174G variant. Therefore, further functional investigations of TREX1 variants found in CADASIL-like patients are warranted to determine any causal link and interrogate the molecular disease mechanism(s).
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CADASIL , Enfermedades Autoinmunes del Sistema Nervioso , Dominio Catalítico , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Estudios de Asociación Genética , Humanos , Mutación Missense , Malformaciones del Sistema Nervioso , FosfoproteínasRESUMEN
CONTEXT: The etiology of central precocious puberty (CPP) includes a spectrum of conditions. Girls younger than age 6 years with CPP should undergo cranial magnetic resonance imaging (MRI), but it remains controversial whether all girls who develop CPP between the ages of 6 and 8 years require neuroimaging examination. OBJECTIVE: To investigate the frequency of brain MRI abnormalities in girls diagnosed with CPP and the relationship between maternal factors, their age at presentation, clinical signs and symptoms, hormonal profiles, and neuroimaging findings. METHODS: Data were collected between January 2005 and September 2019 from 112 girls who showed clinical pubertal progression before 8 years of age who underwent brain MRI. RESULTS: MRI was normal in 47 (42%) idiopathic (I) scans, 54 (48%) patients had hypothalamic-pituitary anomalies (HPA) and/or extra-HP anomalies (EHPA), and 11 (10%) had brain tumors or tumor-like conditions (BT/TL), including 3 with neurological signs. Associated preexisting disorders were documented in 16. Girls with BT/TL had a higher LH peak after GnRH test (Pâ =â 0.01) than I, and those older than age 6 years had a higher craniocaudal diameter of the pituitary gland (Pâ =â 0.01); their baseline FSH and LH (Pâ =â 0.004) and peak FSH (Pâ =â 0.01) and LH (Pâ =â 0.05) values were higher than I. Logistic regression showed maternal age at menarche (Pâ =â 0.02) and peak FSH (Pâ =â 0.02) as BT/TL risk factors. CONCLUSIONS: MRI provides valuable information in girls with CPP by demonstrating that fewer than half have a normal brain MRI and that few can have significant intracranial lesions after the age of 6, despite the absence of suggestive neurological signs.
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Neoplasias Encefálicas , Pubertad Precoz , Niño , Femenino , Hormona Folículo Estimulante , Hormona Liberadora de Gonadotropina , Humanos , Hormona Luteinizante , Neuroimagen , Pubertad Precoz/etiologíaRESUMEN
Our objective is to emphasize the important role of continuous glucose monitoring (CGM) in suggesting adrenal insufficiency in patients affected by type 1 diabetes. We describe an adolescent girl with type 1 diabetes and subsequent latent Addison's disease diagnosed based on a recurrent hypoglycemic trend detected by CGM. In patients with type 1 diabetes, persistent unexplained hypoglycemic episodes at dawn together with reduced insulin requirement arouse souspicionof adrenal insufficiency. Adrenal insufficiency secondary to autoimmune Addison's disease, even if rarely encountered among young patients, may be initially symptomless and characterized by slow progression up to acute adrenal crisis, which represents a potentially life-threatening condition. Besides glycometabolic assessment and adequate insulin dosage adjustment, type 1 diabetes needs prompt recognition of potentially associated autoimmune conditions. Among these, Addison's disease can be suspected, although latent or paucisymptomatic, through periodic and careful evaluation of CGM data.
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Prader-Willi Syndrome (PWS) is a complex genetic disorder with multiple cognitive, behavioral and endocrine dysfunctions. Sleep alterations and sleep disorders such as Sleep-disordered breathing and Central disorders of hypersomnolence are frequently recognized (either isolated or in comorbidity). The aim of the review is to highlight the pathophysiology and the clinical features of sleep disorders in PWS, providing the basis for early diagnosis and management. We reviewed the genetic features of the syndrome and the possible relationship with sleep alterations in animal models, and we described sleep phenotypes, diagnostic tools and therapeutic approaches in humans. Moreover, we performed a meta-analysis of cerebrospinal fluid orexin levels in patients with PWS; significantly lower levels of orexin were detected in PWS with respect to control subjects (although significantly higher than the ones of narcoleptic patients). Sleep disorders in humans with PWS are multifaceted and are often the result of different mechanisms. Since hypothalamic dysfunction seems to partially influence metabolic, respiratory and sleep/wake characteristics of this syndrome, additional studies are required in this framework.