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Coexistence of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and Turner Syndrome (TS) is rare. We report a 6-year-old Portuguese girl with mosaic TS [45,XO(39)/47,XXX(21)] presented with premature pubarche at the age of 5 years. Laboratory findings showed elevated 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione and total testosterone, and sex-determining region Y (SRY) was negative. CYP21A2 gene analysis revealed two mutations (c.[844G>T]; [CYP21A2del]), consistent with the non-classical form of CAH. Complete deletion of CYP21A2 allele occurred de novo. At 6 years and 4 months, she presented accelerated growth velocity and hydrocortisone at the dose of 5 mg/m2/day was initiated. This case highlights the need to perform global examinations looking for virilization signs in TS patients follow-up. It also supports the reported genetic combination of TS and CAH. Therefore, CAH should be kept in mind in TS patients with SRY negative and virilization signs, even in the absence of short stature.

Objectives We intend to describe a case of McCune-Albright Syndrome (MAS), a rare disease characterized by fibrous dysplasia (FD), cutaneous hyperpigmentation and hyperfunctioning endocrinopathies (HFE). Case presentation We report the case of a 13-year-old male child who presented with a café-au-lait macule in the lumbosacral region and disabling polyostotic FD, requiring several surgical interventions and bisphosphonates from the age of 3 years (Y) + 9 months (M) due to persistent and severe pain. Hyperthyroidism (HT) became apparent at 5 Y + 1 M with a T3/T4 ratio greater than 20. Treatment with anti-thyroid drugs (ATD) was carried out for 7 Y and there was a progressive improvement in pain complaints 8 M after starting ATD, allowing treatment with pamidronate to be discontinued. Total thyroidectomy was performed at 12 Y + 5 M. Conclusions This is a case of MAS-associated HT that reflects the deleterious effect of thyroid hormone excess on FD, reinforcing the need of having a low threshold for suspicion of HFE that may arise.

Objectives Polyglandular autoimmune syndromes (PAS) are characterized by the association of two or more autoimmune diseases (AID) and are classified into four types. PAS type 1 is more frequently manifested in childhood, but the prevalence of other PAS in children, less described in the literature, seems to be underestimated. Methods This study aimed to evaluate the prevalence of PAS in a selected pediatric population of 879 children with Diabetes mellitus type 1 (DM1), autoimmune thyroid disease (AITD), and Addison’s disease (AD) followed in our hospital for 10 years and describe and classify the manifestations of different PAS. Results We diagnosed 35 children with PAS, most fulfilled criteria for PAS type 3 (65.7%), and AITD was the AID more frequently detected (74.3%). PAS type 1 was not diagnosed in our sample. Patients with PAS manifested DM1 and AITD at a younger age than children with monoglandular pathology (7.7 vs. 9.3 years, p=0.04 and 7.7 vs. 13.1 years, p Conclusions This is the first study that analyzes the prevalence of different types of PAS in a pediatric population followed by endocrine pathologies, namely DM1, AD, and AITD. As PAS manifestations are often preceded by a long latency period characterized by the presence of autoantibodies, we reinforce the need to value these markers for timely diagnosis and to screen PAS in patients with AD throughout their lives.

Background Postprandial hyperglycemia is one of the biggest challenges in children with type 1 diabetes (T1D). Ultra-fast-acting aspartic insulin (faster aspart) has a quicker onset of action and an earlier maximum activity. The aim of this study is to analyze the impact of faster aspart in metabolic control of pediatric patients with T1D in a “real-world” setting. Methods Retrospective analysis of 60 pediatric patients with T1D who changed their insulin analogue to faster aspart. Anthropometric data, insulin doses, capillary and interstitial glucose recordings and average glycated hemoglobin before and after insulin analogue’s switch were obtained. After all population analyses, patients were analyzed separately according to the type of treatment, multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII), and according to age group. Results Faster aspart significantly improved metabolic control, increasing time in range (TIR) (42 vs.54%, respectively; P = 0.007) and decreasing time above range (TAR) (52 vs.40%, respectively; P = 0.009), without an increased time in hypoglycemia (7% before and after faster aspart’s introduction; P = 0.933). This was reassured in the adolescent years (n = 45), with an increase in TIR (37 vs. 47%, respectively; P = 0.034) and decrease in TAR (51 vs. 45%, respectively; P = 0.022). Patients on CSII (n = 47), also demonstrated an increase in TIR (38 vs. 50%, respectively; P = 0.010). The reduction of A1c was not statistically significant. Conclusion Although the advantage of faster aspart had already been demonstrated in pediatric patients under MDI, “real-world” studies, including patients under CSII, are still lacking. This study highlights the important impact of faster aspart on metabolic control in children with T1D, particularly among adolescents under CSII.

Objectives Since the beginning of the COVID-19 pandemic, there has been a consistent decrease in the number of admissions to the emergency department, leading to a delay in the diagnosis of several pathologies. The time from onset of symptoms to the diagnosis of Type 1 diabetes is highly variable. This treatment delay can lead to the appearance of ketoacidosis. Methods Retrospective study of inaugural Type 1 diabetes cases, from March 2016 to March 2021. The pandemic group was considered between March 2020 to March 2021, and the remaining period was considered as pre-pandemic. Clinical variables were analysed: duration of symptoms, weight loss and value of ketonemia and glycated haemoglobin on admission. The mean differences were considered statistically significant at p Results 103 inaugural episodes of Type 1 diabetes were registered. The pandemic group had a lower mean age when compared to pre-pandemic group, and 51.7% of the episodes had ketoacidosis with a higher relative risk of ketoacidosis and severe ketoacidosis, when compared the pandemic with pre-pandemic group, there was a longer symptom evolution time (34 vs. 20 days), greater weight loss occurred (9.5% vs. 6.3%), the pH and HCO3 − values were lower (7.30 vs. 7.36 and 16.43 vs. 20.71 mmol/L respectively) and ketonemia was higher (5.9 vs. 2.3 mmol/L). Conclusions The COVID-19 pandemic caused a delay in the diagnosis of Type 1 diabetes, greater length of disease, greater weight loss, higher ketonemia and lower pH and HCO3 −. There was greater ketoacidosis relative risk in pandemic group when compared to pre-pandemic group.

Analysis of congenital adrenal hyperplasia (CAH) cases, gynaecological implications, referral reasons to gynaecologist and treatment.Retrospective, longitudinal, single-centre study with female CAH paediatric patients ≥ 10 years-old, followed between 1998-2018 in gynaecology and endocrinology departments at a public university tertiary hospital.47 patients, 34.0% (n = 16) with classic, 66.0% (n = 31) with non-classic forms (NCAH), CYP21 deficit and 46,XX karyotype. We found a normal median menarche age (11.5 IQR 2 [6-15] years-old), but significantly earlier in NCAH (p = 0.003). Precocious puberty occurred in 48.9%, n = 23. Primary amenorrhea occurred in salt-wasting form (21.4%, n = 3). Oligomenorrhea and hirsutism were significantly more prevalent in NCAH (p = 0.018, p = 0.014 respectively) and acanthosis nigricans and virilization signs in classic forms (p = 0.05, p = 0.000 respectively). Sixteen patients (34.0%) were referred to gynaecology, mostly due to menstrual irregularities (50.0%, n = 8). Medical treatment with isolated or combined corticoids, oestrogen and progestogen were chosen in all but one case. Gonadotropin-releasing hormone analogues were used in 19.0% (n = 9). Surgery was performed in 34.0% (n = 16) patients, median age 2.0 IQR 2.5 (0.6-90) years-old.This paper highlights the importance of a multidisciplinary approach. Early treatment contributes to a phenotypical feminine differentiation and normalization of the hypothalamus-pituitary-ovarian axis, which is essential given the gynaecologic and obstetric consequences of untreated cases.

Background Adrenal insufficiency (AI) is a life-threatening disease characterized by deficient production of glucocorticoids and/or mineralocorticoids. It is caused by primary or secondary/tertiary adrenal failure. Prompt diagnosis and management are essential and may even be life-saving. Methods We retrospectively collected clinical, laboratory and radiological data from AI patients observed over 34 years (1984–2017) in a pediatric endocrinology department of a tertiary care hospital. Results Seventy AI patients were identified: 59% with primary adrenal insufficiency (PAI) and 41% with central adrenal insufficiency (CAI). PAI patients were diagnosed at 1.5 ± 4.4 years and followed for 11.6 ± 6.2 years; 85% had classical congenital adrenal hyperplasia (CAH) and 7% had autoimmune PAI. At presentation, 73% had hyponatremia and more than half had mucocutaneous hyperpigmentation, asthenia, anorexia, weight loss, nausea and vomiting. All the patients were treated with hydrocortisone and 90% were also on fludrocortisone. Regarding CAI patients, they were diagnosed at 5.4 ± 5.0 years and they were followed for 9.6 ± 6.4 years; craniopharyngioma was present in 31% of the cases and 14% had pituitary hypoplasia. Besides corticotropin, thyrotropin (93%), growth hormone (63%) and antidiuretic hormone (52%) were the most common hormone insufficiencies. The most frequent manifestations were hypoglycemia (34.5%), nausea/vomiting (27.6%) and infectious diseases (27.6%); all the patients were treated with hydrocortisone. Conclusions Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population. Raising awareness and knowledge in medical teams and population about the disease is of crucial importance to improve clinical outcomes and to reduce disease morbidity/mortality.

SUMMARY Hyperreninemic hypoaldosteronism due to aldosterone synthase (AS) deficiency is a rare condition typically presenting as salt-wasting syndrome in the neonatal period. A one-month-old Portuguese boy born to non-consanguineous parents was examined for feeding difficulties and poor weight gain. A laboratory workup revealed severe hyponatremia, hyperkaliaemia and high plasma renin with unappropriated normal plasma aldosterone levels, raising the suspicion of AS deficiency. Genetic analysis showed double homozygous of two different mutations in the CYP11B2 gene: p.Glu198Asp in exon 3 and p.Val386Ala in exon 7. The patient maintains regular follow-up visits in endocrinology clinics and has demonstrated a favourable clinical and laboratory response to mineralocorticoid therapy. To our knowledge, this is the first Portuguese case of AS deficiency reported with confirmed genetic analysis.

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype–phenotype correlation. Methods: CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype–phenotype correlation. Results: Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A/C>G, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions/conversions were responsible for 86.4% of the mutated alleles. Patients’ stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A/C>G in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype–phenotype correlation (80%). Conclusion: Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype–phenotype correlation observed.

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T&gt, C, GCK c.563C&gt, G, HNF1A c.1623G&gt, A, HNF1A c.1729C&gt, G, HNF4A c.68delG, HNF4A c.422G&gt, C, HNF4A c.602A&gt, C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals.

Introduction: Hypoparathyroidism is characterized by low or inappropriately normal PTH production, hypocalcemia and hyperphosphatemia. Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of this, caused by heterozygous activating mutations in the CASR gene. Some individuals fail to meet treatment goals despite standard therapy. Clinical Case: A 13-year-old male patient was admitted in the emergency department due to syncope during physical activity. There was no reference to seizures or other complaints. Standard screening for metabolic diseases revealed no changes at the 7th day of life and family history was unremarkable. There was a history of febrile seizures up to 5 years of age with several hospitalizations for diagnosis investigation that were inconclusive. Physical examination showed a positive Chvostek signal, without other changes. A basic workup revealed hypocalcemia 1.67mmol/L (NR: 2.19-2.66), hyperphosphatemia 3.06mmol/L (NR: 0.95-1.75), hypomagnesemia 0.62mmol/L (NR: 0.7-1.0), low 25Hydroxyvitamin D 8.7ng/mL (NR: >30ng/mL) and inappropriately low PTH 4.0pg/mL (NR: 16.0-87.0). Cranial computed tomography scan showed bilateral calcifications of the basal ganglia. Dual-energy x-ray absorptiometry revealed bone mineral density z-scores increased 15% in spine lumbar and decreased 7% in left femur. Cardiac ultrasound and electrocardiography were normal. The patient started therapy with intravenous calcium gluconate. During this treatment, he developed significant calcification of the peripheral veins at the site of administration, leading to intravenous therapy suspension. The dose of oral calcium, calcitriol and magnesium was gradually increased and sevelamer started to control hyperphosphatemia. Despite the optimization, the patient maintained hypocalcemia refractory to standard therapy. As a last resource strategy in therapeutic optimization, the patient started on rhPTH (1-34). Ever since, the patient has been clinically asymptomatic with biochemical stability and with a reasonable quality of life. At age 18, renal ultrasound revealed diffuse medullary nephrocalcinosis. The genetic testing revealed a novel variant c.368T>C p.(Leu123Ser) likely pathogenic in heterozygosity in the CASR gene, suggesting the diagnosis of ADH type 1. The patient′s mother did not give her consent for genetic study and patient’s father had already died with a diagnosis of acute leukemia. Conclusion: This case can be explained by the presence of a likely pathogenic variant in heterozygosity in the CASR gene that has been described in the medical literature that has not been identified in gnomAD population database, suggesting the diagnosis of ADH type 1. rhPTH (1-34) may be a treatment option for those individuals who are not well controlled on standard therapy, but long-term follow-up studies are needed to reinforce its safety.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype-phenotype correlation.CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype-phenotype correlation.Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A/CG, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions/conversions were responsible for 86.4% of the mutated alleles. Patients' stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A/CG in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype-phenotype correlation (80%).Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype-phenotype correlation observed.

ResumoA associação de hipotiroidismo e puberdade precoce é pouco frequente e ocorre especialmente em situações graves não tratadas durante um longo período de tempo. A puberdade precoce periférica induzida por hipotiroidismo pode incluir telarca, galactorreia e menarca na ausência de pelo púbico. Outra manifestação importante inclui atraso no crescimento estatural.É apresentado o caso de uma menina de 6 anos com desenvolvimento mamário bilateral com 2 meses de evolução. A ecografia pélvica mostrou endométrio espessado, ovários de dimensões aumentadas e com folículos. A investigação subsequente demonstrou hipotiroidismo decorrente de tiroidite autoimune.AbstractThe association between hypothyroidism and precocious puberty is uncommon in children and occurs in untreated situations for a long period of time. Peripheral precocious puberty induced hypothyroidism may include thelarche, menarche and galactorrhoea in the absence of pubic hair. Other important characteristic include delayed linear growth.The authors present a 6 year old girl with bilateral breast augmentation with 2 months of evolution. Pelvic ultrasonography showed thickened endometrium and enlarged ovaries with follicles. Subsequent investigation showed hypothyroidism due to autoimmune thyroiditis.

Introdução: As neoplasias endócrinas múltiplas do tipo 2A consistem na tríade carcinoma medular da tiroide, feocromocitoma e hiperplasia das paratiroides. Os testes genéticos constituem uma ferramenta importante na deteção e seguimento destes doentes. Este estudo tem por objetivo descrever a experiência dos autores no seguimento de crianças diagnosticadas com neoplasias endócrinas múltiplas do tipo 2A. Métodos: Estudo observacional e descritivo de crianças com neoplasias endócrinas múltiplas do tipo 2A, acompanhadas num centro terciário de endocrinologia pediátrica. Foram utilizados os critérios da American Thyroid Association para a definição de risco das mutações encontradas. Resultados: Foram estudadas cinco crianças com neoplasias endócrinas múltiplas do tipo 2A, com idades entre 3-14 anos. Três apresentavam mutações de alto risco e duas de risco moderado. Quatro foram submetidas a tiroidectomia profilática. Uma criança desenvolveu hipoparatiroidismo pós-cirúrgico. Relativamente à análise histológica, uma peça operatória apresentou alterações. Em dois doentes verificou-se ausência de correlação genotípica-fenotípica. Discussão: De acordo com a experiência dos autores, a referenciação tardia para a consulta resultou no atraso da tiroidectomia profilática em dois casos. Após realização de tiroidectomia profilática é mandatório manter a monitorização destes doentes, que vão necessitar de terapêutica de reposição hormonal e de forma a detetar outras potenciais manifestações da doença., Portuguese Journal of Pediatrics, Vol. 49 No. 1 (2018)

ResumoA doença de Graves é a causa mais comum de hipertiroidismo na mulher em idade fértil e carateriza‐se pela presença de imunoglobulinas séricas que estimulam os recetores da tirotropina (TRAb) e que podem atravessar a placenta. Quando mal controlada tem consequências graves, causando quer hipertiroidismo fetal e/ou neonatal quer hipotiroidismo. Os autores apresentam o caso de um recém‐nascido de mãe com doença de Graves mal controlada durante a gravidez cujo período neonatal precoce decorreu sem incidentes e que na segunda semana de vida desenvolveu um quadro de hipertiroidismo. Foi medicado 2 dias com propranolol para controlo da taquicardia e metimazol que manteve durante 4 meses, com boa evolução clínica e laboratorial.Na mulher com doença de Graves é fundamental o controlo rigoroso da função tiroideia e dos TRAbs durante a gravidez. Todos os recém‐nascidos devem ter a função tiroideia avaliada ao nascer e um adequado seguimento que permita o diagnóstico de hipertiroidismo ou hipotiroidismo transitório. Com esta atitude será possível instituir um tratamento atempado, evitando as complicações a curto e longo prazo.A propósito deste caso, baseado numa revisão bibliográfica, os autores apresentam uma proposta de atuação em recém‐nascidos filhos de mãe com doença de Graves.AbstractGraves’ disease is the main cause of hyperthyroidism in women of childbearing age. It occurs by the presence of serum immunoglobulins which stimulate the thyrotropin receptor (TRAbs) and may cross the placenta. It has serious consequences when uncontrolled, leading to fetal and/or neonatal hyperthyroidism or hypothyroidism. The authors describe the case of a newborn from a mother with poorly controlled Graves’ disease during pregnancy. He had an uneventful early neonatal period but developed hyperthyroidism in the second week of life. He was treated for two days with propranolol to manage tachycardia and metimazol during 4 months, with favourable clinical and laboratory outcome.During pregnancy, it is essential to control thyroid function and TRAbs in women with Graves’ disease. Newborns should be screened for thyroid function at birth and must have a regular follow up as it allows the diagnosis of transient hyperthyroidism or hypothyroidism and its early treatment, avoiding short and long term complications.Based on this case and literature review, the authors present a proposal of protocol in infants born to mothers with Graves’ disease.

Type 1 diabetes mellitus (T1D) is considered a risk factor associated with oral yeast infections. The aim of this study was to evaluate the yeast oral carriage (in saliva and mucosal surface) of children with T1D and potential relation with host factors, particularly the subset of CD4+ T cells. Yeasts were quantified and identified in stimulated saliva and in cheek mucosal swabs of 133 diabetic T1D and 72 healthy control subjects. Salivary lymphocytes were quantified using flow cytometry. The presence of yeasts in the oral cavity (60% of total patients) was not affected by diabetes, metabolic control, duration of the disease, salivary flow rate or saliva buffer capacity, by age, sex, place of residence, number of daily meals, consumption of sweets or frequency of tooth brushing. Candida albicans was the most prevalent yeast species, but a higher number of yeast species was isolated in nondiabetics. T1D children with HbA1c ≤ 7.5 (metabolically controlled) presented higher number of CD4+ T salivary subsets when compared with the other groups of children (non-diabetic and nonmetabolically controlled) and also presented the highest number of individuals without oral yeast colonization. In conclusion, T1D does not predisposes for increased oral yeast colonization and a higher number of salivary CD4+T cells seems to result in the absence of oral colonization by yeasts.

Limbic encephalitis is a rare neurological disorder that may be difficult to recognize. Clinical features include memory impairment, temporal lobe seizures and affective disturbance. We report the case of a 10-year-old girl with type 1 diabetes mellitus that presented with seizures, depressed mood and memory changes. The diagnosis of glutamic acid decarboxylase 65 (GAD65) mediated limbic encephalitis relied on cerebral magnetic resonance imaging lesions and high serological and cerebrospinal fluid GAD65-antibodies titers. High-dose steroidal therapy was started with clinical improvement. Relapse led to a second high-dose steroid treatment followed by rituximab with remission. A correlation between serum GAD65-antibodies levels and symptoms was found, demonstrating GAD65-antibodies titers may be useful for clinical follow-up and immunotherapy guidance. This report raises awareness of this serious neurological condition that may be associated with type 1 diabetes, underlining the importance of an early diagnosis and prompt treatment for a better prognosis.

Summary Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) – thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug. Learning points Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age. It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy). Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.

A 22-year-old gravida 2, para 1 (G2P1) woman with immunoglobulin anti-D prophylaxis, insulin-treated gestational diabetes and first-trimester cytomegalovirus (CMV) infection vaginally delivered a 39-week boy weighing 3720 g (90th centile) and with Apgar scores of 8 and 10 at 1 and 5 min. Prenatal ultrasonographic assessment throughout gestation was normal. Nursery stay was uneventful. He was discharged on day 2, with a normal examination, except for the appearance of jaundice, with a transcutaneous bilirubin of 248 µmol/L (cut-off 250 µmol/L), not meeting the criteria for phototherapy. A follow-up clinic on day 4, arranged for bilirubin measurement and CMV testing, surprisingly revealed poor general appearance, lethargy, very icteric skin and a minor weight loss (9% of birth weight). Both liver and splenic edges were palpable. Vital signs were normal. Blood routine showed haemoglobin of 19 g/dL, haematocrit of 58%, white blood cells 11.6x109/L and platelet count 128x109/L. Biochemistry revealed total serum bilirubin of 694 µmol/L (cut-off 350 µmol/L), indirect bilirubin of 681 µmol/L, and a normal glucose, urea, creatinine and coagulation study. He was admitted for intensive phototherapy, and his total serum bilirubin level decreased to 289 µmol/L in 9 hours, but rebound hyperbilirubinaemia …

Os diagnósticos diferenciais da forma central de diabetes insípida são vários: traumatismo» infecção malformação, neoplasia, situações inflamatórias diversas. Progressivamente» o número de casos considerado como diabetes insípida idiopática tem vindo a diminuir com a melhoria dos meios imagiológicos, nomeadamente Ressonância Magnética Nuclear. Descreve-se o caso de uma adolescente com diabetes insípida central» associado a alterações na Ressonância Magnética Nuclear a nível neurohipafisário, cuja evolução sugere o diagnóstico infundibuloneurohipofisite., Portuguese Journal of Pediatrics, vol. 34 n.º 2 (2003)