Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/48657
CLINICAL AND BIOCHEMICAL FEATURES OF HYPOPITUITARISM AMONG BRAZILIAN CHILDREN WITH ZIKA VIRUS–INDUCED MICROCEPHALY
Autor(es)
Afiliação
Escola Bahiana de Medicina e Saúde Pública. Programa de Pós-graduação em Medicina e Saúde Humana. Salvador, BA, Brasil / Universidade Federal da Bahia. Hospital University Hospital Professor Edgard Santos, Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Associação de Pais e Amigos dos Excepcionais. Salvador, BA, Brasil.
University of Sao Paulo. Ribeirao Preto Medical School. Department of Medical Imaging, Hematology and Oncology. Sao Paulo, SP, Brazil.
Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, Brasil.
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.
University of Sao Paulo. Ribeirao Preto Medical School. Department of Pediatrics. Sao Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.
Associação de Pais e Amigos dos Excepcionais. Salvador, BA, Brasil.
University of Sao Paulo. Ribeirao Preto Medical School. Department of Medical Imaging, Hematology and Oncology. Sao Paulo, SP, Brazil.
Universidade Federal da Bahia. Instituto de Saúde Coletiva. Salvador, BA, Brasil.
Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.
University of Sao Paulo. Ribeirao Preto Medical School. Department of Pediatrics. Sao Paulo, SP, Brazil.
Resumo em Inglês
The Zika virus infects progenitor neuron cells, disrupts cerebral development, and, in
mice, drives hypothalamic defects. Patients with microcephaly caused by congenital Zika infection
present with midline cerebral defects, which may result in hypopituitarism.
OBJECTIVE To analyze postnatal growth and the presence of clinical and biochemical features
associated with hypopituitarism in children with congenital Zika infections.
DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study at 2 public referral
hospitals in Bahia, Brazil, specializing in the treatment of congenital Zika infection, clinical data and
growth parameters of 65 patients with the infection were evaluated. Data were analyzed from April
2017 through July 2018.
EXPOSURE Congenital Zika infection.
MAIN OUTCOMES AND MEASURES Length, weight, and head circumference were measured at
birth and during follow up (ie, at 27 months of life) for each patient. Basal levels of free thyroxine,
thyrotropin, cortisol, corticotropin, prolactin, insulin-like growth factor 1, insulin-like growth factor
binding protein 3, urine and plasma osmolality, electrolytes, glucose, and insulin were evaluated at
the age of 26 months to 28 months. All patients underwent central nervous system computed
tomography scans and ophthalmic and otoacoustic evaluations at the time of this investigation or
had done so previously.
RESULTS Among 65 patients (38 [58.4%] male; median [interquartile range] age at enrollment, 27
[26-28] months), 61 patients presented with severe brain defects (93.8%), including corpus callosum
agenesis or hypoplasia (ie, midline brain defects; 25 patients [38.5%]) and optic nerve atrophy (38
patients [58.5%]). Most patients presented with severe neurodevelopmental delay (62 of 64
patients [96.9%]). Past or present clinical signs of hypopituitarism were rare, occurring in 3 patients
(4.6%). Severe microcephaly, compared with mild or moderate microcephaly, was associated with
a shorter length by median (interquartile range) z score at birth (−1.9 [−2.5 to −1.0] vs −0.3 [−1.0 to 0];
P < .001), but this difference did not persist at 27 months (−1.6 [−2.3 to −0.3] vs −2.9 [−4.0 to −1.2];
P = .06). Growth hormone deficiency or hypothyroidism were not observed in any patients, and
glucose and insulin levels were within reference ranges for all patients. Low cortisol levels (ie, below
3.9 μg/dL) were observed in 4 patients (6.2%). These 4 patients presented with low (ie, below 7.2
pg/mL) or inappropriately low (ie, below 30 pg/mL) corticotropin levels. Low corticotropin levels (ie,
below 7.2 pg/mL) were observed in 6 patients (9.2%). Diabetes insipidus was evaluated in 21
patients; it was confirmed in 1 patient (4.8%) and suggested in 3 patients (14.3%). CONCLUSIONS AND RELEVANCE This study found that congenital Zika infection with
microcephaly was associated with midline brain defects and optic nerve atrophy. Children with
congenital Zika infections presented with prenatal growth impairments with a lack of postnatal
catch-up, as shown by persistent short length from birth until 27 months; these impairments were
not associated with growth hormone deficiency. Patients also presented with severe developmental
delay thatwas not associated with hypothyroidism, while central adrenal insufficiency and diabetes
insipidus occurred in some patients.
Compartilhar