LUCIANI RENATA SILVEIRA DE CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery(2019) CORREA, Fernanda A.; NAKAGUMA, Marilena; MADEIRA, Joao L. O.; NISHI, Mirian Y.; ABRAO, Milena G.; JORGE, Alexander A. L.; CARVALHO, Luciani R.; ARNHOLD, Ivo J. P.; MENDONCA, Berenice B.The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clinicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe.
- Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing(2017) CORREA, Fernanda A.; FRANCA, Marcela M.; FANG, Qing; MA, Qianyi; BACHEGA, Tania A.; RODRIGUES, Andresa; OZEL, Bilge A.; LI, Jun Z.; MENDONCA, Berenice B.; JORGE, Alexander A. L.; CARVALHO, Luciani R.; CAMPER, Sally A.; ARNHOLD, Ivo J. P.Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS -3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.
- Cushing disease due to a somatic USP8 mutation in a patient with evolving pituitary hormone deficiencies due to a germline GH1 splicing variant(2022) LABELLO, Julia Haddad; BENEDETTI, Anna Flavia Figueredo; AZEVEDO, Bruna Viscardi; JORGE, Alexander Augusto de Lima; CESCATO, Valter Angelo Sperling; ROSEMBERG, Sergio; FRASSETO, Fernando Pereira; ARNHOLD, Ivo Jorge Prado; CARVALHO, Luciani Renata Silveira deWe present the unique case of an adult Brazilian woman with severe short stature due to growth hormone deficiency with a heterozygous G to T substitution in the donor splice site of intron 3 of the growth hormone 1 (GH1) gene (c.291+1G>T). In this autosomal dominant form of growth hormone deficiency (type II), exon 3 skipping results in expression of the 17.5 kDa isoform of growth hormone, which has a dominant negative effect over the bioactive isoform, is retained in the endoplasmic reticulum, disrupts the Golgi apparatus, and impairs the secretion of other pituitary hormones in addition to growth hormone deficiency.This mechanism led to the progression of central hypothyroidism in the same patient. After 5 years of growth and thyroid hormone replacement, at the age of 33, laboratory evaluation for increased weight gain revealed high serum and urine cortisol concentrations, which could not be suppressed with dexamethasone. Magnetic resonance imaging of the sella turcica detected a pituitary macroadenoma, which was surgically removed. Histological examination confirmed an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma. A ubiquitin-specific peptidase 8 (USP8) somatic pathogenic variant (c.2159C>G/p.Pro720Arg) was found in the tumor. In conclusion, we report progression of isolated growth hormone deficiency due to a germline GH1 variant to combined pituitary hormone deficiency followed by hypercortisolism due to an ACTH-secreting macroadenoma with a somatic variant in USP8 in the same patient. Genetic studies allowed etiologic diagnosis and prognosis of this unique case.
- Central adrenal insufficiency: who, when, and how? From the evidence to the controversies - an exploratory review(2022) BITENCOURT, Mariana Rechia; BATISTA, Rafael Loch; BISCOTTO, Isabela; CARVALHO, Luciani R.Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated. Arch Endocrinol Metab. 2022;66(4):541-50