ABSTRACT
SUMMARY We 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.
Subject(s)
Humans , Female , Adult , Human Growth Hormone , Pituitary ACTH Hypersecretion , Dwarfism, Pituitary/genetics , Endopeptidases/genetics , Ubiquitin Thiolesterase/genetics , Endosomal Sorting Complexes Required for Transport/genetics , Germ Cells , MutationABSTRACT
Os autores relatam um caso de uma paciente do sexo feminino, com idade cronológica de sete anos, idade óssea de 11 anos, aparecimento de mamas Tanner III bilateralmente, cuja investigação diagnóstica confirmou quadro de puberdade precoce dependente de gonadotrofinas, e a ressonância magnética da hipófise evidenciou duplicação da haste e da glândula hipofisária associada a hamartoma hipotalâmico.
The authors report a case of a female patient with chronological age of 7 years and bone age of 11 years, presenting with bilateral breast stage Tanner III and gonadotrophin-dependent precocious puberty. Magnetic resonance imaging of the sellar region demonstrated duplication of the pituitary gland and stalk associated with a hypothalamic hamartoma.
Subject(s)
Humans , Female , Child , Pituitary Gland, Anterior , Pituitary Gland/abnormalities , Pituitary Gland/physiopathology , Pituitary Diseases , Puberty, Precocious/complications , Leuprolide/administration & dosage , Magnetic Resonance ImagingABSTRACT
A incidência do Carcinoma adrenocortical é aproximadamente de 1 : 1.7000.000. Isso perfaz somente 0.025 dos tumores malignos. A manifestação clínica depende dos hormônios predominantemente produzidos, estando a sindrome de cushing presente em 30-40 (por cento) dos pacientes com carcinoma adrenocortical e a virilização ocorrendo em 20-30 (por cento) dos adultos. Relatamos o caso de uma paciente que se apresentou com quadro clínico de virilização às custas de carcinoma adrenocortical produtor de andrógenos (principlamente testoterona), associado à produção de cortisol, não tendo sido exuberante o quadro clínico de Síndrome de Cushing, devido ao curto tempo de duração da doença