Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty. The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their subunits; and nonfunctioning gonadotropinomas or null cell tumors with negative immunostaining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadenomas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation.
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PMID:Gonadotropinomas. 1253 57

Mutation in the orphan nuclear receptor DAX-1 gene causes X-linked adrenal hypoplasia congenita (AHC). Affected male children classically suffer a salt-losing crisis and adrenal insufficiency in their early infancy or, in some rare exceptions, with late-onset subtype. We report here a patient manifesting late-onset adrenal hypoplasia congenita caused by the premature truncation of the C-terminus of the DAX-1 molecule, which is essential for its function as a transcriptional repressor. A 12-year-old boy was referred to us after being afflicted with generalized skin pigmentation for about 3 years, fatigue and headache. Primary adrenal insufficiency was determined on the basis of a low plasma cortisol level (3.9 microg/dl) despite an extremely high ACTH level (1200 pg/ml). Replacement therapy with hydrocortisone and fludorocortisone acetate was initiated soon thereafter. Hypogonadotropic hypogonadism was confirmed at the age of 18 years, at which time sexual infantilism had become apparent. Direct sequencing of the peripheral lymphocyte-derived DNA revealed a novel 1033del13 mutation on the ligand-binding domain of the NR0B1 (DAX-1) gene, which generated a premature stop codon truncating the C-terminus. This mutation was considered de novo since we could not find it in his mother. This case demonstrates that even a truncated protein lacking the major functional domain of DAX-1 can present late-onset and latent adrenal failure.
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PMID:Late-onset adrenal hypoplasia congenita caused by a novel mutation of the DAX-1 gene. 1860 30