Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the magnitude of Creutzfeldt-Jakob disease (CJD) occurrence among recipients of pituitary-derived human growth hormone (HGH), we conducted an epidemiologic follow-up of 6284 recipients of HGH distributed through the National Hormone and Pituitary Program. Seven neuropathologically confirmed cases of CJD have occurred in this population to date: six patients with clinical CJD presented with ataxia and imbalance, rather than with altered mentation, which is the most common initial manifestation in sporadic CJD, and one patient died in the preclinical incubation state of the disease. All seven cases occurred among the nearly 700 HGH recipients who started therapy before 1970. Since only 10% of the cohort has been followed up for the 15-year average incubation interval from midpoint of HGH treatment to onset of symptoms, the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD. The median duration of HGH therapy of 100 months in the CJD cases was significantly longer than 41 months for all patients starting treatment before 1970; thus, the duration of pituitary HGH therapy is a major risk factor for CJD.
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PMID:Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. 199 85

Genetically obese mice (C57BL/6J-ob/ob), fed ad libitum, demonstrated a precipitous increase in the spontaneous death rate after 50 weeks. The first signs of morbidity were a ruffled hair coat and a progressive motor ataxia. Necropsy revealed that obese mice had pale and fatty livers, urolithiasis and grossly distended bladders. Microscopically, the hepatocellular changes observed in all aged obese mice included: a loss of orientation of hepatocytes, an enormous variability in the size of both hepatocytes and their nuclei, and an extensive deposition of both large and small lipid droplets, confirmed by an increase content of triacylglycerols. A subacute-to-chronic, multifocal, necrotizing hepatitis was also present. Kidneys from aged obese mice contained hypertrophied glomeruli and increased PAS-stained material. Tubular dilation with compaction of the tubular cells was also seen. There were no significant alterations in the microanatomy or mineralization of femurs from obese mice, yet there was a significant increase in plasma alkaline phosphatase activity. In obese mice at 62-63 weeks of age, hyperglycemia was present even in spite of hyperinsulinemia. Pituitary immunoreactive ACTH and its molar ratio to pituitary immunoreactive beta-endorphin were also increased in obese mice at this age. Even though the etiology of the decreased lifespan of genetically obese mice remains uncertain, the possibility is discussed that an overall defect in the central nervous system may be involved.
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PMID:Hormonal, metabolic and morphologic studies of aged C57BL/6J obese mice. 673 67

Pituitary anomaly associated with familial spinocerebellar ataxia (FSCA) is a rare occurrence. This is a report of a child with FSCA who had an empty sella turcica and growth hormone deficiency. Growth hormone therapy accelerated growth velocity and improved muscular strength. Endocrinopathy associated with FSCA is reviewed.
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PMID:Familial spinocerebellar ataxia and empty sella turcica. 929 53

Reelin is a neuronal glycoprotein that plays a crucial role in brain layer formation during prenatal development. The reeler mutant mouse lacks Reelin, leading to abnormalities in the neuronal layering of cerebral cortex and cerebellum, producing ataxia, tremor and abnormal locomotion. Reeler mice are reported to have growth retardation and most of them are sterile or unable to bring up their newborns. Since the brain is one of the main regulator of pituitary hormone secretion and no information was reported regarding pituitary function and structure in these mutant mice, we studied pituitary endocrine activity and morphology in reeler mice. Mice were classified in three groups as reeler homozygote (RHM), reeler heterozygote (RHT) or control (CO). Pituitary hormone blood levels were assessed by enzyme immunoassay (EIA) and immunoradiometric assay (IRMA). Animals and their pituitaries were weighted and pituitaries were studied by histology, immunohistochemistry and electron microscopy. Results showed statistically significant differences in body weight and in adrenocorticotropic hormone (ACTH) and luteinizing hormone (LH) blood levels between the three groups. In contrast, growth hormone (GH) blood levels showed a high individual variation and no decrease in reeler groups compared with CO. Morphological studies revealed no differences in pituitary cell types except that somatotrophs appeared to be slightly smaller in RHM and RHT. Although it seems that pituitary hypofunction is not responsible for growth retardation, more studies are needed to obtain a deeper insight into the endocrine status of these mutant mice to elucidate the cause of their low body weight and reproductive behaviour.
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PMID:Hormonal and morphological study of the pituitaries in reeler mice. 1750 46

The uncommon aggressive pituitary tumors are named carcinomas when metastases are detected, either in the central nervous system and/or systemically. Some cases are associated with hormonal overproduction, but most are diagnosed because of local symptoms. These neoplasias are generally refractory to current treatments. A 51 year-old woman presented sudden onset of headache, left arm paresis and left facial hypoesthesia. Computed tomography scan and magnetic resonance imaging revealed a pituitary tumor invading the left sphenoidal and cavernous sinuses. Laboratory data excluded hormonal hypersecretion. The patient underwent transsphenoidal surgery and histological findings showed a neoplasia with Ki-67 estimated at 75%. Medical imaging excluded both a primary occult tumor and central nervous system or systemic dissemination. Three weeks postoperatively, neurological condition worsened, with new onset of ataxia, bilateral ptosis, ophthalmoplegia and an increase in the size of the lesion, leading to surgical intervention by craniotomy, followed by only a few sessions of radiotherapy, because of severe disease progression. Patient died nearly 2 months after the initial manifestations. This case illustrates the aggressiveness of some pituitary lesions, the limited efficacy of current treatment modalities such as surgery or radiotherapy and the pitfalls of the current pituitary tumors classification. To our knowledge, this case corresponds to one of the most aggressive pituitary neoplasms reported so far, with a very high Ki-67 index (75%) and short survival (2 months). Ki-67 index could be of prognostic value in pituitary tumors. Pituitary tumors World Health Organization (WHO) classification could be revisited.
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PMID:Aggressive pituitary lesion with a remarkably high Ki-67. 2521 50

Background:NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dystonia and chorea) and endocrinological abnormalities (peripheric thyroid disease, and pituitary hormone deficiencies). Dystonia predominated at the father, and myoclonus at the daughter. The father had hypogonadotropic hypogonadism, while the daughter was treated with growth hormone deficiency. Both patients had empty sella on MRI. Candidate gene analyses were negative. Exome sequencing detected a pathogenic stop variation (NM_003317:c.338G>A, p.Trp113*) in the NKX2-1 gene. Conclusions: This case study has two highlights. (1) It draws attention to possible pituitary dysfunction in brain-lung-thyroid syndrome, and provide further evidences that this might be linked to loss of function of the NKX2-1 gene. (2) It underscores the importance of considering NKX2-1 related disorders in the differential diagnosis of myoclonus dystonia.
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PMID:NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement. 3018 10