Endocrine organs

Endocrine disturbances are common manifestations of mitochondrial diseases (Harvey and Barnett, 1992; Quade et al., 1992; Nissenkorn et al., 1999). These involve the hypothalamic-pituitary gland system, the thyroid and parathyroid glands, the adrenals, the ß cells of the pancreas islets and the gonads. Reported disturbances include growth hormone deficiency, adre-nocorticotropic hormone (ACTH) deficiency, hypothala-mopituitary hypothyroidism, gonadotropin deficiency, diabetes insipidus, hypothyroidism, hypoparathyroidism, Addison disease, hyperaldosteronism, hypoglycaemia, diabetes mellitus (insulin and non-insulin dependent) and hypogonadism (Harvey and Barnett, 1992; Quade et al., 1992; Chen and Huang, 1995; Tulinius et al., 1995; Papadimitriou et al., 1996; Nicolino et al., 1997; Wilichowski et al., 1997; Boles et al., 1998; Nissenkorn et al., 1999; Balestri and Grosso, 2000). The mitochondri-al diseases associated with endocrine dysfunction may be caused by mtDNA large-scale deletions as well as mtDNA point mutations, especially those affecting the tRNALeu(UUR) gene (Harvey and Barnett, 1992; Quade et al., 1992; Balestri and Grosso, 2000; DiMauro et al., 2004a). A common cause of diabetes mellitus in 7mitochondrial diseases is mutations in the tRNALeu (UUR) gene (Reardon et al., 1992; Van den Ouweland et al., 1992), and it has been estimated that the tRNALeu

(UUR)A3243G accounts for approximately 0.5-1.5% of non-insulin dependent diabetes mellitus (Gerbitz et al., 1995; Maassen and Kadowaki, 1996; Newkirk etal., 1997).

In addition to the endocrine dysfunction of the pancreatic islets, exocrine dysfunction of pancreas is typically associated with large-scale mtDNA rearrangements in the Pearson bone marrow-pancreas syndrome (Pearson et al., 1979; Rotig et al., 1990; 1995; Van den Ouweland et al., 2000; Krauch et al., 2002).

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