A rare association between acromegaly and pheochromocytoma.
ABSTRACT The occurrence of multiple endocrine tumors is rare; however, they may be found with hereditary diseases such as multiple endocrine neoplasia (MEN). The endocrine tumors involved with these diseases are well documented. We present a case of a patient with a pheochromocytoma and a growth hormone (GH) secreting pituitary adenoma. This association is not described with any of the known MEN syndromes. The association may be a cross-over MEN syndrome or a secondarily induced GH-secreting pituitary adenoma from a pheochromocytoma producing growth hormone releasing hormone (GHRH) instead of catecholamines.
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ABSTRACT: Succinate dehydrogenase (SDH) or mitochondrial complex II is a multimeric enzyme that is bound to the inner membrane of mitochondria and has a dual role since it serves both as a critical step of the tricarboxylic acid (TCA) or Krebs cycle and as a member of the respiratory chain that transfers electrons directly to the ubiquinone pool. Mutations in SDH subunits have been implicated in the formation of familial paragangliomas (PGLs) and/or pheochromocytomas (PHEOs) and in Carney-Stratakis syndrome. More recently, SDH defects were associated with predisposition to a Cowden disease phenotype, renal and thyroid cancer. We recently described a kindred with the coexistence of familial PGLs and an aggressive GH-secreting pituitary adenoma, harboring an SDHD mutation. The pituitary tumor showed loss of heterozygosity (LOH) at the SDHD locus, indicating the possibility that SDHD's loss was causatively linked to the development of the neoplasm. In total, 29 cases of pituitary adenomas presenting in association with PHEOs and/or extra-adrenal PGLs have been reported in the literature since 1952. We speculate that the association of PHEOs and/or PGLs with pituitary tumors is a new syndromic association and a novel phenotype for SDH defects.Endocrine Related Cancer 08/2012; · 5.26 Impact Factor
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ABSTRACT: Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD). Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma. A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors. We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis.The Journal of Clinical Endocrinology and Metabolism 12/2011; 97(3):E357-66. · 6.31 Impact Factor
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ABSTRACT: We present the case of a 56-year-old woman who, 5 years after receiving a diagnosis of unilateral adrenal pheochromocytoma and primary hyperparathyroidism, was diagnosed with acromegaly caused by a growth hormonesecreting pituitary adenoma. No germ-line mutations in RET, VHL and MEN-1 gene were detected. Medullar thyroid carcinoma was also ruled out. Therefore, the present case shows coexistence of a tumor characteristic of MEN 2 syndrome (pheochromocytoma) with a growth hormone-secreting pituitary tumor characteristic of MEN 1 syndrome and primary hyperparathyroidism, which can be observed in both multiple endocrine neoplasia syndromes, but without germline mutations in RET, VHL and MEN-1.Endocrinología y Nutrición 06/2006; 53(6).