Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report what we believe to be the first case of a patient with multiple endocrine neoplasia type 2A (MEN 2A) and renal dysplasia associated with an RET 634 mutation. The proband presented at the age of 29 with medullary thyroid carcinoma (MTC), bilateral pheochromocytomas, and primary hyperparathyroidism. Screening of family members identified the syndrome in his father. Both the proband and his father carry RET 634 germline mutation resulting in cysteine to arginine amino acid substitution. The proband had a left nephrectomy at the age of 10 years. Histologic examination of the resected kidney revealed severe dysplasia. His father had normal renal tract on ultrasonography. The proband's clinical presentation was unusual, and initially thought to be an atypical pneumonia. Surgical management after pharmacologic alpha- and beta-blockage consisted of bilateral adrenalectomy, total thyroidectomy, and subtotal parathyroidectomy as a single procedure.
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PMID:Multiple endocrine neoplasia type 2A: an unusual clinical presentation and association with renal dysplasia. 1260 35

We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A) associated with a rare skin disease primary cutaneous lichen amyloidosis and discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail, and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34-yr-old female. The presence of composite tumor of pheochromocytoma and ganglioneuroma arising in the adrenal glands has been described previously in MEN2A and in sporadic cases. The patient displayed classical signs and symptoms of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed tomography revealed multiple mass lesions in both adrenal glands. It also showed a large heterogeneous mass that clearly discriminated from right adrenal gland in retroperitoneal location. After surgical exploration, both adrenal glands and the suspicious mass in pancreatic tail were removed successfully together with subtotal resection of the retroperitoneal tumor. Histopathologic examinations confirmed the presence of pheochromocytoma in both adrenal glands as well as pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic and biochemical evidence of pheochromocytoma subsided after the operation. Further evaluation for medullary thyroid carcinoma and primary hyperparathyroidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene revealed a missense point mutation at position 634 in exon 11, which gives rise to the substitution of a cysteine codon with a tyrosine residue.
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PMID:Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma. 1627 70

The REarranged during Transfection (RET) proto-oncogene is a receptor tyrosine kinase involved in growth and differentiation during embryogenesis and maintenance of the urogenital and nervous systems in mammals. Distinct mutations across hotspot RET exons can cause Multiple Endocrine Neoplasia Type 2A (MEN2A) characterised by development of medullary thyroid cancer (MTC), phaeochromocytoma (PCC) and primary hyperparathyroidism (PHPT), with a strong correlation between genotype and phenotype. Here, we report a 42-year-old man presented in the clinic with a unilateral PCC, with subsequent investigations revealing a nodular and cystic thyroid gland. He proceeded to thyroidectomy, which showed bilateral C-cell hyperplasia (CCH) without evidence of MTC. His brother had neonatal Hirschsprung disease (HSCR). Genetic testing revealed the presence of a heterozygous variant of unknown significance (VUS) in the cysteine-rich region of exon 10 in the RET gene (c.1846G>C, p.E616Q), in both affected siblings and their unaffected mother. Exon 10 RET mutations are known to be associated with HSCR and MEN2. Variants in the cysteine-rich region of the RET gene, outside of the key cysteine residues, may contribute to the development of MEN2 in a less aggressive manner, with a lower penetrance of MTC. Currently, a VUS in RET cannot be used to inform clinical management and direct future care. Analysis of RETE616Q reveals a gain of function mutant phenotype for this variant, which has not previously been reported, indicating that this VUS should be considered at risk for future clinical management.
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PMID:The RET E616Q Variant is a Gain of Function Mutation Present in a Family with Features of Multiple Endocrine Neoplasia 2A. 2770 98