Stephen J Marx1. 1. Genetics and Endocrinology Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. marxs@mail.nih.gov
Abstract
CONTEXT: Multiplicity of hormone-secreting tumors occurs in a substantial portion of hormone-excess states. Multiplicity increases the difficulty of management and drives the selection of special strategies. EVIDENCE ACQUISITION: This is a synthesis from publications about tumor development and expression, and also about types of clinical strategy for hormone-secreting tumors. EVIDENCE SYNTHESIS: Comparisons were made between patient groups with solitary tumors vs those with multiple tumors. Major themes with clinical relevance emerged. Usually, tumor multiplicity develops from a genetic susceptibility in all cells of a tissue. This applies to hormone-secreting tumors that begin as either polyclonal (such as in the parathyroids of familial hypocalciuric hypercalcemia) or monoclonal tumors (such as in the parathyroids of multiple endocrine neoplasia type 1 [MEN1]). High penetrance of a hereditary tumor frequently results in bilaterality and in several other types of multiplicity. Managements are better for the hormone excess than for the associated cancers. Management strategies can be categorized broadly as ablation that is total, subtotal, or zero. Examples are discussed for each category, and 1 example of each category is named here: 1) total ablation of the entire tissue with effort to replace ablated functions (for example, in C-cell neoplasia of multiple endocrine neoplasia type 2); 2) subtotal ablation with increased likelihood of persistent disease or recurrent disease (for example, in the parathyroid tumors of MEN1); or 3) no ablation of tissue with or without the use of pharmacotherapy (for example, with blockers for secretion of stomach acid in gastrinomas of MEN1). CONCLUSIONS: Tumor multiplicity usually arises from defects in all cells of the precursor tissue. Even the optimized managements involve compromises. Still, an understanding of pathophysiology and of therapeutic options should guide optimized management.
CONTEXT: Multiplicity of hormone-secreting tumors occurs in a substantial portion of hormone-excess states. Multiplicity increases the difficulty of management and drives the selection of special strategies. EVIDENCE ACQUISITION: This is a synthesis from publications about tumor development and expression, and also about types of clinical strategy for hormone-secreting tumors. EVIDENCE SYNTHESIS: Comparisons were made between patient groups with solitary tumors vs those with multiple tumors. Major themes with clinical relevance emerged. Usually, tumor multiplicity develops from a genetic susceptibility in all cells of a tissue. This applies to hormone-secreting tumors that begin as either polyclonal (such as in the parathyroids of familial hypocalciuric hypercalcemia) or monoclonal tumors (such as in the parathyroids of multiple endocrine neoplasia type 1 [MEN1]). High penetrance of a hereditary tumor frequently results in bilaterality and in several other types of multiplicity. Managements are better for the hormone excess than for the associated cancers. Management strategies can be categorized broadly as ablation that is total, subtotal, or zero. Examples are discussed for each category, and 1 example of each category is named here: 1) total ablation of the entire tissue with effort to replace ablated functions (for example, in C-cell neoplasia of multiple endocrine neoplasia type 2); 2) subtotal ablation with increased likelihood of persistent disease or recurrent disease (for example, in the parathyroid tumors of MEN1); or 3) no ablation of tissue with or without the use of pharmacotherapy (for example, with blockers for secretion of stomach acid in gastrinomas of MEN1). CONCLUSIONS:Tumor multiplicity usually arises from defects in all cells of the precursor tissue. Even the optimized managements involve compromises. Still, an understanding of pathophysiology and of therapeutic options should guide optimized management.
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