Primary Hyperparathyroidism Associatiated with Aldosterone-Producing Adrenocortical Adenoma and Breast Cancer: Relation to MEN1 Gene

Abstract

A rare case of primary hyperparathyroidism associated with primary aldosteronism and breast cancer is reported. A 44-year-old woman was admitted to our hospital to undergo surgical removal of breast cancer. She had hypertension with low serum potassium, and slightly but significantly elevated serum calcium levels. Further studies demonstrated an enlarged left superior parathyroid gland and a left aldosterone-producing adrenocortical adenoma. Blood pressure was controlled with spironolactone and nifedipine, and left mastectomy was done for breast cancer. The pathological diagnosis was scirrhous breast carcinoma. Although the postoperative course was uneventful, her serum calcium gradually and progressively rose to higher levels. Left superior parathyroidectomy and left adrenalectomy were then performed simultaneously. The pathological diagnoses of the resected parathyroid gland and adrenal gland were parathyroid chief cell adenoma and adrenocortical adenoma with hyperplasia of zona glomerulosa, respectively. To clarify if the occurence of these tumors may be related to MEN1 gene mutations, we analyzed MEN1 gene in this patient, and found a loss of heterozygosity of the MEN1 locus in the parathyroid adenoma and breast cancer. Thus, we conclude that an alteration of the MEN1 gene and/or another tumor suppressor gene located at the MEN1 locus on chromosome 11q13 may be responsible for the development of parathyroid adenoma and breast cancer in our patient suggesting that the clinical spectrum of MEN1 might include breast cancer. In addition, serum calcium should be interpreted with caution in primary aldosteronism, because hypercalcemia may be masked in the presence of aldosterone excess. (Internal Medicine 43: 310-314, 2004)Key words: multiple endocrine neoplasia type 1 (MEN1), MEN1 gene, loss of heterozygosity, breast cancer, primary hyperparathyroidism, primary aldosteronism

Case Report: A case report of acromegaly associated with primary aldosteronism

“…There are several recent reports which describe the association of PA and different types of tumors 1– 3 . These cases are related mainly to MEN1.…”

“…In the literature only single cases of PA have been described in MEN1 1– 3 . Beckers et al 1 reported a case of PA as a part of MEN1, associated with parathyroid adenoma, prolactinoma and toxic multinodular goiter.…”

“…Kim et al 2 described a case of PA, associated with primary hyperparathyroidism, Hurthle cell thyroid cancer and meningioma with a loss of heterozygosity (LOH) of the MEN1 locus in parathyroid glands, but no germline mutation. Honda et al 3 reported PA associated with primary hyperparathyroidism and breast cancer and a LOH of the MEN1 locus in the parathyroid adenoma and in the breast cancer tissue. None of the reported cases was associated with acromegaly, in contrast to our patient.…”

“…In the literature several patients with primary aldosteronism (PA) associated with endocrine and non-endocrine tumors have been reported 1– 3 . These cases were attributed mainly to multiple endocrine neoplasia type 1 (MEN1), which is an autosomal dominantly inherited condition, characterized by the association of tumors of the pituitary and the parathyroid glands, the endocrine pancreas, the adrenal glands and neuroendocrine tumors 4 .…”

“…These cases were attributed mainly to multiple endocrine neoplasia type 1 (MEN1), which is an autosomal dominantly inherited condition, characterized by the association of tumors of the pituitary and the parathyroid glands, the endocrine pancreas, the adrenal glands and neuroendocrine tumors 4 . Aldosterone-producing adenomas have been described in various combinations, mainly with hyperparathyroidism, prolactinomas and pancreatic endocrine tumors, but none of these have been associated with acromegaly 2, 3, 5 .…”