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omas and hyperpigmentation Patients with Cowden disease develop thyroid abnormalities (66%) such as benign adenomas and follicular adenocarcinomas, along with breast cancer (20 36% in women), and multiple hamartomas that affect the skin and multiple other organs
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Gertner ME et al Multiple endocrine neoplasia type 2 Curr Treat Options Oncol 2004 Aug;5(4):315 25 [PMID: 15233908] Lambert LA et al Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1 Arch Surg 2005 Apr;140(4):374 82 [PMID: 15841561] Skinner MA et al Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A N Engl J Med 2005 Sep 15;353(11): 1105 13 [PMID: 16162881] Waldmann J et al Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years of prospective screening Langenbecks Arch Surg 2007 Aug;392(4):437 43 [PMID: 17235589]
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noma H2-blockers and metoclopramide cause hyperprolactinemia, simulating a pituitary prolactinoma Variants of MEN 1 also occur Kindreds with MEN 1 Burin variant have a high prevalence of prolactinomas, lateonset hyperparathyroidism, and carcinoid tumors, but rarely enteropancreatic tumors
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2 MEN 2A (Sipple s Syndrome)
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MEN 2A is a rare familial multiglandular syndrome that is inherited as an autosomal dominant trait Patients with MEN 2A should have genetic testing for a ret protooncogene (RET) mutation Their first-degree relatives may then be tested for the specific RET mutation Patients with MEN 2A may have medullary thyroid carcinoma (> 90%); hyperparathyroidism (20 50%), due to hyperplasia or multiple adenomas in over 70% of cases; pheochromocytomas (20 35%), which are often bilateral; or Hirschsprung s disease The medullary thyroid carcinoma is of mild to moderate aggressiveness Children harboring an MEN 2A RET gene mutation are advised to have a prophylactic total thyroidectomy by age 6 years Siblings or children of patients with MEN 2A should have genetic testing to determine if they have a mutation of the ret protooncogene (RET) on chromosome 10cen-10q112; this identifies about 95% of affected individuals Each kindred has a certain ret codon mutation that correlates with the particular variation in the MEN 2 syndrome, such as the age of onset and aggressiveness of medullary thyroid cancer The specific mutation as well as case histories of family members should guide the timing for prophylactic thyroidectomy Before any surgical procedure, MEN 2 carriers should be screened for pheochromocytoma There is incomplete penetrance, and about 30% of those with such mutations never manifest endocrine tumors Patients may be screened for medullary thyroid carcinoma with a serum calcitonin drawn after 3 days of omeprazole, 20 mg orally twice daily; calcitonin levels rise in the presence of medullary thyroid carcinoma to above 80 pg/mL in women or above 190 pg/mL in men
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CLINICAL USE OF CORTICOSTEROIDS Mechanisms of Action
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Cortisol is a steroid hormone that is normally secreted by the adrenal cortex in response to ACTH It exerts its action by binding to nuclear receptors, which then act upon chromatin to regulate gene expression, producing effects throughout the body
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Relative Potencies (Table 26-18)
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Hydrocortisone and cortisone acetate, like cortisol, have mineralocorticoid effects that become excessive at higher doses Other synthetic corticosteroids such as prednisone, dexamethasone, and deflazacort (an oxazoline derivative of prednisolone) have minimal mineralocorticoid activity Anticonvulsant drugs (eg, phenytoin, carbamazepine, phe-
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3 MEN 2B
MEN 2B is a familial, autosomal dominant multiglandular syndrome that is caused by a mutation of the ret protooncogene (RET) on chromosome 10 MEN 2B is characterized by mucosal neuromas (> 90%) with bumpy and enlarged lips and tongue, Marfan-like habitus (75%), adrenal pheochromocytomas (60%) that are rarely malignant and often bilateral, and medullary thyroid carcinoma (80%) Patients also have intestinal abnormalities (75%) such as intestinal ganglioneuromas, skeletal abnormalities (87%), and delayed puberty (43%) Medullary thyroid carcinoma is aggressive and presents early in life Therefore, infants having a parent with MEN 2B receive genetic screening; those carrying the RET mutation undergo a prophylactic total thyroidectomy by age 6 months
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