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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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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)

The per-unit impedances of Motor 2 are specified to the motor s own base The impedances converted to the specified base are:

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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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

Past history of varicosities, thrombophlebitis, or postphlebitic syndrome Irregular ulceration, often on the medial aspect of the lower legs above the malleolus Edema of the legs, varicosities, hyperpigmentation, and red and scaly areas (stasis dermatitis) and scars from old ulcers support the diagnosis

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Institution of compression therapy is begun after cleaning of the ulcer with saline or cleansers such as SafClens A curette or small scissors can be used to remove the yellow fibrin eschar; local anesthesia may be used if the areas are very tender The ulcer is treated with metronidazole gel to reduce bacterial growth and odor Any red dermatitic skin is treated with a medium- to high-potency corticosteroid ointment The ulcer is then covered with an occlusive hydroactive dressing (DuoDerm, Hydrasorb or Cutinova) or a polyurethane foam (Allevyn) followed by an Unna zinc paste boot This is changed weekly The ulcer

Patients at risk may have a history of venous insufficiency, either with obvious varicosities or with a past history of thrombophlebitis, or with immobility of the calf muscle group (paraplegics, etc) Red, pruritic

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attributable to metabolic substances including hemosiderin (iron) in purpuric processes; or to homogentisic acid in ochronosis; bile pigments; and carotenes

(10-8)

should begin to heal within weeks, and healing should be complete within 4 6 months If the patient is diabetic, becaplermin (Regranex) may be applied to those ulcers that are not becoming smaller or developing a granulating base Some ulcerations require grafting Full- or split-thickness grafts often do not take, and pinch grafts (small shaves of skin laid onto the bed) may be more effective Cultured epidermal cell grafts may accelerate wound healing, but they are very expensive They should be considered in refractory ulcers, especially those that have not healed after a year or more of conservative therapy

First, determine whether the disorder is hyperpigmentation or hypopigmentation, ie, an increase or decrease in normal skin colors Each may be considered to be primary or to be secondary to other disorders

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