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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: bob zagorin who wrote (29610)	12/14/1999 1:48:00 AM
From: Henry Niman	Respond to of 32384

Look at the volume at the bottom of this page. LGND has traded 1100 shares today. Trades were at 14 1/2, 14 1/2, and 17. The side effects of Targretin (bexarotene) was published on April 8 in the New England Journal of Medicine, a VERY high profile journal. Legg Mason analyst said you should hold LGND at 6! Analyst is clueless and trying to wipe egg off face. Here's the NEJM abstract of April 8: The NEJM article on CTCL side effects associated with Targretin came out APRIL 8! For an analysts to say that such revelations on Dec 13 are new is absurd!: N Engl J Med 1999 Apr 8;340(14):1075-9 Central hypothyroidism associated with retinoid X receptor-selective ligands. Sherman SI, Gopal J, Haugen BR, Chiu AC, Whaley K, Nowlakha P, Duvic M Section of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. sisherma@mdanderson.org BACKGROUND: The occurrence of symptomatic central hypothyroidism (characterized by low serum thyrotropin and thyroxine concentrations) in a patient with cutaneous T-cell lymphoma during therapy with the retinoid X receptor-selective ligand bexarotene led us to hypothesize that such ligands could reversibly suppress thyrotropin production by a thyroid hormone-independent mechanism and thus cause central hypothyroidism. METHODS: We evaluated thyroid function in 27 patients with cutaneous T-cell lymphoma who were enrolled in trials of high-dose oral bexarotene at one institution. In addition, we evaluated the in vitro effect of triiodothyronine, 9-cis-retinoic acid, and the retinoid X receptor-selective ligand LGD346 on the activity of the thyrotropin beta-subunit gene promoter. RESULTS: The mean serum thyrotropin concentration declined from 2.2 mU per liter at base line to 0.05 mU per liter during treatment with bexarotene (P<0.001), and the mean serum free thyroxine concentration declined from 1.0 ng per deciliter (12.9 pmol per liter) at base line to 0.45 ng per deciliter (5.8 pmol per liter) (P<0.001)during treatment. The degree of suppression of thyrotropin secretion tended to be greater in patients treated with higher doses of bexarotene (>300 mg per square meter of body-surface area per day) and in those with a history of treatment with interferon alfa. Nineteen patients had symptoms or signs of hypothyroidism, particularly fatigue and cold intolerance. The symptoms improved after the initiation of thyroxine therapy, and all patients became euthyroid after treatment with bexarotene was stopped. In vitro, LGD346 suppressed the activity of the thyrotropin beta-subunit gene promoter in thyrotrophs by as much as 50 percent, an effect similar to that of triiodothyronine and 9-cis-retinoic acid. CONCLUSIONS: Hypothyroidism may develop in patients with cutaneous T-cell lymphoma who are treated with high-dose bexarotene, most likely because the retinoid X receptor-selective ligand suppresses thyrotropin secretion. PMID: 10194237, UI: 99192004