Post by Max on Jun 13, 2005 16:21:36 GMT -5
Hoffman la Roche itself has found tinnitus and hearing impairment to be associated with (Ro)accutane exposure in human subjects [0].
One result from (Ro)accutane exposure in acne subjects may be lasting tinnitus, or hearing impairment. The thyroid receptor isoform beta2 (TRbeta2) was found to be inhibited by 50-70 % [1]. The TRbeta2 isoform also is highly expressed in the inner ear and is involved in the regulation of auditory function [2]. A decrease in amplitudes for both ears were found in 3 out of 33 acne-subjects (~10%) after three weeks of exposure. It is suggested that these subclinical changes may be due to an isotretinoin-induced synaptic malfunction or to a conduction defect in the auditory nerve fibers [3]. It remains to be answered what frequencies and degrees of severity that are reached when measured after 4 months of exposure in human acne-subjects.
Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system.
J Clin Invest. 1999 Aug;104(3):291-300.
Abel ED, Boers ME, Pazos-Moura C, Moura E, Kaulbach H, Zakaria M, Lowell B, Radovick S, Liberman MC, Wondisford F.
Thyroid Unit, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TR alpha and TR beta isoforms are products of 2 distinct genes, and the beta 1 and beta 2 isoforms are splice variants of the same gene. Whereas TR alpha 1 and TR beta 1 are widely expressed, expression of the TR beta 2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TR beta 2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TR beta 2 isoform. TR beta 2-null mice have preserved expression of the TR alpha and TR beta 1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TR beta-null mice, indicating the important role of TR beta 2 in the regulation of the hypothalamic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TR beta 2-null mice exhibit no evidence of hearing impairment, indicating that TR beta 1 and TR beta 2 subserve divergent roles in the regulation of auditory function.
PMID: 10430610 [PubMed - indexed for MEDLINE]
One result from (Ro)accutane exposure in acne subjects may be lasting tinnitus, or hearing impairment. The thyroid receptor isoform beta2 (TRbeta2) was found to be inhibited by 50-70 % [1]. The TRbeta2 isoform also is highly expressed in the inner ear and is involved in the regulation of auditory function [2]. A decrease in amplitudes for both ears were found in 3 out of 33 acne-subjects (~10%) after three weeks of exposure. It is suggested that these subclinical changes may be due to an isotretinoin-induced synaptic malfunction or to a conduction defect in the auditory nerve fibers [3]. It remains to be answered what frequencies and degrees of severity that are reached when measured after 4 months of exposure in human acne-subjects.
Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system.
J Clin Invest. 1999 Aug;104(3):291-300.
Abel ED, Boers ME, Pazos-Moura C, Moura E, Kaulbach H, Zakaria M, Lowell B, Radovick S, Liberman MC, Wondisford F.
Thyroid Unit, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TR alpha and TR beta isoforms are products of 2 distinct genes, and the beta 1 and beta 2 isoforms are splice variants of the same gene. Whereas TR alpha 1 and TR beta 1 are widely expressed, expression of the TR beta 2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TR beta 2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TR beta 2 isoform. TR beta 2-null mice have preserved expression of the TR alpha and TR beta 1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TR beta-null mice, indicating the important role of TR beta 2 in the regulation of the hypothalamic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TR beta 2-null mice exhibit no evidence of hearing impairment, indicating that TR beta 1 and TR beta 2 subserve divergent roles in the regulation of auditory function.
PMID: 10430610 [PubMed - indexed for MEDLINE]