Thyroid Hormone Deficiency Before the Onset of Hearing Causes Irreversible Damage to Peripheral and Central Auditory Systems

Abstract

Thyroid hormone deficiency before the onset of hearing causes irreversible damage to peripheral and central auditory systems. J. Neurophysiol. 83: 3101-3112, 2000. Both a genetic or acquired neonatal thyroid hormone (TH) deficiency may result in a profound mental disability that is often accompanied by deafness. The existence of various TH-sensitive periods during inner ear development and general success of delayed, corrective TH treatment was investigated by treating pregnant and lactating rats with the goitrogen methimazole (MMI). We observed that for the establishment of normal hearing ability, maternal TH, before fetal thyroid gland function on estrus days 17-18, is obviously not required. Within a crucial time between the onset of fetal thyroid gland function and the onset of hearing at postnatal day 12 (P12), any postponement in the rise of TH-plasma levels, as can be brought about by treating lactating mothers with MMI, leads to permanent hearing defects of the adult offspring. The severity of hearing defects that were measured in 3-to 9-mo-old offspring could be increased with each additional day of TH deficiency during this critical period. Unexpectedly, the active cochlear process, assayed by distortion product otoacoustic emissions (DPOAE) measurements, and speed of auditory brain stem responses, which both until now were not thought to be controlled by TH, proved to be TH-dependent processes that were damaged by a delay of TH supply within this critical time. In contrast, no significant differences in the gross morphology and innervation of the organ of Corti or myelin gene expression in the auditory system, detected as myelin basic protein (MBP) and proteolipid protein (PLP) mRNA using Northern blot approach, were observed when TH supply was delayed for few days. These classical TH-dependent processes, however, were damaged when TH supply was delayed for several weeks. These surprising results may suggest the existence of different TH-dependent processes in the auditory system: those that respond to corrective TH supply (e.g., innervation and morphogenesis of the organ of Corti) and those that do not, but require T3 activity during a very tight time window (e.g., active cochlear process, central processes).

Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin

“…The antithyroid drug (1-methyl-2-mercaptoimidazole, 0.02%), described to safely suppress plasma TH levels in both animals and humans (9,10), was administered in the drinking water of dams before estrus day 17 after conception. This administration ensures that TH levels were suppressed to Ͻ0.5 g͞dl L-thyroxine (T4) and Ͻ15 ng͞dl triiodothyronine (T3) from the onset of fetal thyroid gland function onward (11,12), which in rats takes place on estrus day 17 or 18. The treatment was continued after birth until the animal was killed.…”

“…The treatment was continued after birth until the animal was killed. The control of hypothyroidism was measured after T4 or T3 determination in postnatal pups as described (11). Hypothyroidism was counteracted after s.c. injection of the animals with 0.3 g͞g body weight T4 (Sigma) at indicated ages.…”

“…Cochleae of postnatal untreated (control) and methylmercaptoimidazole-treated (hypothyroid) animals were isolated and dissected as described (12). Cochleae were fixed, decalcified, and cryosectioned as described (11). For Northern blot, tissues were frozen immediately in liquid nitrogen and stored at Ϫ70°C before use.…”

Resting Potential and Submembrane Calcium Concentration of Inner Hair Cells in the Isolated Mouse Cochlea Are Set by KCNQ-Type Potassium Channels

“…Cochleae of mice and rats (between 2 weeks and 3 months old) were isolated, dissected, and fixed as described previously (Knipper et al, 2000). Cochleae were decalcified after fixation for 1 min to 1 hr in Rapid Bone Decalcifier (Eurobio, Fisher Scientific, Nidderau, Germany).…”

Alterações na audiometria de tronco encefálico em mulheres adultas com hipotireoidismo subclínico

“…2 Atualmente, estima-se que 1 a 1,5 bilhão de pessoas em todo o planeta corram um risco potencial de sofrer de desordens decorrentes de deficiência de iodo, incluindo já cerca de 600 milhões de portadores de bócio. 3 Em boa parte dos trabalhos populacionais, a prevalência da forma clínica da doença em adultos fica em torno de 1% a 2%, enquanto que a forma subclínica atinge 5% a 10%. As mulheres são marcadamente mais afetadas que os homens, numa proporção de 4:1, respectivamente, e ocorre aumento da incidência com a progressão da faixa etária, podendo chegar a 15% para o hipotireoidismo subclínico em mulheres com mais de 60 anos de idade [4][5][6] .…”