methimazole and Hearing-Loss

Topics: Antithyroid Agents; Child, Preschool; Choanal Atresia; Female; Graves Disease; Hearing Loss; Humans; Male; Methimazole; Pregnancy; Pregnancy Complications

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency-modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development.

Topics: Acoustic Stimulation; Acoustics; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Antithyroid Agents; Body Weight; Disease Models, Animal; Dose-Response Relationship, Drug; Hearing Loss; Hypothyroidism; Methimazole; Rats; Rats, Wistar; Reflex, Startle; Thyroid Hormones; Vocalization, Animal

A 51-year-old woman with a personal history of vitiligo, normal thyroid hormone studies, a simple hysterectomy for multiple uterine myomas at age 35 years, and childhood adenotonsillectomy was seen for progressive hearing loss. She reported mild asthenia, cold intolerance, mild dysphagia with frequent choking while eating and drinking, and a progressive increase in inspiratory effort, especially in the supine position. Her partner described a progressively worsening history of snoring and witnessed apneic episodes, mostly in the supine position. Mild to moderate daytime sleepiness was also present.

Topics: Antithyroid Agents; Female; Goiter, Nodular; Hearing Loss; Humans; Hyperthyroidism; Lingual Thyroid; Magnetic Resonance Imaging; Methimazole; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Sleep Apnea, Obstructive; Sodium Pertechnetate Tc 99m; Supine Position; Tomography, X-Ray Computed

We report on a 3-year-old boy with bilateral choanal atresia, hypoplastic nipples, and developmental delay who had been exposed to carbimazole in utero because of maternal Graves disease. His combination of abnormalities and facial appearance strongly resembles that of a previously reported child exposed to methimazole (which is the active metabolite of carbimazole) in utero. We suggest that this represents a rare but distinct syndrome of methimazole teratogenicity, probably related to first-trimester exposure. Recognition of such teratogenic effects is clearly important for genetic counselling and for management of subsequent pregnancies.

Topics: Abnormalities, Multiple; Antithyroid Agents; Child, Preschool; Choanal Atresia; Chromosomes, Human, Pair 22; Face; Female; Graves Disease; Hearing Loss; Humans; In Situ Hybridization, Fluorescence; Male; Methimazole; Muscle Hypotonia; Nipples; Pregnancy; Pregnancy Complications; Teratogens