Avaliação terapêutica e posológica da levotiroxina sódica em cães com hipotiroidismo primário adquirido

O hipotireoidismo primário adquirido é uma endocrinopatia frequentemente diagnosticada na espécie canina. A terapia consiste na suplementação oral com levotiroxina sódica (L-tiroxina), no entanto vários protocolos terapêuticos têm sido propostos pela literatura, com doses variando 11 a 44µg/kg uma a duas vezes ao dia, visto à grande variabilidade de absorção e meia-vida plasmática do fármaco. Foram estudados 30 cães com hipotiroidismo primário adquirido (13 machos e 17 fêmeas, idade média de 7,9±1,9 anos e peso médio de 19,1±12,6 kg) atendidos no Hospital Veterinário da Universidade Guarulhos (UnG) e no Serviço de Endocrinologia de duas clínicas particulares da cidade de São Paulo (2009-2011), com o objetivo de avaliar a posologia e a frequência de administração da L-tiroxina, mais frequentemente utilizada, capaz de garantir um controle terapêutico satisfatório, avaliado através dos sinais clínicos e do teste pós-tiroxina, além de correlacionar a dose de tiroxina empregada com o peso dos animais. A dose média de tiroxina utilizada em nossa casuística foi de 16,9±3,1µg/kg, sendo a frequência de administração a cada 12 horas em 50% dos casos. Para se investigar uma possível correlação entre o peso e a dosagem de tiroxina utilizada, uma vez que cães de pequeno porte apresentam maior taxa metabólica que cães de grande porte, os animais foram agrupados em grupo A, cães com peso <10 Kg (n=12/30; 7,7±2,1 kg) e grupo B, cães com peso >10 kg (n=18/30, 26,8±10,7 kg). A dose média de tiroxina empregada nos grupos A e B não apresentaram diferença estatística e foram, respectivamente, 16±3µg/kg e 17±3µg/kg. A frequência de administração foi 50% a cada 24 horas e 50% a cada 12 horas para ambos os grupos. Dessa forma, a dose de tiroxina não parece se correlacionar com o peso do animal, sendo imprevisível quem deverá receber dose e frequência máxima da medicação. O protocolo deve ser individualizado e o paciente devidamente monitorado.

Hypothyroidism in adult male rats alters posttranscriptional mechanisms of luteinizing hormone biosynthesis

BACKGROUND: Studies in men are not consistent regarding the effects of thyroid hormone on the production of gonadotropins. In hypothyroidism consequent to diverse causes, an increase or no change in serum luteinizing hormone (LH) have been reported. The attempt to explain the mechanisms involved in this pathology using rats as an experimental model also seems to repeat this divergence, since hypothyroidism has been shown to induce hypogonadotropic hypogonadism, a hypergonadotropic state, or not to affect the basal levels of LH. Notably, the promoter region of the gene encoding the Lh beta subunit and GnRH (gonadotropin-releasing factor) does not contain a thyroid responsive element. Therefore, we investigated the hypothesis that, in male rats, posttranscriptional mechanisms of LH synthesis are altered in hypothyroidism. We also attempted to determine if hypothyroidism directly affects testicular function in male rats. METHODS: Male Wistar rats, 60 days old, were thyroidectomized or sham-operated. After 20 days, they were decapitated, and the pituitaries were collected and analyzed for Lh mRNA, LH content, poly(A) tail length, and polysome profile. The testes were collected and analyzed for Lh receptor mRNA, LH receptor content, and histology using morphometric analyses. The testis, epididymis, seminal vesicle, and ventral prostate were weighed, and serum concentrations of LH, testosterone, thyrotropin (TSH), and triiodothyronine (T3) were measured. RESULTS: Hypothyroidism was associated, in the pituitary, with an increase in Lh mRNA expression, a reduction in Lh mRNA poly(A) tail length, a reduction in the number of LH transcripts associated with polysomes. Pituitary LH was decreased but serum LH was increased from 102 to 543 pg/mL. Despite this, serum testosterone concentrations were decreased from 1.8 to 0.25 ng/mL. A decreased germinative epithelium height of the testes and a reduced weight of androgen-responsive tissues were observed (ventral prostrate: 74 vs. 23 mg/100 g body weight [BW]; seminal vesicle undrained: 280 vs. 70 mg/100 g BW; and seminal vesicle drained: 190 vs. 60 mg/100 g BW). CONCLUSIONS: Hypothyroidism in adult male rats has dual effects on the pituitary testicular axis. It alters posttranscriptional mechanisms of LH synthesis and probably has a direct effect on testicular function. However, these data suggest the possibility that reduced LH bioactivity may account in part for impaired testicular function.

Effects of thyroid status on NEI concentration in specific brain areas related to reproduction during the estrous cycle

We previously showed that short-term hypo- and hyperthyroidism induce changes in neuropeptide glutamic-acid-isoleucine-amide (NEI) concentrations in discrete brain areas in male rats. To investigate the possible effects of hypo- and hyperthyroidism on NEI concentrations mainly in hypothalamic areas related to reproduction and behavior, female rats were sacrificed at different days of the estrous cycle. Circulating luteinizing hormone (LH), estradiol and progesterone concentrations were measured in control, hypothyroid (hypoT, treated with PTU during 7-9 days) and hyperthyroid (hyperT, l-T4 during 4-7 days) animals. Both treatments blunted the LH surge. Hypo- and hyperthyroidism increased estradiol concentrations during proestrus afternoon (P-PM), although hypoT rats showed lower values compared to control during proestrus morning (P-AM). Progesterone levels were higher in all groups at P-PM and in the hyperT during diestrus morning (D2). NEI concentrations were lower in hypoT rats during the estrous cycle except in estrus (E) in the peduncular part of the lateral hypothalamus (PLH). They were also reduced by both treatments in the perifornical part of the lateral hypothalamus (PeFLH) during P-PM. Hypothyroidism led to higher NEI concentrations during P-PM in the organum vasculosum of the lamina terminalis and anteroventral periventricular nucleus (OVLT+AVPV). The present results indicate that NEI concentration is regulated in a complex manner by hypo- and hyperthyroidism in the different areas studied, suggesting a correlation between NEI values and the variations of gonadal steroid levels during estrous cycle. These changes could be, in part, responsible for the alterations observed in the hypothalamic-pituitary-gonadal axis in these pathologies.