Frequency and phenotypic spectrum of spinocerebellar ataxia 27B and other genetic ataxias in a Spanish cohort of late-onset cerebellar ataxia.

BACKGROUND AND PURPOSE: Dominantly inherited GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene have recently been shown to cause spinocerebellar ataxia 27B (SCA27B). We aimed to study the frequency and phenotype of SCA27B in a cohort of patients with unsolved late-onset cerebellar ataxia (LOCA). We also assessed the frequency of SCA27B relative to other genetically defined LOCAs. METHODS: We recruited a consecutive series of 107 patients with LOCA, of whom 64 remained genetically undiagnosed. We screened these 64 patients for the FGF14 GAA repeat expansion. We next analysed the frequency of SCA27B relative to other genetically defined forms of LOCA in the cohort of 107 patients. RESULTS: Eighteen of 64 patients (28%) carried an FGF14 (GAA)≥250 expansion. The median (range) age at onset was 62.5 (39-72) years. The most common clinical features included gait ataxia (100%) and mild cerebellar dysarthria (67%). In addition, episodic symptoms and downbeat nystagmus were present in 39% (7/18) and 37% (6/16) of patients, respectively. SCA27B was the most common cause of LOCA in our cohort (17%, 18/107). Among patients with genetically defined LOCA, SCA27B was the main cause of pure ataxia, RFC1-related disease of ataxia with neuropathy, and SPG7 of ataxia with spasticity. CONCLUSION: We showed that SCA27B is the most common cause of LOCA in our cohort. Our results support the use of FGF14 GAA repeat expansion screening as a first-tier genetic test in patients with LOCA.

Levothyroxine absorption and difficult management of hypothyroid patients in the intensive care unit: two case reports and a literature review. / Interferências na absorção de levotiroxina e dificuldades no manuseio de pacientes com hipotireoidismo na unidade de terapia intensiva: relato de dois casos e revisão de literatura.

Levothyroxine absorption in hypothyroid patients can be influenced by several factors, particularly medications and concomitant food administration. This is especially evident in intensive care unit patients, where a continual enteral diet and the administration of multiple medications changes its absorption. Changes or adaptations in the hypothalamic-pituitary-thyroid axis, in conjunction with clinical abnormalities possibly related to under-treatment of hypothyroidism, render levothyroxine replacement therapy very challenging. Here, we report two intensive care hypothyroidism patients and their respective levothyroxine replacement management issues, focusing on a number of controversial issues, such as the optimal replacement dose, how fast the levothyroxine doses should be increased, triiodothyronine requirements, the interference of an enteral diet with absorption, and finally, the possible consequences of undertreated hypothyroidism and levothyroxine replacement monitoring useful clinical/laboratory parameters.

Interferências na absorção de levotiroxina e dificuldades no manuseio de pacientes com hipotireoidismo na unidade de terapia intensiva: relato de dois casos e revisão de literatura / Levothyroxine absorption and difficult management of hypothyroid patients in the intensive care unit: two case reports and a literature review

Inúmeros fatores podem influenciar a absorção da levotiroxina nos pacientes hipotireoideos, especialmente medicações e administração concomitante com alimentos. Nos pacientes internados em unidade de terapia intensiva, estes fatores são mais evidentes, principalmente em função da dieta enteral contínua além de diversas medicações que podem interferir na sua absorção. Alterações adaptativas no eixo hipotálamo-hipófise-tireóide e alterações clínicas comumente presentes em pacientes críticos que podem ter contribuição de um hipotiroidismo não tratado se associam tornando ainda mais difícil o manuseio da reposição de levotiroxina. Relatamos dois casos de pacientes com hipotiroidismo internados em unidade de terapia intensiva, com suas respectivas abordagens para reposição de levotiroxina, levantando questões controversas como: qual a dose ideal de reposição, velocidade no incremento das doses, necessidade de associação com triiodotironina, interferência da dieta enteral na absorção, e finalmente as possíveis conseqüências de um hipotiroidismo não tratado e as formas clínicas e laboratoriais para monitorizar as doses hormonais administradas.

Levothyroxine absorption in hypothyroid patients can be influenced by several factors, particularly medications and concomitant food administration. This is especially evident in intensive care unit patients, where a continual enteral diet and the administration of multiple medications changes its absorption. Changes or adaptations in the hypothalamic-pituitary-thyroid axis, in conjunction with clinical abnormalities possibly related to under-treatment of hypothyroidism, render levothyroxine replacement therapy very challenging. Here, we report two intensive care hypothyroidism patients and their respective levothyroxine replacement management issues, focusing on a number of controversial issues, such as the optimal replacement dose, how fast the levothyroxine doses should be increased, triiodothyronine requirements, the interference of an enteral diet with absorption, and finally, the possible consequences of undertreated hypothyroidism and levothyroxine replacement monitoring useful clinical/laboratory parameters.