ABSTRACT
IMPORTANCE: In the last 3 years, we have witnessed the publication of multiple but conflicting guidelines on the management of hypothyroidism during pregnancy. Hypothyroidism is one of the most common endocrinopathies in reproductive-age and pregnant women. Given the prevalence of thyroid disease, it is highly likely that obstetricians will encounter and provide care for pregnant women with thyroid disease. Therefore, a review of current guidelines and management options is clinically relevant. OBJECTIVES: Our goals are to review the changes in thyroid function during pregnancy, the options for testing for thyroid disease, the different categories of thyroid dysfunction and surveillance strategies among subspecialty societies, and the obstetric hazards associated with thyroid dysfunction and review the evidence for benefit of treatment options for thyroid disease. EVIDENCE ACQUISITION: We reviewed key subspecialty guidelines, as well as current and ongoing studies focused on the treatment of hypothyroidism during pregnancy. RESULTS: There are significant differences in the identification and management of thyroid disease during pregnancy among subspecialists. We present our recommendations based on the available evidence. RELEVANCE: Evidence exists that obstetricians struggle with the diagnosis and treatment of hypothyroidism. According to recent surveys, the management of hypothyroidism during pregnancy is the number 1 endocrine topic of interest for obstetricians. A synopsis of recently published subspecialty guidelines is timely. CONCLUSIONS: Recent, evidence-based findings indicate that obstetricians should consider modifying their approach to the identification and treatment of thyroid disease during pregnancy.
Subject(s)
Hypothyroidism/diagnosis , Hypothyroidism/drug therapy , Practice Guidelines as Topic , Pregnancy Complications/diagnosis , Pregnancy Complications/drug therapy , Asymptomatic Diseases/therapy , Autoantibodies/blood , Female , Humans , Hypothyroidism/immunology , Immunoglobulins, Thyroid-Stimulating/blood , Iodine/deficiency , Pregnancy , Pregnancy Complications/immunology , Pregnancy Trimesters , Thyroid Gland/physiology , Thyrotropin/blood , Thyroxine/blood , Thyroxine/therapeutic useABSTRACT
A caspase-3-activated DNase produces internucleosomal DNA cleavage (DNA laddering). We determined whether caspase-3 is activated by lithium-pilocarpine-induced status epilepticus in six brain regions with necrosis-induced DNA laddering. The thymuses of adult rats given methamphetamine or normal saline were used as controls for apoptosis. Some 6-8 h after methamphetamine treatment, thymocytes showed apoptosis by electron-microscopic examination, positive terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), DNA laddering, cleavage of caspase-3 into its active p17 subunit, active caspase-3 immunoreactivity, and a 25-fold increase in caspase-3-like activity. Six hours after SE, necrotic neurons by electron-microscopic examination in hippocampus, amygdala and piriform, entorhinal and frontal cortices showed no TUNEL and no DNA laddering. Twenty-four hours after seizures, most necrotic neurons were negative for TUNEL, some were positive, but all regions showed DNA laddering. However, 6 and 24 h after seizures, active caspase-3 immunoreactivity was negative, caspase-3-like activity did not increase, and western blot analysis failed to show the p17 subunit. In addition, 24 h after seizures,microdialytic perfusion of carbobenzoxy-valyl-alanyl-aspartyl (O-methylester) fluoromethylketone was not neuroprotective. Thus, caspase-3 is not activated in brain regions with seizure-induced neuronal necrosis with DNA laddering. Either caspase-activated DNase is activated by another enzyme, or a caspase-independent DNase is responsible for the DNA cleavage.
