ABSTRACT
Subclinical hypothyroidism or mild thyroid failure is a familiar problem, with a prevalence of 3-15% in a population without any known overt thyroid disorder. The prevalence increases with age and is relatively higher among females. Subclinical hypothyroidism is defined as serum thyroid stimulating hormone (TSH) levels above the upper limit of normal (4 mU/L) while the triiodothyronine (T3) and thyroxine (T4) enduring within the normal range. Additionally, there exists a log-linear relationship between TSH and circulating T3 and T4; hence, measurement of serum TSH becomes mandatory for diagnosing mild thyroid failure when free T3and T4 are lying within normal limits. Though, autoimmune thyroid disease is the most common cause for elevated TSH; thyroid functions can be afflicted by long-term consumption of drugs like lithium, amiodarone. The causal relationship between benzodiazepine class of drugs, particularly clonazepam and subclinical hypothyroidism has never been established clinically, yet there are some pre-clinical studies to claim the effect of benzodiazepine on thyroid functions; operating at various levels – hypothalamus, thyroid gland, peripheral cells and nuclear receptors. Henceforth, we would like to report a rare occurrence of subclinical hypothyroidism in an elderly female receiving clonazepam for her underlying psychiatric illness.
ABSTRACT
Background: Gap junctions (GJs) are clusters of channels that connect the interiors of adjoining neurons and mediate electrical/electrotonic coupling by transfer of ions and small molecules. Electrotonic coupling between principal neurons via GJs is increasingly recognized as one of the mechanisms in the pathogenesis of the abnormal neuronal synchrony that occurs during seizures. Carbenoxolone the succinyl ester of glycyrrhetinic acid obtained from liquorice has been shown to have the property of blocking gap junctional intercellular communication. The objectives were to study if carbenoxolone has in-vivo anticonvulsive activity in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure models and to probe the functional role of GJs in seizures. Methods: Carbenoxolone was tested for anticonvulsive effect in albino rats subjected to seizures by the PTZ and MES at three doses 100 m/kg, 200 m/kg, 300 m/kg. In the PTZ model parameters observed were seizure protection, seizure latency and seizure duration. In the MES model parameters observed were seizure protection and seizure duration. Results: The results showed that the carbenoxolone has anticonvulsant activity in both PTZ and MES induced seizures with better protection in the PTZ induced seizures. In the PTZ model carbenoxolone produced a statistically significant increase in seizure latency, decrease in seizure duration and seizure protection. In the MES model carbenoxolone produced a statistically significant decrease in seizure duration. Conclusions: Carbenoxolone has in-vivo anticonvulsive effect and could be useful in both petitmal (absence) seizures and grand mal (generalized tonic-clonic epilepsy) seizures. The protective effect of carbenoxolone could be due to blockade of GJ channels that mediate electro tonic coupling and thereby prevent the neural synchronization that is characteristic of seizures. The study also supports the view that GJs have a functional role in the electrophysiology of seizures and GJ blockers have potential as a new class of antiepileptic drugs.