Introduction Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a Natural Desiccated Thyroid (NDT) preparation such as Armour Thyroid® or ERFA Thyroid®. These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods The ThyPRO39 (thyroid symptomatology) and EQ-5D-5L-related QoL)/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results There were 28women/3men. The dose range of NDT was 60mg-180mg daily. Age range was 26-77 years with length of time since diagnosis with hypothyroidism ranging from 2-40 years. One person discontinued the NDT because of lack of response; 2 because of cardiac symptoms. EQ-5D-5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241-0.542), t=6.82, p<0.001. EQ-VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95%CI 25.2-50.2), t=-4.9, p<0.001. ThyPRO scores showed consistent fall across all domains with the composite QoL-impact Score improving from 68.3 (95%CI 60.9-75.7) to 25.2 (95%CI 18.7-31.7), a difference of 43.1 (95%CI 33. -53.2) (t=5.6, p<0.001). Conclusion Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism, suggesting the need for further evaluation of NDT in this context.

A document by Emma Magavern. Click on the document to view its contents.

Background and Purpose: Resurgence in the use of chloroquine as a putative treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity. Experimental Approach: In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine, alone, or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits. Randomised, controlled interventional studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during, and (iii) after chloroquine; and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats, and (vi) co-administered with adrenaline. Key Results: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between interventions and control. Diazepam increased heart rate in study (iv) and, as with clonazepam, also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia. Conclusion and Implications: Neither diazepam, nor other ligands for benzodiazepine binding sites, protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity.