Anaesthesia for amiodarone-induced thyrotoxicosis: a case review

Amiodarone-induced thyrotoxicosis is a life-threatening problem that is very effectively managed by total thyroidectomy, although often many of these patients are considered "too unfit" for anaesthesia. The aim of this study was to review the safety of anaesthesia for total thyroidectomy in the acute management of amiodarone-induced thyrotoxicosis. Information was obtained retrospectively from a prospective endocrine surgical database and from hospital records. Data, including outcomes and morbidity, are presented from 12 patients who underwent anaesthesia for total thyroidectomy as an urgent procedure for amiodarone-induced thyrotoxicosis. Despite the fact that these patients had uncontrolled thyrotoxicosis and marked cardiac failure at the time of anaesthesia, no anaesthetic or surgical mortality was seen. We conclude that a challenging patient with amiodarone-induced thyrotoxicosis that has not responded to conservative measures may be considered for total thyroidectomy early in their management. Total thyroidectomy can be performed under general or local anaesthesia with apparent relative safety.     

Cardiac ischaemic stress: cardiomyocyte Ca²⁺, sex and sex steroids

1. Important sex differences exist in ischaemic heart disease. Oestrogen has been conventionally regarded as providing a cardioprotective benefit and testosterone frequently perceived to exert a deleterious effect. However, there is accumulating evidence that argues against this simple dichotomy, suggesting that the influence of oestrogen and testosterone conferring benefit or detriment may be context specific. 2. Cardiomyocyte calcium (Ca(2+)) loading is recognized to be a major factor in acute ischaemia-reperfusion pathology, promoting cell death, contractile dysfunction and arrhythmogenic activity. Ca(2+)/calmodulin-dependent kinase II (CaMKII) is a mediator of many of the cardiomyocyte Ca(2+)-related pathologies in ischaemia-reperfusion. Cardiomyocyte Ca(2+)-handling processes have been shown to be modulated by the actions of oestrogen and testosterone. A role for these sex steroids in influencing CaMKII activation is argued. 3. Although many experimental studies of oestrogen manipulation can identify a cardioprotective role for this sex steroid, there are also numerous reports that fail to demonstrate sex differences in postischaemic recovery. Experimental studies report that testosterone can be protective in ischaemia-reperfusion in males and females in some settings. 4. Further studies of sex steroid influence in the ischaemic heart will allow the development of therapeutic interventions that are specifically targeted for male and female hearts.     

Targeted GLUT-4 deficiency in the heart induces cardiomyocyte hypertrophy and impaired contractility linked with Ca and proton flux dysregulation

There is clinical evidence to suggest that impaired myocardial glucose uptake contributes to the pathogenesis of hypertrophic, insulin-resistant cardiomyopathy. The goal of this study was to determine whether cardiac deficiency of the insulin-sensitive glucose transporter, GLUT4, has deleterious effect on cardiomyocyte excitation-contraction coupling. Cre-Lox mouse models of cardiac GLUT4 knockdown (KD, 85% reduction) and knockout (KO, > 95% reduction), which exhibit similar systemic hyperinsulinemic and hyperglycemic states, were investigated. The Ca²⁺ current (I_Ca) and Na⁺-Ca²⁺ exchanger (NCX) fluxes, Na⁺-H⁺ exchanger (NHE) activity, and contractile performance of GLUT4-deficient myocytes was examined using whole-cell patch-clamp, epifluorescence, and imaging techniques. GLUT4-KO exhibited significant cardiac enlargement characterized by cardiomyocyte hypertrophy (40% increase in cell area) and fibrosis. GLUT4-KO myocyte contractility was significantly diminished, with reduced mean maximum shortening (5.0 ± 0.4% vs. 6.2 ± 0.6%, 5 Hz). Maximal rates of shortening and relaxation were also reduced (20-25%), and latency was delayed. In GLUT4-KO myocytes, the I_Ca density was decreased (− 2.80 ± 0.29 vs. − 5.30 ± 0.70 pA/pF), and mean I_NCX was significantly increased in both outward (by 60%) and inward (by 100%) directions. GLUT4-KO expression levels of SERCA2 and RyR2 were reduced by approximately 50%. NHE-mediated H⁺ flux in response to NH₄Cl acid loading was markedly elevated GLUT4-KO myocytes, associated with doubled expression of NHE1. These findings demonstrate that, independent of systemic endocrinological disturbance, cardiac GLUT4 deficiency per se provides a lesion sufficient to induce profound alterations in cardiomyocyte Ca²⁺ and pH homeostasis. Our investigation identifies the cardiac GLUT4 as a potential primary molecular therapeutic target in ameliorating the functional deficits associated with insulin-resistant cardiomyopathy.     

First parathyroid surgeon: Sir John Bland-Sutton and the parathyroids

Felix Mandl from Vienna has long been acclaimed as having carried out the first parathyroidectomy for primary hyperparathyroidism in 1925. He was not, however, the first surgeon to have seen the parathyroid glands, either at surgery or in the pathology laboratory. There is evidence that the first intentional removal of a parathyroid tumour was probably carried out at the Middlesex Hospital, London, UK, by Sir John Bland-Sutton at least a decade earlier. Indeed, Sir John Bland-Sutton appeared to have been very much aware of the parathyroid gland and the pathology associated with it for many years, even before this first parathyroid operation. He described a post-mortem specimen of a parathyroid tumour in 1886; he surgically removed a parathyroid cyst in 1909; and then carried out an intentional parathyroidectomy for a parathyroid tumour some time before 1917.