Jonathan Unger

Amiodarone and the thyroid: pharmacological, toxic and therapeutic effects

Amiodarone has been reported as an anti-anginal drug in 19h7 [ 11 and as an anti-arrhythmic drug in 1969 [2]. Thyroid side-effects (hypothyroidism and thyrotoxicosis) were suspected as early as in 1971 [3]. Jonckheer et al. reported in 1973 a series of patients with amiodarone-associated thyrotoxicosis presenting worsening angina and arrhythmia for which the patients were taking the drug [4]. In 1976. Burger et al. demonstrated the effects of arniodarone on the peripheral metabolism of thyroid hormones [5], which were shown in 1978 by Jonckheer et al. to result in a low T, syndrome in patients treated chronically with the drug [h]. In 1982. Lambert et al. showed that amiodarone changes the T, production rate (T, PR) by the thyroid [7]. In 1987. Van Reeth et al. took advagtage of the properties of amiodarone for the treatment of thyrotoxicosis [S]. This review deals with the relationship between arniodarone and thyroid hormone metabolism on the one hand, and the risk of dysthyroidism and the antithyroid properties of the drug on the other. Effects of iodine overload on the thyroid gland

Amiodarone-induced thyrotoxicosis suggestive of thyroid damage

Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1 ), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT.

Interference of Serum Tonicity with the Measurement of Red Cell Mean Corpuscular Volume

When red cell mean corpuscular volume (MCV) is determined by use of the Coulter counter, the blood sample is first diluted in a solution with fixed osmolality (Isoton). Therefore we studied the interference of blood osmolality with MCV measured by this method. In 14 patients with hyposmolality, the correction of osmolality was accompanied by an increase in MCV of 4.7% (p less than 0.001) and a decrease in mean corpuscular hemoglobin concentration (MCHC) of 4.8% (p less than 0.001). In 9 patients with hyperosmolality the decrease in MCV was of 5% (p less than 0.001) and the rise in MCHC of 4% (p less than 0.001) after osmolality correction. Before correction of hyposmolality, 1 patient had false microcytosis and 3 had masked macrocytosis. In the hypertonic group 3 patients has initially false macrocytosis. Red blood cells (RBC) from hypotonic patients probably shrink when they are acutely placed in the Isoton which is a hypertonic solution (330 mosm/kg H2O). Conversely RBC from patients with severe hyperosmolality swell in the same conditions. The patients osmolality must be considered to interpret the MCV measured by the Coulter counter correctly, as a 10-mosm/kg H2O change in serum osmolality is responsible for an artefactual change in MCV of 1 fl.

Rhabdomyolysis, Acute Renal Failure, Endocrine Alterations and Neurological Sequelae in a Case of Lithium Selfpoisoning

SummaryAfter ingestion of 15 g of lithium carbonate a 38-year-old man presented hyperthermia, a 4-week stuporous state, muscular and reflex hyperirritability, attacks of opisthotonos, nontraumatic rhabdomyolysis, acute renal failure, and a severe, prolonged but reversible primary testicular failure. Cerebral atrophy, dysmetria, dysarthria, ataxia and hyperreflexia were still present after one year.Thus, acute lithium overdosage may be lifethreatening, affect various organs, and cause persistent brain damage.

Relationship between Aldosterone and Sodium, Potassium, and Uric Acid Clearance in Cirrhosis with and without Ascites

We have suggested that cirrhotic patients with high uric acid clearances had an increased effective vascular volume. This hypothesis was tested by studying the relationship between the excretion of uric acid, sodium, potassium, and aldosterone in cirrhosis. In 29 consecutive cirrhotic patients, of whom 17 had ascites, and in a control group, the logarithm of urinary sodium and aldosterone excretion highly correlated in control (r = -0.79, p less than 0.001) and cirrhotic patients without (r = -0.72, p less than 0.01) and with (r = -0.80, p less than 0.001) ascites. The regression line significantly shifted to the left in the cirrhotic patients (p less than 0.001). The urinary ratio K/K + Na also correlated with urinary aldosterone in controls (r = +0.66, p less than 0.001) and in cirrhotic patients (r = +0.77, p less than 0.001); this regression line shifted to the right in cirrhosis patients (p less than 0.02). The fractional uric acid excretion significantly correlated with urinary aldosterone only in cirrhotic patients (r = -0.76, p less than 0.001). These data confirmed the existence of hypoaldosteronism in many cirrhotic patients and are consistent with tubular hypersensitivity to aldosterone and emphasize the major role of the effective vascular volume in the control of urid acid clearance in cirrhosis.

Bartter’s Syndrome with a Salt Reabsorption Defect in the Cortical Part of Henle’s Loop

The pathogenesis of Bartters syndrome remains uncertain. The prevailing theory postulates a defect in salt reabsorption, more frequently described in the thick ascending limb of Henles loop. The patient we studied presents a normal urinary concentration capacity associated with impaired dilution, a free water clearance at the lower end of normal (5.4 ml/min/100 ml glomerular filtrate), a decreased distal fractional chloride reabsorption (54%) when studied during hypotonic saline diuresis, and a normal decrease in free water clearance after furosemide (2.1 ml/min/100 ml glomerular filtrate), suggesting a defect in the cortical part of Henles loop. When studied during oral water diuresis, the fractional chloride reabsorption was normal (82%). This could be explained by a relative inability of the cortical diluting segment to reach maximal absorptive rates for NaCl. An inappropriate kaliuria related to an excessive delivery of salt load to the distal tubule is suggested by the correlation between urinary potassium and chloride excretion (r = 0.84; p less than 0.001). Aldosterone secretion participates also partially in the urinary potassium loss.

Modulation of thyroglobulin release by dog thyroid slices

Nonbutanol-extractable 131I (NBE131I) release by dog thyroid slices in vitro has been shown previously to be primarily thyroglobulin (Tg); it is stimulated by TSH. NBE131I (Tg) release has therefore been considered as an in vitro model of thyroglobulin secretion and was further characterized in this work. TSH-stimulated NBE131I (Tg) release, like TSH-stimulated BE131I (T4, T3 and iodide) release was reproduced by forskolin, an activator of adenylate cyclase. TSH-, (Bu)2cAMP- and forskolin-stimulated NBE131I (Tg) release was inhibited by 10(-5) M carbamylcholine, an effect relieved by 10(-5) M atropine, but not by 10(-4) M 1-methyl-3-isobutylxanthine. NBE131I (Tg) release was observed in the presence of 2 mM methimazole and 2 mM perchlorate. Cooling the slices to 20 degrees C or addition of 10(-5) M monensin completely blocked the formation of apical pseudopods and BE131I release but not NBE131I (Tg) release. Inhibition by 500 microM chloroquine of intralysosomal Tg hydrolysis and BE131I release did not enhance NBE131I (Tg) release. Cytochalasin B induced a concentration-dependent increase in basal and TSH-stimulated NBE131I (Tg) release at concentrations which depressed TSH-stimulated BE131I release. Removal of Ca2+ from the medium and slices by 10(-3) M or 10(-4) M EGTA increased NBE131I (Tg) release. In conclusion, in dog thyroid slices, TSH-stimulated NBE131I (Tg) release was mediated by cAMP and inhibited by 10(-5) M carbamylcholine at a step beyond cAMP. It was not neosynthesized Tg. It did not seem to require the formation of apical pseudopods or to result from the escape from lysosomes of undegraded thyroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of atrial fibrillation associated with hyperthyroidism by amiodarone and methimazole.

We treated a 78-year-old patient with hyperthyroidism and atrial fibrillation with amiodarone 1200 mg/day for 3 days and methimazole 60 mg/day. Sinus rhythm was restored within 3 days and serum levels of triiodothyroxine returned to normal within 4 days. A transient increase in serum rT3 concentrations was observed. Amiodarone associated with methimazole was useful in the management of atrial fibrillation and hyperthyroidism in our patient.

Psychosis, central hyperventilation and inappropriate secretion of antidiuretic hormone in systemic lupus erythematosus

A case of systemic lupus erythematosus with reversible psychosis and hyperventilation related to hyponatraemia secondary to a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is presented. The SIADH was treated successfully by oral urea for more than 8 months.

Association of Discoid Lupus and Malignant Lymphoma

A patient with an association of discoid lupus and lymphoma is described. A relation between these two diseases, as in systemic lupus erythematosus, is suggested, perhaps via a viral etiology.