Hyperthyroidism

 HYPERTHYROIDISM

Pathogenesis and Pathophysiology

Thyroid hormones affect mitochondrial oxidative capacity, protein synthesis and degradation, tissue sensitivity to catecholamines, muscle fiber differentiation, and capillary growth. Excess thyroid hormone produces accelerated muscle protein catabolism and enhanced lysosomal protease activity, and interferes with the anabolic effects of insulin on muscle. Despite this understanding, the exact pathophysiology of thyrotoxic myopathy remains unknown. CNS observations include elevated rates of cerebral circulation, faster posterior dominant rhythms, alterations in the sensitivity of some brain enzymes and neurotransmitter systems, and altered metabolic responses. At present, the specific pathophysiological processes causing these manifestations remain unknown. It has been proposed that alterations in central and peripheral beta-adrenergic tone may be responsible for hyperthyroid-related tremor and chorea, and that brisk tendon reflexes may reflect faster muscle contraction and relaxation times.

Epidemiology and Risk Factors

Hyperthyroidism is more common in women than in men (10:1 ratio) and often shows a strong familial predisposition. During pregnancy, hyperthyroidism occurs more commonly than hypothyroidism, with an incidence ranging from 0.05 to 0.2 percent, most commonly related to Graves' disease, acute (i.e., subacute) thyroiditis, toxic nodular goiter, and toxic adenoma. The incidence of low-birth-weight infants is significantly increased, and neonatal mortality is slightly increased.

Clinical Features and Associated Disorders

The general clinical features of thyrotoxicosis:
Subjective - Impaired concentration and memory, emotional lability, nervousness, irritability, palpitations, heat intolerance, increased sweating and appetite, weight loss, frequent defecation, menstrual abnormalities, insomnia, headaches;
Objective - Impaired attention span and memory, hypervigilance, systolic flow murmurs, skin changes (warm, moist, smooth), EKG changes (sinus tachycardia, atrial fibrillation), psychiatric problems (depression, mania, bipolar disorder, manic psychosis), chorea, thyrotoxic penodic paralysis, thyroid storm, ocular features.

Neuropsychiatric signs include impaired attention, concentration, and memory, as well as emotional lability, nervousness, hypervigilance, lethargy, depression (i.e., apathetic hyperthyroidism), mania, psychosis, insomnia, and agitated delirium. Apathetic hyperthyroidism most frequently occurs in the elderly, lacks the usual hyperadrenergic features, and may easily be confused with depression or dementia.

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