INTRODUCTION

Hypothyroidism is a common medical condition in the general population. Common systemic manifestations include fatigue, constipation, cold intolerance, weight gain, hair loss, dry skin, and hoarseness. A variety of central and peripheral nervous system manifestations are common in patients with hypothyroidism (table 1). In many cases, the neurologic manifestations occur in conjunction with the systemic features of the disease and may be noted only incidentally. However, symptoms and signs of neurologic dysfunction may be the presenting feature in some patients and can contribute significant disability. Most of these complications are partially or fully responsive to thyroid replacement.

This topic reviews the common neurologic manifestations of hypothyroidism. Other clinical manifestations of hypothyroidism are discussed separately. (See "Clinical manifestations of hypothyroidism".)

PERSISTENT AFFECTS OF CONGENITAL HYPOTHYROIDISM

Cretinism refers to the sequelae of hypothyroidism in the development of the fetus and/or young infant. Although the effects of postnatal hypothyroidism can be ameliorated by prompt treatment, the sequelae of gestational hypothyroidism, particularly in the first trimester, persist throughout life. A common cause of congenital hypothyroidism is maternal and infant iodine deficiency, which is still endemic in some parts of Europe and elsewhere in the world.

Neurologic sequelae include:

• Mental retardation. The severity of cognitive impairments is associated with both the degree and duration of thyroid (or iodine) deficiency in utero and early life [1]. Severe deficiency in the first trimester of pregnancy in particular is associated with severe irreversible intellectual as well as motor impairment [2,3].
  
  Even children exposed to mild degrees of iodine deficiency in gestation and those with postnatal congenital hypothyroidism that is promptly recognized at birth, are likely to have mild, often subclinical, neuropsychiatric deficits when compared with siblings and other control groups [4]. Studies suggest that in postnatal hypothyroidism, earlier administration of higher-dose thyroxine treatment is associated with less severe deficits [5]. (See "Treatment and prognosis of congenital hypothyroidism".)
• Impaired motor development. Severe gestational and postnatal hypothyroidism are associated with dysfunction of pyramidal and extrapyramidal motor systems. Typical deficits include rigidity and spasticity of the trunk and proximal extremities, with relative sparing of the distal arms and legs [6]. Neuroimaging studies have revealed calcification in the basal ganglia and subcortical areas on computed tomography (CT), as well as magnetic resonance imaging (MRI) signal abnormalities in the globus pallidus and substantia nigra [6,7].
  
  Up to 40 percent of children and adolescents with congenital hypothyroidism have been shown to demonstrate mild findings of cerebellar dysfunction, such as intention tremor, difficulty with tandem gait, clumsy running, fine motor dysfunction, and unsteady stance [8,9]. The findings were more prominent in those diagnosed with hypothyroidism during the first few months of life compared with those diagnosed after the first year of life. A delay to treatment also influences the severity of findings in these children [10]. Animal studies have shown that hypothyroidism interferes with cerebellar development [11,12].
• Other deficits can include strabismus and sensorineural hearing loss.