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Hyperthyroidism The neurology of thyrotoxicosis has proved to be elusive Allusions to psychosis are frequent in the medical literature, and thyrotoxic patients have been observed with mental
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THE ACQUIRED METABOLIC DISORDERS OF THE NERVOUS SYSTEM
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cases have we noted a signi cant change in cerebral function When such a change has been observed, we have been especially impressed with drowsiness, inattentiveness, and apathy In two cases observed by our colleagues, the somnolence was so extreme that the patients could not stay awake long enough to be fed or examined They were in a state of hypothermic stupor but exhibited no other neurologic abnormality The extreme somnolence can be reversed within a few days by thyroid medication Hypothyroidism is associated with a number of distinctive myopathic disturbances, which are discussed in Chap 51 The ataxia and peripheral neuropathy that are sometimes observed in patients with myxedema were described earlier and in Chap 46 Cretinism and Neonatal Myxedema This form of severe hypothyroidism, occurring during intrauterine life (hypothyroidism in mother and fetus) or postnatally as a hereditary or acquired thyroid disease, is probably the most frequent and potentially preventable and correctable metabolic mental defect in the world A perspective on its relative frequency among neonatal metabolic disorders is given in Table 37-1 Although the condition is most common in goitrous regions where there is a lack of iodine, it may also be due to any of several genetically determined defects in thyroxin synthesis that have come to light in recent years (Vassart et al) In areas of endemic cretinism, additional factors may be operative, such as the widespread ingestion of cassava, which contains a toxic goitrogen that inhibits the uptake of iodine by the thyroid As a rule, the symptoms and signs of congenital thyroid de ciency are not recognizable at birth but become apparent only after a few weeks; more often the diagnosis is rst made between the sixth and twelfth months of life Physiologic jaundice tends to have been severe and prolonged (up to 3 months), and this, along with widening of the posterior fontanelle and mottling of the skin, should raise suspicion of the disease In general, two types of early life hypothyroidism are recognized sporadic and endemic The sporadic type occurs occasionally in developed countries (less than once in 4000 births) and is a consequence of a congenital metabolic or anatomic disorder of the thyroid gland At birth, the gland is either absent or represented by cysts, indicating a failure of development or a destructive lesion In the sporadic form, in the latter part of the rst year, stunting of growth and delay in psychomotor development become evident Untreated, the child is severely retarded but placid and good-natured; such children sleep contentedly for longer periods than normal children Sitting, standing, and walking are delayed Movements are slow, and if tendon re exes can be obtained, their relaxation time is clearly delayed The body temperature is low, and the extremities are cold and cyanotic Although the head is small, the fontanelles may not close until the sixth or seventh year, and there is delayed ossi cation This type of hypothyroidism is preventable by treatment with thyroid hormone Endemic cretinism is most common in developing countries, with an estimated incidence in some areas of 5 to 15 percent Stanley and DeLong and colleagues, on the basis of epidemiologic surveys in Ecuador, Zaire, and western China, have distinguished two forms of endemic cretinism neurologic and myxedematous The occurrence of the two different types is governed by the timing, duration, and severity of the iodine de ciency (Thilly et al) The neurologic form of endemic cretinism is characterized by varying degrees of deaf-mutism or lesser degrees of hearing loss, dysarthria, proximal limb and truncal rigid-spastic motor disorder involving mainly the lower extremities, and mental de ciency of a
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characteristic type In the most severely affected, there is also strabismus, kyphoscoliosis, underdevelopment of leg muscles, and frontal lobe release signs Bone age, head size, and height are normal and there are none of the coarse facial features of the myxedematous form In the so-called myxedematous form of endemic cretinism, short stature, microcephaly, coarse facial features, and retarded psychomotor development are the main features There is no deafness or spastic rigidity of the limbs In typical instances, the face is pale and puffy; the skin dry; the hair coarse, scanty, and dry; the eyelids thickened; the thickened lips parted by the enlarged tongue; the forehead low; and the base of the nose broad There are fat pads above the clavicles and in the axillae The abdomen is protuberant, often with an umbilical hernia, and the head is small a physical appearance that prompted William Boyd to remark: What was intended to be created in the image of God has turned out to be the pariah of nature, all for the want of a little thyroid DeLong and others attribute neurologic cretinism to a lack of available iodine in the mother and fetus during the second and third trimesters of pregnancy; neither mother nor fetus elaborate thyroxine The rst and part of the second trimester developmental period, which does not require iodine or thyroxine, passes normally and the general morphology of the brain is normal It is during the latter part of the second trimester, when the cochleas and the neuronal population of the cerebral cortex and basal ganglia are forming, that these structures suffer irreparable damage The effects of this midfetal hypothyroidism and iodine de ciency cannot be corrected by giving thyroid hormone at birth and thereafter It can be prevented only by providing iodine therapy to the mother before and during the rst trimester of pregnancy (Cao et al) The myxedematous form of cretinism is more likely to occur from lack of thyroid hormone in the late second and the third trimesters The mental defect ranges from apathy and absence of social interaction to an alert, cooperative state, but a backwardness in higher-order thinking and verbal facility is always evident Retentive memory and apperception are commensurate with overall intellectual competence as judged by the level of mental associations and capacity for abstract thought The status of the thyroid gland varies; among neurologic cretins, about half are goitrous or have palpable glands; in the rest, the glands are atrophied; practically all the myxedematous cretins are athyreotic Although typical examples of neurologic and myxedematous hypothyroidism are readily distinguished, both types may exist in the same endemic area, and the stigmata of both forms may be recognized in the same individual The QRS complex of the ECG is of low voltage; the EEG is slower than normal, with less alpha activity; the CSF contains an excess of protein (50 to 150 mg/dL); and the serum T3 and T4, protein-bound iodine, and radioactive iodine uptake are all subnormal Serum cholesterol is increased (300 to 600 mg/dL) At autopsy the brain of neurologic cretinism, though small, is normally formed, with all central and brainstem structures and cortical sulcation intact A reduction in number of nerve cells was described by Marinesco, especially in the fth cortical layer, but others have not con rmed this nding The use of Golgi and other silver techniques has shown decreased interneuronal distances (packing density is increased, as in the immature cortex) where there is a de ciency of neuropil The latter change is due to a poverty of dendritic branchings and crossings, and presumably there is a decrease of the synaptic surfaces of cells (Eayrs) Thyroid hormone appears to be essential, not for neuronal formation and migration but for dendritic-axonal development and organization There is substantial evidence that the administration of iodi-
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