Myasthenia is discussed fully in Chap. 46. Here only a few remarks are made on its special relationship to thyrotoxicosis. Myasthenia gravis in its typical autoimmune, anticholinesterase-responsive form may accompany hyperthyroidism or rarely, hypothyroidism, which are also autoimmune in nature. Approximately 5 percent of patients with myasthenia have hyperthyroidism and the frequency of myasthenia gravis in patients, while low, is 20 to 30 times higher in hyperthyroidism than in the general population. Either condition may appear first, or they may coincide. The weakness and atrophy of chronic thyrotoxic myopathy may be added to that of the myasthenia without appearing to affect the requirement for or response to anticholinesterase medications. By contrast, hypothyroidism, even of mild degree, seems to aggravate the weakness of myasthenia gravis, greatly increasing the need for pyridostigmine and at times inducing a myasthenic crisis. In these cases, thyroxine is beneficial and, with respect to myasthenia, restores the patient to the status that existed before the onset of thyroid insufficiency. The myasthenia should probably be regarded as an autoimmune disease independent of the thyroid disease and each must be treated separately.
Abnormalities of skeletal muscle consisting of diffuse myalgia and increased volume, stiffness, and slowness of contraction and of relaxation are common manifestations of hypothyroidism, whether in the form of myxedema or cretinism. These changes probably account for the relatively large tongue and dysarthria that one observes in myxedema. Weakness, however, is not a prominent feature. The presence of action myospasm and myokymia (both of which are rare) and of percussion myoedema and slowness of both the contraction and relaxation phases of tendon reflexes assists the examiner in making a bedside diagnosis. The administration of thyroxine corrects the muscle disturbance.
Cretinism in association with these muscle abnormalities is known as the Kocher-Debré-Semelaigne syndrome, and myxedema in childhood or adult life with muscle hypertrophy is the Hoffmann syndrome; the latter simulates hypertrophia musculorum vera and myotonia congenita. In neither cretinism nor myxedema, however, is there evidence of true myotonia, either by clinical testing or by EMG, although muscle action potentials are myopathic and often show bizarre high-frequency discharges. Serum transaminase values are normal but CK levels are usually elevated, often markedly so. Muscle biopsies have disclosed only the presence of large fibers or an increase in the proportion of small fibers (either type 1 or 2) and slight distention of the sarcoplasmic reticulum and subsarcolemmal glycogen (probably all a result of disuse atrophy).
Pathogenesis of the Thyroid Myopathies
How thyroid hormone affects the muscle fiber is still a matter of conjecture. Clinical data indicate that thyroxine influences the contractile process in some manner but does not interfere with the transmission of impulses in the peripheral nerve across the myoneural junction or along the sarcolemma. In hyperthyroidism an undefined functional disorder enhances the speed of the contractile process and reduces its duration, the net effect being fatigability, weakness, and loss of endurance of muscle action. In hypothyroidism, muscle contraction is slowed, as is relaxation, and its duration is prolonged.
The speed of the contractile process is related to the quantity of myosin adenosine triphosphatase (ATPase), which is increased in hyperthyroid muscle and decreased in hypothyroid muscle. The speed of relaxation depends on the rate of release and reaccumulation of calcium in the endoplasmic reticulum. This is slowed in hypothyroidism and increased in hyperthyroidism (Ianuzzo et al). The myopathic effects of hypothyroidism need to be distinguished from those of a neuropathy, which may rarely complicate hypothyroidism (see Chap. 43).