This disorder, first noted by Graves and Basedow in the early nineteenth century, is characterized by progressive weakness and wasting of the skeletal musculature, occurring in conjunction with overt or covert (“masked”) hyperthyroidism. The thyroid disease is usually chronic and the goiter is usually of the nodular rather than the diffuse type. Exophthalmos and other classic signs of hyperthyroidism are often present but need not be. This complication of hyperthyroidism is most frequent in middle age, and men are more susceptible than women. Some degree of myopathy has been found when sought in more than 50 percent of thyrotoxic patients, although the manifestations may be subtle. The onset is insidious, and the weakness progresses over weeks and months. The muscular disorder as noted is most often mild in degree, but it may be so severe as to suggest progressive spinal muscular atrophy (motor system disease). Muscles of the pelvic girdle and thighs are weakened more than others (Basedow paraplegia), although all are affected to some extent, even the bulbar muscles and, albeit rarely, the ocular ones. However, the shoulder and hand muscles show the most conspicuous atrophy (not an obligatory feature). Tremor and twitching during contraction may occur, but we have not seen fasciculations. The tendon reflexes are of average briskness, possibly more lively than normal. Both the contraction and relaxation phases of the tendon reflexes are shortened, but usually this cannot be detected by the clinician.
Serum concentrations of muscle enzymes are not increased and may be reduced. The EMG is typically normal, although the action potentials may be abnormally brief or polyphasic. Biopsies of muscle, except for slight atrophy of both types 1 and 2 fibers and an occasional degenerating fiber, have been normal. Muscle power and bulk are gradually restored when thyroid hormone levels are reduced to normal levels.
Exophthalmic Ophthalmoplegia (Graves Ophthalmopathy) (See discussion in Chap. 13)
This refers to the cooccurrence of weakness of the ocular muscles and exophthalmos in patients with Graves disease (pupillary and ciliary muscles are always spared). The exophthalmos varies in degree, sometimes being absent at an early stage of the disease, and it is not in itself responsible for the muscle weakness. Often there is some degree of orbital pain. Both the exophthalmos and the weakness of the extraocular muscles may precede the signs of hyperthyroidism, be associated with the other classic features of hyperthyroidism (tachycardia, weight loss, tremor), or may follow effective treatment of the disorder.
The eye signs, both ocular paresis and exophthalmos, become apparent over days or weeks and may occasionally be unilateral, especially at the onset. Any of the external eye muscles may be infiltrated, usually one more than others, accounting for strabismus and diplopia; the inferior and medial recti are the most frequently affected, but upward movements are usually limited as well. The typical but not invariable sign of lid retraction imparts a staring appearance. Subtle exophthalmos can be appreciated by standing above and behind the seated patient and observing the relative positions of the lids and the eyelashes. Conjunctival edema and vascular engorgement over the insertions of the medial and lateral rectus muscles can be appreciated by inspecting and palpating the globe in its extreme lateral positions. These swollen muscles are easily visible on orbital ultrasonography, CT, and MRI. The differential diagnosis of this imaging appearance is from orbital pseudotumor, a usually painful condition, which is discussed in Chap. 13.