GRAVES : DEVELOPMENT OF THE CLINICAL PICTURE AND THE COURSE OF THE DISEASE

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Graves’ Disease and the Manifestations of Thyrotoxicosis

DeGroot LJ.

ncbi.nlm.nih.gov/books/NBK2...

DEVELOPMENT OF THE CLINICAL PICTURE AND THE COURSE OF THE DISEASE

Graves' disease displays an array of possible clinical patterns extending from that of goiter and thyrotoxicosis, but without ophthalmopathy, to that of ophthalmopathy without goiter or thyrotoxicosis.

In classic exophthalmic goiter, or Graves' disease, the most common onset is the simultaneous and gradual development, over a period of weeks or months, of the symptoms of thyrotoxicosis, enlargement of the thyroid, and prominence or related abnormality of the eyes (Figure 10-4). It is quite possible for classic Graves' disease to develop in a patient with preceding (probably unrelated) nontoxic goiter. This is common in a goitrous country. Often the onset of symptoms is so gradual that it is difficult or impossible for the patient or physician to fix its date. The more abrupt onset may sometimes be sufficiently rapid to justify the term fulminating. The picture of classic full- blown exophthalmic goiter has appeared in a person apparently previously well in as short a period as two to five days. Rare patients have first developed hypothyroidism and later thyrotoxicosis [54], probably because the initial development of TBAb is followed by some natural immune modulation and development of stimulatory antibodies. Continuous significantly elevated titers of anti-TSH-R antibodies in the months after diagnosis are positively correlated with serious ophthalmopathy (55).

In many patients, the symptoms of Graves' disease are first noted after some emotional trauma. These associations are certainly of importance in understanding the patient's backgound, but, as noted above, whether or not they bear a causal relationship to the development of Graves' disease remains conjectural.

As noted in Chapter 14,Graves' disease is frequently partially or totally suppressed during pregnancy, and initial or recurrent manifestations can occur in the postpartum period. (Figure 10-10) Sometimes the "painless thyroiditis" characteristic of this period co-exists and masks the development of Graves' disease .

Weight reduction, as mentioned above, has also constituted an activating episode in Graves' disease.

At present, the natural history of the thyrotoxic process is usually altered by definitive therapy. Before the general availability of good treatment, hyperthyroidism tended to progress through periods of exacerbation and remission. In perhaps a quarter of the patients, especially those with a mild form of the disease, the process was self-limited to one year or more, as the patients returned spontaneously to a euthyroid state.

M.S., 27-Year-Old-Man: Thyrotoxicosis with Spontaneous Remission

This young physician developed tachycardia, hyperkinesis, decreased heat tolerance, slight tremor, and weight loss over three or four months. On examination, blood pressure (BP) was 150/50, pulse rate 86, and the skin was sweaty. There was a fine tremor. The eyes were entirely normal. There was a grade 1 precordial systolic murmur. The thyroid was about twice the normal size, diffusely enlarged, and firm. There were several cervical lymph nodes bilaterally. PBI was 11(nl 4--8ug/dl), and the rT3U level was elevated. RAIU was 57% and BMR-10. All tests were repeated once, and the results all remained as indicated.

The patient was given 100 mg PTU three times daily and was maintained on this program for 18 months. During this time, the T4 level was maintained in the range of 7.3 ug/dl and the FTI in the range of 6 (nl 4-10); the white cell count remained normal. The TGHA titer was 1/320, and there was a borderline positive TSAb bioassay response. During the course of therapy, the 20-minute technetium uptake test was repeatedly measured while the patient received both antithyroid drugs and suppressive doses of T3; suppressibility of the thyroid gradually fell to the normal range. Eighteen months after the initiation of therapy, the patient developed an acute gastroenteritis and was briefly hospitalized. At this time, because of the possible association of PTU with gastric irritation, the medication was discontinued.

He subsequently remained well for three months, but then developed symptoms of mild hyperthyroidism. The thyroid was again found to be two to three times the normal size, the T4 level to be 10.3 µg/dl, and the FTI to be 11.9. Since the symptoms were mild, it was elected to observe events without therapy for a period. Initially, the symptoms, signs, and laboratory test results remained abnormal, but over several months the mild tachycardia, increased sweating, and increased nervousness gradually dissipated. Six months later, the T4 level was 6.7 µg/dl and the FTI 8. The TSAb bioassay result remained positive. No further treatment was given, and the patient has remained entirely well with a moderate thyroid enlargement, normal thyroid function test results, and no symptoms over the subsequent 30 years.

In one of the few documented reports of untreated thyrotoxicosis, White [270] found that of 12 patients, 7 died in an average of three and a half years and the remainder lived on without therapy. From a large series, Sattler estimated that in the past mortality was up to 11% [271]. Fortunately, death due to hyperthyroidism is now rare, but we are aware of two patients who died of severe undiagnosed and untreated thyrotoxicosis in Chicago within the past few years (259). Deaths most frequently are attributed to cardiovascular complications such as myocardial infarction, arrhythmia, or heart failure, or infections secondary to debility. Some patients become spontaneously hypothyroid, and in fact most individuals apparently cured of Graves' thyrotoxicosis demonstrate evidence of hypothyroidism decades later. Coincident autoimmune thyroiditis presumably plays a role in such thyroid atrophy. Since in some patients treatment of thyrotoxicosis is associated with the spontaneous reestablishment of thyroid homeostasis after a period of enforced reduction in hormone formation (by drugs, surgery, or 131I treatment), it is obvious that the thyrotoxic phase of the disease can be self-limiting.

Toxic crisis, or thyroid storm, was also a frequent feature of Graves' disease in the past. This serious and often fatal development was a marked accentuation of the thyrotoxicosis, with hyperthermia, uncontrolled tachycardia, weakness, and delirium. This situation, now rarely encountered, is discussed in Chapter 12.

The ophthalmopathy of Graves' disease may follow a course quite different from that of thyrotoxicosis. This topic is also discussed in Chapter 12.

[helvella Administrator Thyroid UK]

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