III-1.
HYPERTHYROIDISM: GRAVES'S DISEASE AND TOXIC NODULAR GOITER
At present, the indications for surgical treatment
for patients with Graves-Basedow’s disease differ significantly from country
to country. In the United States and in the majority of European countries,
surgical therapy for Graves-Basedow’s disease is not considered primary
treatment, but is selected when other treatments fail or are contraindicated
because of an allergic reaction to antithyroid drugs or unusually low iodine
uptakes by the thyroid. For toxic adenoma and toxic multinodular goiter,
thyroidectomy remains the treatment of choice in most countries. In Japan,
unlike Western countries, many patients with Graves-Basedow’s disease are
treated surgically because of the excellent long-term results and few complications
(Harada 1997). The distinct advantages of surgery over other treatment
methods are as follows: (1) it can be carried out with the highest rate
of remission, and (2) euthyroidism can be achieved in the shortest
duration as concerns the three possible modalities of treatment. Unfortunately,
with the passage of time, the number of surgeons skilled in treating Graves-
Basedow’s disease has decreased, because of a lack of surgical experience.
These problems can be reduced by referring patients to centers specializing
in endocrine surgery. According to a survey carried out by the European
Thyroid Association, surgery is only infrequently used as a primary treatment
for patients with Graves-Basedow’s disease. Thus, overall only 7.3% of
patients were selected for surgical treatment and the primary indication
was a large goiter. Even in cases of recurrent hyperthyroidism after antithyroid
drug treatment, the rate of thyroidectomy did not exceed 10% (Glinoer
1987). Worldwide, the number of patients with Graves-Basedow’s disease
who are treated surgically is decreasing. In 1972, Hamburger noted that
“surgery is indicated only (a) when antithyroid drugs fail; (b) when
antithyroid drugs are likely to fail; (c) when medical management is feared
by patient or doctor; and (d) when surgery is the safest treatment.” (Hamburger
1972). Today, therefore in the majority of Western countries, surgery
is primarily indicated for patients with a recurrence of hyperthyroidism
after the withdrawal of properly managed medical treatment and the suspicion
or documentation of coexistent Graves-Basedow’s disease with a malignant
neoplasm, or for those in whom other forms of treatment are unacceptable
(Hamburger 1972, McFarland 1988, Menegaux 1993).
In patients with a solitary toxic adenoma
or a multinodular toxic goiter, thyroidectomy is generally considered the
first choice of treatment worldwide, except when the patient is at
risk. Antithyroid drugs and radioiodine
are not very efficient in these patients and are not always successful
(Eyre- Brook 1988, Heimann 1978).
It is imperative to render the patient
euthyroid before thyroidectomy by administering antithyroid drugs with
or without propranolol. Lugol’s solution is recommended for a period
of 5 or 6 days preoperatively to decrease the vascularity of the
thyroid gland and hence the possibility of intraoperative bleeding.
The technique for subtotal thyroidectomy
(resection of the bilateral thyroid lobes with the isthmus, leaving a small
amount of the posterior rim of each lobe) was developed after much trial
and error but, is now established as a standard procedure.
Total excision of one thyroid lobe
and subtotal resection of the other side has also been recommended (Andaker
1992, Menegaux 1993).The risk of complications with this procedure
is similar to that in subtotal thyroidectomy. However, there has been a
slight decrease in the incidence of recurrent hyperthyroidism and a higher
incidence of hypothyroidism (Andaker 1992).
The factors that predispose a patient to
recurrent hyperthyroidism or the development of hypothyroidism have not
been clearly elucidated. Many factors may have some influence on postoperative
hypothyroidism and recurrent hyperthyroidism, but the remnant size is
the most important factor determining the postoperative thyroid function
(Cusick 1987, Toft 1987, Okamoto 1992). An increased incidence of
hypothyroidism may be anticipated with a small remnant, and an increased
incidence of recurrent hyperthyroidism with a larger remnant. Controversy
exists regarding the optimal size of the remnant to be left after subtotal
thyroidectomy. In patients with Graves-Basedow’s disease, the optimal remnant
weight reported by many authors has differed significantly, ranging from
2 to 30 g (Hedley 1972, Michie 1972, Gough 1974, Farnell 1981, Bradley
1983). A euthyroid rate of 94% has been obtained with modified subtotal
thyroidectomy leaving an accurately measured 5 g thyroid remnant and an
intact inferior thyroid artery on each side (Bradley 1980). One suggestion
is to base the remnant size on the severity of the hyperthyroidism: 1.0
g in severe cases, 2.0-3.0 g in moderate cases, and 6.0 to 10 g in mild
cases (Kuma 1958). Currently, there is general agreement
on leaving a remnant weighing from 4 to 8 g (Harada 1984) and
few surgeons recommend leaving a remnant larger than 10 g (Cusick 1987).
An exact estimation of the remnant weight is difficult (Tweedle
1977). In our practice the weight of the remnant is compared
with that of a part of the resected thyroid lobe, which part is weighed.
These remnants ranged from 4 to 6 g.
See
and
Thyroid remnants smaller than 5 g result
in an increased incidence of postoperative hypothyroidism; a remnant smaller
than 5 g should, in most patients, be avoided (Tweedle 1977, Michie
1978).
Many other factors have also been proposed
to explain the development of postoperative hyperthyroidism and hypothyroidism.
A comparative study of th outcome of surgical treatment for Graves-Basedow’s
disease revealed that the prevalence of postoperative hypothyroidism
was 5 times lower, but recurrent hyperthyroidism was 5 times higher in
an area with a high iodine level than in one with a low iodine level
(Thjodleifsson 1977). The extent of lymphocytic infiltration
in the thyroid tissue has also been proposed to be associated with
an increased frequency of postoperative hypothyroidism (Harada 1984).
The level of antimicrosomal antibody rates may also influence Graves-Basedow’s
disease. Some studies suggest that a higher antimicrosomal antibody
level predicts an increased risk of postoperative hypothyroidism (Kuma
1958, Michie 1978). It was hoped that TBII assays would be predictable
indicators of the postoperative thyroid function. Unfortunately, surgery
does not affect the TBII levels in all cases, and there is no good correlation
between the postoperative TBII levels and postoperative thyroid function
(Harada 1987, Kuma 1991).
Today, surgical deaths and postoperative
thyrotoxic crises are virtually unknown, because patients are well controlled
preoperatively and the patients at highest risk are not subjected to thyroidectomy.
Postoperative determination of the serum
calcium level and examination of the vocal cords by indirect or direct
laryngoscopy are indicated. In experienced surgical hands, permanent
laryngeal nerve palsy and hypocalcemia develop in less than 1% of the patients
(Harada 1987, Sugino 1993). Transient palsy of the recurrent
nerve as a result of a retraction of the nerve or some other
cause is uncommon and the nerve usually recovers within several months.
Transient hypocalcemia is thought to be due to damage or ischemia of
the parathyroid glands. We have audited the postoperative complications
in a group of 252 patients with toxic nodular goiter
(171 pts) or with Graves-Basedow’s disease (81 pts) who were operated on
in our unit in a 4- year period
Table 3.
Complications of subtotal
thyroidectomy in 252 patients with Graves-Basedow’s disease and toxic nodular
goiter
| |
Toxic nodular goiter
n=171
|
Graves-Basedow’s disease
n=81
|
| Laryngeal
nerve palsy |
| Transient |
2.3%
|
2.8%
|
| Permanent |
0.5%
|
1.2%
|
| Hypocalcemia |
| Transient |
5.2%
|
6.1%
|
| Permanent |
1.1%
|
1.2%
|
| Hemorrhage |
3.5%
|
3.7%
|
There is considerable variation in the reported
incidence of postoperative hypothyroidism and recurrent hyperthyroidism
after thyroidectomy in patients with Graves-Basedow’s disease. Some series
in the literature include patients with toxic diffuse goiters, toxic multinodular
goiters or toxic adenomas (Toft 1978, Sugrue 1983). In such series,
the incidence of hypothyroidism might be lower because postoperative hypothyroidism
occurs less commonly in patients with toxic nodular goiters (Simms 1983).
The reported incidence of postoperative permanent hypothyroidism ranges
from 10 to 50% (Michie 1972, Gough 1974, Blichert-Toft 1977).
Kuma et al characterized the type of postoperative hypothyroidism in patients
with Graves-Basedow’s disease who underwent subtotal thyroidectomy (Kuma
1991). Interestingly, nearly 40 to 50% of the patients experienced
subclinical hypothyroidism during the first 4 years after surgery, and
most of them experienced euthyroidism later without any treatment (Kuma
1991).
Postoperative thyroid functions in
a group of 201 patients with a 2-year follow-up period after
operation in our unit are recorded in Table 4.
Table 4.
Postoperative thyroid function
test results (2- year follow-up - subtotal thyroidectomy)
n=201
| |
Toxic nodular goiter
|
Graves-Basedow’s disease
|
| Euthyroid |
88.1%
|
71.3%
|
| Latent hypothyroid |
10.4%
|
25.7%
|
| Recurrent hyperthyroidism |
1.5%
|
3%
|
Our results regarding the surgical complications
(Table 3.) and the postoperative thyroid function (Table 4) are comparable
with those reported from other centers (Farnell 1981, Sugrue 1983,
Kuma 1991, Harada 1997), and justify the recommendation of our surgical
policy.
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