DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

commonly begun with a loading dose of 250-500 μg followed by a
daily full replacement dose, although some clinicians omit the loading
dose. Some clinicians recommend adding liothyronine (10 μg
intravenously every 8 hours) with the initial dose of levothyroxine,
until the patient is stable and conscious. The limited studies that are
available suggest that excessive treatment with either levothyroxine
(>500 μg per day) or liothyronine (>75 μg) may be associated with
an increased mortality rate.
Congenital Hypothyroidism. Success in the treatment of
congenital hypothyroidism depends on the age at which
therapy is started. Because of this, newborn screening
for congenital hypothyroidism is routine in the U.S.,
Canada, and many other countries. In cases that do not
come to the attention of physicians until retardation of
development is clinically obvious, the detrimental
effects of thyroid hormone deficiency on mental development
will be irreversible. If, however, therapy is instituted
within the first 2 weeks of life, normal physical
and mental development can be achieved (Rose et al.,
2006). Prognosis also depends on the severity of the
hypothyroidism at birth and may be worse for infants
with thyroid agenesis.
To rapidly normalize the serum thyroxine concentration in
the congenitally hypothyroid infant, an initial daily dose of levothyroxine
of 10-15 μg/kg is recommended. This dose will increase the
serum FT 4
concentration to the upper half of the normal range in
most infants within 1-2 weeks. A dose of up to 17 μg/kg has been
suggested for the most severely hypothyroid infants, which can normalize
the serum T 4
in 3 days (LaFranchi and Austin, 2007).
Laboratory evaluations of TSH and FT 4
are performed 2 and 4 weeks
after treatment is initiated, every 1-2 months in the first 6 months,
every 3-4 months between 6 months and 3 years of age, and every
6-12 months from age 3 years until the end of growth. The goal is to
maintain serum FT 4
in the upper half of the reference range and the
TSH in the lower normal range during the first 3 years of life.
Assessments that are important guides for appropriate hormone
replacement include physical growth, motor development, bone maturation,
and developmental progress.
Management of premature infants with hypothyroxinemia
(~50% of those born at <30 weeks of gestation) remains a therapeutic
dilemma. Despite impaired psychomotor development in these
patients (Reuss et al., 1996), it is not clear whether levothyroxine
therapy may be beneficial, and in some settings it may be detrimental
(van Wassenaer et al., 2005).
Thyroid Nodules. Nodular thyroid disease is the most
common endocrinopathy. The prevalence of clinically
apparent nodules is 4-7% in the U.S., with the frequency
increasing throughout adult life. When ultrasound
and autopsy data are included, the prevalence of
thyroid nodules approaches 50% by age 60. As with
other forms of thyroid disease, nodules are more frequent
in women. Exposure to ionizing radiation, especially
in childhood, increases the rate of nodule
development. Approximately 5% of thyroid nodules
that come to medical attention are malignant.
The evaluation of the patient with nodular thyroid disease
includes a careful physical examination, biochemical analysis of thyroid
function, and assessment of the malignant potential of the nodule
(Cooper et al., 2006). Thyroid nodules usually are asymptomatic,
although they can cause neck discomfort, dysphagia, and a choking
sensation. Most patients with thyroid nodules are euthyroid, which
should be confirmed by TSH measurement. The most useful diagnostic
procedures generally are ultrasound imaging and a fine-needle
aspiration biopsy.
TSH suppressive therapy with levothyroxine sometimes is
prescribed for the patient with a benign thyroid nodule and a normal
serum TSH. The rationale is that a benign nodule will either stop
growing or decrease in size after TSH stimulation of the thyroid
gland has been suppressed. However, a meta-analysis of randomized
trials reveals the shortcomings of this approach (Sdano et al., 2005).
Only 22% of nodules decrease in volume by >50% with levothyroxine
versus 10% with placebo. Eight patients need to be treated to
have one response, and limited data suggest that the nodule will
regrow if the levothyroxine is stopped. Furthermore, a 50% decrease
in volume represents only about a 20% decrease in linear dimension,
a very modest change. The minimum level of TSH suppression
needed to achieve this modest response is not known, and long-term
exposure to excess thyroid hormone carries risks such as osteoporosis
and atrial fibrillation. Thus the use of levothyroxine to suppress
TSH in euthyroid individuals with thyroid nodules cannot be recommended
as a general practice. However, if the TSH is elevated, it is
appropriate to administer levothyroxine to bring the TSH into the
lower portion of the reference range.
Thyroid Cancer. The mainstays of therapy for welldifferentiated
thyroid cancer (papillary, follicular) are
surgical thyroidectomy, radioiodine, and levothyroxine
to suppress TSH (Cooper et al., 2006; Tuttle et al.,
2007). The rationale for TSH suppression is that TSH is
a growth factor for these cancers. These interventions
mainly benefit those patients with stage 2 or higher thyroid
cancer (Jonklass et al., 2006).
Given the generally excellent prognosis of well-differentiated
thyroid cancer, a prospective randomized controlled trial to assess
which patients benefit from suppressive therapy, how low the TSH
should be, or how long the suppression should be maintained has
not been done. For most low-risk patients with stage 1 or 2 disease,
maintaining the TSH just below the reference range for not more
than 5 years is one reasonable approach. A greater degree of TSH
suppression for a longer duration is recommended for higher risk
patients and those with metastatic disease (Cooper et al., 2006).
Non-thyroidal Illness (Sick Euthyroid) Syndrome. Although the circulating
free T 3
is low in the non-thyroidal illness syndrome, the current
standard of care is not to treat with thyroid hormone because
there is no convincing evidence that the low T 3
state contributes to
the patient’s prognosis or that thyroid hormone therapy would alter
the course of the illness. However, there have been very few randomized
controlled trials, and these generally involve small numbers
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CHAPTER 39
THYROID AND ANTI-THYROID DRUGS