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

Thyroid and Anti-Thyroid Drugs
Gregory A. Brent
and Ronald J. Koenig
Thyroid hormone is essential for normal development,
especially of the central nervous system (CNS). In the
adult, thyroid hormone maintains metabolic homeostasis
and influences the function of virtually all organ systems.
Thyroid hormone contains iodine that must be supplied
by nutritional intake. The thyroid gland contains large
stores of thyroid hormone in the form of thyroglobulin.
These stores maintain systemic concentrations of thyroid
hormone despite variations in iodine availability and
nutritional intake. The thyroidal secretion is predominantly
the prohormone thyroxine, which is converted in
the liver and other tissues to the active form, triiodothyronine.
Local activation of thyroxine also occurs in target
tissues (e.g., brain and pituitary) and is increasingly
recognized as an important regulatory step in thyroid
hormone action. Serum concentrations of thyroid hormones
are precisely regulated by the pituitary hormone,
thyrotropin (TSH), in a classic negative-feedback system.
The predominant actions of thyroid hormone are
mediated through binding to nuclear thyroid hormone
receptors (TRs) and modulating transcription of specific
genes. Thyroid hormones share a common mechanism
of action with steroid and steroid-like hormones, such as
vitamin D and the retinoids, whose receptors are members
of a superfamily of nuclear receptors (Chapter 3).
Although the predominant actions of thyroid hormone
are nuclear, actions of thyroid hormone outside the
nucleus have been reported.
Disorders of the thyroid are common. Thyroid
nodules and goiter, thyroid enlargement, are the most
common abnormalities and can be either benign or
malignant processes. In most of these patients, circulating
thyroid hormone levels are normal. Overt hyperthyroidism
and hypothyroidism, thyroid hormone
excess or deficiency, are usually associated with dramatic
clinical manifestations. Milder disease often has
a more subtle clinical presentation and is identified
based on abnormal biochemical tests of thyroid function.
Screening of the newborn population for congenital
hypothyroidism occurs in all developed countries,
and when followed by the prompt institution of appropriate
thyroid hormone replacement therapy, has dramatically
decreased the incidence of mental retardation
and cretinism. Maternal and neonatal hypothyroidism,
due to iodine deficiency, remains the major preventable
cause of mental retardation worldwide, although
much progress has been made in eradicating iodine
deficiency.
Effective treatment of most thyroid disorders is
readily available. Treatment of the hypothyroid patient
consists of thyroid hormone replacement. Treatment
options for the hyperthyroid patient include anti-thyroid
drugs to decrease hormone synthesis and secretion,
destruction of the gland by the administration of
radioactive iodine, or surgical removal. In most
patients, disorders of thyroid function can be either
cured or have their diseases controlled. Likewise, thyroid
malignancies are most often localized and
resectable. Metastatic disease often responds to radioiodide
treatment but may become highly aggressive and
unresponsive to conventional treatment. Newer therapies
that target specific genetic mutations in malignancies
have shown significant activity in both medullary
and papillary thyroid cancers.
THYROID
The thyroid gland is the source of two fundamentally
different types of hormones. The thyroid follicle produces
the iodothyronine hormones thyroxine (T 4
) and
3,5,3′-triiodothyronine (T 3
). These hormones are essential
for normal growth and development and play an