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

1144 Subclinical Hypothyroidism. Subclinical hypothyroidism
is the presence of a mildly elevated serum TSH concentration
and a normal free T 4
without obvious symptoms.
Population screening has shown that subclinical
hypothyroidism is very common, with a prevalence of
up to 15% in some populations and up to 25% in the
elderly. The prevalence is strongly influenced by the
definition of the upper limit of normal of serum TSH,
which itself is controversial (Surks and Hollowell,
2007). The decision to use levothyroxine therapy in
these patients to normalize the serum TSH must be
made on an individual basis because treatment may not
be appropriate for all patients.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
An elevated TSH, especially common among elderly patients
and among centenarians, may even be associated with longevity
(Atzmon et al., 2009). Patients with subclinical hypothyroidism who
may benefit from levothyroxine therapy include those with goiter,
autoimmune thyroid disease, hypercholesterolemia, cognitive dysfunction,
or pregnancy, and those patients who have nonspecific symptoms
that could be due to hypothyroidism (Biondi and Cooper, 2008).
Hypothyroidism During Pregnancy. The dose of levothyroxine
in the hypothyroid patient who becomes pregnant
usually needs to be increased (Abalovich et al.,
2007), perhaps due to the increased serum concentration
of TBG induced by estrogen, the expression of type
3 deiodinase by the placenta, and the small amount of
transplacental passage of levothyroxine from mother to
fetus. In addition, pregnancy may “unmask” hypothyroidism
in patients with preexisting autoimmune thyroid
disease or in those who reside in a region of iodine deficiency.
Overt hypothyroidism during pregnancy is associated
with fetal distress and impaired psychoneural
development in the progeny. In addition, studies have
suggested that subclinical hypothyroidism during pregnancy
is associated with mildly impaired psychomotor
development in the children and preterm delivery. An
increase in miscarriage rate is strongly associated with
the presence of anti-thyroid peroxidase antibodies, and
early treatment with thyroxine may reduce miscarriages
and preterm delivery. These findings strongly suggest
that any degree of hypothyroidism, as judged by an elevated
serum TSH or perhaps a relatively low T 4
, should
be treated during pregnancy.
The increased levothyroxine requirement averages 30-50%
and can become apparent as early as the fifth week of gestation. The
magnitude of thyroxine dose adjustment is greatest for women who
are athyreotic from surgical thyroidectomy or radioiodine ablation
(Loh et al., 2009). The optimal way to anticipate this increased
dosage need and hence to avoid an elevated TSH is not known. Some
experts recommend that women increase their levothyroxine
dosage by ~30% as soon as pregnancy is confirmed, which can be
accomplished by taking two extra pills per week. Most measure a
serum TSH in the first trimester and then adjust the thyroxine dose
based on this result. Subsequent dosage adjustments would be based
on serum TSH, measured 4-6 weeks after each adjustment. For nonpregnant
women of reproductive age not using contraception, maintaining
the TSH in the lower portion of the reference range (~0.3-2.0
mIU/L) will allow room to move within the reference range during
the early part of pregnancy. For similar reasons, dosage adjustments
during pregnancy should be made to bring the TSH into the lower
portion of the reference range. The increased dosage requirement
plateaus at about gestation week 16-20, and dosage needs fall back
to prepregnancy levels immediately after delivery.
Myxedema Coma. Myxedema coma is a rare syndrome
that represents the extreme expression of severe, longstanding
hypothyroidism (Kwaku and Burman, 2007).
It is a medical emergency, and even with early diagnosis
and treatment, the mortality rate can be as high as
60% (Yamamoto et al., 1999). Myxedema coma occurs
most often in elderly patients during the winter months.
Common precipitating factors include pulmonary infections,
cerebrovascular accidents, and congestive heart
failure. The clinical course of lethargy proceeding to
stupor and then coma is often hastened by drugs, especially
sedatives, narcotics, antidepressants, and tranquilizers.
Indeed, many cases of myxedema coma have
occurred in hypothyroid patients who have been hospitalized
for other medical problems.
Cardinal features of myxedema coma are:
• hypothermia, which may be profound
• respiratory depression
• decreased consciousness
Other clinical features include bradycardia, macroglossia,
delayed reflexes, and dry, rough skin. Dilutional hyponatremia is
common and may be severe. Elevated plasma creatine kinase (CK)
and lactate dehydrogenase (LDH) concentrations, acidosis, and anemia
are common findings. Lumbar puncture reveals increased opening
pressure and high protein content. Hypothyroidism is confirmed
by measuring the serum FT 4
and TSH. Ultimately, myxedema coma
is a clinical diagnosis.
The mainstay of therapy is supportive care, with
ventilatory support, rewarming with blankets, correction
of hyponatremia, and treatment of the precipitating
cause. Due to a 5-10% incidence of coexisting
decreased adrenal reserve in patients with myxedema
coma, intravenous steroids are indicated before initiating
thyroxine therapy and should be continued until
adrenal function has been proven normal (Chapter 42).
There are no randomized controlled clinical trials to evaluate
the optimal form of thyroid hormone therapy in myxedema coma.
Intravenous administration of thyroid hormone is advised due to
uncertain absorption through the gut. Therapy with levothyroxine is