Inherited condition resulting in clinical euthyroidism
or hypothyroidism in the presence of elevated serum thyroxine levels.
End-organ unresponsiveness to thyroid hormone. Other features include
congenital deafness, goiter, and exophthalmos.
Thyroid Hormone Unresponsiveness; Thyroid Hormone
It has been suggested that both autosomal dominant
and recessive forms exist because of different mutations in the same gene.
However, mutations that affect the TH receptors are called dominant-negative
Thyroid Hormone Resistance Syndromes may be
classified as Generalized Thyroid Hormone Resistance (GTHR) or Pituitary
Thyroid Hormone Resistance (PTHR). Although both GTHR and PTHR result from
similar mutations, PTHR is selective in that only the pituitary gland is
affected. Mutation of the c-erbA beta gene results in a beta-thyroid hormone
receptor that is dominant and has an inhibitory effect on normal beta and
alpha thyroid hormone receptors, rendering affected tissues refractory to
the effects of thyroxine. The molecular mechanisms of this inhibitory effect
are currently under investigation. GTHR is usually heterozygous (one mutant
beta allele) The GTHR phenotype is variable and may reflect variable
expression of mutant alleles or the presence of other genetic regulatory
factors as yet undefined. Refetoff syndrome is caused by complete absence of
the beta receptor. A variant in which patients are homozygous for the mutant
beta allele (two dominant negative alleles expressed) is also described.
Elevated serum T4 and T3. Normal or moderately
elevated serum thyroid-stimulating hormone, which is inappropriate in
context of the elevated T4 and T3. Clinically euthyroid or
hypothyroid. In PTHR, the clinical picture is of hyperthyroidism.
Goiter is common in GTHR. Delayed speech
development, mental retardation, and delayed skeletal maturation represent
subtle signs of hypothyroidism. Florid clinical signs and symptoms of
hypothyroidism are unusual. Attention deficit disorder is commonly
associated with GTHR. GTHR has been erroneously diagnosed as thyrotoxicosis
on the basis of laboratory investigations; however, GTHR does not
demonstrate depression of thyroid-stimulating hormone levels as is seen in
thyrotoxicosis. Treatment is not required for GTHR except in the presence of
growth retardation or delayed skeletal maturation. PTHR results in loss of
negative feedback to the pituitary with normal peripheral tissue response to
thyroxine causing clinical hyperthyroidism which has been treated
successfully with d-thyroxine. The condition should be distinguished
from a primary pituitary thyroid-stimulating hormone-secreting tumor.
Examine for signs of clinical
hypothyroidism (GTHR) and hyperthyroidism (PTHR). Consider ECG in presence
of bradycardia or history suggestive of dysrhythmia. Review and continue
current drug therapy perioperatively. Review thyroid function.
Euthyroid patients should not cause
great concern; however, the possibility of differential resistance to
thyroxine between tissues exists. The occurrence of tachydysrhythmias under
anesthesia may represent hyperthyroid effects on cardiac muscle requiring
beta blockade. Overt clinical hypothyroidism (or hyperthyroidism) should be
controlled in consultation with an endocrinologist prior to anesthesia.
Regional anesthesia may be useful when the procedure permits.
Esmolol is probably the perioperative ...