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CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 7: H Y P E R T H Y R O ID ISM /ST E R O ID
M E S SE N G E R R E G U L A T IO N O F T R A N SL A T IO N
Summary:
A 39-year-old female has symptoms of nervousness, weight loss,
gastrointestinal and skin alterations, heart palpitations, heat intolerance, and
physical signs of hyperreflexia and a goiter.
Likely diagnosis: Hyperthyroidism, likely Graves disease.
Biochemical mechanism: The most frequent cause of hyperthyroidism,
Graves disease, is an autoimmune process in which thyroid hypersecretion
is caused by circulating immunoglobulins that bind to the TSH receptor on
the thyroid follicular cells and stimulate thyroid hormone production. The
diagnosis is confirmed by increased thyroid stimulating IgG antibodies and
is frequently seen in other family members.
C L IN IC A L C O R R E L A T IO N
This 39-year-old woman has symptoms of hyperthyroidism, thyroid excess.
This causes a tachycardia, tremor, nervousness, thin skin, weight loss through the
hypermetabolic state, and hyperreflexia. If unchecked, the high levels of thyroid
hormone can sometimes even cause adrenergic crisis (so called thyroid storm),
which has a high rate of mortality. Normally, the thyroid hormone (thyroxine)
is under tight control. The pituitary release of thyroid stimulating hormone is
stimulated by insufficient thyroxine, and suppressed by excess thyroxine. In
Graves disease, the most common cause of hyperthyroidism in the United
States, an autoimmune immunoglobulin is produced that stimulates the TSH
receptor of the pituitary. This is confirmed by either assaying for the thyroid-
stimulating immunoglobulin, or a radionuclide scan revealing diffuse
increased uptake throughout the thyroid gland. Treatment acutely includes
P-adrenergic antagonists and agents that inhibit the catabolism of thyroid
hormone such as propylthiouracil (PTU).
A PPR O A C H TO ST E R O ID M E SSE N G E R R E G U L A T IO N
O F T R A N SL A T IO N
O bjectives
1.
Understand the general mechanisms of hormone action.
2.
Know about some of the specific mechanisms by which hormones acti-
vate receptors.
a. Know about hormones that bind to cell membrane receptors.
b. Know about hormones that act through cyclic nucleotides.
c. Know about hormones that act through calcium and the PIP2 system.
d. Know about hormones that bind intracellular receptors and activate
genes.
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