Hyperthyroidism/Steroid Messenger Regulation of Translation Case

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https://medical-phd.blogspot.com/2021/03/hyperthyroidismsteroid-messenger.html

Eugene C.Toy, MD, William E. Seifert, Jr., PHD, Henry W. Strobel, PHD, Konrad P. Harms, MD

❖ CASE 7
A 39-year-old female presents to the clinic for a routine health maintenance exam. The patient reports she is
feeling nervous and anxious all the time with frequent palpitations. On further questioning she reports having
diarrhea and has been losing weight. She has also noticed a change in hair and fingernail growth and frequently
feels warm while others are cold or comfortable. She denies any history of depression or anxiety disorder and is
not taking any medications. On examination, her heart rate is 110 beats per minute. She has a slight tremor and
has increased reflexes in all extremities. A nontender thyroid enlargement is appreciated in the thyroid region.
Her TSH level is low at 0.1 mIU/mL. The patient is told that she has an autoimmune antibody process.

◆ What is the most likely diagnosis?

◆ What is the biochemical mechanism for this disorder?

ANSWERS TO CASE 7: HYPERTHYROIDISM/STEROID MESSENGER REGULATION

OF TRANSLATION
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.

CLINICAL CORRELATION
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 thyroidstimulating immunoglobulin, or a radionuclide scan revealing diffuse increased uptake
throughout the thyroid gland. Treatment acutely includes β-adrenergic antagonists and agents that inhibit the
catabolism of thyroid hormone such as propylthiouracil (PTU).

APPROACH TO STEROID MESSENGER REGULATION OF TRANSLATION

Objectives
1. Understand the general mechanisms of hormone action.
2. Know about some of the specific mechanisms by which hormones activate 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.
3. Be familiar with how immunoglobulins of Graves disease cause hyperthyroidism.
4. Be aware of the mechanism of action of PTU and methimazole.
5. Understand the regulation of hormone levels.

Definitions
Effector: The protein in a signal transduction pathway (e.g., a hormonal response) that produces the cellular
response.
G protein: A guanosine triphosphate (GTP)–binding protein that serves as a transducer in a signal transduction
pathway. On binding GTP and releasing guanosine diphosphate (GDP), a G protein is able to activate the
effector enzyme (e.g., adenylate cyclase).
Graves disease: An autoimmune disease in which the B lymphocytes synthesize an immunoglobulin (thyroid-
stimulating immunoglobulin, TSIg) that binds to and activates the TSH receptor in such a way that the thyroid
hormones do not feedback inhibit the receptor–effector interaction, leading to a hyperthyroid condition.
Hormone: A chemical signal that is produced in one set of cells and directs the activity in another set of cells
that can be endocrine, paracrine, or autocrine.
Receptor: A protein that will perceive the signal of a hormone or other chemical signal (e.g., a
neurotransmitter) by binding it and transmitting that signal further down the signal transduction pathway.
Second messenger: A molecule that is synthesized within a cell in response to a receptor binding a hormone.
Transducer protein: A protein (such as the α-subunit of a G protein) that transmits the signal from a hormone-
bound receptor to the effector protein.