Question 1

What is the Meaning of Type 3 Deiodinase?

Accepted Answer

Type 3 Deiodinase (DIO3) is a selenoenzyme that inactivates thyroid hormones. It removes an iodine atom from the inner ring of active triiodothyronine (T3), converting it to inactive diiodothyronine (T2). DIO3 also transforms thyroxine (T4) into inert reverse triiodothyronine (rT3). This enzymatic action ensures precise local control of thyroid hormone concentrations within tissues.

Question 2

What is the Context of Type 3 Deiodinase?

Accepted Answer

DIO3 is highly expressed in tissues needing protection from excessive thyroid hormone, including the placenta, brain, and skin. Its activity increases during fetal development, shielding tissues from premature active thyroid hormone exposure. Within the endocrine system, DIO3 functions as a critical local regulator, fine-tuning cellular thyroid hormone availability rather than influencing systemic circulation broadly.

Question 3

What is the Significance of Type 3 Deiodinase?

Accepted Answer

Clinically, Type 3 Deiodinase is significant for its impact on tissue-specific thyroid status. Elevated DIO3 activity can induce localized or systemic hypothyroidism, even with normal circulating thyroid hormones. This occurs in critical illness or large vascular tumors like hemangiomas, where increased function alters thyroid profiles. Understanding its role is crucial for interpreting complex thyroid function tests.

Question 4

What is the Mechanism of Type 3 Deiodinase?

Accepted Answer

Type 3 Deiodinase's enzymatic action involves reductive deiodination at the 5-position of the iodothyronine inner ring. As a deiodinase, it requires selenium as a critical cofactor in its active site. This deiodination renders resulting metabolites, rT3 and T2, biologically inert. This mechanism is essential for tightly regulating cellular thyroid hormone action, preventing overstimulation.

Question 5

What is the Application of Type 3 Deiodinase?

Accepted Answer

DIO3 activity is clinically relevant in various physiological and pathological states. Its upregulation occurs when reduced active thyroid hormone is needed, such as physiological stress, chronic illness, or tissue hypoxia. Clinicians consider its influence when evaluating patients with unexplained hypothyroid symptoms or abnormal thyroid function tests, especially in conditions inducing high DIO3 activity. This helps explain low T3 in critical care patients.

Question 6

What is the Metric of Type 3 Deiodinase?

Accepted Answer

Direct DIO3 activity measurement is not routinely performed clinically. Clinicians infer its activity using indirect serum markers. Elevated reverse T3 (rT3) concentration is a key indicator, especially alongside normal or low free T3 and free T4. Comprehensive thyroid panels, including TSH, free T4, free T3, and rT3, offer a holistic view of thyroid hormone metabolism and potential deiodinase involvement.

Question 7

What is the Risk of Type 3 Deiodinase?

Accepted Answer

Dysregulation of DIO3 activity poses specific clinical risks. Abnormally high enzyme activity can induce severe tissue-specific or systemic hypothyroidism, even with intact pituitary-thyroid axis function, as seen in consumptive hypothyroidism from large infantile hemangiomas. This causes significant hypothyroid symptoms. Insufficient DIO3 activity is less common but could contribute to localized thyrotoxicosis. Clinical management requires careful consideration.

Type 3 Deiodinase

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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