major steps in thyroid hormone synthesis
- Uptake of iodide ion (I–) by the thyroid gland.
- Oxidation of iodide to iodine.
- Iodination of tyrosyl groups of thyroglobulin.
- Coupling of iodotyrosine residues to generate the thyroid hormones.
- Resorption of the thyroglobulin colloid from the lumen into the cell.
- Proteolysis of thyroglobulin and the release of thyroxine and triiodothyronine into the blood.
T_ acts more rapidly and is more potent than T_
because it is __ tightly bound to plasma proteins and binds more avidly to TH receptors
T3 acts more rapidly and is more potent than T4
because T3 is less tightly bound to plasma proteins and binds more avidly to TH receptors
physiological effects of thyroid hormone
mechanisms thyroid hormone is metabolized
- Deiodination (most important)
- Glucuronidation
- Sulfation
Deiodination of T4 by ____ results in the production of either T3 (more potent than T4) or reverse T3 (metabolically inactive)
Deiodination of T4 by 5′deiodinase results in the production of either T3 (more potent than T4) or reverse T3 (metabolically inactive)
5′deiodinase inhibited by:
- Drugs such as (4)
- Severe illness and starvation
- Iodinated compounds such as the radiographic agents iopanoic acid and ipodate
5′deiodinase inhibited by:
- Drugs: propylthiouracil, propranolol, corticosteroids, amiodarone
- Severe illness and starvation
- Iodinated compounds such as the radiographic agents iopanoic acid and ipodate
T4 and T3 are also conjugated in the ___ to form sulfates and glucuronides
These conjugates enter the __ and pass into the intestine where they are hydrolyzed
some are ___ (enterohepatic circulation), others are excreted in stool
T4 and T3 are also conjugated in the liver to form sulfates and glucuronide
These conjugates enter the bile and pass into the intestine where they are hydrolyzed
some are reabsorbed (enterohepatic circulation), others are excreted in stool
In the intestine, ____ (e.g. __) bind to and prevent the enterohepatic cycling of thyroid hormones
In the intestine, Bile acid sequestrants (e.g. cholestyramine) bind to and prevent the enterohepatic cycling of thyroid hormones
Deiodinase and UDP-glucuronosyltransferase enzymes are inducible, ___ the metabolism of T3 and T4
Enzyme inducer: ___
Clinical use for this?
Deiodinase and UDP-glucuronosyltransferase enzymes are inducible, increasing the metabolism of T3 and T4
Enzyme inducer: rifampin
Patients dependent on T4 replacement medication may require increased dosages to maintain clinical effectiveness if they are also on an enzyme inducer
clinical manifestations of hypothyroidism
- goiter
- muscle weakness, lethary
- dry coarse skin and hair
- yellowish tint of the skin
- cold intolerance, cold skin
- decreased sweating
- thick tongue
- delayed DTRs
___ is the most common cause of hypothyroidism in the USA
___ is the most common cause worldwide
Hashimoto’s thyroiditis the most common cause of hypothyroidism in the USA
Iodine deficiency is the most common cause worldwide
list other causes of hypothyroidism
- thyroidectomy
- external neck irradiation
- RAI therapy
- drug-induced
Drugs that can cause hypothyroidism
- Thioamides
- Iodides
- Amiodarone
- Lithium
- Aminoglutethimide
- Rifampin
- TKI’s (e.g., imatinib, sunitinib, sorafenib)
- Interleukin 2
- Interferon-α
- Sulfonylureas
treating amioderone-induced hypothyroidism
Levothyroxine even after amioderone discontinuance (bc of amioderones very long half-life)
Levothyroxine Vs. Liothyronine
Synthetic _____ is the preparation of choice for thyroid hormone replacement therapy
Synthetic levothyroxine (T4) is the preparation of choice for thyroid hormone replacement therapy
Thyroid replacement therapy AEs
- hyperthyroid-like manifestations
- ↑ risk of atrial fibrillation and osteoporosis
____ is a severe and long-standing form of hypothyroidism
describe cardinal features
Myxedema coma is a severe and long-standing form of hypothyroidism:
Hypothermia
Respiratory depression
Decreased consciousness
Management of myxdemea coma: IV ___
___ may be added until the patient is stable and conscious
Management of myxdemea coma: IV levothyroxine
Liothyronine may be added until the patient is stable and conscious
During pregnancy, adequate dose of ___ is important as early development of the fetal ___ depends on maternal thyroxine
During pregnancy, adequate dose of levothyroxine is important as early development of the fetal brain depends on maternal thyroxine
A higher dose of levothyroxine is usually required in pregnant patients - why?
- ↑ [TBG] induced by estrogen
- Expression of 5′deiodinase 3 (D3) by the placenta
- Small amount of transplacental passage of levothyroxine from mother to fetus
Congenital hypothyroidism treatment depends on the __ and ___ with which hypothyroidism is corrected
If ____ is instituted within ___, normal physical and mental development can be achieved
Congenital hypothyroidism treatment depends on the age and speed with which hypothyroidism is corrected
If levothyroxine is instituted within first 2 weeks of life, normal physical and mental development can be achieved
Clinial features of hyperthyroidism
- nervousness, heat intolerance
- increased sweating, palpitations
- fatigue, weakness, dyspnea
- weight loss with increased appetite
- signs: goiter with bruit over thyroid, tachycardia, skin changes and eye signs
____ is most common cause of hyperthyroidism
Other causes?
Grave’s disease (toxic diffuse goiter) is most common cause of hyperthyroidism
- toxic adenoma
- toxic multinodular goiter
- factitious hyperthyroidism
- Drug-induced
-
Anemia40
-
Anticancer65
-
Respiratory Pharm49
-
Antimalarials70
-
Antimycobacterials44
-
Antibacterial: Cell Wall Synthesis Inhibitors23
-
Laxatives & Antidiarrhea22
-
Antiemetics24
-
Antidiabetics34
-
Antidiabetics II58
-
Upper GI Drugs50
-
Lower GI Drugs34
-
Hypothalamic & Pituitary Hormones51
-
Thyroid Drugs49
-
Micro Infection drugs43
-
Gonadal Hormones46
-
OCPs38
-
Uterus Drugs30
-
Adrenocorticosteroids43
