Thyroid Gland Flashcards
The thyroid gland produces iodothyronines ____ and _____
Tetraiodothyronine (T4) aka thyroxine
Triiodothyronine (T3)
Peripheral conversion of iodothyronines by ____ is key
Deiodinases
The functional unit of the thyroid gland
Thyroid follicle
The thyroid follicle is lined by _____ epithelial cells and the lumen is filled with _____. Follicles also contain parafollicular C cells which secrete _____
Cuboidal; colloid; calcitonin
What is the main secretory product of the thyroid?
T4 (10x more than T3)
Colloid is composed of newly synthesized thyroid hormones attached to ____
Thyroglobulin
Conversion of T4 to T3 occurs in the thyroid and peripherally through the action of ______
Deiodinase
[90% is peripherally converted vs. 10% that is directly secreted]
What are some clinical states that are associated with reduced conversion of T4 to T3?
Fasting
Medical and surgical stress
Catabolic disease
_______ is often associated with elevated levels of type 1 deiodinase, contributing to elevated T3 in the blood
Hyperthyroidism
T4 may be converted to T3 by ____ ring deiodination (activation) by deiodinases type ___ and ___
Outer; 1; 2
What is the primary source of dietary iodine?
Iodized table salt
[also from dairy products and fish]
Synthesis of thyroid hormone involves basal to apical movement of 2 precursors ____ and _____
Thyroglobulin
Iodide
[iodide is taken up from blood; thyroglobulin is assembled from translated amino acids]
______ is the process of binding iodine with thyroglobulin
Organification
What are the important transporters in the basolateral membrane of cells synthesizing thyroid hormone?
Na/K-ATPase
Na/I symporter (NIS, 2:1 ratio)
What are the important transporters in the apical membrane of cells synthesizing thyroid hormone?
Pendrin — Cl/I countertransporter
Peroxidase — oxidizes iodide for combination with thyroglobulin (aka TPO)
After iodination by thyroid peroxidase, thyroglobulin is stored in the lumen of the follicle as colloid.
Within the colloid, thyroglobulin binds to ____, ____, and intermediates ___ and ____
T4; T3; MIT; DIT
When iodide availability is restricted, formation of _____ is favored
T3
Intracellular steps of thyroid hormone synthesis involve _______ of colloid droplet, at which time ______ cleave T4 and T3 from thyroglobulin for release into circulation
Pinocytosis; proteases
[purpose is to rapidly deiodinate MIT and DIT molecules that have been released during proteolysis of thyroglobulin. This iodide is then recycled into T4 and T3 synthesis]
T/F: a deficiency in intrathyroidal deiodinase mimics a dietary iodide deficiency
True
What are some inhibitors of NIS transporter in basolateral membrane?
Perchlorate; thiocynate
What is the primary inhibitor of TPO?
Propylthiouracil (PTU) - inhibits production of final thyroid products
The wolff-chaikoff effect results in inhibition of what step in thyroid hormone synthesis?
Organification (process of binding iodine with TG)
Iodine is stored as iodinated _____ of thyroglobulin
Enough hormone is stored as iodinated TG in the follicular colliod to last 2-3 mos. Each TG molecule contains 30 ____ molecules and a few ___ molecules
Tyrosine
T3; T4
Activity of the thyroid gland can be assessed by radioactive iodine uptake. Compare levels at 24 hrs in normal thyroid, hyperthyroid, and hypothyroid
Normal = 25% at 24 hrs
Hyperthyroid = >60% at 24 hrs
Hypothyroid = <5% at 24 hrs
The majority of thyroid hormone circulates bound to plasma proteins (only 1% is free). What are the main plasma proteins that bind thyroid hormones?
Thyroxin-binding protein (TBG) = 70%
Transthyretin (TTR) = 10-15%
Albumin = 15-20%
The main plasma protein that binds thyroid hormone is TBG. It is synthesized by the ____ and has greater affinity for ____
Liver; T4
Circulating TBG can be indirectly assessed with what test?
T3 resin uptake test
Describe T3 resin uptake test
Add labeled T3 then add resin as secondary binder
If TBG levels are already occupied, less radioactive T3 will bind and more spots will be available to secondary resin
The amount of T3 bound to resin is then measured
What would T3 resin uptake test results be in the case of hyperthyroid vs. hypothyroid?
Hyperthyroidism = high T3 resin uptake
hypothyroidism = low T3 resin uptake
What would T3 resin uptake test results be in the case of high TBG levels?
Increased T4 but decreased T3 resin uptake
What would the T3 resin uptake test results be in the case of low TBG?
Decreased T4, but increased T3 resin
What would T3 resin uptake test results be in the case of hepatic failure?
Decreased TBG, but increased T3 resin uptake
What would the T3 resin uptake test results be in pregnancy
Increased TBG, but decreased T3 resin uptake
Changes in blood TBG and free thyroid hormones in the case of hepatic failure
Decreased blood TBG
Transient increase in level of free T3 and T4 followed by inhibition of synthesis of T3 and T4 via negative feedback
Changes in blood TBG and free thyroid hormones in pregnancy
Increased blood levels of TBG
Increased bound forms of T3 and T4 (decreased free)
Transient decrease in free T3; T4 increases synthesis and secretion of T3 and 4
Increase in total levels of T3 and 4 but levels of free, physiologically active thyroid hormones are normal (clinically EUTHYROID)
TSH is released from thyrotrophs of anterior pituitary, leading to _____ effect on thryoid gland itself and secretion of thyroid hormone
TSH is regulated by _____ and _____
TRH; free T3 (feedback)
What transporter is responsible for the entry of T3 and T4 from blood across cell membrane into cytosol?
MCT8/10 transporters
[can also occur by diffusion]
What are some nuclear receptors/TFs important for conversion of T4 to T3?
TRalpha1 (cardiac/muscle)
TRalpha2
TRbeta1 (brain, liver, kidney)
TRbeta2 (pituitary)
Physiologic effects of T3 on growth
Growth
Bone maturation
Physiologic effects of T3 on nervous system
CNS maturation
Physiologic effects of T3 on BMR
Increased Na/K ATPase
Increased O2 consumption
Increased heat production
Increased BMR
Physiologic effects of T3 on metabolism
Increased glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, and protein synthesis/degradation
Physiologic effects of T3 on cardiovascular system
Increased cardiac output Upregulation of beta 1 adrenergic receptors
T3 generally activates nuclear receptors and _____ second messenger system leading to increased metabolic activity, growth, cardiovascular effects, GI motility, CNS development, and others
cAMP
Thyroid hormones typically have ____ onset and ____ duration
Slow; long
There is a 2-3 day latent period before ____ activity begins, and activity persists 6-8 weeks once started
Actions of ____ are more rapid, with a 6-12 hour latent period and 2-3 day maximum
T4; T3
Thyroid hormone has direct and indirect effects on the CV system including:
______ TPR/systemic resistance
_____ inotropic effects
______ blood volume/preload
Decreased
Increased
Increased
Thyroid hormone works synergistically with ___ and ___ to promote bone formation
GH; somatomedins
What are the general effects of thyroid deficiency during perinatal period?
Abnormal synaptic development
Decreased dendritic branching and myelination
Cretinism
Effects of hyperthyroidism vs. hypothyroidism on metabolism
Hyper:
Heat intolerance
Weight loss
Increased BMR
Hypo:
Cold intolerance
Weight gain
Decreased BMR
Effects of hyperthyroidism vs. hypothyroidism on bone
Hyper: Osteoporosis (or stunted growth in adolescents)
Hypo: stunted growth
Effects of hyperthyroidism vs. hypothyroidism on CNS
Hyper: Agitation Anxiety Difficulty concentrating Hyperreflexia
Hypo: Cretinism Listlessness Slowed movement Somnolence Impaired memory Decreased mental capacity
Effects of hyperthyroidism vs. hypothyroidism on skin
Hyper:
Sweating
Hypo:
Dry
Myxedema
Effect of hyperthyroidism vs. hypothyroidism on CV system
Hyper: Tachycardia Afib Palpitations High output heart failure
Hypo: Bradycardia Decreased contractility Decreased CO Heart failure
Effect of hyperthyroidism vs. hypothyroidism on GI system
Hyper: Diarrhea
Hypo: constipation
Most common cause of primary hyperthyroidism
Graves disease
Example of secondary hyperthyroidism
TSH-secreting pituitary tumor
Major clinical signs of graves disease
Exophthalmos
Periorbital edema
Diagnosis of graves disease
Elevated serum free and total T4 and T3 levels
Goiter and ophthalmopathy
Presence of circulating thyroid stimulating immunoglobulins (helps distinguish graves from adenoma of pituitary thyrotrophs)
Why are TSH levels low in graves disease?
Thyroid stimulating immunoglobulins stimulate the TSH receptor without TSH present - so there is loss of feedback and TSH levels are lower
In what condition would you see rapid uptake of radioactive iodine within 6 hrs followed by high turnover rate?
Graves disease
Primary causes of hypothyroidism
Agenesis Gland destruction (surgical, hashimotos, irradiation) Inhibition of thyroid hormone synthesis and release (iodine def)
[may also be transient d/t postpartum, thyroiditis, etc.; hypothalamic disease, pituitary disease, resistance to thyroid hormones]
Treatment for hypothyroidism involves replacement doses of ___
T4
[note that metabolism of T4 decreases with age, higher doses needed in younger patients; also overprescription in postmenopausal women contributes to osteoporosis]
Hashimoto’s thyroiditis
Thyroid hormone synthesis impaired by antibodies against thyroglobulin or TPO, leading to decreased T3 and T4 secretion
TSH levels are high - trophic effect leading to goiter
What causes cretinism?
Iodide deficiency
Maternal intake of antithyroid meds
Impaired development of thyroid gland
Inherent deficit in synthesis of thyroid hormones
Symptoms of cretinism
Feeding problems Respiratory difficulty Protruding tongue Growth retardation Mental retardation Jaundice Dry skin Hypotonia
Hypothyroidism due to iodine deficiency leads to transient decrease in synthesis of thyroid hormones, _____ levels of TSH, and goiter
elevated
Goiters can develop in response to multiple imbalances and diseases within the HPT axis
What are examples of these imbalances?
Hyperthyroidism - Grave’s disease or secondary cause
Primary hypothyroidism - lack of adequate iodine, sporadic hypothyroid of unknown etiology, chronic thyroiditis
