Thyroid Physiology and Testing Flashcards
The thyroid is embryologically derived from which duct?
thyroglossal duct
The thyroid is located below which cartilage?
CRICOID cartilage
What is the pyramidal lobe?
normal variant that may be inserted into the isthmus or medial aspects of one of the lobes, and is a remnant of the THYROGLOSSAL DUCT
What are some complications as a result of an enlarged thyroid?
Compression of trachea: SOB, stridor
Compression of esophagus: Dysphagia
Compression of recurrent laryngeal nerves: Hoarseness
What are some complications of thyroidectomy?
Damage to recurrent laryngeal nerves causing hoarseness (1% permanent)
Damage to parathyroid glands causing difficulties with calcium balance
What are the 2 cell types in thyroid and what do they produce/secrete?
Follicular cells: Make and secrete T4 and T3
Parafollicular (C cells): Secrete Calcitonin- has a role in inhibiting bone resorption
What secretion amount per day for T3 and T4?
T4 (thyroxine) 100 nmol/day (pro-hormone)
T3 (triiodothyronine) 5 nmol/day (active hormone)
List the roles of thyroid hormones:
Promote normal fetal and childhood growth
Promote normal CNS development
Regulate heart rate, myocardial contraction and relaxation
Affect GI motility
Influence renal water clearance
Modulate energy expenditure, heat generation, weight
Affect lipid metabolism
What form of iodine is carried in the circulation?
Ingested iodine is absorbed in the gut and carried in the circulation as iodide.
What kind of pump transports iodide into the thyroid?
NIS: sodium-iodide symporter
Na+ goes down its concentration gradient (high in plasma)
I- goes against it concentration gradient (high in thyroid)
Once iodide is transported into thyroid cells where does it go?
Transported to the lumen of follicles (made of follicular cells)
When iodide supply is sufficient what is the rate limiting step?
H2O2 produced by this NADPH-dependent protein is the limiting step of protein iodination
What are the two key proteins in thyroid hormone synthesis and their roles?
- Thyroglobulin (Tg), secreted into the follicle lumen
Acts as a scaffold to which Iodine is added
Contains Tyrosine residues
2. Thyroid Peroxidase (TPO) Oxidizes iodide (using H2O2) and attaches it to tyrosine residues of Tg Produce MITs and DITs (monoiodotyrosine and diiodotyrosine) and couples them to produce T3 (MIT + DIT) and T4 (2 DITs)
What is the collective name for Oxidation and Iodination?
Organification
List the key steps of thyroid hormone synthesis:
- Iodine trapping
- Organification (lumen) –> oxidation of I- and then iodination to Tyr residues of Tg
- Coupling (lumen) –> T3 + T4
- Proteolysis of Tg and release of hormones to circulation (via basal membrane facing vessels)
True or False: About 70% of thyroid iodide pool is in the form of MITs and DITs?
True
How is iodine recycled internally?
Iodotyrosine deiodinase removes iodide from MITs and DITs and returns most of it to the intrathyroidal iodide pool for future use
What is the effect of TSH and where does it originate?
the stimulator that affects nearly every stage of thyroid Hormone production and release, including iodide metabolism
Acute control: Activates cellular and enzyme machinery
Chronic control: Gene expression of key proteins
Secreted by thyrotroph cells in the Anterior Pituitary gland
What kind of subunits make up TSH and what are some of their characteristics?
Glycoprotein composed of alpha and beta subunits
Alpha subunit is common to FSH, LH and hCG (can weakly bind each others’ receptors)
Beta subunit confers specificity of action
TSH binds to a cell surface receptor on thyroid
List some control measures for TSH release:
Stimulatory: TRH (Thyrotropin Releasing Hormone) secretion from the hypothalamus
Inhibitory: T3 level- High levels of T3 lead to reduced TSH (Negative feedback) and TRH (indirectly)
What happens during iodine deficiency?
inadequate thyroid hormones, increased TSH, and goiter
What is the Wolff-Chaikoff Effect and when does it occur?
Temporary inhibition of thyroid hormone synthesis in the setting of an excess iodine load
Acute inhibition of organification of iodine, preventing incorporation of iodine onto tyrosine residue
What is Iodine-induced Hypothyroidism?
Stress of excess iodine and acute Wolff-Chaikoff can trigger hypothyroidism and tip to autoimmune thyroid failure (Hashimoto’s)
- Iodine is also immunogenic and can increase autoimmune attack on the gland
What happen in Iodine-induced hyperthyroidism?
Failure of Wolff-Chaikoff response (ie. Jod Basedow effect) and eventual:
- Multinodular goitre
- Latent Graves’ disease
How is thyroid hormones transported in blood?
> 99% are bound to plasma proteins
Thyroxine-binding globulin (TBG) (75%)
Transthyretin (20%)
Albumin (5%)
True or False: bound thyroid hormones can exert effect onto cells?
False: Only 0.04% of T4 and 0.4% of T3 are free (unbound) or active and available to enter target tissues to exert an effect
Where are the receptors located for thyroid hormones and how are they transported into cell?
Nucleus and active transport
Which thyroid hormone is biologically active, and how is the precursor turned active?
It is the T3 that is biologically active
Small amounts of T3 are secreted directly from the thyroid, while the majority is produced from T4 to T3 conversion within the target cell
Mediated by Deiodinase enzyme, which removes iodine from outer ring of T4
List factors that prevent conversion of T4 to T3:
- Fetal life
- Caloric restriction
- Hepatic disease
- Major systemic disease
- Drugs (glucocorticoids, propranolol)
- Selenium deficiency
List the effects of thyroid hormone on metabolism:
- Increased BMR (basal metabolic rate), associated with increased 02 consumption and increased heat production
- Increased hepatic gluconeogenesis, glycolysis, intestinal glucose absorption
Reduced insulin sensitivity
Clinical effect: worsen glycemic control (in coexisting diabetes) - Increased protein breakdown (muscle)
- Increased fat breakdown
- Increased cholesterol metabolism
Decreased serum cholesterol (LDL)
List the effects of thyroid hormone on growth and development:
Act as “tissue growth factors”
Essential for CNS maturation in fetus
- Maternal hypothyroidism results in poor fetal CNS development and cognitive impairment
List the effects of thyroid hormone on cardiovascular system:
Increase HR, increase cardiac contractility, increase BP
Potentiation of SNS (beta-2 adrenergic receptors)
List the effects of thyroid hormone on bone:
Stimulate osteoclasts leading to increased bone resorption, hypercalciuria
List the effects of thyroid hormone on resp sys:
Increased respiratory drive, effects on resp muscle function
List the effects of thyroid hormone on GI:
Increased intestinal motility, appetite stimulation
List the effects of thyroid hormone on endocrine sys:
Hyperprolactinemia (in hypothyroidism)
Amenorrhea to Menorrhagia and anovulation
Increased aromatisation of androgens to estrogens → gynecomastia in men
Effects on cortisol secretion and clearance
What is the Best screening test to evaluate thyroid function?
TSH:
Cost-effective
Widely available
High sensitivity (few false negatives)
True or False: TSH is highly sensitive to changes in T4 levels and TSH abnormalities are more detectable relative to T4 abnormalities
True
What is progressive testing for thyroid?
measuring free T4 (for both hypo and hyper) and free T3 (hyper) after finding of abnormal TSH
In clinical practice, is TRH measured?
NO
What are the hormone levels in subclinical hypo/hyerthyroidism?
SUBCLINICAL HYPOTHYROIDISM
Definition: Normal FT4, FT3, elevated TSH (and serum cholesterol). –> treatment recommended
SUBCLINICAL HYPERTHYROIDISM
Definition: Normal FT4, FT3, suppressed or low TSH (and usually associated with osteopenia).
–> treatment based on a # of factors
What are the usual causes of elevated T4 AND TSH?
Pituitary Tumor Producing TSH
or
Thyroid Hormone Resistance
What is the cause of both low T4 and TSH?
Hypopituitarism
List the autoimmune thyroid diseases:
Hashimoto’s thyroiditis (hypothyroid)
Graves’ disease (hyperthyroid?)
Silent and postpartum thyroiditis
What are the three major thyroidal antigens?
TG (thyroglobulin)
TPO (thyroid peroxidase)
TSH receptor
What is is the most sensitive test to determine the presence of thyroid autoimmunity and is it specific?
Anti-TPO, but not specific (both Hashimoto and Graves positive)
What is anti-TSH mainly used for?
Used to:
Differentiate Graves’ disease from other kinds of hyperthyroidism (very specific to it)
Evaluate risk for fetal / neonatal thyrotoxicosis in pregnant women with hx of Graves’ disease
Diagnose Graves’ opthalmopathy in euthyroid patients
What is thyroglobulin’s main role in monitoring?
Tumor marker in monitoring of thyroid cancer after thyroidectomy
Used to detect residual or recurrent thyroid cancers
What is the significance of anti-thyroglobulin
Only used to determine if Thyroglobulin can be used as a tumor marker in thyroid cancer monitoring for recurrence
If positive (before monitoring), cannot use thyroglobulin levels as a marker
No other clinical role
What is structural thyroid imaging and what does it assess?
Structural imaging: Thyroid Ultrasound, CT
Goiter, thyroid nodule(s), cervical lymph nodes
Assessing the gland anatomy
What is thyroid functional imaging and what does it assess?
Functional imaging: Thyroid scan, Iodine uptake
Thyroid gland and /or nodule activity in the setting of hyperthyroidism
True or False: Ultrasound cannot identify nodule features that favor malignancy vs benign?
False: it can detect presence and size of nodules and thyroid size
What features are common in Ultrasound that favor thyroid malignancy?
Hypoechogenicity
Irregular nodule capsule
Microcalcifications (HIM)
What does a CT scan for thyroid assess?
substernal goiter
tracheal deviation / compression
metastatic disease outside of the neck (eg. lungs, abdomen)
Functional thyroid imaging is contraindicated in which scenarios?
in pregnancy and breastfeeding
Whats the use of functional imaging in relation to thyroid?
Radioactive isotopes: I-131 or technetium activity is assessed to see if of metastatic thyroid cancer, or ectopic thyroid tissue exists (figuring out the underlying reason for hyperthyroidism)
Which functional imaging technique can determine distribution of excess thyroid hormone production?
Thyroid scan using technetium that highlight areas in gland that are highly active in production
If Ultrasound identifies nodules indicating malignancy, what would the next step to confirm?
Fine Needle Aspiration Biopsy
What does a thyroid uptake scan (RAIU) determine?
- is overactive if gland (hyperthyroidism) ie. Graves disease
- if there is growth on the gland
- hyperactive nodule
- if thyroid cancer has spread
