Thyroid Physiology and Disorders Quiz

Thyroid Gland and Hormone Function

• Located below the jaw, above the clavicles
• One of the largest endocrine glands
• Affects nearly all organ systems
• Crucial for growth and development in all ages
• Maintains metabolic stability
• Not essential for life, but imbalances cause disease
• Absence in newborns leads to severe intellectual disability
• Reservoir for hormones, maintaining consistent blood levels.
• Controlled by the hypothalamic-pituitary-thyroid axis (maintains hormone levels).
• Patients seek care due to symptoms of imbalance, enlarged gland, or palpable nodules.

Hypothalamic-Pituitary-Thyroid Axis

• Hypothalamus releases thyrotropin-releasing hormone (TRH)
• TRH signals the anterior pituitary to release thyroid-stimulating hormone (TSH).
• TSH stimulates follicular cells to produce thyroglobulin, leading to T3 and T4 production.
• Understanding these steps is essential.
• Certain substances can disrupt this cascade.

Thyroid Hormone Synthesis

• Follicular cells constantly synthesize and release thyroglobulin into the follicle lumen (for iodination and storage).
• Thyroglobulin becomes active after iodination
• Butterfly-shaped, below the larynx. Secretes T3, T4, and calcitonin.
• Hormones synthesized in the colloid of follicular cells.
• Capillaries remove synthesized hormones into circulation.
• Iodide (iodine) attached to tyrosine creates thyroid hormones

Factors Affecting Thyroid Hormone Production

• Bromine, fluorine, and lithium block iodide transport, thus reducing hormone production.
• Sulfonylureas and sulfonamides impair organification and coupling of hormones.
• Large doses of iodine or lithium can suppress hormone secretion

Steps of Thyroid Hormone Production in Follicular Cells

• Sodium-iodide symporter brings iodide into the cell
• Pederin transporter moves iodide into follicle colloid
• Cells synthesize enzymes & thyroglobulin for colloid
• Thyroid peroxidase adds iodine to thyroglobulin tyrosine, resulting in T3 and T4
• Active thyroid hormones are T3 and T4
• Thyroglobulin is taken into follicular cells in vesicles
• Intracellular enzymes detach T3 and T4 from thyroglobulin
• Hormones enter bloodstream via capillaries.

Coupling Reactions in Thyroid Hormone Production

• Tyrosine iodination forms monoiodotyrosine (MIT) or diiodotyrosine (DIT).
• MIT and DIT combine to form triiodothyronine (T3)
• Two DITs combine to form thyroxine (T4)
• Reverse T3 (RT3) is an inactive form of T4, made by deiodinase enzymes.

Thyroid Hormone Transport in Circulation

• Once released, T3 and T4 bind to three proteins:
  • Thyroxine-binding globulin (TBG)
  • Transthyretin (TTR)
  • Albumin
• T3 and T4 have strongest affinity for TBG; T4 also bonds with albumin.
• TTR has higher affinity for T4 than T3.
• Unbound T3 and T4 are active forms.
• Free T4's half-life is 6-7 days; T3's is 6-24 hours.
• 99% of T3 and T4 are bound to proteins.

Factors Affecting Thyroid Hormone Binding

• Steroid use or liver cirrhosis can increase free hormone levels via reduced albumin production.
• Pregnancy increases TBG, and subsequently lowers free hormone levels.

Hypothalamic-Pituitary-Thyroid Axis Feedback Loop

• Cold temperatures affect TRH production
• T3 creates negative feedback on hypothalamus, reducing TRH production if levels are high.
• Anterior pituitary stimulated to release TSH from the hypothalamus
• T3 and T4 create negative feedback on the anterior pituitary, reducing TSH production if levels are high.
• Iodine levels affect thyroid
• Physiological or emotional stress can impact the entire process.

Comparison of T3 and T4

• T3 has higher biological activity, but lower production compared to T4.
• T4 is a reservoir, produced in higher quantities, converted to T3 by peripheral deiodinase enzymes
• This process can also produce inactive reverse T3.

Physiological Effects of T3 and T4

• Increased basal metabolic rate (BMR)
• Increased heat production and oxygen expenditure
• Increased gluconeogenesis
• Increased glycolysis
• Increased glucose absorption into cells
• Increased lipolysis
• Increased protein turnover
• Promotes bone maturation and growth
• Increased cardiac output by influencing heart rate and contractility

Thyroid Function Tests (TFTs)

• Measure thyroid hormone components
• Common tests: TSH, free T3, and free T4
• TSH is very sensitive due to feedback loops
• Rare tests include total T4 & T3, T3 resin uptake, reverse T3, TRH, TBG, and thyroglobulin.

TFT Interpretation

• Specific values are crucial in diagnosing conditions.
• Misinterpretations lead to incorrect treatment

###Factors Affecting TFTs

• Non-thyroidal factors influence TFTs:
  • Acquired pituitary dysfunction
  • Changes in TBG levels
  • Increased free fatty acids
  • Decreased conversion of T4 to T3
  • Altered T3/reverse T3 ratio

Reference Ranges for TFTs

• TSH (0.5-4.7 mU/L)
• Total T4 (5-12 mcg/dL)
• Free T4 and Free T3 values are dependent on TSH levels, must be interpreted with TSH

TFT Interpretation Summary

• TSH high, free T4/T3 normal: Mild/Subclinical hypothyroidism
• TSH high, free T4/T3 low: Definite hypothyroidism
• TSH low, free T4/T3 normal: Mild/Subclinical hyperthyroidism
• TSH low, free T4/T3 high: Hyperthyroidism
• TSH low, free T4/T3 low: Non-thyroidal illness or rare pituitary dysfunction

Symptoms of Hypothyroidism

• Fatigue, cold intolerance, eyebrow hair loss, sleep problems, muscle aches, infertility, slow heart rate, weight gain, constipation, headache

Causes of Hypothyroidism

• Worldwide, iodine deficiency is most common
• Prevalence of spontaneous hypothyroidism is 1-2%, more common in older women.
• 10x more common in women compared to men.
• Primarily: Hashimoto's thyroiditis, surgery, radiation, postpartum thyroiditis, post-inflammatory thyroiditis, iodine deficiency, medications
• Secondarily: Pituitary/hypothalamic disorders.

Treatment Goals for Hypothyroidism

• Normalize hormone levels
• Provide symptom relief
• Prevent deficits in children

Symptoms of Hyperthyroidism

• Heat intolerance, fine/straight hair, bulging eyes, facial flushing, enlarged thyroid, tachycardia, elevated systolic BP, breast enlargement, weight loss, muscle wasting, lower extremity edema, clubbed fingers, tremors, diarrhea, menstrual irregularities

What is Hyperthyroidism?

• Excessive T3/T4 exposure, or overactive thyroid
• Estimated prevalence of 1.2%, peaking between 20 and 39.
• Common causes: Grave's disease, multinodular goiter, toxic nodules, thyroiditis

Graves' Disease

• Autoimmune disease, more common in women
• Typically enlarged thyroid (40-60g)
• Eye bulging and extra-thyroidal manifestations present
• Low TSH due to T3/T4 feedback

Other Causes of Hyperthyroidism

• Thyroid/pituitary tumors
• Thyroid toxicosis (accidental or intentional consumption of thyroxine).

Treatment Goals for Hyperthyroidism

• Eliminate excess hormones
• Minimize symptoms
• Prevent lasting effects
• Personalized therapy (medications, radioactive iodine, surgery)

Effects of Thyroid Hormones on Organ Systems

• Heart: Increases beta receptors
• Adipose tissue: Stimulates lipolysis
• GI tract: Increases tone & motility
• Nervous system: Affects development
• Skeletal system: Stimulates bone maturation & growth

Evaluation of Outcomes

• Monthly level evaluations until within normal ranges
• Documentation of hypo/hyperthyroidism symptoms

Key Points

• Hypothalamus-pituitary-thyroid axis controls hormone production
• Thyroid transports iodide, creating T3 & T4
• T3 is more active; T4 more abundant
• Thyroid hormones are mostly bound, with free forms being active
• Imbalances cause illnesses related to under or overactive hormone production