Thyroid and Adrenal Glands

Anatomy of thyroid gland

• Follicle

• Colloid

• Parafollicular cells

• 2 (connected) lobes just inferior to the thyroid cartilage (highly vascularized)

• Follicle: the smallest functional unit

  • Fluid (colloid) filled sphere lined by simple cuboidal epithelial cells (follicle cells)

  • Synthesis/release of thyroid hormone

• Parafollicular cells: C cells

  • Synthesis/release of calcitonin hormone

Calcitonin

• Released when there is too much calcium in the blood

• Inhibit osteoclasts

• Increase excretion of calcium by the kidney

• Prevent absorption of calcium by the digestive system

Thyroid hormones

• Derived from the amino acid tyrosine

• Iodine: is an essential dietary element: required for synthesis of thyroid hormones

• Two forms of thyroid hormone:

  • T4 → thyroxine

    • Contains 4 iodine atoms

  • T3 → triiodothyronine

    • Contains 3 iodine atoms

• T4 is the most abundant form of thyroid hormone

• T3 is the most biologically active form of thyroid hormone

• T4 that is released into blood stream from thyroid gland is able to be de-iodinated into the most active form (T3) in some target cells including the kidney and the liver

Synthesis of thyroid hormones

• Iodide ions are transported FROM the blood into the follicular cell - TSH dependent (active transport)

• Iodide ions converted into iodine atoms by thyroid peroxidase (then paired with thyroglobulin)

• In colloid T3 and T4 are formed within thyroglobulin

• Endocytosis of thyroglobulin

• Lysosomal degradation of thyroglobulin to release T3 and T4

• Diffusion of thyroid hormones into plasma

• Transport in plasma

Regulation of thyroid hormone where?

• Hypothalamus

• Anterior pituitary

• Thyroid gland

Hypothalamus - regulation of thyroid hormone

• TRH: thyrotropin releasing hormone

• Action → synthesis/release of TSH from anterior pituitary

Anterior pituitary - regulation of thyroid hormone

• TSH: thyroid stimulating hormone

• Action → synthesis and release of thyroid hormones

Thyroid gland- regulation of thyroid hormone

• Thyroid hormones

  • Effects on target cells

  • Negative feedback on hypothalamus and anterior pituitary

    • Mediated by levels of thyroid hormone (going to release less TRH → less TSH → less thyroid hormones)

Actions of thyroid hormones

• Stimulate growth and metabolism

• Affects almost every cells of the body

  • Fast, strong, short increase in rate of cellular respiration

3 receptor locations within a cell

• Cytoplasmic receptors: storage

• Mitochondria receptors: increase rate of ATP production

• Nucleus: increase gene transcription

  • Ex: sodium-potassium pump, glycolytic enzymes

Specific actions of thyroid hormones

• Increased metabolic rate (heat production) leads to increased body temperature; true for children, little/no effect in adults

• Increased heart rate and blood pressure

• Simulate red blood cell formation - increase oxygen delivery

• Accelerate turnover of minerals in bone (stimulate osteoclasts)

Hypothyroidism

• Deficient thyroid hormone

• Most common cause worldwide: iodine deficiency

• Symptoms:

  • Tiredness, weakness

  • Dry skin

  • Feeling cold

  • Hair loss

  • Difficulty concentrating

  • Constipation

  • Weight gain with poor appetite

• Goiter: abnormal enlargement of thyroid

Hyperthyroidism

• Excess thyroid hormone

• Most common cause: Grave’s disease (autoimmune disorder)

  • Antibody activates TSH receptor on thyroid gland → thinks TSH is present → produces a lot of thyroid hormone

  • Goiter and increased T4 and T3

• Symptoms:

  • Increased: metabolism, food intake, weight loss, sweating, muscle weakness, nervousness, heart rate

  • Diarrhea and Polyuria

• Graves opthalmopathy

  • Eye bulging

  • Anti-body binds to soft tissue around eye to fat → pushes eye forward

Parathyroid glands

• 4 small glands embedded on posterior surface of thyroid

• Collection of parathyroid hormone (PTH) in response to decreases blood ca²⁺ levels

Effects of parathyroid hormone

• Simulates osteoclasts

• Enhances reabsorption of Ca²⁺ by kidney

• Stimulates formation of calcitriol by kidney (promotes absorption of Ca²⁺ from digestive system)

Physiological roles of calcium

• Normal plasma levels - 8.8-10.2 mg/dL

• Nerve and muscle excitation

• Muscle contraction

• Blood coagulation

• Bone mineral balance

• Intracellular signaling

Anatomy of the adrenal glands

• Retroperitoneal above each kidney

• Composed of:

  • Outer cortex: corticosteroids (2 dozen steroid hormones)

  • Inner medulla: epinephrine and norepinephrine

• Outer cortex further divided into

  • Zona glomerulosa

  • Zona fasiculata

  • Zona reticularis

Hormones of the adrenal cortex

• All adrenocortical hormones are steroids and are derived from cholesterol

  • Mineralcorticoids

  • Glucocorticoids

  • Adrenal androgens

Mineralcorticoids - give example

• Zona glomerulosa

• Regulation of sodium potassium levels in ECF

• Ex: Aldosterone: released in response to low levels of Na”

  • Reabsorption of Na+ (and water) from forming urine in kidney, sweat glands, salivary glands at the expense of K+

Glucocorticoids - example

• Zona fasiculata

• Regulation of carbohydrate levels in ECF

• Anti-inflammatory properties

• Cortisol, corticosterone: speed up rate of glucose synthesis (gluconeogenesis) and glycogen formation

Adrenal androgens

• Zona reticularis

• “Weak” androgens, useful as precursors for the production of estrogen and testosterone by other tissues

• Influence muscle mass and sex drive in adult women

How is cortisol regulated

• Hypothalamic pituitary adrenal (HPA) axis

  • Release of CRH is increased by stressors

  • Inhibition of release of CRH is initiated by cortisol (negative feedback loop)

  • Chronic high levels of cortisol desensitize receptor cells in the brain

    • Effect: continued release of CRH and continued production of cortisol

  • Chronic stress leads to chronically high levels of cortisol

Short term and long term stress response

• Stress results from changes in the external environment

• → Neural signals from sensory receptors

• Hypothalamus

Short term stress response

• → Neural sympathetic impulses

• → Norepinephrine releases and

• → Adrenal medulla

• → Hormonal signals (epinephrine and norepinephrine released)

• → short term “fight or flight” or alarm stage

  • Blood glucose increases

  • Blood glycerol and fatty acids increase

  • Heart rate increases

  • Blood pressure rises

  • Breathing rate increases

  • Air passages dilate

  • Pupils dilate

  • Blood flow redistributes

Long term stress response

• → Hormonal CRH released

• → Anterior pituitary

• → Hormonal ACTH released

• → Adrenal cortex

• → Hormonal cortisol released

• → Long term adjustment or resistance stage

  • Increase in blood concentration of amino acids

  • Increased release of fatty acids

  • Increased glucose formed from non-carbohydrates - amino acids