49 Thyroid Physiology

Question 1

Describe the anatomy of the thyroid gland and where and how thyroid hormones are made and secreted.

Answer 1

• Butterfly gland: two lobes and isthmus located on trachea below Adam’s apple
  
  • Sympathetic innervation
• Thyroid follicles = functional unit of thyroid. Composed of single layer of cuboidal epithelial cells surrounding colloid. Main constituient of colloid is Thyroglobulin.
• Parafollicular cells secrete calcitonin
• TSH stimulates the expression of NIS, a Na/I symporter on basolateral membrane of cell (inhibitied by iodide)  Iodide crosses membrane and leaves apical side through pendrin transporter  iodide immediately oxidized to iodine and attached to tyrosine (attached to thyroglobulin) (Enzyme to make this happen is Thyroid peroxidase)
• Secretion: Thyroglobulin binds to megalin  endocytosis/lysosomal degradationin thyroid cell  leave cell into blood.

Question 2

Describe the functions of the thyroid hormones. What are the target cells of the thyroid hormones? Where are thyroid hormone receptors located (on cell surface or intracellular)?

Answer 2

• Important for maintaining energy homeostasis/regulating energy expenditure
  
  • Stimulate cell metabolism/activity
  • Increase in Cardiac Output, cause rise in cholesterol in blood
  • Important in development, differentiation, and maturation (mental retardation if defect)
• Thyroid hormone receptors located in nuclei of target cells, bound to or near thyroid hormone response element. Receptor also associated with retinoid X receptor. Faster response on ion influx affects in cardiovascular system. Hormone found virtually in all tissues.

Question 3

Describe the effects of too much or too little thyroid hormone. What is cretinism?

Answer 3

• Prolonged increase in TSH can cause throid enlargement (goiter)
• Deficiency: failure of body growth  mental retardation; tiredness, lethargy, constipation, decreased appetite, cold intolerance, hari loss, swelling of hands, reduced stroke volume, decreased CO
• Excessive: Palpitations, exercise impairment, widened pulse pressure, tachycardia, goiter, nervousness, irritability, weight loss, more bowel movements
• Cretinism: caused by extreme hypothyroidism in early life (extreme mental retardation, stunted physical growth)

Question 4

Explain why clinicians measure TSH. Describe the negative feedback circuits that control TSH release.

Answer 4

• Clinicians measure TSH as soon as possible after birth to prevent permanent mental retardation.
• Assumed that if thyroid hormone concentration in blood is low, then patient will have a higher than normal concentrarion of TSH and vice-versa.
• Free formed Thyroid hormones feedback to decrease the anterior pituitary secretion of TSH and hypothalamus. Also inhibited by stress and warmth. Incrased my cold.

Question 5

Describe the cause and effects of Graves’ disease and Hashimoto disease.

Answer 5

• Graves’ Disease: immune system problem where autoantibodies bind to and stimulate TSH receptors leading to production of excessive amounts of thyroid hormone.
• Hashimoto Disease: autoimmune disease where thyroid gland is attacked that reduces thyroid function

Question 6

Describe how thyroid hormones are transported in the blood. What is the major thyroid hormone binding protein in the blood? Is there another specific thyroid binding hormone? If there is what is its name? What other non-thyroid specific proteins bind and transport thyroid hormones?

Answer 6

• The are transported in the blood bound to plasma proteins. The major protein is Thyroxine-binding globulin (TBG). Transthyretin (TTR) is another that also transports retinol.
• Albumin and lipoproteins also transport thyroid hormones.

Question 7

Be able to define the following terms and/or describe the process: iodide trapping; organification

Answer 7

iodide trapping: Process of concentrating iodide in the cell

- organification: Process of binding iodine with the thyroglobulin

Question 8

Be able to give the role (and/or alternate name) of the following:
thyroxine-binding prealbumin; transthyretin; thyroglobulin; thyrotropin; thyrotropin-releasing hormone TRH

Answer 8

• Thyroxine-binding prealbumin: AKA transthyretin
• Transthyretin: transfer retinol and thryroxine in blood
• Thyroglobulin: Storage of thyroid hormones
• Thyrotropin aka TSH
• Thyrotropin-releasing hormone (TRH): released by hypothalamus to anterior pituitary to release prolactin and thyroid stimulating hormone

Question 9

Be able to briefly describe a goiter and give possible reasons for goiter formation.

Answer 9

Goiter: swelling of the neck resulting from enlargement of the throid gland. This could be due to an persistance of thyroid stimulating hormone.

Question 10

Be able to state if T4, TSH and TRH increase or decrease in patients with the following conditions: primary hypothyroidism; pituitary hypothyroidism; hypothalamic hypothyroidism; pituitary hyperthyroidism; grave’s disease

Answer 10

• Primary hypothyroidism: low free T4, high TSH and TRH
• Pituitary hypothyroidism: low T4, low TSH, high TRH
• Hypothalamic hypothyroidism: low T4, low TSH, low low TRH
• Pituitary hyperthyroidism high T4, high TSH, low TRH
• Grave’s disease: high T4, low TSH, low TRH