Case 9

Question 1

What are the hormones the thyroid gland secretes?

Answer 1

• Thyroxine
• triiodothyronine
• calcitonin

Question 2

Which thyroid hormoen is more potent?

Answer 2

triiodothyronine

Question 3

What is the function of calcitonin

Answer 3

calcium metabolism

Question 4

How are T4 and T3 transported in the blood?

Answer 4

• T4 and T3 are bound to plasma proteins
• on entering the blood the T4 and T3 combine immediately with several of the plasma proteins which are synthesized by the liver
• T4 and T3 are released slowly to tissues

Question 5

How do thyroid hormones affect carbohydrate metabolism?

Answer 5

• stimulation of carbohydrate metabolism
• rapid uptake of glucose by cells
• enhanced glycolysis
• enhanced gluconeogenesisi
• increased rate of absorption from GI tract
• increased insulin secretion

Question 6

How do thyroid hormones affect fat metabolism?

Answer 6

• Lipid mobilised rapidly from fat tissue decreasing fat stores of the body to a greater extent than almost any other tissue element
• increases the free fatty acid concentration in the plasma and accelerates oxidation of FFA by cells

Question 7

How do thyroid hormones affect plasma and liver fats?

Answer 7

• Decreases level of cholesterol, phospholipids and triglycerides
• increases rate of cholesterol secretion in the bile and consequent in faeces
• Thyroid hormone induces increased numbers of LDL receptors on the liver cells leading to rapid removal of LDL from the plasma by the liver and subsequent secretion of cholesterol in the lipoproteins by liver cells

Question 8

How do thyroid hormones affect the basal metabolic rate?

Answer 8

• Thyroid hormone increases metabolism in almost all cells of the body, excessive quantities of the hormone can occasionally increase the basal metabolic rate
• when there are no thyroid hormones basal metabolic rate drops

Question 9

How do thyroid hormones affect the muscles?

Answer 9

• Effect on the function of the muscles - slight increase in thyroid hormone usually makes the muscles react with vigor but when the quantity of hormones becomes excessive muscles become weakened because of excess protein catabolism, lack of thyroid hormone causes the muscles to become sluggish and relax slowly after contraction
• Muscle tremor - caused by increased reactivity of neuronal synapses in the areas of the spinal cord that control muscle tone, the tremor is improtant for assessing the degree of thyroid hormone effect on CNS

Question 10

What effects does TSH have on the thyroid gland?

Answer 10

• ​Increased proteolysis of the thyroglobulin stored in follicles
• increased activity of the iodide pump
• increased iodination of tyrosine to form thyroid hormones
• increased size and increased secretory activity of the thyroid cells
• increased number of thyroid cells

Question 11

Describe the mechanism of TSH binding to thyroid gland?

Answer 11

• TSH binds to receptors on bassal membrane of the thyroid cell
• activates adenyl cyclase in the membrane increasing formation of cAMP inside the cell
• cAMP acts as a second messenger to activate protein kinase causing phosphorylation in the cell
• this results in increased secretion of the thyroid hormones and prolonged growth of glandular tissue

Question 12

Describe the hypothalamic pituitary axis?

Answer 12

• The hypothalamus releases TRH (thyrotropin hormone, which travels and acts on the anterior pituitary gland
• The anterior pituitary releases TSH (thyroid stimulating hormone)
• TSH stimulates the thyroid gland to make 2 hormones T3 and T4 which act on periphery tissues and also on the anterior pituitary gland as a negative feedback loop

Question 13

Describe the synthesis of thyroid hormones?

Answer 13

• TSH comes through the circulation stimulating the thyroid gland
• stimulates production of the thyroglobulin
• iodine is concentrated in the thyroid, iodine is added to the thyroglobulin by a process termed organification to make a xomplex of T4
• The complex fo T4 returns to the colloid into the cell to be recycled and then secrete the hormone
• thyroid gland stores the hormone
• if the hormone is infected and inflames it dumps out all of the stored thyroid hormone and this leads to thyrtoxicity

Question 14

What are colloids?

Answer 14

Stores of thyroid hormone, they cause the thyroid gland to become nodullar

Question 15

Describe the synthesis of T4 and T3 from tyrosine

Answer 15

• T4 and T3 are made from tyrosine amino acid
• An iodine molecule is added to tyrosine to form monoidotyrosine
• another iodine is added to form diodotyrosine
• when a 3rd iodine is added this forms T3 addition of another forms T4
• removal of an iodine from T3 forms an inactive form dioodothyronine T2
• Removal of iodine from T4 forms triiodothyronine forms an inactive form T3

Question 16

How is thyroid hormone metabolised in peripheral tissues and in the circulation?

Answer 16

• Thyroid hormoens are released from the gland into the circulation and peripheral tissues
• T4 loses an iodine molecule via selenodeiodinase enzyme 1 and becomes the active form T3 and does its biological activity
• T4 may lose iodine via selenodeiodinase 3 and becomes the inactive reverse T3 which is excreted
• Selenodeiodinase 3 may act on T3 and form an inactive T2

Question 17

Descibe the mechanism of thyroid action on cells?

Answer 17

• it acts as a nuclear homone, ligand for T3 nuclear hormone receptor
• fT3/4 enters the cell
• selenodeiodinase enzyme transforms T3 to T4 which enters the nucleus
• The T3 binds to receprots RXR and TR on DNA
• TR acts in the nucleus on gene expression
• this forms mRNA which is translanted into protein resulting in the action of T3

Question 18

What are thehalf lives of T4 and T3 respectively?

Answer 18

• T4 : 5 - 7 days
• T3 : 1 - 3 days

Question 19

If a goitre doesn’t move what does it suggest?

Answer 19

its a sign of cancer

Question 20

What is the aetiology of hypothyroidism?

Answer 20

• Chronic autoimmune thyroditis (Hashimoto’s disease)
• surgical removal of the thyroid gland
• Destruction with radioactive iodine
• replacement of thyroid gland by tumour
• drugs: lithium or interferon, amiodarone
  *

Question 21

What are the clinical features of hypothyroidism?

Answer 21

• fatigue
• dry skin
• hoarseness
• constipation
• decreased concentration
• ireggular or heavy menses
• weight gain due to fluid retention
• cold intolerance
• ataxia
• memory and mental impairement
• depression
• infertility

Question 22

What does a patient with reduced ft4 and fT3 and an increases TSH get treated with?

Answer 22

• Treat with thyroxine

Question 23

What does a patient with normal thyroid hormones and an increased TSH get treated with?

Answer 23

• Thyroxine if the symptoms are present if the symptoms are not it suggests subclinical hypothyroidism

Question 24

What does a patient with reduced TSH, fT4, fT3 suggest?

Answer 24

potential pituary disease/ sick euthyroid syndrome

Question 25

How is hypothyroidism treated?

Answer 25

* Once daily thyroxine, lifelong usually 100mcg * The goal is to normalise TSH,r epeat blodo test after 4 - 6 weeks

Question 26

What is the aetiology of hyperthyroidism?

Answer 26

* Toxic diffuse goitre - Graves disease (autoimmune) it is associated with other features * Toxic multinodular goitre (Plummer's disease) * painful subacute thyroditis, silent thyroditis, including lymphocytic and post partum variation * excessive ingestion of thyroid hormone or excessive pituitary TSH or trophoblastic

Question 27

What are the signs and symptoms of hyperthyroidism?

Answer 27

* nervousness/irritability * palpitations/tachycardia * tremor * heat intolerance * weight loss/gain * sudden paralysis * hyperactivity * dyspnoea * weakness and fatigue * insomnia * hair loss * sore throat

Question 28

What are the differential diagnosis of hyperthyroidism?

Answer 28

* Transient thyroditis * Graves disease * Toxic nodule (part of multinodular goitre)

Question 29

Describe the pathophysiology of Graves disease?

Answer 29

* Antibodies to the TSH receptor, thyroid follicular cells in response to interferon gamma produced by infiltrating T cells express HLA class II molecule * Allowing presentration of TSH receptor to activated T cells and initiation of the autoimmune cascade * Anti - TSH receptor antibodies cause T4 hyperproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells

Question 30

What is the treatment of hyperthyroidism?

Answer 30

* Surgery - pregnant patients with hyperthyroidism who are intolerant of anti thyroid drugs, may result in hypo-parathyroidism and vocal cord paralysis in a small proportion of patients * Anti-thyroid drugs * **Methimazol** * **prapylthiouracil** * **​**Radioactive iodine - safe some patients become hypothyroid

Question 31

What are the risk factors of Graves?

Answer 31

* Female sex * family history * tobacco usage * lithium therapy * high iodine intake * radiation

Question 32

What are the effects of thyroid hormones on the cardiovascular system?

Answer 32

* T3 affects the basal metabolic rate by altering oxygen consumption in peripheral tissues thermogenesis * T3 dilates reisstance arterioles reducing system vascular resistance this decline stimulates renin release and sodium reabsorption resulting in an expansion of blood volume and an increase in venous return to the heart * Erythropoietin stimulation contributies to blood glow * heart rate and cardiac contractility both increase * the net effect is a rise in systolic blood pressure and widening pulse

Question 33

What are the consequences of hyperthyroidism?

Answer 33

* Atrial arrhythmias (atrial fibrillation) * pulmonary hypertension * left ventricular hypertrophy * heart failure

Question 34

What is graves orbitopathy and how is it treated?

Answer 34

* Inflammation of the extraocular muscles causing increased retro-orbital pressure * Treated with artificial tears, immunosupression

Question 35

What are the effects of graves disease on pregnancy?

Answer 35

* sspontaneous abortion * premature labour * small birth weight * congestive cardiac failure * pre-eclampsia