PA20321 Pharmacology Vertical Theme

Question 1

What is the hypothalamo-pituitary axis?

Answer 1

The hypothalamus is part of the brain that monitors many aspects of the state of the body systems, integrating a large amount of information from many sensory pathways. With regards to the endocrine system it is recognised as being closely linked with the pituitary gland, a small gland hanging from underneath the hypothalamus. There are two parts to the pituitary gland, an anterior part (the adenohypophysis) and a posterior part (the neurohypophysis).

Question 2

What can pituitary disease cause?

Answer 2

• Over- or underactivity of each of the hypothalamic-pituitary-end-organ axes
• Benign pituitary tumours (adenomas) are the most common cause (90%)
• Vision loss due to compression of the optic chiasm is a common comorbidity

Question 3

What is Hypopituitarism?

Answer 3

• Diminished hormone secretion by the pituitary gland, causing dwarfism in children and premature ageing in adults
• Rare
• Managed by replacement therapy with the appropriate hormone

Question 4

Explain different types of thyroid hormones

Answer 4

• Triiodothyroxine (T3) and Thyroxine (T4: 90% of total)
• T4 regarded as a prohormone for T3
  : has a lower affinity
  : T4 is convereted to T3 in peripheral tissues by Type I and Type II deiodinases
  : Half-life of T3 (1day) is shorter than T4 (6days)
• Thyroid hormones circulate bound to plasma proteins (>99%)
  : thyroxine-binding globulin (TBG), transthyretin (TTR) and thyroxine binding prealbumin
• Thyroid hormones regulate BMR and enhance actions of cathecholamines

Question 5

What is Pendrin and how does it contribute to thyroid hormone synthesis?

Answer 5

• Pendrin is a sodium-independent chloride/iodide transporter and acts as an antiporter anion exchanger protein
• Pendrin presents at the apical (luminal) membrane of follicular cells in the thyroid gland, where it transports iodide from cytoplasm to follicle lumen. Its activity is necessary for production of thyroid hormone

Question 6

What are Thyroid Oxidase (TO) and Thyroid peroxidase (TPO) responble of?

Answer 6

• iodination of tyrosyl residues in TG (thyroglobulin) and coupling reactions

Question 7

What are the physiological effects of thyroid hormone in the following targets?

1. Cardiovascular system
2. Bone
3. Respiratory system
4. GI system
5. Blood
6. Neuromuscular function
7. Carbohydrate metabolism
8. Lipid metabolism
9. Sympathetic nervous system

Answer 7

1. Cardiovascular system
   - Increases HR and Cardiac Output
2. Bone
   - Increases bone turnover and resorption
3. Respiratory system
   - Maintains normal hypoxic and hypercapnic drive in respiratory centre
4. GI system
   - Increases gut motility
5. Blood
   - Increases RBC 2, 3-BPG faciliating oxygen release to tissues
6. Neuromuscular function
   - Increases speed of muscle contraction and relaxation and muscle protein turnover
7. Carbohydrate metabolism
   - Increases hepatic gluconeogenesis/ glycolysis and intestinal glucose absorption
8. Lipid metabolism
   - Increases lipolysis and cholesterol synthesis and degradation
9. Sympathetic nervous system
   - Increases cathecholamine sensitivity and b-adrenergic receptor numbers in heart, skeletal muscle, adpose cells and lymphocytes
   - Decreases cardiac a-adrenergic receptors

Question 8

What is Hypothyroidism?

Answer 8

• Abnormally low activity of the thyroid gland, resulting in retardation of growth and mental development in children and adults.
• One of the most common endocrine disorders
• Usually primary (disease of thyroid) but can be secondary (decreased TSH)
• Most common form is atrophic (autoimmune) hypothyrodism

Question 9

What are clinical features of hypothyroidism?

Answer 9

• Tiredness
• Weight gain
• Cold intolerance
• Goitre (swelling in neck)
• Mental Slowness
• Dry skin and hair
• Bradycardia
• Slow-relaxing reflexes

Question 10

What is diagnosis and management of Hypothyroidism

Answer 10

Diagnosis
- Serum TSH ( increased level confirms primary hypothyroidism)
: low free T4 confirms the diagnosis and excludes TSH deficiency (secondary hypothyroidism)

Management
- Replacement therapy with levothyroxine (lifelong)

Question 11

What is Hyperthyroidism?

Answer 11

• Over-activity of the thyroid gland, resulting in a rapid heartbeat and an increased rate of metabolism

Question 12

What is diagnosis and management of Hyperthyroidism

Answer 12

Diagnosis
- Serum TSH (↓< 0.05 mU/L)
: raised T3 (more sensitive) or T4 confirms the diagnosis

• TSHR-Ab usually present (80%) but not routinely measured
• Thyroid peroxidate (TPO) and thyroglobulin antobodies usually present

Management
1. Antithyroid drugs e.g Carbimazole

2. Radioiodine
3. Surgery

Question 13

What are the hormones secreted by endocrine pancreas?

Answer 13

B cells

• produce and release insulin
• stimulates glucose utilisation and uptake

a-cells

• produce and release glucagon
• increases breakdown of glycogen and glucose release

Question 14

What features does insulin have regarding plasma levels?

Answer 14

• Decrease glucose
• Decrease amino acids
• Decrease FFAs
• is Anabolic

Question 15

What features does glucagon have regarding plasma levels?

Answer 15

• Increases glucose
• Increase ketons
• is Catabolic

Question 16

What is Diabetes Mellitus?

Answer 16

• Characterised by hyperglycaemia

- Fasting blood glucose >7mmol/L

Question 17

What is Type 1 diabetes mellitus (T1DM)?

Answer 17

• The body is unable to produce any insulin
• Usually appears in childhood and before age of 40
• Sudden onset
• Accounts for between 5-15% of all people with diabetes