Session 8 ILOs - Hypothalamic pituitary axis and pituitary disorders

Question 1

Name the hormones produced by the hypothalamus (6) and briefly describe their biological roles

Answer 1

6 tropic hormones:

1. CRH - corticotropin releasing hormone
2. GHRH - growth hormone releasing hormone
3. GHIH/Somatostatin - growth hormone inhibiting hormone
4. GnRH - gonadotropin releasing hormone (causes LH and FSH release)
5. PIH - prolactin release-inhibiting hormone (Dopamine)
6. TRH - thyrotropin releasing hormone (stimulates thyroid hormone release)

Question 2

Name the hormones produced by the anterior pituitary gland (6) and briefly describe their biological roles

Answer 2

6 anterior pituiary hormones:
1. ATCH - adrenocorticotropin hormone
(secretion of hormones from adrenal cortex - mainly cortisol)
2. GH - Growth hormone
(stimulates growth and energy metabolism)
3. FSH - follicle stimulating hormone
(stimulates development of sperm and egg)
4. LH - luteinising hormone
(stimulates ovulation and secretion of sex hormones)
5. PRL - prolactin
(stimulates mammary gland development and milk secretion)
6. TSH - thyroid stimulating hormone
(stimulates secretion of thyroid hormones from thyroid gland)

Question 3

Describe the factors controlling GH secretion (long and short loop negative feedback)

Answer 3

Growth hormone is produced in the anterior pituitary
However, control is mediated by the hypothalamus by the following tropic hormone
- Stimulated by GHRH
- Inhibited by GHIH/somatostatin

Liver cells and skeletal muscle responds to GH and produce IGF (insulin-like growth factors)

GH controlled by short and long feedback mechanisms:
Short feedback = GH itself feedbacks back by stimulating GHIH/somatostatin
Long feedback = Mediated by IGFs, feeds back to the hypothalamus (stop GHRH release and stimulates GHIH/somatostatin release) AND feeds back to anterior pituitary directly (prevent GH release)

Question 4

Describe how GH exerts its effects on cells both directly and indirectly through Insulin like growth factors

Answer 4

Direct effect:
- Growth hormone binds to its receptor on target cells to activate intracellular signaling cascades that promote growth and regulate cellular metabolism

Indirect effect:

• Growth hormone stimulates (via the GH receptor) cells in the liver and skeletal muscle to secrete insulin like growth factors (IGFs/somatomedins)
• IGFs (mainly IGF-1) are hormones that also act to stimulate body growth and regulate metabolism in target cell (by binding to and activating IGF receptors)

Question 5

Describe the clinical feature of disease states resulting from malfunction of the hypothalamic pituitary axis

Answer 5

Pituitary disorders:

Acromegaly

• Excess growth hormone in adults caused by a GH-secreting pituitary tumour
• Results in large extremities

Prolactinoma

• Prolactin secreting tumour
• Can because menstrual disturbances, fertility issues etc.

Non-functioning pituitary adenoma

• No secretion of biologically active hormones caused by a non-functioning pituitary adenoma
• Clinical symptoms arise from mass effect

Cushing’s disease

• ATCH-secreting tumour
• Can result classical moon face, purple striae etc.

Diabetes Insipidus

• Excessive water loss due to vasopressin deficiency pituitary disease (either decreased production, or resistance to vasopressin)
• Can result in severe dehydration and hypernatraemia

Pituitary apoplexy
- Sudden vascular event (stroke!) which leads to reduced blood flow to the pituitary gland

Question 6

Outline the endocrine tests use to asses pituitary function

Answer 6

• MRI to see tumours
• Suppression-stimulation tests (e.g. Dexamethasone test uses high and low doses to figure out whether there is an issue with the hypothalamus, anterior pituitary or the adrenal glands)
• Visual field tests to see if optic nerve is compressed

Question 7

Outline management and treatment options for pituitary disorders

Answer 7

Treatments for the pituitary disorders:
Acromegaly
- Can remove GH secreting tumour
- Radiotherapy
- Drugs (e.g. dopamine agonist)

Prolactinoma
- Treated with TABLETS (dopamine agonist)

Non-functioning pituitary adenoma
- Dopamine agonist

Cushing’s disease

• Depends on what’s causing it!
• Caused by steroids: dose will be gradually reduced or stopped
• Caused by a tumour: surgery, radiotherapy or medicine e.g. Ketoconazole

Diabetes Insipidus
- Synthetic vasopressin

Pituitary apoplexy
- Made on an individual basis, could be surgery