Session 11 ILOs - Hypothalamic pituitary axis and pituitary disorders Flashcards
Understand the relationship between the hypothalamus and the posterior pituitary
- The hypothalamus and pituitary gland form a complex functional unit that serves as the major link between the endocrine and nervous systems (hypothalamic pituitary axis)
- The posterior pituitary is physically connected to the hypothalamus, since the hypothalamus drops down through the infundibulum to form the posterior pituitary
- Hypothalamus synthesises Oxytocin and ADH and they are released by the hypothalamus to have direct effects on distant target tissues
- Oxytocin and antidiuretic hormone produced by magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei of the hypothalamus.
What is the hypothalamic pituitary axis?
Where does the pituitary gland sit in relation to the hypothalamus?
- The pituitary gland sits beneath the hypothalamus in a socket of bone called the sella turcica
Name the hormones produced by the hypothalamus (6+2) and briefly describe their biological roles
6 tropic hormones:
These have direct effects on the release of anterior pituitary hormones
- CRH - corticotropin releasing hormone (regulates adrenocorticotropic hormone)
- GHRH - growth hormone releasing hormone
- GHIH/Somatostatin - growth hormone inhibiting hormone
- GnRH - gonadotropin releasing hormone (causes LH and FSH release)
- PIH - prolactin release-inhibiting hormone (Dopamine)
- TRH - thyrotropin releasing hormone (stimulates thyroid stimulating hormone release and has minor +ve control on prolactin)
The following 2 hormones are produced in the hypothalamus but released from the posterior pituatry:
- OT Oxytocin
(Milk let down and uterus contractions during birth) - ADH Antidiuretic hormone (also called vasopressin) (Regulation of body water volume)
Name the hormones produced by the anterior pituitary gland (6) and briefly describe their biological roles
6 anterior pituiary hormones:
1. ACTH - adrenocorticotropic hormone
(secretion of hormones from adrenal cortex - mainly cortisol)
2. GH - Growth hormone
(stimulates growth and energy metabolism and stimulates IGF’s - insulin - like growth factors)
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)
Describe the factors controlling GH secretion (long and short loop negative feedback)
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 loop negative feedback = Mediated by GH itself by stimulating GHIH/somatostatin release
Long loop negative feedback = Mediated by IGFs:
- Feeds back to the hypothalamus to inhibit GHRH release and stimulates GHIH/somatostatin release
- Inhibits the release of GH from the anterior pituitary
Describe how GH exerts its effects on cells both directly and indirectly through Insulin like growth factors
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 (IGF-1 - Adult growth, IGF-2 - Fetal growth) are hormones that also act to stimulate body growth and regulate metabolism in target cell (by binding to and activating IGF receptors)
Describe the clinical feature of disease states resulting from malfunction of the hypothalamic pituitary axis
Pituitary disorders:
Acromegaly (4)
- Excess growth hormone in adults caused by a GH-secreting pituitary tumour
- Results in large extremities - large hands and feet
- Gradual changes in features over years
- Can cause diabetes and high BP
Prolactinoma (4)
- Prolactin secreting pituitary tumour
- Bigger than 1cm = macro-adenoma
- Smaller than 1cm = micro-adenoma
- Can because menstrual disturbances, fertility issues, galactorrhea (milk production outside of pregnancy)
Non-functioning pituitary adenoma (4)
- No secretion of biologically active hormones
- May secrete inactive hormones
- Clinical symptoms arise due to the lump or hypopituitarism
- Hypopituitary bloods with disinhibition hyperprolactinaemia
Cushing’s disease
- caused by a benign pituitary adenoma secreting ACTH
- Can result classical moon face, purple striae, abdominal obesity, thin and weak arms and legs etc…
Diabetes Insipidus (3)
- Excessive water loss due to insufficicent ADH release (so you are unable to reabsorb water back into the blood)
- Can result in severe dehydration and hypernatremia
- Large quantities of pale (insipid) urine
Pituitary apoplexy (5)
- Apoplexy is old fashioned word for stroke
- Sudden vascular event in a pituitary tumour which leads to reduced blood flow to the pituitary gland
- You have either had a heamorrhage within the tumour (bleeding)
- On an infarction within the tumour (blood supply cut off)
- Sudden onset headache, double vision, cranial nerve palsy, hypopituitarism - cortisol deficiency is most dangerous
Outline the endocrine tests use to asses pituitary function
3 Main test types: imaging, visual fields and biochemical assessment
Imaging:
- MRI to see tumours
Visual fields:
- Visual field tests to see if optic nerve is compressed
Biochemical assessment :
- Basal (one off) blood test for: Thyroid axis - fT4, TSH Gonadal axis - LH, FSH testosterone - men oestradiol - women Prolactin axis - serum prolactin
- Dynamic tests (adrenal/HPA and growth hormone) : Stimulation tests if suspect deficiency Suppression tests if suspect excess Adrenal - cortisol at 09:00am Growth hormone - GH or IGF-1
Adrenal axis: Deficiency/under active adrenal gland • Synacthen test • Insulin stress test Excess • Dexamethasone suppression test
GH axis: Deficiency • Insulin stress test Excess • Glucose tolerance test
Outline management and treatment options for pituitary disorders
Treatments for the pituitary disorders:
Acromegaly
- Can surgically remove GH secreting tumour (Trans-sphenoidal surgery)
- Radiotherapy
- Drugs (e.g. dopamine receptor agonist - Bromocriptine and somatostatin analogue - SSA)
Prolactinoma
- Treated with TABLETS (dopamine receptor agonist - Bromocriptine) - NOT OPERATION
Non-functioning pituitary adenoma
- Dopamine receptor agonist - Bromocriptine
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 (nasal spray, tablet, injection)
Pituitary apoplexy
- Made on an individual basis, could be surgery
Understand the relationship between the hypothalamus and the anterior pituitary gland
- The hypothalamus and pituitary gland form a complex functional unit that serves as the major link between the endocrine and nervous systems (hypothalamic pituitary axis)
- The hypothalamus secretes tropic hormones which have direct effects on the release of anterior pituitary hormones
