E6 - Hypothalamus & pituitary Flashcards
What is the clinical relevance of pituitary tumours?
- Most common cause of pituitary disease (adenomas)
- Mostly benign/slow-growing (years)
- Cause problems as pressure on surrounding structures (due to location); greater intra-cranial pressure, close to optic nerve = headaches/visual disturbances
What problems can pituitary tumours cause?
- Over-production of a pituitary hormone (hypersecretion)
- Inadequate production of other remaining hormones (squeezing/squashing other pituitary cells; hyposecretion)
- Local effects on anatomically-related structures (e.g. visual disturbances, headaches; greater intra-cranial pressure)
What is hypopituitarism?
Inadequate secretion of pituitary gland hormones causing dwarfism in children and premature aging in adults
What is the relationship between the hypothalamus and the anterior pituitary with regards to cell bodies etc?
- Cell bodies located in the hypothalamus: arcuate, ventromedial and preoptic nuclei, give signal for hormone synthesis at anterior pituitary
- Releasing factors pass along portal vessels to reach the capillary bed of the anterior pituitary
What is the relationship between the hypothalamus and the posterior pituitary with regards to cell bodies etc?
- Cell bodies of the paraventricular (PVN) and supraoptic (SON) nuclei located in the hypothalamus - site of hormone synthesis ‘neuro’
- Hormones oxytocin and vasopressin respectively stored in the axon terminus of the posterior pituitary before release
Where is growth hormone synthesised, what does it do (briefly) and where does it act?
- Synthethised in somatotrophs in the anterior pituitary
- Has a major role in growth & development (particularly linear growth; elongation of long bones) + affects metabolism
- Acts via GH receptor on target cells
What does the hormone prolactin do?
- Stimulates mammary glands to produce milk (lactation) and promotes growth & development of breasts
- Inhibits GnRH release
- Synthesised in lactotrophs (/mammo-)
What does ACTH do?
- Adrenocorticotropic hormone
- Stimulates synthesis/release of cortisol
- Synthesised from a very large precursor glycoprotein known as pro-opiomelanocortin (POMC)
What does TSH do?
- Thyroid-stimulating hormone
- Stimulates synthesis and release of thyroid hormones
What is LH (luteinizing hormone)?
- Stimulates steroid hormone synthesis (e.g. testosterone)
- Causes ovulation/formation of corpus luteum
What is FSH?
- Stimulates follicular development (ovaries) and spermatogenesis (testes)
Which anterior pituitary hormones are single-chain polypeptides with disulfide bonds?
- Somatotropes(trophs) e.g. somatotropin (growth hormone, GH)
- Lactotropes(trophs) e.g. prolactin
Which anterior pituitary hormone is a small peptide?
Corticotrope(trophs) e.g. corticotropin (adrenocorticotropic hormone, ACTH)
Which anterior pituitary hormones are glycoproteins with 2 subunits?
- Thyrotropes(trophs) e.g. thyrotropin (thyroid stimulating hormone, TSH)
- Gonadotropes(trophs) e.g. LH, FSH
What is the difference between tropic and trophic?
- Tropic: ‘turning’; affecting activity of an endocrine gland
- Trophic: ‘feed, grow’; promoting growth, tissue integrity
Describe the OG endocrine axis.
- Hypothalamus:
Releasing hormone
+/- Anterior pituitary:
Tropic hormone (short -ve feedback to hypothalamus)
+ Peripheral endocrine glands
Peripheral hormone (long -ve feedback to ant pit. and hypo.)
+ Target cell response (some -ve feedback to hypo.)
What effect does hypothalamic stimulation usually have on the anterior pituitary and which hormone is the exception?
- Hypothalamus usually exerts stimulatory influence on the anterior pituitary (e.g. on LH/FSH, GH, TSH, ACTH)
- Prolactin is the exception; under major inhibitory influence (from dopamine from hypothalamus) unless stimulated by TRH
What are the direct actions of growth hormone (somatotropin)?
On metabolism:
- Increases lipolysis (catabolic; triglycerides broken down to fatty acid + glycerol)
- Increased AA uptake and protein synthesis (anabolic)
- Increased hepatic glucose output (gluconeogenesis) & decreased glucose uptake (fat/adipose, skeletal muscle)
Anti-insulin (diabetogenic; counter-regulatory to insulin)
- NET effect, shift of fuel source from CHOs to fats
- GH elevates blood glucose; secondary cause of diabetes
What are the indirect actions of growth hormone (somatotropin)?
Promotes growth:
- Stimulates release of growth factors such as IGF-I (insulin-like GF) & II (somatomedins) from liver (and other cell types)
How does growth hormone stimulate growth and what are the processes that are stimulated?
Growth is via the action of IGF-I on cells:
- Stimulate protein synthesis, increase cell size (hypertrophy) increasing lean body mass
- Stimulate cell division, increase cell number (hyperplasia) increasing size of individual organs
- Promotes skeletal growth (increasing linear growth = height)
(Not about fat accumulation)
How is GH release controlled?
Hint: re. endocrine axis
- Environmental stimuli: sleep, stress, exercise
- Nutrient stimuli: decrease glucose, decrease [FFA], increased [AA]
HYPOTHALAMUS
+ GHRH/ - SST (somatostatin)
ANTERIOR PITUITARY
+ GH > direct effect on metabolism
> Short feedback loop to hypothalamus
LIVER/OTHER TISSUES
+ Somatomedins (e.g. IGF-I) > indirect effect increasing growth
> Long feedback loop to Liver + Hypothalamus
What is the pattern of GH secretion throughout the day/throughout life?
Day:
- 70% of total daily GH released during sleep (pulsatile release)
Life:
- Mean daily secretions are high during childhood reaching a peak at puberty
- Fall to lower concentrations in adulthood
- Fall in GH in later life partially responsible for some signs of aging
What can occur as a result of GH (growth hormone) deficiency?
- Stunted growth in children (pituitary dwarfism; no long bone development)
- Deficiencies in adulthood:
> psychological changes,
> malaise, excessive tiredness, anxiety, depression
> osteoporosis
> poor muscular tone, decrease in lean body mass
> impaired hair growth
> increase in adipose tissue
Normally signs associated with old age.
How is GH deficiency treated?
Recombinant human growth hormone (anabolic effects abused in sport)
What is the result of excess growth hormone?
- Gigantism (accelerated growth in children)
- Acromegaly (adults)
What are some of the common characteristics of acromegaly?
- Coarsening of facial features (enlarged jaw/brow/chin etc.)
- Enlarged hands and feet (soft tissue expansion; bone growth on existing growth and not long bone growth like gigantism)
- Headaches, visual disturbances (pituitary tumour pressure)
- Sleep apnoea, general tiredness
- Hypertension, cardiomegaly (enlarged heart)
- Glucose intolerance (DM)
What most often causes excess growth hormone release and how is it treated?
- Most often due to GH-secreting tumour
Treatment:
- Surgery/radiotherapy
- Or inhibit GH release with somatostatin analogues
- Some tumours respond to dopamine receptor agonists (some GH-adenomas acquire dopamine receptor expression)
What is the net result of prolactin inhibiting GnRH release?
- Inhibiting GnRH release means breastfeeding women have no menstrual cycle; aiding lactation
What is the result of excess prolactin and what is it caused by?
- Hyperprolactinaemia
- Cause: prolactinoma (pituitary tumour making too much prolactin)
What are the symptoms of hyperprolactinaemia and how is it treated?
Symptoms:
- Loss of fertility/libido (inhibited GnRH = inhibited menstruation)
- Galactorrhoea (dilute, milky discharge)
Treatment:
- Dopamine receptor agonists; inhibit prolactin secretion and shrink tumour
- Surgery/radiotherapy considered when prolactinoma resistant to drug therapy
What the main hormones released at the posterior pituitary?
- (Arginine) Vasopressin (AVP;ADH)
- Oxytocin
- Made in cell bodies in the hypothalamus (supraoptic/paraventricular nuclei), travel down axons and stored at the end (axon termini) until release
What is vasopressin release triggered by?
Stimulated by:
- increase in body fluid osmolality (osmotic control)
- fall in blood volume/pressure (haemodynamic control)
- (acute) stress
What are the actions of vasopressin (ADH)?
- Blood vessels: vasoconstriction, via V1 receptors (high [AVP])
- Kidney: DCT and CD see increased permeability via insertion of aquaporins (via V2 receptors)
- Stimulates ACTH release
What disease state is as a result of vasopressin deficiency?
Diabetes insipidus (different from DM):
- Pituitary DI
- Nephrogenic DI
What does pituitary diabetes insipidus entail and how is it treated?
Inadequate release of AVP (ADH) results in:
- Polyuria (large volumes of dilute urine excreted)
- Resulting polydipsia (dehydrated thus thirsty)
Treatment:
- Desmopressin (synthetic ADH analogue, has no vasoconstrictor activity)
What does nephrogenic diabetes insipidus entail and how is it treated?
As a result of:
- Inadequate response in collecting ducts to ADH
- Results in polyuria and resulting polydipsia as Pituitary DI
Treatment:
- Diuretics
What disease state is as a result of vasopressin excess?
Syndrome of inappropriate ADH secretion (SIADH):
- Retention of water = small urine volume, highly concentrated (even with fluid excess)
- Hyponatraemia (due to dilutional effect; not Na+ depletion)
How is SIADH treated?
- Treat underlying cause (CNS pathologies, malignancy, CHS drugs; isn’t a tumour of posterior pituitary though)
- Restrict water intake
- If ineffective, block ADH action in kidney using V2 receptor antagonist
How is oxytocin release stimulated and how is it regulated?
- Stimulated by suckling and cervical stimulation (parturition; giving birth)
- Release is via positive feedback control
What are the actions of the posterior pituitary hormone oxytocin?
- Stimulate ‘milk let-down’, expression of breast milk
- Uterine smooth muscle contraction
- Maternal behaviour/social behaviour/social bonding
