1010 - Hypothalamic-Pituitary Axis

Question 1

What are the two functional parts of the pituitary gland? What is its embryology?

Answer 1

Small outgrowth of forebrain, consisting of two functional parts:
Adenohypophysis (anterior pituitary) - Comes from Rathke’s pouch - ectoderm above mouth
Neurophypohysis (posterior pituitary) - Comes from Hypothalamus - Neural Crest ectoderm

Question 2

How does the hypothalamus communicate with the pituitary?

Answer 2

Anterior - releases ‘releasing hormones’ into the portal system at median eminence of hypothalamus, where they are delivered straight to pituitary.
Posterior - Supraoptic and paraventricular nuclei in hypothalamus, with axons descending to posterior pituitary.

Question 3

Which four ‘glands’ are dependent on inputs from the anterior pituitary?

Answer 3

Thyroid, Adrenal cortex, gonads, growth hormone (not gland)

Removal results in atrophy of these glands and hormone deficiency, with cortisol deficiency possibly leading to death.

Question 4

What are the long and short feedback loops in the hypothalamic-pituitary axis? What hormones are involved in each?

Answer 4

Short - feedback on hypothalamus by pituitary hormone. LH, ACTH, GH
Long - Feedback on hypothalamus by hormone released from target gland - Thyroxin, cortisol

Question 5

What are the major hormones from the posterior pituitary?

Answer 5

Vasopressin (ADH) - anti-diuretic

Oxytocin - causes milk let-down, bonding etc.

Question 6

Briefly outline vasopressin What happens in deficiency and excess?

Answer 6

Produced by supraoptic nucleus in hypothalamus. Serves to conserve water and concentrate urine by increasing water reabsorption in the collecting tubule.
Deficiency leads to peripheral diabetes insipidus - extreme thirst, polyuria, ↑ plasma sodium and osmolality.
Excess (SIADH) leads to water intoxication.

Question 7

What are the six major hormones of the anterior pituitary?

Answer 7

TSH - Thyrotrophin/Thyroid stimulating hormone
ACTH - Adrenocorticotrophic hormone
LH - Luteinising hormone
FSH - Follicle stimulating hormone
GH - Growth Hormone
Prolactin

Question 8

Provide a brief overview of thyrotrophin

Answer 8

Thyrotrophin (Thyroid stimulating hormone) released by anterior pituitary.
Stimulates thryoxine synthesis and thyroid growth.
Regulation via TRH (stimulates release), inhibited by feedback from thryoid hormones (T3, T4).
Acts via cAMP

Question 9

Provide a brief overview of Adrenocorticotrophin

Answer 9

Corticotrophin (ACTH) released by anterior pituitary.
Released as a prohormone - pro-opio-melanocortin
Serves to maintain adrenal cortical function (particularly cortisol and androgens).
Controlled by Corticotrophin Releasing Hormone, negative feedback by blood cortisol levels.

Question 10

Provide a brief overview of Luteinising Hormone

Answer 10

Luteinising hormone (LH) - released by anterior pituitary and works synergistically with FSH.
Males - Acts on leydig/interstitial cells of testes to produce testosterone, which provides negative feedback.
Females - Acts on interstitial cells of ovaries to produce oestrogen, androgens, and progestins. Oestrogen provides negative feedback.

Question 11

Provide a brief overview of Follicle Stimulating Hormone

Answer 11

Follicle stimulating hormone (FSH) - regulates gametogenesis. Released by anterior pituitary and works synergistically with LH.
Males - Acts on sertoli cells in testes to develop spermatozoa. Inhibited by inhibin.
Females - Acts on granulosa cell of ovarian follicle to induce ovulation. Inhibition is complex.

Question 12

Provide a brief overview of Prolactin

Answer 12

Prolactin - Lactation, and inhibition of reproductive hormone secretion. Secreted by lactotrophs of anterior pituitary.
Release inhibited by dopamine (“prolactin inhibitory factor”).
In animals, has osmoregulation and controls growth.
Pituitary stalk transection raises prolactin levels.

Question 13

Provide a brief overview of growth hormone

Answer 13

Growth Hormone - released by anterior pituitary at night, during growth stages.
Promotes growth - skeletal, muscular, visceral.
Anabolic, promotes positive nitrogen balance, and anti-insulin (keep glucose levels up).
Effects mediated by somatomedins.
Release stimulated by GHRH, stress, and exercise. Inhibited by somatostatin.

Question 14

What are the characteristics of the hypothalamic/pituitary releasing hormones?

Answer 14

Hypothalamic releasing hormones - travel from hypothalamus to ant. pituitary to stimulate release of anterior pituitary hormones.
Small peptides that are active at high concentrations and are rapidly degraded.
Portal system allows high concentrations to reach targets, while keeping low concentration in peripheral circulation.

Question 15

What are the seven major hypothalamic/pituitary releasing hormones? What are their effects?

Answer 15

Seven major hypothalamic/pituitary releasing hormones
CRH - Corticotrophin RH - Stimulates ACTH
TRH - Thyrotrophin RH - Stimulates thyrotrophin (TSH)
GHRH - Growth Hormone RH - stimulates GH
Somatostatin - inhibits GH
GnRH - Gonadotrophin (Luteinising hormone, Follicle Stimulating hormone) RH - Stimulates gonadotrophins
Dopamine - inhibits Prolactin
Vasopressin - stimulates ACTH

Question 16

Briefly outline the cause and symptoms of pituitary hyperfunction.

Answer 16

Usually caused by tumour.
Prolactin commonest hormone involved - causes galactorrhoea (women) and infertility (due to amenorrhoea in women, lack of testosterone in men).
If involves ADH, presents as SIADH.
If involves GH, presents as acromegaly (adulthood), or gigantism (childhood)
If involves ACTH, presents as Cushings Syndrome
TSH, LH, FSH, Oxytocin are exceedingly rare involvements.

Question 17

Briefly outline the cause and effects of pituitary hypofunction

Answer 17

Can involve any hormone except prolactin or oxytocin (no recognised syndrome for those)
Ranges from mild (GH) to lethal (ACTH)
Can be caused by tumour, trauma, infection, developmental issues.
May be combined hormones - panhypopituitarism.

Question 18

What are the mass effects of a pituitary tumour?

Answer 18

Growth, impingement on optic chiasm with bitemporal hemianopia.
Can also cause cranial Nn effects, hydrocephalus, hypopituitarism, diabetes insipidus (suprasellar tumours) and mild hyperprolactinaemia.
Note headaches are often absent.

Question 19

What are the clinical features of acromegaly

Answer 19

Increase in size (shoe, glove, hat, ring etc) after adulthood.
Increase in side of facial features after adulthood
Deep, cavernous voice
Fleshy, large hands and feat
Increased metabolic rate (sweating, warm skin)
Skin tags
Joint problems.

Question 20

What are the metabolic/visceral features of acromegaly?

Answer 20

Hypertension
Glucose intolerance
Cardiac enlargement and failure
Enlargement of viscera
Mortality doubled - 50% die <50yo

Question 21

What is the treatment for acromegaly?

Answer 21

Surgery (trans-sphenoidal or transfrontal)
Somatostatin agonists
Radiotherapy (several years for effect)
Dopamine agonists - promocriptine or cabergoline (not very effective).