Hypopituitarism

Question 1

What is meant by Hypopituitarism?

Answer 1

Hypo = underactive

So underactive pituitary gland

Question 2

What are the 5 anterior pituitary hormones?

Why is aldosterone not under the control of ACTH?

Answer 2

GH - promotes growth
Prolactin - lactation
Ganadotrophins (LH and FSH) - oestrogen in women / testosterone in men
TSH - stimulates the thyroid to produce T3 and T4
ACTH - tells adrenal cortex to make cortisol

Aldosterone is under the control of the renin-angiotensin system, and so is not controlled by ACTH

Question 3

What does the anterior pituitary function and regulation rely on?

Answer 3

Releasing and inhibiting factors from the hypothalamus that travel via the portal circulation (down the pituitary stalk) into the anterior pituitary

Question 4

What occurs in anterior pituitary failure?

What are the differences between primary and secondary failure?

Answer 4

The anterior pituitary is unable to produce 1 or more of its hormones, which then have a knock on effect onto the functions of other glands / hormones

Primary = issue within the gland itself
Secondary = issue within another gland that is no longer stimulating the gland in question

Question 5

Primary vs secondary hypothyroidism?

Which is more common?

Answer 5

Primary = autoimmune damage to the thyroid gland itself, there is no negative feedback due to lack of T3 and T4 production, resulting in high TRH and TSH levels

Secondary - nothing wrong with the thyroid gland itself, damage elsewhere leading to lack of signalling e.g. no TSH production leads to no T3 or T4

Question 6

What does the adrenal cortex produce?

Primary Vs Secondary Hypoadrenalism?

Answer 6

Adrenal cortex produces cortisol and aldosterone

Primary = autoimmune damage to the adrenal cortex itself, aldosterone falls, cortisol falls so ACTH goes up. Can lead to Addison’s disease due to high ACTH = increased melanin production

Secondary = signalling issue from anterior pituitary (e.g. pituitary tumour) = low ACTH (there is no increased melanin production) = low cortisol

Question 7

Primary Vs secondary Hypogonadism?

Answer 7

Primary = e.g. MUMPS, or chemo may damage gonads directly = low oestrogen / testosterone = high LH / FSH to try compensate due to lack of negative feedback (GnRH would also be high)

Secondary = damage to anterior pituitary = low LH / FSH = signal issue = low oestrogen and testosterone production

Question 8

What are some causes of hypopituitarism?

HINT: Congenital / born-with causes Vs acquired / environmental causes

Answer 8

Congenital causes:
Rare, mutation in genes can cause abnormal development of anterior pituitary (children often short due to missing GH); shows up as underdeveloped pituitary on fMRI scans
Acquired:
Common - tumours, radiation, infection (e.g. meningitis), traumatic brain injury, pituitary surgery, inflammatory, haemorrhage (apoplexy), Sheehan’s syndrome

Question 9

What is the total loss of anterior and posterior pituitary function called?

Answer 9

Panhypopituitarism

Question 10

What 2 glands are sensitive to radiation?

Answer 10

Hypothalamus and pituitary gland

Question 11

How does radiation affect the pituitary gland?

How does radiation affect the hypothalamus?

When does damage settle in from radiation?

Answer 11

Dosage of radiation correlates positively with damage to pituitary gland
GH and gonadotrophins are most sensitive to radiation damage
Hypothalamic dopamine becomes switched off from radiation - leads to increased prolactin production

Damage settles in many years after radiation exposure - as late as 10 yrs later

Question 12

Why are the gonads so sensitive to chemotherapy?

What is menopause?

Answer 12

The ovaries stop working gradually - oestrogen falls, negative feedback , LH and FSH increase
Secondary hypogonadism = no LH or FSH production

Question 13

How do patients present with under-functioning pituitary glands (hypopituitarism)?

Answer 13

Missing LH and FSH - reduced oestrogen / testosterone leading to reduced libido, secondary amenorrhoea, erectile dysfunction, reduced pubic hair
Missing ACTH - cannot make cortisol = weight loss, excessive tiredness, but you still have aldosterone as that is controlled by the renin-angiotensin pathway (ONLY cortisol affected)
Missing TSH - fatigue
Missing GH - in children = reduced growth, in adults = reduced quality of life, psychological effects
Prolactin - cannot breastfeed

Question 14

What is Sheehan’s Syndrome?

Why is it present in pregnant women post-partum?

How does this present?

Is the posterior pituitary affected?

Answer 14

Consequence of anterior pituitary damage - post-partum hypopituitarism secondary to hypotension
Due to blood loss in women from childbirth

During pregnancy anterior pituitary gets bigger - lactotrophs increase in size
Therefore sudden loss in blood (post-partum haemorrhage) = lack of blood flow in the anterior pituitary = infarction (tissue dies due to lack of blood supply)

Presentation - anorexic, tired, weight loss, lethargic (feeling inactive), cannot lactate due to loss of prolactin, lack of FSH and LH = no return of periods

Posterior pituitary normally not affected

Question 15

What is the best radiological way to visualise the pituitary gland?

Answer 15

Pituitary MRI

Question 16

What is acromegaly?

Answer 16

When the pituitary gland produces too much GH in adulthood, leading to increase in size of bones, hands, feet and face

Question 17

What is pituitary apoplexy?

How does pituitary apoplexy present?

What is the bitemporal hemianopia?

What structures within the cavernous sinus may be affected by pituitary apoplexy??

Answer 17

Haemorrhage into the pituitary gland, happens suddenly leading to infarction - often in patients with pituitary tumours
Can be triggered by blood thinners (anti-coagulants) especially if the patient has a pituitary tumour

Sudden headache, v. painful

Cannot see peripheral vision due to compression of optic chiasm

Cranial nerve (III, IV, VI) compromise due to them running through the cavernous sinus = droopy eyelid, partial loss of vision, CN palsy

Question 18

How can you diagnose hypopituitarism using biochemical methods?

What are the barriers?

Answer 18

Must be careful interpreting basal hormone concentrations as they change throughout the day or depending on a cycle

Cortisol: morning = high, night = low
T4: long half life, stays for 6 days
FSH/LH: cyclical in women
ACTH/GH: pulsatile

Question 19

How can biochemical diagnosis tests for hypopituitarism be carried out and the barriers be avoided / rectified?

Answer 19

ACTH and GH: Introduce a stressor - lower BGL to below 2.2 mM
The body compensates by making ACTH and GH to counteract the hypoglycaemia
Use this stressor to see if the patient produces enough of these 2 hormones

TSH: TRH stimulates TSH release

FSH/LH: GnRH stimulates FSH/LH release

Question 20

What can be seen on pituitary MRIs?

Why not CT scans to look at the pituitary?

Answer 20

May reveal specific pituitary pathology
eg haemorrhage (apoplexy), adenoma
Empty sella – thin rim of pituitary tissue

CT not so good at delineating (portraying precisely) the pituitary gland

Question 21

What are the treatments for hypopituitarism?
(HINT: what replaces GH, TSH, ACTH, FSH / LH)
What hormone is required for fertility?

Answer 21

GH: replacement via daily injection - leads to increase in QoL and psychological well being - measure IGF-1 and QoL to see if effectiveness of dosage

TSH: replacement by giving levothyroxine - aim for fT4 (free T4) to be above the middleof reference range

ACTH: replacement by cortisol instead of ACTH, but difficult to mimic diurnal variation

FSH is required for fertility
FSH / LH: in men, if no fertility required = topical or intramuscular testosterone replacement, if he needs fertility = FSH and LH injections (may take up to 6-12mo til sperm production); in women, if no fertility = oestrogen replacement and monthly progesterone to prevent endometrial hyperplasia (increased thickening of the endometrium lining of the uterus that can lead to cancer), if she needs fertility = LH and FSH injections carefully timed to induce ovulation

Question 22

What happens with ACTH deficiency?

Answer 22

When on cortisol replacement, patients must also take replacement steroid (e.g. corticosteroid) every day due to:
Risk of adrenal crisis (secondary adrenal failure) from intercurrent illnesses, lack of aldosterone = unwell quickly
Steroid dosage doubled when ill
Corticosteroids help with cortisol and aldosterone production

V. important to take the steroids everyday, so all patients must wear a steroid alert bracelet and go straight to A&E if they’re vomiting and cannot swallow the pill

Question 23

45F - bitemporal hemianopia
Pituitary MRI = pituitary macrodenoma (tumour)
Baseline blood tests show:
Normal cortisol, low T4 and low TSH

What is the likely cause of this?

Answer 23

Secondary hypothyroidism - lack of TSH = low T4

Question 24

She starts on levo-thyroxine replacement at 100mcg per day.

How do you assess this is the correct dosage for her?

Answer 24

See if it increases fT4 (free T4) into the reference range

Question 25

Her last period was 6 months. Her family is complete (not looking to have any more kids)

Why is it not menopause?

What treatment should she be given?

Answer 25

Her FSH and LH are also low, which are typically high during menopause

Oestrogen replacement plus a progesterone monthly