Hypopituitarism Flashcards
What is meant by Hypopituitarism?
Hypo = underactive
So underactive pituitary gland
What are the 5 anterior pituitary hormones?
Why is aldosterone not under the control of ACTH?
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
What does the anterior pituitary function and regulation rely on?
Releasing and inhibiting factors from the hypothalamus that travel via the portal circulation (down the pituitary stalk) into the anterior pituitary
What occurs in anterior pituitary failure?
What are the differences between primary and secondary failure?
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
Primary vs secondary hypothyroidism?
Which is more common?
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
What does the adrenal cortex produce?
Primary Vs Secondary Hypoadrenalism?
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
Primary Vs secondary Hypogonadism?
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
What are some causes of hypopituitarism?
HINT: Congenital / born-with causes Vs acquired / environmental causes
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
What is the total loss of anterior and posterior pituitary function called?
Panhypopituitarism
What 2 glands are sensitive to radiation?
Hypothalamus and pituitary gland
How does radiation affect the pituitary gland?
How does radiation affect the hypothalamus?
When does damage settle in from radiation?
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
Why are the gonads so sensitive to chemotherapy?
What is menopause?
The ovaries stop working gradually - oestrogen falls, negative feedback , LH and FSH increase
Secondary hypogonadism = no LH or FSH production
How do patients present with under-functioning pituitary glands (hypopituitarism)?
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
What is Sheehan’s Syndrome?
Why is it present in pregnant women post-partum?
How does this present?
Is the posterior pituitary affected?
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
What is the best radiological way to visualise the pituitary gland?
Pituitary MRI
What is acromegaly?
When the pituitary gland produces too much GH in adulthood, leading to increase in size of bones, hands, feet and face
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??
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
How can you diagnose hypopituitarism using biochemical methods?
What are the barriers?
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
How can biochemical diagnosis tests for hypopituitarism be carried out and the barriers be avoided / rectified?
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
What can be seen on pituitary MRIs?
Why not CT scans to look at the pituitary?
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
What are the treatments for hypopituitarism?
(HINT: what replaces GH, TSH, ACTH, FSH / LH)
What hormone is required for fertility?
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
What happens with ACTH deficiency?
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
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?
Secondary hypothyroidism - lack of TSH = low T4
She starts on levo-thyroxine replacement at 100mcg per day.
How do you assess this is the correct dosage for her?
See if it increases fT4 (free T4) into the reference range
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?
Her FSH and LH are also low, which are typically high during menopause
Oestrogen replacement plus a progesterone monthly
