ChemPath 22: Pituitary Flashcards
Why doesn’t hypopituitarism cause low blood pressure?
The adrenals are still able to produce aldosterone
Which hypothalamic hormones affect prolactin release?
Dopamine – negative
TRH – positive hence hypothyroidism causes hyperprolactinaemia
How might pituitary failure present in women?
Amenorrhoea and galactorrhoea
What physical manifestation might a macroadenoma of the pituitary gland (> 1 cm) cause?
Bitemporal hemianopia
NOTE: this can be tested using a visual field test
What is the main problem with prolactinomas?
It might reduce/stop the production of other pituitary hormones (e.g. ACTH, TSH, GH)
High prolactin in itself is not much of an issue
What is the CPFT?
Combined Rapid Anterior Pituitary Evaluation Panel
Test for pituitary function
Which three stimuli of pituitary hormone secretion are used in the CPFT? what do they increase
Hypoglycaemia – increases CRF/ACTH and increases GHRH/GH
TRH – increases TSH and prolactin
LHRH – increases LH and FSH
What safety precautions must you take before subjecting a patient to hypoglycaemia?
No cardiac risk factors (needs a normal ECG)
No history of epilepsy
Ensure good IV access
Describe the manifestations of increasing hypoglycaemia?
Initially, activation of the sympathetic nervous system will result in sweating, tachycardia etc.
When the blood glucose reaches < 1.5 mM, neuroglycopaenia may occur (loss of consciousness and confusion)
What blood glucose concentration is normally required to stimulate the pituitary gland?
< 2.2 mM
How should a patient be rescued if they experience severe hypoglycaemia during this (CPFT) test?
50 mL 20% dextrose
How much insulin should the patient receive in CPFT?
0.15 U/kg
Outline the dosing of various drugs in the CPFT - what adverse reaction can happen when this is administered
5 mL syringe
Insulin (0.15 U/kg)
TRH 200 µg
GnRH (LHRH) 100 µg
NOTE: the patient may experience a warm flush and vomit when the drug is administered
What should be measured n the blood during CPFT? How often?
What result is expected?
Glucose
Cortisol GH LH and FSH TSH Prolactin
Every 30 mins for 60 mins – LH, FSH, TSH, prolactin
Every 30 mins for 120 mins – glucose, GH, cortisol
Everything should rise except glucose which goes down
Describe the response you would expect from a normal pituitary gland undergoing the CPFT?
+ What level of cortisol and GH is considered a normal response?
Blood sugar will go down but then it will rise again without any external help
This is due to production of GH and ACTH (and hence cortisol) in response to the metabolic stress
Cortisol > 550 nM
GH > 10 IU/L
What should be done if a response isn’t observed to CPFT at a plasma glucose of 2.2 mM?
Give more insulin
List the order of hormone replacement in someone with panhypopituitarism.
HYDROCORTISONE
Thyroxine
Oestrogen
GH
NOTE: fludrocortisone is not necessary because the adrenals can still produce aldosteron
How should a patient with a prolactinoma be treated?
What hormones should be replaced in prolactinoma + how? Which is most important?
Dopamine agonists (e.g. cabergoline) - This reduces the size of the tumour and can avoid surgery
ACTH - Corticosteroids (MOST IMPORTANT - Otherwise Addisonian crisis)
GH - GH
TSH - T4
LH /FSH - Oestrogen/ testosterone/progesterone
What is disconnection hyperprolactinaemia?
Compression of the pituitary stalk by a tumour cuts off the negative effect of dopamine on pituitary prolactin secretion
This results in hyperprolactinaemia
Why do non-functioning adenomas need surgery?
They do NOT respond to dopamine agonists
Why might prednisolone replace hydrocortisone as the first-line steroid replacement agent?
It has a longer half-life meaning that once daily dosing is possible
How should you investigate a child with poor growth who is suspected of having a GH deficiency?
Take a random plasma GH measurement (GH is pulsatile but if you happen to measure it during a pulse and they have detectable GH then it shows that they are producing GH)
Exercise test
Insulin tolerance test (effective but dangerous so should NOT be done straight away)
What hormones are released by the hypothalamus and what is their action on the ANTERIOR pituitary? + where do their products act and how?
GNRH -> GH (nb: inhibited by somatostatin) -> IGF-1, IGF-2 (Liver)
CRH -> ACTH -> Cortisol (Adrenals)
TRH -> TSH -> T3/T4 (Thyroid)
TRH -> Prolactin -> Breast milk + inhibits FSH+LH
Dopamine -> Inhibits Prolactin -> Produce breast milk + inhibits FSH+LH
GnRH (LHRH) -> LH/FSH -> Testosterone / Oestrogen (Gonads)
What is released by the hypothalamus and what is their action on the POSTERIOR pituitary?
Neuronal signals in hypothalamus -> Oxytocin and Vasopressin (ADH)
Oxytocin - Expresses breast milk (breast) + Uterine contractions (Uterus)
Vasopressin - Vasoconstriction (V1) + Water reabsorption (V2)
Causes of hypopituitarism?
Infection - Meningitis (TB)
Inflammation - Sarcoidosis
Malignancy - Pituitary adenoma (func + non-func), Craniopharygiomas (hypothalamic)
Vascular - Sheehans syndrome (pituitary apoplexy)
Iatrogenic - Surgery, radiation
What is the most common type of pituitary adenoma? Finding?
Prolactinoma - Usually has prolactin >6000
Note- doesnt always have to be that highly raised
Size of macroadenomas?
> 1cm
How do non-funcitoning macroadenomas vary to prolactinomas in how they cause the same issue?
They compress the pituitary stalk -> decreased dopamine hence increased prolactin
How do prolactinomas and non-functioning macroadenomas cause hypopituitarism?
Non-func macroadenoma:
- Compression of stalk -> less dopamine (hence less inhibition) -> Prolactin inhibits FSH/LH
Prolactinoma:
- Compression of nearby hormone producing cells
- Prolactin inhibiting FSH/LH
(This can also cause inhibition of other hormones in a similar way)
Signs + Symptoms of Acromegaly?
Symptoms (insidious onset)
- Headaches
- Hyperhidrosis
Signs
- Spade-like hands
- Prominent supraorbital ridges
- Increased interdental spaces
- Macroglossia
- Prognathism
- Bitemporal hemianopia
Ix of Acromegaly?
Increased IGF-1
Combined pituitary function test (CPFT)
Oral glucose tolerance test - Measure GH after this (should be high in acromegaly)
MRI pituitary
Mx of Acromegaly?
1st Line = Trans-sphenoidal surgery
D2 receptor agonists (cabergoline/octreotide)
Somatostatin analogues (octreotide/lanreotide)
GH receptor antagonists (pegvisomant)
Why do anti-psychotic medications cause high prolactin levels?
They are dopamine antagonists (D2 receptors)
and dopamine normally inhibits prolactin
Tolvaptan - What is it’s mechanism of action?
Tolvaptan (vaptan) is a medication used to treat SIADH
hence MoA is V2-receptor antagonist
A 31 year old lady is 38 weeks pregnant. Whilst in labour, she had a prolonged 2nd stage which required induction and subsequently caused blood loss of 900 ml. Over the next 48 hours, she complains of headache, lethargy and she is unable to breast feed.
What is the likely cause?
Sheehan’s syndrome
A woman presents with headache and bitemporal hemianopia. She is found to have a 2 cm pituitary adenoma on MRI. Her blood results reveal the following: Raised Prolactin (1400), rest is normal
What is the most likely diagnosis?
Non-functioning pituitary macroadenoma - raised prolactin = secondary to reduced dopamine due to compression of pituitary stalk
A woman presents with headache and bitemporal hemianopia. She is found to have a 6 mm pituitary adenoma on MRI. Her blood results reveal the following: Raised Prolactin (24000), rest is normal
What is the most likely diagnosis?
Prolactinoma
A woman presents with headache and bitemporal hemianopia. She is found to have a 4 mm pituitary adenoma on MRI. Her blood results reveal the following: Raised Prolactin (1400), rest is normal
What is the most likely diagnosis?
Prolactinoma
