Chemical Pathology - Pituitary Flashcards
What hormones are produced by the hypothalamus?
- GHRH
- GnRH
- TRH
- Dopamine
- CRH (corticotrophin-releasing hormone)
Which hormones are produced by the anterior pituitary?
- GH
- LH
- FSH
- TSH
- Prolactin
- ACTH (adreno-corticotrophic hormone)
Which hormones produced by the hypothalamus have effects on which pituitary hormones, and what kind of effect?
- GHRH > Stimulates GH
- GnRF > Stimulates LH + FSH
- TRH > Stimulates TSH + Prolactin
- Dopamine > Inhibits Prolactin
- CRH > Stimulates ACTH
What hormone inhibits GH and where is it produced?
Somatostatin (Pancreas)
Where does GH act and what does it produce?
Liver
- IGF-1
- IGF-2
Where does TSH act and what does it produce?
Thyroid
- T3
- T4
Where does prolactin act and what does it produce?
Breast
- Milk
Where does ACTH act and what does it produce?
Kidneys
- Cortisol
What is Sheehan’s Syndrome?
Pituitary apoplexy (ischaemia of pituitary gland) secondary to PPH
What is the MoA of an antipsychotic?
- Dopamine antagonists
- Act on D2-receptors
- Increase prolactin production
What are some contraindications to a combined pituitary test?
- Ischaemic heart disease
- Epilepsy
- Untreated hypothyroidism (impairs GH + cortisol response)
What are some side effects to the combined pituitary test?
- Sweating
- Palpitations
- LOC
- Convulsions with hypoglycaemia (rarely)
TRH Injection:
- Metallic taste in mouth
- Flushing
- Nausea
What is the process of the combined pituitary function test?
- Administer LHRH (GnRH), TSH + Insulin
- Measure pituitary hormone levels at 0, 30, 60, 90 + 120 minutes + glucose
Why is insulin given in the combined pituitary function test?
To induce stress to cause a hypoglycaemic state, thus triggering GH + ACTH
What is the procedure for the combined pituitary function test?
- Fast pt overnight, ensure good IV access, weigh pt
- Mix into 5ml syringe (insulin - 0.15IU/kg, 200ug TRH + 100ug LHRH), give IV
- Chest bloods every 30 mins + up to 2 hours
- Replacement: urgent hydrocortisone, T4, oestrogen + GH
Which hormone levels are measured for up to one hour only and which are measured for up to 2 hours in the combined pituitary function test?
- Glucose, cortisol, GH for 2 hours
- Thyroxine plus glucose, FHS, TSH, prolactin for 1 hour
What is the outcome of insulin tolerance test?
- Adequate cortisol response (increase >170nmol/L)
- Adequate GH response (increase >6ug/L)
What is the outcome of the thyrotrophin releasing hormone test?
- Normal result = TSH rise >5mU/L
- Hyperthyroidism = TSH remains suppressed
- Hypothyroidism = Exaggerated response
- Not needed to diagnose hyperthyroidism anymore
What is the outcome of the gonadotrophin releasing hormone test?
- Normal: peaks at 30-60mins; LH >10U/L, FSH >2U/L
- Inadequate response = early indication of hypopituitarism
- Pre-pubertal children should have no response of LH/FSH to LHRH
How is a gonadotrophin deficiency diagnosed?
- Basal levels, not dynamic testing
- Males = low testosterone in absence of raised basal gonadotrophins
- Females = low oestradiol without elevated basal gonadotrophins + no response to clomiphene
What is a microadneoma?
- <10mm
- Usually benign (prolactinoma)
What is a macroadenoma?
- > 10mm
- Aggressive
- Usually non-functioning
What can happen as a result of a pituitary tumour?
Compression of the optic chiasm leading to bitemporal hemianopia
What are some generic symptoms of a pituitary tumour?
- Bitemporal hemianopia/superior quadrantanopia
- Headache
- Hormone-related symptoms
What are some symptoms of acromegaly?
- Soft tissue growth (hands, feet, tongue)
- Organomegaly
- Sx of HF, HTN, Diabetes
- Carpal tunnel
How does a non-functioning adenoma lead to increased prolactin levels?
- It can crush the stalk, increasing levels but lowering dopamine inhibition as there’s reduced blood flow
- Increased prolactin will be relatively small
What are the 3 types of prolactinaemia, their classification + causes?
Mild elevation (<1000 miu/L)
- Stress
- Recent breast examination
- Vaginal examination
- Hypothyroidism
- PCOS
Moderate elevation (>1000 miu/L, <5000 miu/L)
- Hypothalamic tumour
- Non-functioning pituitary tumour compressing hypothalamus
- Microprolactinoma
- PCOS
- Drugs (e.g. phenothiazides, domperidone)
Extreme elevation (>5000 miu/L)
- Macroprolactinoma
What’s the most common pituitary tumour, its symptoms and investigation findings?
Prolactinoma
Sx:
- Amenorrhoea
- Galactorrhoea Sx (gynaecomastia, loss of libido, impotence)
Ix:
- Increased prolactin (>6000)
- No increase in GH + cortisol
What is the management for a prolactinoma?
- Replacements (hydrocortisone, T4, oestrogen, GH) + D2 agonists (cabergoline, bromocriptine)
- Transphenoidal excision (if visual/pressure sx not responding to medical Tx)
What is the second most common pituitary tumour, its investigation findings and management?
Non-functioning pituitary adenoma
Ix:
- Increased prolactin (1000-5000)
Mx:
- D2 agonists (cabergoline/bromocriptine)
- Watch + wait if asymptomatic
What is the gold standard investigation for acromegaly + its management?
Ix:
- OGTT: Increased GH (even before baseline), Increased prolactin, no increase in cortisol
MX:
1. Transphenoidal surgery
2. Pituitary radiotherapy
3. Cabergoline
4. Octreotide (somatostatin analogue) -> can’t be stopped once started
5. GH antagonist (pegvisomant)
What is the follow-up for a patient with Acromegaly?
Yearly:
- GH, IGF-1 +/- OGTT
- Visual fields
- Vascular assessment
- BMI
- Photos
What are some clinical signs of a patient with acromegaly?
- High glucose
- High calcium
- High phosphate
What hormones are produced in the posterior pituitary, where do they act and what is the result?
ADH (vasopressin)
- Blood vessels (vasoconstriction = V1)
- Kidneys (water resorption = V2)
Oxytocin
- Breast (lactation)
- Uterus (childbirth)
What can cause an excess in ADH?
Lung
- Lung paraneoplasias (small cell lung cancer, pneumonia)
Brain
- TBI
- Meningitis
- Primary/secondary tumours
Iatrogenic
- SSRIs
- Amitrptylline
- Carbamazepine
- PPIs
Effect
- SIADH (euvolaemic hyponatraemia)
What can cause ADH failure and how?
- Diabetes insipidus: increased diuresis due to failure of production or insensitivity to ADH, leads to decreased urine osmolality + increased serum osmolality
What are the different types of diabetes insipidus and their causes?
Neurogenic (failure of production)
- 50% = idiopathic
Nephrogenic
- Iatrogenic
- Lithium
- Hypercalcaemic
- Renal failure
Dipsogenic (failure/damage to hypothalamus + thist drive, hypernatraemia without increased thirst response)
What are some symptoms of hypopituitarism?
- Lethargy
- Weight gain
- Hypotension
- Hair loss
- Myalgia
- Hormone-specific sx
What is the management of hypopituitarism?
Hormone-replacement (start with hydrocortisone)
What are some causes of hypopituitarism?
- Infection = meningitis (TB)
- Inflammation = sarcoidosis
- Malignancy = pituitary adenomas (functioning + non-functioning)
- Vascular = Sheehan’s syndrome, pituitary apoplexy
- Iatrogenic = surgery + radiation
- Tertiary = Kallman’s syndrome
