19 - Pituitary Endocrinology Flashcards
Why is it important to know when in the day hormones are secreted in the body?
Need to know if diurnal or circadian variation for endocrine tests to decide what time of day to do the test
What endocrine tests do you do when you suspect gland failure or gland excess?
Gland failure: stimulation test e.g synACTHen test
Gland excess: suppression test e.g dexamethasone suppression
What is the embryological origin of the pituitary gland?
Anterior: upgrowth of gut tissue
Posterior: downgrowth of primitive brain tissue
Sits in the pituitary fossa with the optic chiasm sitting superiorly and cavernous sinuses laterally
Oxytocin and ADH are released by the posterior pituitary gland, originating from the hypothalamus.
What are the different hormones released by the anterior pituitary gland and what control are they under?
- GH: Released in pulsatile manner and acts on liver to produce IGF-1. Positive control by GHRH and negative control by Somatostatin
- ACTH: Peak pulses early in morning then lowest at midnight. Stimulates cortisol release. Positive control by CRH, negative control by Cortisol
- FSH/LH: FSH causes follicle maturation and LH causes ovulation and corpus luteum formation. Positive control by GnRH, negative control by testosterone, oestrogen, Prolactin
- TSH: Causes thyroxine release. Positive control by TRH, negative control by thyroxine
- Prolactin: Causes lactaction. Positive control by TRH, negative control by Dopamine so anything that blocks dopamine will cause PRL rise
How may a pituitary tumour present?
Symptoms either due to hormone excess or compression affect of tumour:
- Bitemporal hemianopia: pushing on optic chiasm
- Hypopituitarism but HyperPRL: compression affect, look for signs of hyperprolactinaemia
- Headaches: pressure effect
- Cranial Nerve Palsies: III, IV, VI
What are some signs and symptoms of insufficient levels of the following hormones:
- GH
- Gonadotrophins (FSH/LH)
- TRH
GH: central obesity, atherosclerosis, dry skin, osteoporosis, decreased well being
FSH/LH: oligomenorrhoea, decreased fertility, decreased libido, osteoporosis, breast atrophy, impotence, decreased muscle bulk, small testes
TRH: hypothyroidism
What investigations can you do to assess the functioning of the pituitary gland?
Basal Tests
- Prolactin and TSH anytime
- Fasting 9am LH/FSH in first 5 days of menstrual cycle + testosterone in men
- 9am cortisol
- IGF-1 to look at GH
Dynamic Tests
- Synacthen test: adrenal cortex won’t respond after 2 weeks ACTH deficiency due to atrophy. Looks at pituitary reserve of ACTH
- Insulin Tolerance Test: looks at ACTH and GH reserve, put patient into hypogylcaemia and this should cause rise in ACTH and GH if reserves
Imaging
- MRI: can use contrast
What does the size of a pituitary tumour determine?
<1cm = microadenoma
>1cm = macroadenoma
How are pituitary tumours treated?
- Start hormone replacement: give steroids before levothyroxine as thyroxine can lead to adrenal crisis
- Transphenoidal Surgery
- Dopamine agonist: 1st line for prolactinoma
- Radiotheraphy: residual or recurrent adenomas
What should you warn patients having transphenoidal surgery for a pituitary tumour about?
- Recurrence
- Fertility issues, op may cause decreased gonadotrophins
What is pituitary apoplexy and how does it present?
Bleeding into a pituitary tumour or reduced blood supply to the pituitary gland
Can cause mass effects, cardiovascular collapse due to acute hypopituitarism and death
Presentation: acute onset headache, meningism, visual field defects, reduced GCS
How should you treat pituitary apoplexy?
- Urgent steroids (IV hydrocortisone)
- Fluid balance
- Cabergoline (dopamine agonist - if prolactinoma)
- Surgery
Who should you not perform an insulin tolerance test on?
Patients with IHD or epilepsy as risk of trigerring coronary ischaemia and seizures
Should have 50% glucose, hydrocortisone and IV access when performing this test on anyone
What are some causes of hypopituitarism?
Hypothalamus: Kallman’s syndrome, tumour, inflammation, infection (meningitis, TB), ischaemia
Pituitary Stalk: traumatic brain injury, surgery, mass lesion, carotid artery aneurysm
Pituitary: tumour, irradiation, inflammation, autoimunity, pituitary apoplexy
How may hypopituitarism present?
Non-specific symptoms e.g lethargy, weight gain, sexual dysfunction
Can present as hypo-adrenal crisis with hypoNa and hypotension as lack of ACTH
What tests should you do for hypopituitarism?
Same as if suspect pituitary tumour:
- Exclude adrenal insufficiency
- Basal hormone tests
- Dynamic tests
- MRI: may show empty fossa or tumour
How should you treat hypopituitarism?
Hormone replacement
ACTH deficiency: Hydrocortisone
TSH deficiency: Thyroxine
Gonadotrophin deficiency: Testosterone gel or injection for symptom control and prevent osteoporosis. Oestrogen/Progesterone replacement with COCP/HRT
GH deficiency: somatotrophin subcut injection
What is the definition and what are some causes of hyperprolactinaemia?
PRL>390
- Prolactinoma (usually >5000)
- Disinhibition by compression of pituitary stalk by adenoma so less local dopamine (usually <5000)
- Dopamine antagonist drugs
- Pregnancy/Breast feeding
- Stress
- Hypothyroidism
What are some examples of drugs that can cause hyperprolactinaemia?
Usually anti-emetics and anti-psychotics:
- Metoclopramide
- Haloperidol
- Methyldopa
- Oestrogens
- Excrasy
- Antipsychotics
AND OTHER DOPAMINE ANTAGONISTS
What are some symptoms of hyperprolactinaemia?
Women:
- Amenorrhea
- Infertility
- Galactorrhea
- Decreased libido
- Dry vagina
Men:
- Erectile dysfunction
- Decreased facial hair
- Galactorrhea
What are micro-prolactinomas?
- More common
- Usually <1cm
- Presentation: with menstrual disturbance or hypogonadaism, galactorrhea, infertility
How can you distinguish between PCOS and a microprolactinoma?
- PCOS will have androgenic symptoms and less elevated prolactin (<1000)
- PCOS will also not have a pituitary lesion on MRI
What are macro-prolactinomas?
- Over 1cm
- More common in men
- Prolactin usually >5000. Can have hook effect
- Presentation: decreased visual acuity as push on optic chiasm, diplopia, visual field loss, opthalmoplegia, infertility
What investigations should you do for suspected hyperprolactinaemia e.g infertility, galactorrhea?
- Basal PRL (between 9am-4pm)
- Pregnancy test to rule out prenancy
- TFTs to check for hypothyroidism
- U+Es
- MRI pituitary
- Check medication history
How are prolactinomas causing hyperprolactinaemia treated?
- D2 agonists like Cabergoline or Bromocriptine
- Surgery if visual field issues/pressure effects but risks of permament hormone deficiency so not recommended
- Sometimes radiation therapy
What are some side effects and warnings you need to tell people before starting them on Cabergoline/Bromocriptine for a prolactinoma?
- S/E: nausea, depression, postural hypotension, cannot take in pregnancy
- If macroprolactinoma, the D2 agonists can shrink the tumour rapidly causing a CSF leak and meningitis
- Risk of cardiac valve abnormalities with high doses so look at any cardiac symptoms with ECHO
What are some signs and symptoms of acromegaly?
Symptoms: acroparaesthesia, snoring due to enlargement of tongue, carpal tunnel syndrome from puffy hands, increased sweating, headaches, hypertension
Signs (see image): increased size of hands and feet, coarse facial features, frontal bossing of forehead, protrusion of chin, diabetes
What are some complications with acromegaly?
- Risk of premature death to CVD (HTN, CCF due to LVH, cardiomyopathy, stroke)
- Diabetes mellitus or Impaired glucose tolerance
- Risk of colon cancer
What investigations should you do if you suspect acromegaly? (image important)
- Serum IGF-1: first line, raised, do OGTT if this is raised
-Oral Glucose Tolerance Test: GH not suppressed by high glucose means acromegaly
- Pituitary MRI: look for tumour
- Old photos
How is acromegaly treated?
Surgical (1st line):
Transphenoidal surgery to remove tumour, if microadenoma high likelihood of remission
Medical (if surgical fails)
- Somatostatin analogues: monthly injection of octreotide or lanreotide
- Stereotactic radiotherapy: if away from optic chiasm
- Sometimes use GH antagonists like Pegvisomat
What are some symptoms of growth hormone deficiency in adults?
- Reduced QoL
- Reduced muscle and bone mass
- Increased fat mass
- Cardiovascular risk
What are some symptoms of hyponatraemia and what complications can it cause?
Early: headache, nausea, vomiting, malaise
Late: confusion, agitation, drowsiness
Acute Severe: seizures, respiratory depression, coma, death
What are some causes of hyponatraemia?
- SIADH
- Drugs e.g diuretics
- GI losses e.g diarrhoea, vomiting
- IV fluids with constant 5% dextrose
- Burns
- Renal failure
- Water overload
- Addison’s
- Hypothyroidism
How do you work out the underlying cause of hyponatraemia?
If acute severe with neurological compromise the cause does not matter just consider hypertonic saline to prevent cerebral oedema
Otherwise, follow algorithm
How is hyponatraemia managed?
Hypovolaemic: normal saline slowly (15mmol per day if chronic) to prevent central pontine myelinolysis
Hypervolaemic: treat underlying cause (e.g cirrhosis, CCF) and fluid restrict
SIADH: fluid restriction, demeclocycline (ADH antagonist) and tolvaptan (vasopressor receptor antagonist)
How is acute sevre hyponatraemia managed (seizures, coma etc)?
Seek expert help!!!!!!
- Hypertonic saline 3% to prevent cerebral oedema
- Limit increase to 10mmol Na per day to prevent central pontine demyelinolysis
How may central pontine myelinolysis present?
What is SIADH and what are some causes of this?
High levels of ADH causing the kidneys to retain more water and therefore hyponatraemia. Can be from pituitary or ectopic
- Malignancy: small cell lung, bowel
- CNS disorders: meningitis, SAH, head injury
- Drugs: anticonvulsants like phenytoin, SSRIs, opiates,
- Idiopathic: need to rule out malignancy with cross sectional imaging
What is the diagnostic criteria for SIADH? (important card)
First need to rule out hypothyroidism, total salt depletion and ACTH deficiency
- Low serum osmolality <275
- Hyponatraemia <125
- Urine osmolality >100
- Urine sodium >30
All of the above in absence of hypovolaemia, oedema or diuretics
How is SIADH treated?
- Treat underlying cause
- Fluid restrict
- Vaspopressin receptor antagonists e.g Tolvaptan
- Demeclocycline (ADH antagonist)
What is diabetes insipidus and how does it present?
Vasopressin deficiency or vasopressin resistance that leads to the passed of large volumes (>3L) of dilute urine a day
Symptoms: polyuria, polydipsiea, dehydration, symptoms of hypernatraemia,
What are some of the cause of DI?
Cranial:
- Idiopathic
- Genetically inherited
- Trauma to pituitary stalk
- Meningoencephalitis
- Pituitary tumour
Nephrogenic
- Inherited
- Drugs e.g lithium, demeclocycline
- Chronic renal disease
- Metabolic e.g hypoK and hyper Ca
What is primary polydipsia and why is this sometimes difficult to distinguish from DI?
Excessive fluid intake in the absence of physiological stimuli to drink. Often due to Schizophrenia
Leads to polydipsia and polyuria but dilutional hyponatraemia
Kidneys often lose their ability to fully concentrate urine due to a wash out of the normal concentrating gradient in the renal medulla
What investigations are done to support a diagnosis of DI?
- U+Es
- Calcium
- Glucose to exclude DM
- Serum and urine osmolalities (excluded if serum <300 and urine >600)
How do you distinguish central DI from nephrogenic DI?
Desmopressin Water Deprivation Test
Stage 1:
- Stop drinking from 8am till 4pm, empty bladder and only eat dry food
- Weigh hourly. If >3% lost take urgent serum osmolality, if >300 go to stage 2 straight away
- After 8h if urine osmolality >600 can exclude DI, if not go to stage 2
Stage 2:
- Give desmopressin 2mcg IM*
- Drink water now and measure urine osmalilty for next 4h
Who should you not peform the desmopressin water deprivation test on?
If they have frank DI rather than partial, they will lose too much weight and symptoms will become too severe.
Can try co-peptin (AVP precursor) test instead
What is the emergency management for DI causing hypernatraemia?
- Urgent U+Es and serum/urine osmolalityies
- Monitor urine output
- IVI fluids to keep up fluids with urine output. If severe HyperNa lower Na slowly so as not to cause cerebral oedema and cause a brain injury
- Consider desmopressin s/c or IM
What are the complications with DI?
- Severe dehydration
- Hypernatraemia leading to brain shrinkage so SAH, seizures, comas, brain damage, death
