Pituitary - Clinical Flashcards
What are causes of hyperprolactinaemia?
- Prolactinoma
- Co-secretion of prolactin in tumours causing acromegaly
- Stalk compression - pituitary adenomas
- PCOS
- Primary hypothyroidism
- Idiopathic
- Oestrogen therapy
- Renal failure
- Liver failure
- Drugs - anti-psychotics, anti-emetics
How would you distinguish whether a tumour was a macroprolactinoma or was causing stalk compression?
Macroprolactinoma would have a relatively bigger increase in prolactin levels compared to stalk compression
What is acromegaly?
Clinical syndrome caused by excess secretion of GH. GH stimulates skeletal and soft tissue growth. GH excess therefore produces gigantism in children (if acquired before epiphyseal fusion) and acromegaly in adults. Both are due to a GH secreting pituitary tumour (somatotroph adenoma) in almost all cases.
What are causes of GH excess in ACromegaly?
- Pituitary tumour - 99%
- Hyperplasia due to ectopic GH secreteing tumour - carcinoid
Which MEN syndrome is acromegaly most commonly associated with?
MEN-1
What symptoms seen in acromegaly?
- Change in appearence
- Sweaty
- Increased size of hands and feet
- Headaches
- Visual deterioration
- Tiredness
- Weght loss
- Amenorrhoea/Oligomenorrhoea
- Galactorrhoea
- Impotence/poor libido
- Deep voice
- Goitre
- Breathlessness
- Poluria/polydipsia
- Joint pain
What are signs of acromegaly?
- Prominent supraorbital ridge
- Prognathism
- Interdental separation
- Large tongue
- Hirsutism
- Thick greasy skin
- Spade like hands and feet
- Tight rings
- Carpal tunnel syndrome
- Colonic polyps
- Visual field defects
- Galactorrhoea
- HTN
- Oedema
- Arthropathy
- Proximal myopathy
- Glycosuria
What is prognathism?
Abnormal protrusion of one or both jaws, particularly the mandible, relative to the broader facial skeleton
What is proximal myopathy?
Weakness of the proximal muscles of the girdle including the quadriceps and biceps. Can be easily demonstrated by asking the patient to rise from a seated position and/or to pretend to be brushing their hair or hanging out washing.
What is macroglossia?
Enlargement of the tongue disproportionate to jaw and oral cavity size; also described as a resting tongue that protrudes beyond the teeth or alveolar ridge.
True macroglossia is defined as macroglossia with characteristic hypertrophied or hyperplastic histological findings. Pseudomacroglossia is said to be tongue enlargement seen in relation to a small mandible but also with histological abnormalities
What is hirsuitism?
Excessive hair growth on the face and body, in particular associated with a male-type pattern of hair growth in women.
What is galactorrhoea?
Lactation occurring in non-breastfeeding females. It is always pathological in males.
What is the mechanism behind galactorrhoea?
Hyperprolactinaemia and galactorrhoea may be caused by:
- Excess prolactin secretion
- Disruption of the normal inhibitory process of dopamine
- Failed excretion of prolactin.
What is the mechanism of galactorrhoea in acromegaly?
- Mass effect of the pituitary adenoma causing stalk compression
- Excess growth hormone that has a stimulatory effect on prolactin
- Very rare cases, a pituitary adenoma may produce both growth hormone and prolactin.
How does stalk compression cause hyperprolactinaemia?
Stalk compression by any cause (e.g. craniopharyngioma, trauma, pituitary adenoma) disrupts or destroys the normal tuberoinfundibular pathway that allows dopamine to travel from the arcuate nucleus, via the portal circulation, to the lactotrophs to inhibit prolactin secretion. Hyperprolactinaemia follows.
What are prolactinomas?
Prolactinomas are a type of pituitary adenoma, a neoplastic growth of pituitary lactotroph tissue. Prolactinomas secrete prolactin in large quantities and are not effectively inhibited by normal levels of dopamine.
Why does hyperprolactinaemia occur in primary hypothyroidism?
In hypothyroidism, thyrotrophin-releasing hormone (TRH) is elevated as a compensatory response to low thyroxine. TRH is a potent prolactin-releasing factor.
What visual problems might someone have if they have acromegaly?
Bitemporal haemianopia
If you suspected acromegaly, what investigations would you perform?
- Bloods - Ca2+, PO43-, GH day curve, Prolactin levels, IGF-1
- OGTT
- Formal visual field examination
- MRI scan - pituitary
- Pituitary function
If you found on investigation of someone with suspected acromegaly raised GH and IGF-1 levels, what investigation might you do?
OGTT
What result on OGTT might indicate acromegaly?
Lack of suppression of GH - diagnostic if there is no suppression of GH. Acromegalics fail to suppress GH below 0.3 µg/L and some show a paradoxical rise; about 25% of acromegalics have a positive diabetic glucose tolerance test.
What might you find on investigation of prolactin levels in someone with suspected acromegaly?
Mild to moderate hyperprolactinaemia occurs in 30% of patients. In some, the adenoma secretes both GH and prolactin.
What would indicate active disease in someone with acromegaly?
- Sweaty skin
- Boggy tissue
What are complications of acromegaly?
- Impaired glucose tolerance - may present DKA
- Heart - CCF, Cardiomyopathy, Arrhythmias, Hypertension
- Colon cancer
How would you manage someone with acromegaly?
- Trans-sphenoidal surgery
- Somatostatin analogue
- Pituitary radiotherapy
- Colonoscopy - from age 40
When taking a history from someone who you suspect has acromegaly, what questions might you like to ask them?
- Headaches?
- Visual Problems?
- Tingling in you hands at night? - carpal tunnel
- Tingling in your feet? - diabetic neuropathy
- Do you sweat easily?
- Difficulty having sex?
- Increase in shoe/glove size?
What might you do as part of your examination in someone with suspected acromegaly?
- Examine visual fields
- Examine BP and cardiovascular assessment
- Check urine for glucose
- Check axilla/pubic hair - for hypopituitary
- Examine feet/hands
- Serial photographs
- Check for goitre
What are causes of macroglossia?
- Down’s syndrome
- Amyloid
- Congenital hypothyroidism
- Acromegaly
How do somatostatin analogues work when used in acromegaly?
Octreotide and lanreotide are synthetic analogues of somatostatin that selectively act on somatostatin receptor subtypes (SST2 and SST5), which are highly expressed in growth-hormone-secreting tumours. These drugs were used as a short-term treatment whilst other modalities become effective, but now are sometimes used as primary therapy. They reduce GH and IGF levels in most patients but not all achieve treatment targets
What is involved in trans-sphenoidal surgery?
A type of surgery in which an endoscope and/or surgical instruments are inserted into part of the brain by going through the nose and the sphenoid bone (a butterfly-shaped bone forming the anterior inferior portion of the brain case) into the sphenoidal sinus cavity. Transsphenoidal surgery is used to remove tumors of the pituitary gland. (Such tumours, although within the skull, are outside the brain itself).
What are the features of hyperprolactinaemia in women?
- Amenorrhoea/Oligomenorrhoea
- Infertility
- Galactorrhoea
- Visual field abnormalities
- Headache
- Extraocular muscle weakness
- Decreased libido
- Weight loss
- Vaginal dryness
What are features of hyperprolactinaemia in men?
- Galactorrhoea
- Impotence/ED
- Visual field abnormalities
- Headache
- Extraocular muscle weakness
- Increased weight
- Decreased facial hair
What investigations would you do in someone who you suspected had hyperprolactinaemia?
- Bloods - Serial prolactin levels/macroprolactin levels, TFTs, U+Es, Pregnancy test
- Formal Visual fields testing
- Anterior pituitary function test
- MRI of the pituitary
Why would you do a pregnancy test In someone who you suspected might have hyperprolactinaemia?
Check if pregnant (duh) - most common cause of amenorrhoea in women is pregnancy!!!!
What classes as a macroprolactinoma?
Tumour >10mm
What are features which might indicate someone has a macroprolactinoma?
- Decreased acuity
- Diplopia
- Opthalmoplegia
- Visual field loss
- Optic atrophy
How would you manage someone with hyperprolactinaemia?
- Treat cause
- Dopamine agonists - carbergoline, bromocriptine,
- Trans-sphenoidal surgery
- Radiotherapy
When would you consider tran-sphenoidal surgery in someone with hyperprolactinaemia?
Used more often for Microadenomas
Rarely completely successful with macroadenomas and risks damage to normal pituitary function.
What classes as a microadenoma?
<10mm
What are clinical signs that someone might have a pituitary tumour?
Features of local pressure
- Headache
- Visual field defect
- Cranial nerve palsies
- Diabetes insipidus
- Hydrocephalus
- CSF rhinorrhoea
-
Disturbance of hypothalamic centres
- Temp control
- Sleep
- Appetite
What tests would you do if you suspected a pituitary tumour?
- Screening - PRL, IGF-1, TFTs, LH, FSH, ACTH, Cortisol, Testosterone
- MRI
What is pituitary apoplexy?
Rapid pituitary enlargement caused by bleeding into or impaired blood supply of the pituitary gland at the base of the brain.
It can cause mass effect, cardiovascular collapse and death
When would you suspect someone had pituitary apoplexy?
Ususally in context of known tumour
- Headache
- Decreased GCS
- Meningism
- Opthalmoplegia/visual field defect
What is hypopituitarism?
This entails decreased secretion of anterior pituitary hormones. They are affected in the following order:
- GH
- FSH
- LH
- TSH
- ACTH
- PRL
Panhypopituitarism is decreased suppression of all homrones
What are hypothalamic causes of hypopituitarism?
- Kallman’s syndrome
- Tumour
- Inflammation
- Infection - Meningitis, TB
- Ischaemia
What problems with the pituitary stalk can cause hypopituitarism?
- Trauma
- Surgery
- Mass Lesions - Craniopharyngioma
- Meningioma
- Carotid artery aneurysm
What are pituitary causes of hypopituitarism?
- Tumour
- Irradiation
- Inflammation
- Autoimmunity
- Infiltration - haemochromatosis, amyloidosis, mets
- Ischaemia - apoplexy, DIC, Sheehan’s syndrome
What are general features of hypopituitarism?
- Tiredness
- Weight gain
- Depression
- Reduced libido
- Impotence
- Menstrual problems
- Skin pallor
- Reduced body hair
What are features of decreased GH secretion?
- Central obesity
- Atherosclerosis
- Dry wrinkly skin
- Weakness
- Loss of balance
- Impaired exercise capacity
- Decreased cardiac output
- Hypoglycaemia
What are features of gonadotrophin deficiency in women?
- Oligo/amenorrhoea
- Infertility
- Decreased libido
- Osteoporosis
- Breast atrophy
- Dyspareunia
What are features of gonadotrophin deficiency in men?
- ED
- Decreased libido
- Decreased muscle bulk
- Hypogonadism - decreased testes volume, decreased ejaculate volume and spermatogenesis
What tests would you do if you suspected hypopituitarism?
- Pituitary Screening - PRL, IGF-1, TFTs, LH, FSH, ACTH, Cortisol, Testosterone
- Bloods - U+E’s,
- Tests for each axis e.g. synacthen etc.
- MRI
How would you manage someone with hypopituitarism?
Replace hormones
What cranial nerves are most commonly affected in pituitary lesions?
Those in the cavernous sinus
- Optic nerve
- IIV, IV, VI
What drugs can cause hyperprolactinaemia?
- Anti-psychotics
- Anti-emetics
What is important to exclude causes of hyperprolactinaemia when initially managing someone with hyperprolactinaemia?
- Hypothyroidism
- Pregnancy
- Renal failure
How might you distinguish between a microprolactinoma and a macroprolactinoma clinically?
- Microprolactinoma - no signs of effects
- Macroprolactinoma - signs of local effects e.g. headache, hemianopia
How would you follow up someone who you have treated for acromegaly?
Yearly
- GH and IGF-1 measurement +/- OGTT
- Visual fields
- Clinical photos
- Cardiovascular assessment
- Colonoscopy - age 40 onwards
