Mr Stevens, a 52 year old male, presents to the GP (which is you) complaining of worsening headaches over the last few months. He explains that he hasn’t really had any trouble with headaches in the past. If you haven’t already checked out our headache history taking guide, it may prove helpful if you get stuck.
“Doctor, I’m really getting fed up of these headaches, I’ve been trying my best to deal with them but they’ve not being going on for months, which is beyond a joke!”
Gain more detail about the headache
Site – unilateral (e.g. migraine) / frontal bilateral (e.g. tension headache)
- Was the onset acute or gradual? (sudden onset “thunderclap” headache is suggestive of subarachnoid haemorrhage)
- For chronic headaches, in a month of 30 days, for how many of those days would the patient have a headache? For how many days out of the month would the headache be severe?
Character – aching / throbbing / pounding / pulsating / pressure / pins and needles / stabbing
Radiation – neck (meningitis) / face (e.g. trigeminal neuralgia) / eye (e.g. acute closed angle glaucoma)
- Nausea / vomiting – may suggest raised intracranial pressure (ICP)
- Visual disturbance – aura related / intracranial lesion / bleeding / stroke
- Photophobia – raised ICP / meningitis
- Neck stiffness – meningitis (may be related to infection or subarachnoid haemorrhage)
- Fever – suggestive of an infective process (e.g. bacterial meningitis / abscess)
- Rash – non-blanching purpuric rash may indicate meningococcal sepsis (not relevant given the duration of this patient’s symptoms.)
- Weight loss – suggestive of malignancy – consider cerebral metastases
- Sleep disturbance – headaches causing sleep disturbance are concerning (raised ICP)
- Temporal region tenderness – consider temporal arteritis
- Neurological deficits – weakness / sensory disturbance / impaired coordination / cognitive symptoms / altered level of consciousness – consider space occupying lesions / intracranial bleeding / stroke
Timing – Duration of headache? / Recurrent? / Is it episodic? / Pattern? / Diurnal variation?
Exacerbating / relieving factors:
- Exacerbating factors – are there any obvious triggers for the symptom? (e.g. caffeine / codeine / stress / postural change)
- Relieving factors – does anything appear to improve the symptoms (e.g. improvement upon lying flat suggestive of reduced ICP).
- Ask the patient to rate the pain on a scale of 1-10
- Is the pain getting worse?
- How is it impacting their daily life?
Any past medical history of malignancy?
Any previous cranial or facial surgery?
Mr Stevens feels his headaches started around 3 months ago, at which point they were around 3/10 in severity. They have gradually worsened over time and he now feels they are about 6/10 in severity. The headache tends to be worse in the morning. He describes them as a dull ache behind his eyes. The headaches tend to last a few hours at a time and nothing makes them particularly worse or better. He denies nausea, vomiting, fever, neck stiffness, rash, weakness, sensory changes, speech disturbance and loss of consciousness. He does mention that recently he seems to be bumping into things, such as door frames, but despite that he feels his vision is ok and doesn’t feel that his balance is reduced. He has no significant past medical or surgical history.
1) Upper and lower limb neurological examination
2) Cranial nerve examination
On examination there is no focal motor or sensory deficit in the upper or lower limbs.
On assessment of vision, pupils are equal and reactive, visual acuity is recorded as 6/6 and eye movement is normal in all axes, with no nystagmus. Visual field testing reveals a bitemporal hemianopia. Colour vision is normal.
Assessment of all other cranial nerves is unremarkable.
Other space occupying lesions – e.g. metastases / meningioma / craniopharyngioma
Stroke – given the visual field defect (however doesn’t fit with the headache)
Aneurysm – Anterior communicating artery aneurysm
Full blood count
Pituitary hormone profile:
- Serum IGF1 – correlates with amount of growth hormone secreted over last 24hrs
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Luteinizing hormone (LH) / Follicle stimulating hormone (FSH)
- Antidiuretic hormone (ADH)
CT head (+/- contrast) – useful for identifying lesions / bleeding
- Provides higher resolution imaging than CT
- Sensitive at picking up pituitary fossa lesions
- FBC / U&Es / CRP – all unremarkable
- Pituitary hormone profile demonstrates a low TSH, but nil else.
The MRI reveals a pituitary lesion with elevation and compression of the optic chiasm (arrow indicates area of optic chiasm). The ventricles are normal size. No other abnormalities are noted.
Non-functioning pituitary adenoma
Growth hormone secreting adenoma
Adreno-corticotrophic secreting adenoma
Biopsy – histology of the lesion is required to confirm the diagnosis
Watchful waiting, with regular imaging to monitor the rate of growth and identify compression of local structures. In this case the patient is symptomatic with clinical and radiological evidence of optic chiasmal compression, therefore surgical intervention to excise and decompress the pituitary fossa is indicated.
Transsphenoidal excision of the adenoma:
- Minimally invasive approach
- Allows reduction in mass effect of lesion
Can be used if surgical excision is incomplete, or if recurrence of the pituitary lesion occurs.
The story continues…
The patient recovers well after surgery, however at 3 days post-op the patient complains of feeling nauseated and generally unwell.
A blood sample is taken and reveals the following…
Na – 152 (ref 133-146 mmol/L)
K – 3.8
Cr – 78
Serum osmolality- 328 (ref 275 – 295 mmol/kg )
Random urine osmolality – 38 (ref 50-1400 mOsm/kg)
Postoperative diabetes insipidus
- Not uncommon after pituitary surgery.
- ADH is normally released from the posterior pituitary.
- Surgery can damage this area and as a result cause reduced ADH secretion.
- Lack of ADH results in the body being unable to retain water effectively.
- As a result the kidneys produce inappropriately large volumes of dilute urine.
- The patient therefore becomes dehydrated – leading to a rise in serum sodium concentration
How could this be treated?
- The underlying issue in this particular patient is a lack of endogenous ADH which is resulting in inappropriate water loss at the kidneys.
- Therefore the patient requires an ADH analogue such as desmopressin (this would need discussion with the endocrine team).
- A strict fluid balance and regular monitoring of U&Es would also be essential
- Often postoperative diabetes insipidus is transient and will resolve a few days post-op. However in the short term desmopressin is often required, until the patient remains consistently normonatremic.
A few days later…
The patient is given desmopressin on advice of the endocrine team and over the next 4 days the patient’s sodium levels normalise, with no more desmopressin required. However 7 days post-op the patient again feels unwell, so some further blood tests are performed.
Na – 121 (ref 133-146 mmol/L)
K – 4.1
Cr – 85
Serum osmolality – 240 (ref 275 – 295 mmol/kg )
Urine osmolality – 600 (ref 50-1400 mOsm/kg)
- Despite the patient initially presenting with hypernatraemia, they are now significantly hyponatraemic.
- The patient is hyponatraemic with a low serum osmolality, however despite this they are still excreting inappropriately high amounts of sodium into the urine.
- This type of picture is seen in SIADH, where there is an excess of ADH in the circulation.
- This is the opposite of the earlier presentation (where a lack of ADH was causing hypernatraemia).
- SIADH is a state of normovolaemic dilutional hyponatraemia.
- Often the first line of management for this condition is to fluid restrict the patient.
- This management strategy attempts to avoid further dilution and increase sodium concentration.
As a result the patient is fluid restricted to 1.5 litres daily, with a strict fluid balance.
A few more days later…
The patient is fluid restricted, however 4 days later the patient develops dysphagia in addition to dysarthria. You recheck the patient’s bloods which reveal the following results…
Na – 163 (ref 133-146mmol/L)
K – 4.8
Serum osmolality – 347 (ref 275 – 295 mmol/kg )
Urine osmolality – 38 (ref 50-1400 mOsm/kg)
The triphasic response is a well recognised post-operative complication of pituitary surgery.
It involves the following 3 stages…
1. Transient diabetes insipidus
- There is a lack of ADH within the blood circulation
- The lack of ADH is due to local trauma to the neurons and blood supply involved in its production.
- This results in the patient producing large volumes of dilute urine and developing hypernatraemia.
- This phase typically begins 24-48hrs post-op and lasts between 5-7 days.
- This occurs due to the uncontrolled release of ADH from degenerating posterior pituitary tissue that was damaged during surgery.
- As a result the kidneys retain excessive volumes of water causing dilutional hyponatraemia.
- The duration of this phase is highly variable and can last from 2-14 days.
3. Chronic diabetes insipidus
- Once all stores of ADH released from the degenerating pituitary tissue are depleted, there is no source of further production of ADH, leading to a sudden drop in circulating ADH levels.
- As a result the kidneys begin to lose high volumes of water, leading to a sharp rise in sodium concentration.
- This rise in sodium can be further exacerbated if the patient is still being treated for hyponatraemia during the second SIADH phase (NaCl 0.9% IV fluid / NaCl tablets / Fluid restriction).
- This sudden fluctuation in sodium levels can lead to catastrophic irreversible complications such as central pontine myelinolysis.
- Once the third stage of the tri-phasic response is reached, the patient will likely continue to have diabetes insipidus long term, which will require specialist endocrine input.
Central pontine myelinolysis
- A disease characterised by severe damage of the myelin sheath in the area of the pons.
- It is caused by a rapid changes in serum osmolarity – most often due to rapid correction of hyponatraemia.
- This occurs because brain cells adjust to hyponatraemic state by absorbing free fluid to increase the surrounding fluids osmolarity (swelling up).
- If the serum osmolarity then increases suddenly, it leads to rapid mass movement of free fluid out of the cells into the surrounding fluid, which causes cell damage and subsequent demyelination.
- Common symptoms include dysphagia, dysarthria and paralysis.
- To avoid this complication, sodium levels should be monitored frequently and correction should be no faster than 10 mmol/L/24hr.
- Patients presenting with headaches need a thorough history and examination to narrow the differential diagnosis and guide further investigations.
- Pituitary tumours are not always hormone producing (functional), therefore a normal pituitary hormone profile does not rule out the presence of a pituitary lesion.
- Pituitary tumours can be treated conservatively if small and not causing significant compression of surrounding structures.
- Postoperative electrolyte imbalances are common in pituitary surgery.
- Frequent monitoring of electrolytes is essential to recognise issues early and prevent complications.
- The triphasic response should always be considered in patients with sodium imbalances post-op.
- Specialist endocrine opinion should be sought before commencing sodium replacement in this patient group.
- Rapid correction of hyponatraemia is dangerous and can result in catastrophic complications.
- Weed MC, Longmuir RA, Thurtell MJ. Pituitary Adenoma Causing Compression of the Optic Chiasm: 49-year-old white female with painless progressive vision loss. EyeRounds.org. September 9, 2013; available from http://EyeRounds.org/cases/177-pituitary-adenoma.htm