1. Endocrine emergencies
Roger Stanworth
Endocrinology
Small proportion of your workload but potential vital to know about for some patients
Endocrine patients present non-specifically- unlike for example the respiratory (or orthopaedic) patient
therefore the challenge is to be aware and be in position to make the diagnosis

2. Common themes in acute cases Case studies
Recommended treatment regimes
Common misconceptions/ pitfalls
Case histories- classic presentations but also deliberately picked some cases which are outside of the usual obvious endocrine patient

3. Endocrine emergencies
New case or known patient
Acute problem often needs a precipitant
ie like DKA
Often a non-specific longer illness
ie history can be vital
Problem can be;
Metabolic- hormone imbalence
Structural- bleed into tumour
It is clearly easier to identify that an acutely unwell patient has an endocrine problem if the underlying diagnosis is already known but unfortunatly that’s not always the case- but there are some patients who are at risk of acute endocrine problems because of their other history so that can be helpful. The fact that a separate acute illness is the reason for an acute decompensation is a key concept. Generally speaking these are ongoing metabolic derangements which have been going on for some time but present acutely in the context of a further physiological challenge.

4. ML 16 male Presented to MAU via A&E Vomiting 9 days
No diarrhoea or abdo pain
Nausea, malaise and mild right sided back pain for 3 weeks
No PMH or medications. Farmers son.
OE p BP 108/64
Nil specific noted on examination

5. Bloods on initial presentation
Na 129
k 4.7
Ur 11.8
Cr 77
Calcium 2.55
ALT 46
Other LFT normal
CRP 0.9
FBC N

6. ML Case progress Feeling better the next day Discharged from MAU
‘Gastroenteritis’
Represented and discharged from A&E the following day with recurrent symptoms

7. ML 3rd presentation to RDH
Symptoms ongoing but more pronounced
P 100
BP 106/74
Admitted from A&E to Paediatric ward
Rehydration overnight

8. ML Bloods 3rd presentation
Na 128
K 4.8
Ur 9.7
Cr 63
SOsm 274
UOsm 924
USodium 177
TSH 1.44
Cortisol 60
….standing BP 72/42

9. ML 3rd Presentation Results
ACTH 1969 (15-40)
Aldosterone <81 ( )
Renin 600 (5.4-60)
Prolactin 287
LH 7.8
FSH 2.0
Testosterone 12
fT4 16.4
fT3 6.1

10. ML Case progression Continued iv saline
Commenced high dose iv hydrocortisone
100mg STAT and qds
Switched to oral hydrocortisone day 2
20/10/10 mg followed by 10/5/5 mg
Fludrocortisone added when daily hydrocortisone exposure <100mg

11. ML Case progression Primary adrenal insufficiency
Almost certainly Addison’s disease
Feeling well at time of discharge
Due Endocrine follow-up March 2014

12. ML Reflection Why was this case missed on initial presentation?
Relatively short duration of symptoms?
Hyponatraemia had alternative explanation and lack of hyperkalaemia
Postural BP not checked
Heed the returning patient

13. Adrenal Insufficiency
Addison’s
93-140/million
Hypopituitary
/million
CAH
1: ,000
CRF
+ve
ACTH
Cortisol
-ve
… and long term steroids- common

14. Acute adrenal insufficiency Management (1)
iv access
U&E, glucose, calcium, cortisol, ACTH
ACTH is EDTA sample ON ICE
100mg hydrocortisone iv STAT
100mg hydrocortisone im qds

15. Management (2) iv fluids- STAT to stabilise BP/ replenish
then 3L per day (starting point)
normal saline unless hypoglycaemic
50ml 50% dextrose if BM< 2mmol/l
Usual treatment of hyperkalaemia

16. Patients on long term steroids
Physiological replacement
Usually under endocrinology
Will have received education
Likely to carry steroid card
Pharmacological treatment
We don’t know many of these people
Less likely to be aware of potential steroid deficiency and implications

17. Severe Illness- adrenal insufficiency including pituitary disease
Single dose IM hydrocortisone for home use
Emergency card and letter
Hydrocort 100 qds in hospital

18. Efcortesol Single use IM injection If vomiting If very unwell
If found unconscious

19. EC 58 male Profound weight loss December 2012 Poor appetite
Context of psychiatric illness
Known schizophrenia
Medications- (Lithium), Procyclidine, Flupenthixol, Thiamine, VitBCoStrong

20. EC 58 male Referred to Endocrinology- ‘Thyrotoxicosis’
Attends with care worker who does not know him well
Denies weight loss
Reports poor appetite
Doesn’t know if he has been on thyroid medication

21. EC 58 male OE
P80 BP 124/82
Thin and unkempt
No goitre
No tremor

22. EC Results February 2013 May 2013 July 2013 (time of clinic)
TSH < fT fT3 17.2
May 2013
TSH fT4 4.3
July 2013 (time of clinic)
TSH fT4 9.7
September 2013
TSH fT4 7.1
Subsequently commenced on levothyroxine

23. EC Meanwhile….. Poor oral intake continued
Weight loss actually ongoing
Referred as 2 week wait to Gastroenterology

24. EC Progress with Ix History not forthcoming Continued weight loss
Care workers increasingly concerned
Substantial investigations……

25. EC Bloods CXR CT Chest/Abdo/Pelvis CT brain FDG PET ECHO Gastroscopy
Bone marrow aspirate and trephine
Anaemia -
Brochiectasis
PFO
Duodenitis

26. EC Admitted with worsening and ongoing symptoms Jan 2014
Temporary dysphagia which then resolved
During admission very little progress in the first week
Sodium normal on admit- gradually falling during admission

27. EC 23rd Jan 2014 Severe hypoglycaemia 1.7 mmol/l Insulin 15 (low)
C-peptide 230 (low)
Cortisol <28
No response to Synacthen

28. EC ACTH <5 Aldosterone 255 Renin- processing problem
CT Brain- normal
Prolactin 803
LH 18
FSH 11
Testosterone 17
TSH <0.05
fT4 28 (thyroxine reduced)
IGF (low)

29. EC Commenced on saline and hydrocortisone (see other case)
Hypoglycaemia resolved
Appetite improved
Weight started to increase
Liaison with care workers re hydrocortisone
Discharge home

30. EC Diagnosis of partial hypopituitarism ACTH +/- GH deficiency
Preservation of gonadatroph function
No evidence of TSH deficiency
Mildly raised prolactin whilst on antipsychotic
Neuroimaging normal
Could suggest inflammatory cause of hypopituitarism

31. Hypopituitarism Prevalence 46 per 100000
Incidence 4 per per year
Lamberts. Lancet 1998
Mortality increase in hypopituitarism
Nielsen et al. JCEM Burman et al. JCEM 2013

32. Hypopituitarism Causes of hypopituitarism
Bates et al. JCEM 1996; 81:1169
76% Pituitary tumours (and treatment thereof)
13% Extra pituitary tumours (and treatment thereof)
8% Unknown
1% Sarcoidosis
0.5% Sheehan’s syndrome

33. Hypopituitarism with (pituitary) tumour
Direct ‘pressure’ effect of tumour
Including presentation following pituitary apoplexy
Following surgical management
Hypophysectomy can also improve hypopituitarism (Arafah et al. JCEM 1986)
Following radiotherapy
Occurs months to years later
Conventional RTX- Snyder et al. Am J Med 1986
Stereotactic radiosurgery- Sheehan et al. J Neurosurg 2005

34. Hypopituitarism not due to tumours (diagnosis often challenging)
Hypophysitis
Lymphocytic
Granulomatous/ TB
Others
Sheehan’s
Haemochromatosis
Sarcoid
(Langerhan’s)
Brain injury
Genetic
Growth failure unless isolated deficiency
Post meningitis
?CVA
?SAH
…or could be tumour after all…

35. EC Reflection Why was this case difficult to diagnose?
Concurrent psychiatric problem
‘Red herring’ of lithium induced thyroiditis
Lack of any electrolyte disturbance until 13 months into illness

36. Summary- Adrenal insufficiency
GI symptoms a common presenting feature
adrenal and pituitary cases
Low threshold for investigating for hypoadrenalism
Can be due to adrenal disease, pituitary problem or long term steroids
At time of diagnosis must send an ACTH sample- even though it’s a nuisance

37. Summary (2)
Acute treatment well established- if in doubt start treatment after sending initial tests- DO NOT DELAY- risk vs benefit principle is to treat when in doubt
Long term management requires ongoing specialist attention- key themes;
Education about managing acute illness
Minimising daily dose within safe limits

38. Case 2 HW 22 yr 10th September 2016 Presented to A&E
Seen by co-located GP
Vomiting, headache and visual blurring (left worse than right)
Initial onset 7th September- ongoing
Diagnosed migraine and discharged- advised optician review
16th September 2016 Seen in Opthalmology
Blurred vision left eye- finger counting only
Right eye temporal field loss
Same day CT scan non-diagnostic
MR brain requested as urgent outpatient

39. Case 2 HW Initial MRI 21/9/16

40. Case 2 HW Initial MRI 21/9/16

41. Case 2 HW 22 yr 21st September 2016 21st-26th September
MR Brain performed
2 x 2.5 x 4 cm macroadenoma
Evidence of bleeding and chiasmal compression
Same day admission under Endocrine Royal Derby
21st-26th September
Hydrocortisone and levothyroxine commenced and continued
Left eye continued finger counting only
Right eye continued hemianopia
No significant change during admission
Initial conservative management after discussion with Neurosurgical team

42. Case HW Post-op MR Nov 2017

43. Case 2 HW 22 yr Admitted QMC Neurosurgery Mr Dow 3rd-6th October ‘17
Transphenoidal debulking of apoplexy/adenoma
Normal vision post operatively
Post-op hormone investigations- recovery of pituitary function- normal synacthen test. Levothyroxine currently continued.
Learning points
Possibility of normal visual function even after surgical intervention 4 weeks post event
Failure to improve rather than presence of deterioration as the indication for intervention

44. Case 2 HW Questions
Delayed presentation/intervention- is the good outcome unusual?
Are we clear that ‘failure to improve’ rather than deterioration after presentation is the indication for intervention?
Is our pathway slick enough to ensure timely intervention when needed?

45. Case 3 PA 48 year old Day 1 24/10/2014 7pm
Day leave from Psychiatry Ward
Unable to get out of bath
Ambulance called- brought to A&E
Known schizophrenia- on risperidone and depot antipsychotic- current section 17
No other PMH

46. PA 48y Male Pulse 66 Na 129 BP 92/60 K 4.1 RR 14 Ur/Cr- Normal
SATS 98% CRP 3
T 32 degrees C WBC 3.04
BM 2.4
GCS 8….and then 14/15
Nil else specific noted on initial exam
Initial treatment with rewarming, fluids and dextrose

47. PA 48 yr Male Day 2 Cortisol added to bloods – result 32
CT- pituitary tumour
TSH 1.13
fT4 10.3
fT3 2.9
Prolactin 32 ( in past)
Hydrocortisone 100mg given afternoon of 25th October STAT and QDS
(Signed for and Cortisol >1750 the next morning)

48. PA 48 yr Male Day 3 Ongoing fluctuation of GCS 3-10
Not related to hypoadrenalism- GCS 18 hours post hydrocortisone with cortisol >1750 at that time
Not thought safe for MRI due to low GCS
Various ICU reviews
Initially unkeen to support without a clear diagnosis
Developed neck stiffness and squint
ICU transfer
Cover CNS infection
MR pituitary (deferred until next day after d/w neurosurgery)

49. PA MRI following Apoplexy October 2017

50. PA MRI following Apoplexy October 2017

51. PA 48Y Day 4
Much better
GCS but confused and difficult to examine
MR pituitary discussed with neurosurgical on-call
No immediate intervention advised
GCS stable all day so transferred to Endocrine ward overnight

52. PA 48 y Day 5-6 Seen on Endocrine ward Difficult to assess
Answering questions but only variably following commands….then not talking at all the next day
Probable lateral field loss but difficult to be sure
May well have reduced acuity but uses vision reasonably at other times
Does have bilateral ptosis
Referred for formal field assessment- patient unable to perform

53. PA 48y Decision Time
To operate or not to operate???

54. PA 48 yr Subsequent progress
Eventual treatment conservative
Variable cognitive/verbal/engagement responses in following weeks/months- ?delirium/catatonia
Didn’t initially engage with Neuro-rehab and then felt not to need it
Often hypothermic (?hypothalamic damage)
Discharge 3rd December 2015 to Neurorehab- on hormone replacements

55. PA MRI following Apoplexy October 2017

56. PA MR on discharge Dec 2015 (6 weeks post apoplexy)

57. PA MR Follow-up Feb 2016 (4 months post apoplexy)

58. PA 48 y Subsequent progress
In and out of hospital until February 2016
Remarkably well in self on review in Autumn 2016
See field assessment from that time- mainly right eye lateral hemianopia
Generally happy with vision although aware that right eye is ‘weaker’
Prolonged psychiatry admission late
Quite stressed when seen but pituitary treatments stable

59. PA 48 male Fields 2016

60. PA MR Follow-up January 2017

61. Case 3 PA Questions Did we do the right thing?
What does this tell us about low GCS as a presentation of apoplexy- and as an indication for treatment?
Intervene when GCS low?
Intervene if GCS improves if abnormal neuropthalmology/fields?
How can we judge clinical progress in apoplexy when patient confused?

62. Case 1 DL Questions
How confident are we that the pituitary tumour is not causing the field abnormality?
Has anybody seen a similar field restriction improve with pituitary surgery?
Are there any specific assessments or investigations that may help decision making in similar future cases?

63. Case 2 HW Questions
Delayed presentation/intervention- is the good outcome unusual?
Are we clear that ‘failure to improve’ rather than deterioration after presentation is the indication for intervention?
Is our pathway slick enough to ensure timely intervention when needed?

64. Case 3 PA Questions Did we do the right thing?
What does this tell us about low GCS as a presentation of apoplexy- and as an indication for treatment?
Intervene when GCS low?
Intervene if GCS improves if abnormal neuropthalmology/fields?
How can we judge clinical progress in apoplexy when patient confused?

65. Pituitary disease -mechanism of problems
Hypersecretion of a hormone
Hyposecretion of hormones
Mass/local effects
Headache
Blindness/ visual field problem
CSF rhinnoroea

66. Left- deteriorating vision Right- normal scan

67. ‘Pituitary’ pattern of results Low TSH and low fT3/ fT4
Hypothalamic
hormone
Pituitary
Hormone
Negative
feedback
Systemic
‘Pituitary’ pattern of results
Low TSH and low fT3/ fT4
Low ACTH and low cortisol
Low LH/FSH and low sex hormone
Low GH and IGF-1
(Raised prolactin)

68. Investigations in acute hypopituitarism
ACTH Cortisol
TSH fT4
Prolactin
LH, FSH, testosterone or oestradiol
IGF-1
Plasma and urine osmolalities
U&E Calcium Glucose FBC

69. Management of acute hypopituitarism
Acute precipitant?
Management of hypoadrenalism
iv hydrocortisone plus iv saline
Consider iv liothyronine (T3)
If reason to suspect hypothyroid crisis
MUST have hydrocortisone first

70. Pituitary apoplexy
Definition; Acute vascular event occuring within a preexisting pituitary tumour

71. Apoplexy- presentation
Headache 95%
Vomiting 70%
Visual field defect 66%
Opthalmoplegia 75%
Visual acuity 50%
(Assymptomatic)

72. Headache in apoplexy Acute onset Often retroorbital Can mimic SAH
Dural stretch in sella turnica
Direct effect- trigeminal nerve
Subarachnoid blood

73. Endocrine effects Frequently results in acute hypopituitarism
Management of resultant adrenal insufficiency crucial to survival
May also present subacutely with hypopituitarism

74. Who is at risk? All those with pituitary tumour
Commonly a tumour first presents with apoplexy
Commoner in males (2:1) and large tumours

75. Pituitary disease- Summary
Acute secondary adrenal insufficiency the main concern in acutely unwell pituitary patient
Pituitary apoplexy enters the differential of acute severe headache and may need acute surgical management

76. Results of hypopit patient recently seen
Na 130 K 5.2
Cortisol >2000
TSH <0.05 fT fT3 5.8
Other results normal
How do you explain these results?

77. Pt C 57y female Anxious and stressed at work Weight loss Shaky
Palpitations
2 months
SOB
Leg swelling
2 days

78. P 130 BP 190/95 Temp 38.5
SATS 95% (air) RR 22
Tremor
Agitated /argumentative
TSH <0.05
fT4 59.6
fT3 26.4

79. Seen in triage- prescription
ECG sinus tachycardia
Seen in triage- prescription
Propylthiouracil 200mg
Hydrocortisone 200mg
Whilst medication pending- cardiac arrest

80. ……… …..did survive arrest ICU transfer iv esmolol NG propylthiouracil
iv hydrocortisone

81. Management of thyrotoxic crisis
Bloods include T3 T4 TSH
ECG, CXR, cultures and other tests to assess for precipitant
Beta-blocker- propranolol 60-80mg qds
Propylthiuracil 200mg STAT 4 hrly
Lugols iodine
Cholestyramine 3g tds

82. Beta blockers in thryotoxic storm
Propranolol mg qds
Esmolol infusion mcg/kg/min and monitored (CCU/ICU) bed

83. TFT patterns TSH 0.4-4.5 fT4 10-20 fT3 3.5-6.5 TSH 5.5 fT4 5.1 fT3 2.0
(normal ranges)
TSH 5.5 fT4 5.1 fT3 2.0
What do you want to do for this lady who is ‘non-specifically unwell’

84. What about these results TSH <0.05 fT4 5.1 fT3 2.0
(normal ranges)
What about these results
TSH <0.05 fT4 5.1 fT3 2.0

85. …resultant practice point
Do not treat hypothroidism if TSH not very high
May be hypopituitarism
treatment could precipitate adrenal crisis
…and is a missed chance to diagnose pituitary problem

86. BF 38yr male Gradually more weak and lethargic for 2 weeks
Found semi-conscious in collapsed state at home by family
No witnessed seizure
Orientated but mentally slow

87. P 80 BP 120/80
RS/CVS/Abdo/Neuro NAD
JVP normal, no oedema
Na <95 K 3.3 Ur 5.6 Cr 79
What further history do you want?

88. Drug History
Lansoprazole
Fluoxetine
Lisinopril
Aliskirin
Indapamide…for last 2 weeks
(Na 139 pre indapamide)

89. Tests in hyponatraemia what do each of these tell us?
Serum osmolality
(Lipids, alcohol, glucose)
Urine osmolality
Urine sodium
Cortisol
Thyroid function

90. Results for BF SOsm 190 UOsm 400 UNa 55 Cortisol 800 TSH 1.9
Glu 5.9 CK 2200

91. What shall we do? Inaction- risks seizures- has he had one already?
Action- reversal of hyponatramia too quickly risks central pontine myelinolysis

92. Central pontine myelinolysis
Spastic paraplegia
Pseudobulbar palsy
Encephalopathy
Non-inflammatory demyelination
Likely due to osmotic fluid shifts causing oedema

93. Central pontine myelinolysis
At risk patients;
Alcoholics
Liver failure
Hyponatraemia/ hypernatraemia
Especially if corrected quickly

94. Central pontine myelinolysis
Treatment ‘supportive
ie no treatment
Therefore important to avoid

95. Setting aims when correcting hyponatraemia
Maximal rate of increase
1mmol/l/hr (eg first few hours)
8-12mmol/l in 24 hours
Only treat aggressively if patient compromised (eg coma or seizures)

96. Formula for working out required saline infusion
Change in serum Na with 1 litre fluid=
([Na]fluid – [Na]serum)/ (TBW +1)
(Total Body Water is eg 60%)
Eg effect of 1L 3% saline=
512-95/43= 9.7mmol

97. Potential problems with use of formula
The underlying process causing hyponatraemia may worsen or improve
Oral intake can be a confounding factor
Therefore standardise oral intake and reassess regularly

98. BF progress Referred to HDU/ICU- refused
N Saline 500 ml over 4 hours then reassess and reduce to 500 ml 8 hrly if sodium mmol/l
Na < h after the above so saline continued at same rate
Na h
Na h

99. Subsequent reversal <8mmol/day
Developed central pontine myelinolysis
I think main contributor was lack of clear baseline value (actual baseline probably about 90)

100. Hyponatraemia summary
Must get matched urine and serum to lab to assess aetiology
Only commence acute reversal of hyponatraemia if patient compromised
I think if this is being done its best in HDU
Use formula or ask Clinical Chemistry/ Endocrine advice about correction regime

101. Thankyou