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Endocrine emergencies. Roger Stanworth Endocrinology. Common themes in acute cases Case studies Recommended treatment regimes Common misconceptions/ pitfalls. Endocrine emergencies. New case or known patient Acute problem often needs a precipitant ie like DKA
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Endocrine emergencies Roger Stanworth Endocrinology
Common themes in acute cases • Case studies • Recommended treatment regimes • Common misconceptions/ pitfalls
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
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 p105 BP 108/64 Nil specific noted on examination
Na 129 k 4.7 Ur 11.8 Cr 77 Calcium 2.55 ALT 46 Other LFT normal CRP 0.9 FBC N Bloods on initial presentation
ML Case progress • Feeling better the next day • Discharged from MAU • ‘Gastroenteritis’ • Represented and discharged from A&E the following day with recurrent symptoms
ML 3rd presentation to RDH • Symptoms ongoing but more pronounced • P 100 • BP 106/74 • Admitted from A&E to Paediatric ward • Rehydration overnight
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 ML Bloods 3rd presentation
ACTH 1969 (15-40) Aldosterone <81 (111-440) Renin 600 (5.4-60) Prolactin 287 LH 7.8 FSH 2.0 Testosterone 12 fT4 16.4 fT3 6.1 ML 3rd Presentation Results
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
ML Case progression • Primary adrenal insufficiency • Almost certainly Addison’s disease • Feeling well at time of discharge • Due Endocrine follow-up March 2014
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
Adrenal Insufficiency CRF +ve Addison’s 93-140/million ACTH +ve Cortisol -ve Hypopituitary 150-280/million CAH 1:5000-14,000 Cortisol … and long term steroids- common
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
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
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
Severe Illness- adrenal insufficiency including pituitary disease Single dose IM hydrocortisone for home use Emergency card and letter Hydrocort 100 qds in hospital www.addisons.org.uk
Efcortesol • Single use IM injection • If vomiting • If very unwell • If found unconscious
EC 58 male • Profound weight loss December 2012 • Poor appetite • Context of psychiatric illness • Known schizophrenia • Medications- (Lithium), Procyclidine, Flupenthixol, Thiamine, VitBCoStrong
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
EC 58 male • OE • P80 BP 124/82 • Thin and unkempt • No goitre • No tremor
EC Results • February 2013 • TSH <0.05 fT4 37.9 fT3 17.2 • May 2013 • TSH 47.2 fT4 4.3 • July 2013 (time of clinic) • TSH 20.3 fT4 9.7 • September 2013 • TSH 60.5 fT4 7.1 Subsequently commenced on levothyroxine
EC Meanwhile….. • Poor oral intake continued • Weight loss actually ongoing • Referred as 2 week wait to Gastroenterology
EC Progress with Ix • History not forthcoming • Continued weight loss • Care workers increasingly concerned • Substantial investigations……
Bloods CXR CT Chest/Abdo/Pelvis CT brain FDG PET ECHO Gastroscopy Bone marrow aspirate and trephine Anaemia - Brochiectasis - - PFO Duodenitis - EC
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
EC 23rd Jan 2014 • Severe hypoglycaemia 1.7 mmol/l • Insulin 15 (low) • C-peptide 230 (low) • Cortisol <28 • No response to Synacthen
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-1 1.7 (low) EC
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
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
Hypopituitarism • Prevalence 46 per 100000 • Incidence 4 per 100000 per year Lamberts. Lancet 1998 • Mortality increase in hypopituitarism Nielsen et al. JCEM 2007Burman et al. JCEM 2013
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
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
Hypophysitis Lymphocytic Granulomatous/ TB Others Sheehan’s Haemochromatosis Sarcoid (Langerhan’s) Brain injury Genetic Growth failure unless isolated deficiency Post meningitis ?CVA ?SAH Hypopituitarism not due to tumours(diagnosis often challenging) …or could be tumour after all…
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
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
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
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
Case 2 HW 22 yr • 21st September 2016 • 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
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
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?
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
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
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 (600-800 in past) • Hydrocortisone 100mg given afternoon of 25th October 2015- STAT and QDS • (Signed for and Cortisol >1750 the next morning)
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)