Endo on the acute take

“Call the Med Reg” day

16.7.19
LNR Bondugulapati
 What you may see on the take…
 DKA
 HHS
 Recurrent / severe
hypoglycaemia
 Thyrotoxicosis / thyroid storm
 Myxoedema coma
 Hypocalcaemia
 Hypercalcaemia
 Addisonian crisis
 Pituitary apoplexy
 Hyponatraemia
 Phaeo crisis
 29 F presented with polyurea, polydipsia and wt
loss for 1 month. No PMH. Family h/o
autoimmune thyroid disorders. She was
dehydrated clinically. Blood glucose was 21.1
and Capillary ketones were 4.9. Blood tests
showed leucocytosis, raised lactate, metabolic
acidosis (pH 7.1; HCO3 14).

Case 1

Diagnosis ?
DKA - Pathophysiology
 DKA
• Incidence: 4.6 to 8 episodes per 1,000
patients with diabetes / yr
• 5-10% whilst inpatient !
• Mortality in UK fallen from 8% to the current
0.67% over the last 25 yrs
• In the UK, the average cost for an episode of
diabetic ketoacidosis is estimated to be
£2064 per patient
• Protocol in place:
• IV Fluids

• Insulin (IV sliding scale)

• K+

• Thromboprophylaxis

• Treat the underlying cause

Key caveats

 Can occur in T1 (more common) or T2 (less common)

 Continue patient’s usual basal insulin (or if a new diagnosis – start 0.2 u/kg
of basal insulin…..approx 10 units once a day)
 Remember to add dextrose 10% when the blood glucose falls below 14
mmol/L and if the pt is still ketotic (WHY?)
 Beware of “euglycaemic DKA” in the context of SGLT-2 inh / Alcohol /
Chronic Liv disease / Low carb diets / Pregnancy
  76 M admitted with cough, confusion, decreased
conscious levels for a day. PMH: HTN, T2DM, IHD and
currently takes Losartan, Metformin, Sitagliptin, Bisoprolol,
Simvastatin and Aspirin.
 On examination – severely dehydrated; GCS 12/15 (E4,
M4, V4); There were coarse rt basal crepts. BP 90/50, PR
Case 2 118/min, T 38 c, RR 24/min, Sats 91% on air
 CXR – Rt basal pneumonia; ECG – Sinus tachy; ABG: pH
7.31; HCO3 18; Serum Glucose 48, Cap Ket 1.3; Na – 152,
K 5.6, Urea 27, Create 210 (baseline 100);
 Diagnosis ?
HHS
HHS
 Rare !
 Mostly Eldelry T2 pts
 10-20% mortality
 More severe degree of
dehydration
 Absence of significant
ketosis/ketonaemia
 Local Protocol is available
 Fluids
 Electrolytes
 Insulin when necessary
(Half of DKA infusion rate)
 Thromboprophylaxis
Criteria for resolution
Key caveats for HHS

 Maintain BG between 10-15 mmol/l in the first 24 hrs to avoid precipitous fall
in osmolarity
 Note - insulin, when used, is at a lower rate : 0.05 u / kg / hr (if cap ket >1 or
inadequate BG fall in spite of IVF i.e <5 mmol/l/hr)
 Avoid rapid correction of hyperglycaemia – cerebral oedema !
Case 3

 82 F from residential home, was admitted with severe hypoglycaemia. Nursing

staff noticed pt to be drowsy, unresponsive when went in to serve tea at 6:45
PM, delayed by 45 min than usual time. She has T2DM and is on Novomix30, 28
units AM + 16 units PM. She hasn’t been eating and drinking well for 3 days
further to being started on Abx for possible UTI by the GP.
 Paramedic glucose was 2.1 which improved with IV 200 ml 10% Dex stat
treatment to 4.3 initially but on admission to A&E, it was again 3.7. GCS 15/15 at
this point. She was treated appropriately.
 She was cachectic on examination but had lumpy areas on the abdo. Bloods
showed AKI (Create 214 / baseline 80). CRP 102; Urine loaded with leucs and
nitrates; CXR clear.

 What are the contributory factors for her hypo ?

 People with type 1 diabetes mellitus (T1DM):
 experience around 2/week mild hypos
 the annual prevalence of severe hypo has been reported at 30-40%
 Approx 25% have impaired hypo awareness
 Patients with insulin treated T2DM are more likely to require hospital
admission for severe hypoglycaemia than those with T1DM (30% versus 10%
of episodes)
 Elderly patients or those with renal impairment are at particular risk
 Hypoglycaemia in pts known to have DM
CAUSES:
• Mild - if the episode is self-treated
 Excess insulin in the absence of enough
and “severe” if assistance by a third
Carbs
party is required
 Alcohol
• For the purposes of people with
diabetes who are inpatients, any  Lipohypertrophy
blood glucose less than 4.0mmol/L
 Infection/Sepsis
should be treated
 Renal / Liver dysfunction
• Symptoms:
 Cortisol deficiency / hypopit
Adrenergic symptoms
 Early pregnancy/Breast feeding
Neuroglycopaenic symptoms
 Drugs – Quinine, Chloroquine, Beta-
blockers
Prescription errors causing I/P
hypoglycaemia
Misreading poorly written
prescriptions – when ‘U’ is
used for units (i.e. 4U
becoming 40 units)
Confusing the insulin
strength with the dose (e.g.
100 unit dose inadvertently
prescribed)
Confusion between the
prescription of a glucose
and insulin infusion for
hyperkalaemia and
glucose and insulin infusion
for blood glucose control
Confusing the insulin name
with the dose (e.g.
Humalog Mix25 becoming
Humalog 25 units)
Inappropriately
withdrawing insulin using a
standard insulin syringe
(100units/ml) from prefilled
insulin pens containing
higher insulin
concentrations (e.g.
200units/ml or 300 units/ml)
 Treatment
Local protocol is available on
intranet:
Pts who are conscious: Pts who are unconscious and/or having seizures and/or
 15-20 gm of short acting carb – Rpt BM in 15 min are very aggressive:

 Once BM>4, follow it up with a long-acting carb  Check ABC

 If pt on SU or Basal insulin – at risk of hypos for 24-36  If IV access present: 150-200 mls of 10%D / rpt BM in
hrs 15 min

 Do not omit insulin but review the regime/dose  No IV Access: 1mg IM Glucagon
 34 F, FIT & WELL REFERRED BY GP WITH HR:140/MIN, BLOOD TESTS: FT4 - 46;
PALPITATIONS, WEIGHT BP:160/96; TSH<0.01; FT3 - 26;
LOSS, EXCESS
SWEATING FOR THE
LAST THREE MONTHS.

Case 4

ECG: SINUS TACHY EXAMINATION: WHAT IS THE HOW WILL YOU

SWEATY PALMS, DIAGNOSIS? MANAGE THE PATIENT
TREMOR, DIFFUSE ?
GOITRE, ORBITAL
CONGESTION WITH
PERI-ORBITAL
OEDEMA
Thyrotoxicosis

 Aetiology: Graves vs toxic MNG

 Raised free hormones /
suppressed TSH
 Treatment:
 Anti-thyroid drugs
 Beta blockers
 Anti-coagulate if AF
 MRI Orbits / Ophthalmic referral if
active thyroid eye disease
Thyroid storm

• Mortality: 20-25%
• HDU/ITU
• Respiratory / Haemodynamic support
• Anti-thyroid drugs + Drugs to inhibit thyroid hormone release
• Treating the underlying cause
 83 year old lady – Lives alone, on
thyroxine 125 mcg/day was found
collapsed in home

On arrival to A & E, BP 90 /60,

GCS is 9, temperature
Case 5 33; HR: 38/min;

What is the
Blood tests: CRP 1; Na diagnosis and
– 126; R glucose 3.8; how will you
manage the
Free T4 2.1; TSH 102;
patient?
Myxoedema coma

 Rare these days

 Level 2/3 care
 Mortality 25-30%
 Ventilatory support
 Management of hypothermia by passive external rewarming
 IV T3/T4; Fluids ; Abx as necessary; Steroids
Case 6

 44 F was referred by GP with tingling and numbness in hands for 2 weeks.

Routine bloods by GP revealed C Ca of 1.86 mmol/L hence sent in. Her
past medical history is significant for total thyroidectomy for papillary thyroid
carcinoma 1 month ago. She was on T4 100mcg/day. Bloods revealed 25-
OH Vit D of 42 mmol/Ltr, normal Mg, normal TFT. Chvostek’s and Trousseau’s
signs positive. ECG showed prolonged QTc at 500 ms.

 What is the likely diagnosis and how would you manage this Pt ?
 CAUSES: INVx:
 Disruption of parathyroid function  Serum Ca, PO4, Mg
due to neck surgery (Transient /
Permanent)  25-OH Vit D
 Severe Vit D deficiency  PTH
 Mg deficiency  U&E
 Cytotoxic induced
 Rhabdomyolysis
 Blood transfusions
TREATMENT of severe hypocalcaemia
(<1.9)
 IV Calcium gluconate Stat (10 ml 10% in 100 ml 5%D over 10 min – Cardiac
monitoring)
 IV Ca Glu infusion (100 ml 10% in 1ltr Saline/Dex over 12-24 hrs)
 Treat the underlying cause:
 1-alpha calcidiol or calcitriol in hypoparathyroidism
 Stop PPI / replace Mg if Mg deficient
 Monitor calcium
  65 F was referred by GP with hypercalcaemia (3.4).
She was treated for Breast cancer 3 years ago
(surgery / chemo); Last mammogram 6 months ago
was normal; Other bloods:
 PO4 – 1.8 (0.8 – 1.5)

Case 7  Create 88 (eGFR 74)

 PTH 0.9 pmol/Ltr (2 – 9)
 25-OH Vit D: Normal

 What is the likely diagnosis and how do you treat ?

 Hypercalcaemia
CAUSES:
 Malignancy related:
 Humoral (PTHrP related)
 Osteolytic
 Excess 1,25-OH Vit D synthesis related
 Ectopic PTH related
 Primary hyperparathyroidism
 Uncommon (10%):
 Familial conditions (FHH, MEN)
 Vit D / Vit A toxicity
 Infiltrative disorders
 Drugs
 Tertiary hyperparathyroidism
 Parathyroid Ca
TREATMENT

Depending upon the cause but in the acute setting

 IV fluids
 Bisphosphonates once rehydrated & if C Ca is still >3
 Dialysis (If CKD4 or beyond)
 Calcimimetics - Cinacalcet
 Denosumab
 Calcitriol
  29M, lethargy / unwell for few months; increased skin
pigmentation, wt loss
 Hypotensive; No e/o infection; GCS 14/15
 R Glu 3.6; Na 99; K 5.9
 S Osm: 256; U Osm 899; U Na 70
Case 8  TFT: Normal
 ACTH: 75 ng/Ltr (7-50)
 Random 10 AM cortisol: 64 nmol/L
 Other Ant Pit Function – Normal
Causes of Acute Adrenal insufficiency

 Primary adrenal insufficiency

 Auto-immune (80-90% OF CASES)
 TB, HIV
 Amyloid, Sarcoid, Haemochromatosis
 Metastatic malignancy to adrenals
 Adrenoleukodystrophy
 Acute destruction of the adrenals can occur with bleeding in the adrenals
 Sepsis
 DIC
 Complication of anticoagulant therapy

 Secondary adrenal insufficiency

 Drugs
 CAH & other rare familial conditions
 MRI Adrenals – Bilat Atrophy
 Adrenal AB negative
 Serum VLCFA – slightly raised
 MRI Brain/Pit/Spine - Normal
 Genetics – Carrier of ABCD gene
 Rx: HCT / Fludro
Adrenoleukodystrphy

 X linked, Gene encoding Peroxysomal Transporter Protein ABCD1

 1 in 20,000 Males
 Fatty acid breakdown affected; Gradual accumulation leads to Sx
 Usually presents in childhood/adolescence
 Progressive Dementia, Quadriparesis
 Milder form: Adrenomyeloneuropathy (10-20%; only Adrenal involvement)
Case 9

 64 Y M, Fit & well, Non smoker, Occasional alcohol

 No regular meds
 No relevant family history
 Admitted with sudden onset severe frontal headache, generally unwell for
1 week, nausea, diarrhoea intermittently for 2 days
 Family report that he was confused for 2 days
 O/E : drowsy but rousable
 GCS 14/15; Obs stable, apyrexial
 Chest / CVS / Abdo : Normal
 CNS: Wide based unsteady gait
but otherwise normal
 BM: 5.7
 CXR : Nil focal
 Initial Bloods:
- FBC: Normal
- Na 107, K 4.6, U 2.2, Creat 62
- S Osmolarity 221, Urine osmolarity
390, Urine Na 109
 CT brain : reported as normal
 TFT: TSH 0.14 (0.35-5.5)
FT4 7.3 (7-17 pmol/L)
FT3 3.7 (3.5-6.5 pmol/L)
 SST : 29, 272 (0, 60 min values respectively)
 Rest of ant pit function:
FSH 1.7 U/L (1.4 – 18.1)
LH 0.4 U/L (1.5 – 9.3)
Testosterone <0.4 nmol/L (9-46.8)
IGF-1 10.1 nmol/L (9.8-27.6)
Prolactin 22.3 (60-560)
 Started on IV glucocorticoids immediately along with IV fluids (N saline)
 MRI Brain/Pituitary:
Abnormal pituitary – s/o recent haemorrhage into pre-existing
adenoma; Apoplexy due to acute haemorrhage
Pituitary Apoplexy
 Clinical syndrome characterized
by sudden onset severe
headache / vomiting / visual signs
/ decreased consciousness
caused by hae’ge and / or
infarction of the gland
 First described 1898
 Rare emergency
 Incidence in pts with PIT
adenoma – 2 to 7%
 Most often in non-functioning
macroadenoma
 >80% of pts with apoplexy: often
the first presentation of the
underlying tumour
 5th / 6th decade
 Male preponderance (1.6:1)
 Pathophysiology
 Clinical manifestations are due to
acute increase in the intrasellar
pressure
 Headache / N / V
 Chiasmal compression –
Bitemporal hemianopia,
decreased visual acuity (approx
75%)
 lateral compression affecting the
contents of cavernous sinus –
ocular palsies
- 3rd N palsy (commonest, approx
50%)
 Extravasation of blood into SA
space – meningism/meningitis
 Rarely – cerebral ischaemia due to
mechanical compression of the
carotid artery
Endocrine assessment

Majority of pts (80% approx) will have one or

more ant pit horm deficiency at presentation
 Most crucial – ACTH def (70% approx)
Hyponatraemia – 40 % approx (Hypocortisolism
+/- SIADH)
 Check ant pit function ASAP when suspected
Management – Cons vs Surgical

Conservative unless severely reduced visual

acuity, severe & persistent/deteriorating visual
field defects, decreased level of consciousness
→ Surgical Mx should be considered
Hyponatraemia

 Its not really Endocrine – Could be due to a variety of systemic causes

 See the trends – Acute / Chronic ??
 History, volume status, IP-OP are the key !
 Common causes : Drugs / GI losses
 Its not always SIADH !! Osmolarities are waste of time for pts on diuretics
 Please don’t check Random Cortisol at midnight

Things to remember:
 If CNS disturbance / GCS low – Involve HDU/ITU and consider hypertonic saline
 Be aware of partial/complete HPA axis suppression in patients on chronic
steroids of any form (Inhaled / oral / injectables / topical) – If in doubt, do give
hydrocortisone stat …. its not going to harm !
Phaeo Crisis

 Rare these days

 Uncontrolled hypertension / tachyarrhythmias
 Send 24 hr Urine Cats/Mets (or Plasma metanephrines) for analysis
 ALPHA-BLOCKADE prior to BETA BLOCKADE
 Should be managed in HDU/ITU
TAKE HOME MSGS

 KEEP CALM & COMPOSED

 TAKE BREAKS – NOURISH & HYDRATE YOURSELF WELL
 LOGICAL THINKING / COMMON THINGS ARE COMMON
 NOT SURE WHAT TO DO – SEEK HELP; IT’s OK TO ASK !
 REMEMBER THE HIPPOCRATIC OATH – DO NO HARM
 BE INQUISITIVE – KEEP LEARNING
 TEACH / TRAIN / LEAD / MANAGE & INSPIRE TEAMS