What's new in endocrine emergencies? - น.ต.หญิง สมโชดก ชาครียรัตน์

1. Somchodok Chakreeyarat, MD.
Endocrine Unit, Department of Medicine
Bhumibol Adulyadej Hospital

2. • Thyroid storm
• Myxedema coma
• Thyrotoxic periodic paralysis
• Hyperglycemic crisis
• Severe hypoglycemia
• Hypercalcemia
• Hypocalcemia
Somchodok Chakreeyarat, MD.
Endocrine Unit, Department of Medicine
Bhumibol Adulyadej Hospital
• Adrenal insufficiency

7. Hypokalemic periodic paralysis Thyrotoxic periodic paralysis
Age at onset First or second decade > 20 years
Attack frequency Infrequent Infrequent
Attack duration Hours to days Hours to days
Precipitants Exercise, CHO load, stress Exercise, CHO load, stress
K+ level during attack Low Low
Associated features Later onset myopathy Symptoms of thyrotoxicosis
Low TSH, high FT4 or FT3
Etiology AD inherited defect in calcium or
sodium ion channel on muscle
membrane
Thyrotoxicosis
Possible inherited predisposition
Penetrance Nonpenetrance common, esp in
woman
Epidemiology M > F M > F, high incidence in Asians
Preventive treatment Carbonic anhydrase inhibitors
K+ sparing diuretics
Euthyroid state
Propanolol

9. ST depression
Prominent
U wave

10. Occurs in early morning or late evening
Prodromal symptoms: muscle aches, cramps, muscle stiffness
Begins in proximal muscle of the lower extremities
 progress to flaccid quadriplegia
Symmetrical, spared bulbar, respiratory and ocular muscle
Serum K+ ↓, but not always during attack
Spontaneous resolution within a few hours to 2 days
“Thyrotoxic myopathy” persistent muscle weakness, soreness
and normokalemia
TPP can occur with any causes of hyperthyroidism

11. ECG finding
- Sinus tachycardia or sinus arrhythmia
- First degree AV block
- LVH pattern
Electrolytes and biochemistry in blood and urine
- Hypo K+ with low urine excretion rate
- Relatively normal blood acid-base balance
- Hypo PO4 with low urine PO4 excretion
- Normal or increased serum calcium with hypercalciuria
- Hypocreatinemia ( increased GFR )
Therapeutic course
- Lower K+ dose to achieve recovery
- Rebound hyperkalemia if high K+ dose is given

12. K+
supplementation
Nonselective
beta blockers
Acute
Chronic
Avoid precipitating
factors
Definite therapy
for
hyperthyroidism

13. Aim
- To raise serum K+ rather than to fill a large K+ deficit
- For the treatment of paralysis and prevention of fatal cardiac
arrhythmia
Close cardiac monitoring is absolutely warranted
Exogenous KCl administration  rebound hyperkalemia
Total KCl dose given less than 50 mEq, ↓ risk of rebound
hyperkalemia
KCl should be given at the rate of no more than 10 mEq/hr

14. Nonselective beta blockers
Parenteral KCl might be given in saline instead of glucose
solution
Avoid oral route of KCl administration if bowel sounds are absent
or diminished
“ Hypokalemia-induced pseudointestinal obstruction”
“Paradoxical hypokalemia” , a further fall in plasma K+
concentration during KCl therapy, associated with more severe
hyperthyroidism and hyperadrenergic activity
The maximum dose of KCl should be kept at 20-40 mEq/hr in
case of ventricular arrhythmia or impending respiratory failure

15. Mechanism
- To block K+ uptake via Na-K-ATPase
Oral propanolol 3-4 mg/kg/day
Shorten the duration of attack and promote recovery in TPP

16. Life-threatening arrhythmia or
respiratory failure?
NO YES
Standart IV KCl infusion
≤ 10 mEq/hr
Rapid IV KCl infusion
20-40 mEq/hr, then ≤ 10 mEq/hr
Paradoxical hypokalemia
after KCl infusion
NO YES
Worsening hypokalemia and
life-threatening arrhythmia
YES
Keep the rate and stop KCl
Infusion when muscle strength
Increased
Consider IV or oral non-selective
beta blocker
Recover from paralysis
Chronic treatment for the
underlying hyperthyroidism
TPP
NO

17. 1. Avoid precipitating factors
- High-carbohydrate diet
- Exercise
- Stress
2. Definitive therapy for hyperthyroidism
- Radioactive iodine ablation
- Surgery
- Antithyroid drugs
3. Non-selective beta blockers
- Preventing recurrent attacks of TPP

18. Most patients with TPP do not manifest typical
symptoms and signs related to hyperthyroidism
• Lab tests and ECG may help establish the diagnosis of TPP
• In acute therapy, the dose of KCl should be minimal to
rebound hyperkalemia, except in case of ventricular
arrhythmia or impending respiratory insufficiency
• High-dose non-selective beta blockers may be used to
terminate muscle paralysis , esp for those who developed
paradoxical hypokalemia

20. Diabetic Ketoacidosis
(DKA)
Hyperglycemic
Hyperosmolar State
(HHS)

21. DKA HHNS
DKA
Mild Moderate Severe HHNS
Plasma glucose (mg/dl) >250 >250 >250 >600
Arterial pH 7.25-7.30 7.00-7.24 <7.00 >7.30
Serum bicarbonate (mEq/l) 15-18 10-15 <10 >15
Urine ketones* Positive Positive Positive Small
Serum ketones* Positive Positive Positive Small
Effective serum osmolality
Variable Variable Variable >320
(mOsm/kg)
Anion gap± >10 >12 >12 <12
Alteration in sensorium
or mental obtundation
Alert Atert/drowsy Stupor/coma Stupor/coma
*Nitroprusside reaction method; calculation: 2[measured Na (mEq/l)] + glucose (mg/dl)/18;
±calculation (Na+) – (HCO3
- + CI- ) (mEq/I).

22. ADA; 2009

26. Beta-hydroxybutyrate,
the most important
Beta-hydroxybutyrate,
the most important ketone
ketone

27. Joint British Diabetes Society Inpatient (JBDS IP);2013
recommend :
- Rapid near-patient technology  3-beta-hydroxybutyrate
(BHB, ßHBA))

28. DKA
• To improve circulatory
volume and tissue
perfusion
• Decrease blood glucose
• Correct the acidosis
and electrolyte
imbalances
HHS
• To gradually and safely
normalize the
osmolarity
• Replace fluid and
electrolyte loss
• Normalize blood
glucose
Other goals include prevention of :
• Arterial or venous thrombosis
• Other potential complications e.g.
cerebral oedema/ central pontine
myelinolysis
• Foot ulceration

29. ADA 2009
• Blood glucose > 250 mg/dL
• Ketonemia
• Metabolic acidosis (pH ≤ 7.3)
or serum HCO3 < 18 mEq/L
JBDS IP 2013
• BHB > 3 mmol/L or Urine
ketone ≥ 2+ on standard
urine sticks
• Blood glucose > 200 mg/dL or
known DM
• Venous or arterial HCO3 < 15
mEq/L and/or pH < 7.3

30. ADA 2009
• Blood glucose < 200 mg/dl
• Venous pH > 7.3
• Serum bicarbonate ≥ 15
mEq/l
• Calculated anion gap ≤12
mEq/l
JBDS IP 2013
• Venous pH > 7.3
• Bicarbonate > 15.0 mEq/L
• BHB level < 0.6 mmol/L
(rather than < 0.3 mmol/L)

31. 1. Bedsides ketone (BHB) testing now represents the best
practice in monitoring the response to treatment
2. Fixed Rate Insulin Infusion (FRII) with short acting or
rapid acting insulin 0.1 unit/kg/hr should be used with
an infusion pump
3. Do not use a priming (bolus) dose of insulin

32. 4. Adjusted insulin dose if the metabolic target are not met
- Reduction of blood ketone(BHB) at least 0.5
mmol/L/hour
- Increase in venous HCO3 at least 3 mEq/L/hour
- Reduction in CBG at least 50 mg/dL/hour
5. Increase insulin infusion rate by 1.0 unit/hr increments
hourly until the ketones are falling at target rates
6. Measure venous blood gas for pH,HCO3, and K+ at 60
min, and then q 2 hr

33. The difference between venous and arterial pH is
0.02- 0.15 pH units
The difference between arterial and venous bicarbonate
is 1.88 mmol/L
It is not necessary to use arterial blood to measure acid
base status

34. Fluid Volume
1 L 0.9% NaCl 1,000 mL over first hour
1 L 0.9% NaCl with KCl 1,000 mL over next 2 hr
1 L 0.9% NaCl with KCl 1,000 mL over next 2 hr
1 L 0.9% NaCl with KCl 1,000 mL over next 4 hr
1 L 0.9% NaCl with KCl 1,000 mL over next 4 hr
1 L 0.9% NaCl with KCl 1,000 mL over next 6 hr
* A slower infusion rate should be considered in young adults

35. K+ Level in first 24 hr
(mEq/L)
K+ Replacement in mEq/L
of infusion solution
> 5.5 Nil
3.5-5.5 40 mEq/L
< 3.5 Senior review

36. DKA : Criteria for diagnosis and Resolution
ADA 2009 JBDS IP 2013
Diagnosis • Blood glucose > 250 mg/dL
• Ketonemia
• Metabolic acidosis(pH ≤ 7.3)
or serum HCO3 < 18 mEq/L
• BHB > 3 mmol/L or
Urine ketone ≥ 2+ on
standard urine sticks
• Blood glucose > 200 mg/dL
or known DM
• Venous or arterial HCO3
< 15 mEq/L and/or
pH < 7.3
Resolution • Venous pH > 7.3
• Serum bicarbonate ≥ 15
mEq/l
• Blood glucose < 200 mg/dl
• Calculated anion gap ≤12
mEq/l
• Venous pH > 7.3
• Bicarbonate > 15 mEq/L
• BHB level < 0.6 mmol/L
(rather than < 0.3 mmol/L)

37. DKA : Insulin (RI or RAA) and IV fluid
ADA 2009 JBDS IP 2013
Start
insulin
• 0.1 unit/kg IV bolus
• 0.1 unit/kg/hr CII
• No bolus
• 0.1 unit/kg/hr CII
Adjust
insulin
Bolus 0.14 unit/kg if
• serum glucose < 10%/hr
Increase insulin infusion
rate by 1.0 unit/hr If
• BHB  < 0.5 mmol/L/hr
• Venous HCO3  < 3
mEq/L/hour
• CBG  < 50 mg/dL/hour
IV fluid • Change IV to 5% glucose
if glucose < 200 mg/dL
• Add 10% glucose if
glucose < 250 mg/dL

39. Characteristic features of a person with HHS:
• High osmolality, often 320 mosmol/kg or more
• High blood glucose, usually 30 mmol/L
• •
(540 mg/dL) or more
• Severely dehydrated and unwell

40. Typical fluid and electrolyte losses in HHS (Kitabashi 2009)

41. General rules
1. The goal of initial therapy is to expand the intra- and
extravascular volume and to restore peripheral
perfusion
2. An optimal rate of decline in serum sodium of 0.5
mEq/L/hr has been recommended for hypernatremic
dehydration and not fall exceed 10-12 mEq/L/day
3. If BHB > 1 mmol/L = hypoinsuilinemia  start insulin
If BHB is not present insulin should not be started

42. Is
4. Insulin treatment prior to adequate fluid
replacement may result in cardiovascular collapse
5. The recommended insulin dose is an FRII given at
0.05 units/kg/hr . A fall of glucose at a rate of up to
90 mg/dL/hr is ideal
6. Avoid hypoglycemia. Target blood glucose is 180-270
mg/dL in the first 24 hr
7. If blood glucose < 180 mg/dL commence 5% or 10%
dextrose at 125 mL/hr with NSS

43. The target:
The aim of treatment should be to replace
approximately 50% of estimated fluid loss within the
first 12 Hours
The remainder in the following 12 hours
A target blood glucose of between 180 and 270 mg/dL
Complete normalisation of electrolytes and osmolality
may take up to 72 hours.

44. HHS : Criteria for diagnosis and Resolution
ADA 2009 JBDS IP 2013
Diagnosis • Blood glucose >600
mg/dL
• Effective serum
osmolarity ≥320
mosm/kg
• High osmolality, often
320 mosm/kg or more
• High blood glucose,
usually 30 mmol/L
(540 mg/dL) or more
• Severely dehydrated
and unwell
Resolution • Normal osmolality
• Regain of normal
mental status
• Normal osmolality
• Regain of normal
mental status

45. HHS : Insulin (RI or RAA) and IV fluid
ADA 2009 JBDS IP 2012
Start
insulin
• 0.1 unit/kg IV bolus
• 0.1 unit/kg/hr CII
• No bolus
• 0.05 unit/kg/hr CII if
BHB > 1 mmo/L or
serum glucose < 90
mg/dL after adequate
fluid resuscitation
Adjust
insulin
Bolus 0.14 unit/kg if
• serum glucose < 10%/hr
• Increase insulin
infusion rate by 1.0
unit/hr if not achieve
target
IV fluid • Change IV to 5% glucose
if glucose < 300 mg/dL
• Add 5% or 10% glucose
if glucose < 180 mg/dL

46. แนวทางการสืบค้นสาหรับผู้ป่วยที่มีระดับน้าตาลในเลือดต่า
Clotted
blood 10 ml
for :
1.Cortisol
2. Insulin
3. C-peptide
blood glucose < 50 mg/dL

47. Tetany, seizures, laryngospasm, or cardiac dysfunction
with proven or strong suspicion of low calcium
10-20 mL of 10% calcium gluconate in 50-100 mL 5% dextrose
(or 0.9% saline) given over 10 min with EKG monitoring
Repeat above treatment until symptom-free
• Treat hypomagnesemia (if present) with IV magnesium
sulfate
Start IV infusion of 100 mL of 10% calcium gluconate in 1 L of
normal (0.9%) saline (or 5% dextrose) at a rate of 50-100 mL/hr
Adjust rate to normalize calcium
Start oral calcium and potent vitamin D
(eg, calcitriol or alfacalcidol)
• Investigate the underlying cause (if not known) and treat

49. Cushing’s
syndrome

50. Septic shock/severe sepsis
Replacement
therapy
No Yes
Morning cortisol 8 AM
3-18 μg/dl > 18-20 μg/dl
Exclude
< 3 μg/dl
ACTH
stimulation test
Cortisol level

51. No
Septic shock/severe sepsis
Morning cortisol 8 AM
> 15 μg/dl
Cortisol rise
> 34 μg/dl
Adrenal
failure
Replacement
therapy
Cortisol rise
> 9 μg/dl
No adrenal
failure
Cortisol rise
≤ 34 μg/dl
Tissue resistance
to CS?
No treatment Replacement
therapy?
Cortisol rise
≤ 9 μg/dl
< 15 μg/dl
Adrenal failure
Replacement
therapy
Cortisol level
ACTH Stimulation test
Yes

52. • Thyroid storm
• Myxedema coma
• Thyrotoxic periodic paralysis
• Hyperglycemic crisis
• Severe hypoglycemia
• Hypercalcemia
• Hypocalcemia
Somchodok Chakreeyarat, MD.
Endocrine Unit, Department of Medicine
Bhumibol Adulyadej Hospital
• Adrenal insufficiency