Somchodok Chakreeyarat, MD.

Endocrine Unit, Department of Medicine

Bhumibol Adulyadej Hospital

 Thyroid storm
Myxedema coma
Thyrotoxic periodic paralysis

Hyperglycemic crisis
Severe hypoglycemia
Hypercalcemia
Hypocalcemia

Somchodok Chakreeyarat, MD.

Endocrine
Unit, Department of Medicine
Adrenal
insufficiency
Bhumibol Adulyadej Hospital

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

ST depression
Prominent
U wave

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

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

Acute

Chronic
K+
supplementation

Nonselective

beta blockers

Avoid precipitating
factors

Definite therapy

for
hyperthyroidism

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

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

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

TPP
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
YES

NO

Worsening hypokalemia and

life-threatening arrhythmia
Keep the rate and stop KCl
Infusion when muscle strength
Increased

NO
Consider IV or oral nonselective beta blocker

Recover from paralysis

Chronic treatment for the

underlying hyperthyroidism

YES

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

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

Diabetic Ketoacidosis
(DKA)

Hyperglycemic
Hyperosmolar State
(HHS)

DKA

HHNS

DKA
Mild
>250
7.25-7.30
15-18
Positive
Positive
Variable

Moderate
>250
7.00-7.24
10-15
Positive
Positive
Variable

Severe
>250
<7.00
<10
Positive
Positive
Variable

HHNS
>600
>7.30
>15
Small
Small
>320

Plasma glucose (mg/dl)

Arterial pH
Serum bicarbonate (mEq/l)
Urine ketones*
Serum ketones*
Effective serum osmolality
(mOsm/kg)
Anion gap
>10
>12
>12
<12
Alteration in sensorium
Alert
Atert/drowsy
Stupor/coma Stupor/coma
or mental obtundation
*Nitroprusside reaction method; calculation: 2[measured Na (mEq/l)] + glucose (mg/dl)/18;
+
calculation (Na ) (HCO3 + CI ) (mEq/I).

ADA; 2009

Beta-hydroxybutyrate,
the most important
ketone

Beta-hydroxybutyrate,
the most important ketone

Joint British Diabetes Society Inpatient (JBDS IP);2013

recommend :

- Rapid near-patient technology 3-beta-hydroxybutyrate

(BHB, HBA))

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
Other goals include prevention of :
Replace fluid and
electrolyte
Arterial
or venousloss
thrombosis
Other
potential complications
e.g.
Normalize
blood
cerebral
oedema/ central pontine
glucose
myelinolysis
Foot ulceration

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

ADA 2009

JBDS IP 2013

Blood glucose < 200 mg/dl

Venous pH > 7.3

Venous pH > 7.3

Bicarbonate > 15.0 mEq/L

Serum bicarbonate 15
mEq/l

BHB level < 0.6 mmol/L

(rather than < 0.3 mmol/L)

Calculated anion gap 12

mEq/l

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

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

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

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

K+ Level in first 24 hr
(mEq/L)
> 5.5

K+ Replacement in mEq/L
of infusion solution
Nil

3.5-5.5

40 mEq/L

< 3.5

Senior review

DKA : Criteria for diagnosis and Resolution

ADA 2009
Diagnosis

Resolution

JBDS IP 2013

Blood glucose > 250 mg/dL BHB > 3 mmol/L or

Ketonemia
Urine ketone 2+ on
Metabolic acidosis(pH 7.3)
standard urine sticks
or serum HCO3 < 18 mEq/L Blood glucose > 200 mg/dL
or known DM
Venous or arterial HCO3
< 15 mEq/L and/or
pH < 7.3
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)

DKA : Insulin (RI or RAA) and IV fluid

ADA 2009
Start 0.1 unit/kg IV bolus
insulin 0.1 unit/kg/hr CII

JBDS IP 2013
No bolus
0.1 unit/kg/hr CII

Increase insulin infusion

Adjust Bolus 0.14 unit/kg if
insulin serum glucose < 10%/hr 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 Add 10% glucose if

if glucose < 200 mg/dL

glucose < 250 mg/dL

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

Typical fluid and electrolyte losses in HHS (Kitabashi 2009)

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

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

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.

HHS : Criteria for diagnosis and Resolution

ADA 2009
Diagnosis Blood glucose >600
mg/dL
Effective serum
osmolarity 320
mosm/kg

Resolution Normal osmolality

Regain of normal
mental status

JBDS IP 2013
High osmolality, often
320 mosm/kg or more
High blood glucose,
usually 30 mmol/L
(540 mg/dL) or more
Severely dehydrated
and unwell
Normal osmolality
Regain of normal
mental status

HHS : Insulin (RI or RAA) and IV fluid

ADA 2009
Start 0.1 unit/kg IV bolus
insulin 0.1 unit/kg/hr CII

JBDS IP 2012
No bolus
0.05 unit/kg/hr CII if
BHB > 1 mmo/L or
serum glucose < 90
mg/dL after adequate
fluid resuscitation

Increase insulin
Adjust Bolus 0.14 unit/kg if
infusion rate by 1.0
insulin serum glucose < 10%/hr

unit/hr if not achieve

target

IV fluid Change IV to 5% glucose Add 5% or 10% glucose

if glucose < 300 mg/dL

if glucose < 180 mg/dL


blood glucose < 50 mg/dL

Clotted
blood 10 ml
for :
1.Cortisol
2. Insulin
3. C-peptide

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

Cushings
syndrome

Septic shock/severe sepsis

Yes

No

Cortisol level

Morning cortisol 8 AM

< 3 g/dl

3-18 g/dl

> 18-20 g/dl

Replacement
therapy

ACTH
stimulation test

Exclude

Septic shock/severe sepsis

Yes

No
Morning cortisol 8 AM

< 15 g/dl
Adrenal failure

Cortisol level

ACTH Stimulation test

Cortisol rise
9 g/dl

> 15 g/dl
Cortisol rise
> 9 g/dl

Cortisol rise
> 34 g/dl

Cortisol rise
34 g/dl

Adrenal
failure

No adrenal
failure

Tissue resistance
to CS?

Replacement
therapy

No treatment

Replacement
therapy?

Replacement
therapy

 Thyroid storm
Myxedema coma
Thyrotoxic periodic paralysis

Hyperglycemic crisis
Severe hypoglycemia
Hypercalcemia
Hypocalcemia

Somchodok Chakreeyarat, MD.

Endocrine
Unit, Department of Medicine
Adrenal
insufficiency
Bhumibol Adulyadej Hospital