ACTEP2014: What's new in endocrine emergency

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

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

• Thyroid storm • Myxedema coma • Thyrotoxic periodic paralysis

• Hyperglycemic crisis • Severe hypoglycemia

• Hypercalcemia • Hypocalcemia

• Adrenal insufficiency

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

Prominent U wave

ST depression

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

K+ supplementation

Nonselective

beta blockers

Acute

Avoid precipitating factors

Definite therapy

for hyperthyroidism

Chronic

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

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

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 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 (mOsm/kg)

Variable Variable Variable >320

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).

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, ßHBA))

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

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

• 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)

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)

K+ Replacement in mEq/L of infusion solution

> 5.5 Nil

3.5-5.5 40 mEq/L

< 3.5 Senior review

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)

DKA : Criteria for diagnosis and Resolution

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

DKA : Insulin (RI or RAA) and IV fluid

• •

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)

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

General rules

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.

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

HHS : Criteria for diagnosis and Resolution

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

HHS : Insulin (RI or RAA) and IV fluid

แนวทางการสบคนส าหรบผปวยทมระดบน าตาลในเลอดต า

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

blood glucose < 50 mg/dL

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

Cushing’s syndrome

Septic shock/severe sepsis

Replacement therapy

3-18 µg/dl > 18-20 µg/dl

Morning cortisol 8 AM

Exclude

< 3 µg/dl

ACTH stimulation test

Yes No

Cortisol level

Morning cortisol 8 AM

No

> 15 µg/dl

Cortisol rise > 34 µg/dl

Adrenal failure

Replacement therapy

Cortisol rise > 9 µg/dl

No adrenal failure

No treatment Replacement therapy?

Cortisol rise ≤ 34 µg/dl

Tissue resistance to CS?

Cortisol rise ≤ 9 µg/dl

< 15 µg/dl

Adrenal failure

Replacement therapy

Cortisol level

ACTH Stimulation test

Septic shock/severe sepsis

Yes

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

• Thyroid storm • Myxedema coma • Thyrotoxic periodic paralysis

• Hyperglycemic crisis • Severe hypoglycemia

• Hypercalcemia • Hypocalcemia

• Adrenal insufficiency