Endocrine Emergencies

Professor Ikram S IsmailProfessor Ikram S IsmailPhD (Wales) FRCP (Edin) FAMM FACE

Endocrine Emergencies Diabetic Coma

Hypoglycaemia Diabetic Ketoacidosis Hyperosmolar nonketotic coma

Thyroid storm

UnconsciousDiabetic

Normal

BelowNormal

Look for non-diabetic cause

HypoglycaemicComa

High

Hyperventilation?

Yes

No

pH Low?No

Yes

Look forother illness

Hyperosmolarity?

Yes No

DiabeticKetoacidosis

Plasma Ketones orUrine Ketones +++

Yes No

Consider LacticAcidosis

Other Acidoses

HyperosmolarNonketotic

Coma

Consider CVA, othercauses after checking

ketones

BloodGlucose?

Diabetic Ketoacidosis Results from lack of insulin Occurs in people with type 1 diabetes.

Can also occur in type 2 DM in severe stress.

Medical emergency that needs urgent hospitalization

Accounts for approximately 5% mortality

Causes of DKAA. Absolute Insulin Deficiency: Omission or reduction of

insulin Undiagnosed diabetes

Causes of DKAB. Relative Insulin Deficiency:

(excess catabolic hormone secretion with fixed insulin dosage)

Acute illness: Infection Myocardial infarction Stroke Trauma Severe emotional disturbance

Endocrine Disorders Steroid therapy Adrenergic agonists Phaeochromocytoma Thyroid storm

DKA: Pathophysiology

DKA: Pathophysiology

DKA - Symptoms Symptoms develop over several hours

Thirst, Polyuria Osmotic Diuresis

Fatigue Dehydration, protein loss

Weight lossProtein loss, catabolism, dehydration

Nausea, vomiting ?Ketosis, gastric stasis

Abdominal pain ?ileus, gastric stasis, K deficit

Muscle cramps ?K deficiency

DKA - Signs

Dehydration Osmotic Diuresis, vomiting

Tachycardia Dehydration

Hypotension Dehydration, acidosis

Warm skinAcidosis (peripheral vasodilatation)

Hyperventilation Ketosis, acidosis

Coma, drowsiness Hyperosmolality

DKA - Diagnosis

Diagnostic procedures Determine blood glucose level

and test for ketones Send blood to laboratory for

estimation of glucose, urea, electrolytes,arterial pH, pO2, pCO2, Hb, and WBC

Send for culture of blood, urine and lung secretions

Blood Ketone TestingIndications Asymptomatic patients with glucose >

16.70 mM Symptomatic patients with possible DKA Monitoring in established DKA To assist in making decision on admission To assist in making decisions for intensive

medical therapy

<0.6 Check clinical status

0.6 – 1.5 Retest glucose and ketones in 2-4hrs

>1.5 If concurrent stress and poor compliance - admit

>3.0 Established DKA

DKA – InvestigationsHyperglycaemia, hyperketonaemia

Insulin deficiency

Decreased pH, PCO2, bicarbonate

Increased ketogenesis

Hyponatraemia Hyperglycaemia

Variable KInsulin deficiency, acidosis, urine loss

Raised WCC Hyperketonaemia

Raised haematocrit Dehydration

DKA - DeficitsWater 5 to 8 liters

Sodium 400-700 mmol

Chloride 300-500 mmol

Potassium 300-1000 mmol

Calcium 100 mmol

Magnesium 50 mmol

Phosphate 50 mmol

Bicarbonate 350 to 400 mmol

Treatment of ketoacidosis Initiation of treatment must be

immediate Treatment includes

Rehydration Insulin administration Electrolyte correction Stabilization of cardiovascular and

and renal function

Treatment of ketoacidosis Fluids

Most urgent and first line treatment Rehydration alone will cause fall in glucose

Increase urine flow Allow perfusion

Saline given rapidly 1 L in 30min, then hourly for 3 hrs CVP monitoring in elderly/CVS disease

Treatment of ketoacidosis Insulin

Aim to switch off gluconeogenesis, lipolysis, ketogenesis

Insulin regimens Intramuscular:

20 units stat, then 5U/hr Children: 0.25 U/kg stat, then 0.1 U/kg/hr

Intravenous infusion Adults: 6 U/hr Children 0.1 U/kg/hr

Once glucose fallen to below 15 mmol/L, replace saline with 10%Dextrose with 20-40 mmol K, reduce insulin to 3 U/hr

Treatment of ketoacidosis Potassium

Hypokalemia most common cause of death Potassium will fall during therapy:

Move into cells resulting from insulin, correction of acidosis, and restoration of volume

Haemodilution Urinary loss

Begin with insulin treatment: 20 mmol/h

Treatment of ketoacidosis

Hazards of acidosispH<7

Hazards of alkali therapy

Negative inotropismPeripheral vasodilatationCerebral depressionInsulin resistanceEnzyme depression

HypokalaemiaIncreased anaerobic glycolysisImpaired tissue oxygen deliveryParadoxical fall in CSF pHRebound alkalosisSodium overload

Acid-base

Treatment of ketoacidosis Acid-base

Give 100 mmoL with KCl 200 mmol when pH < 7, repeat until pH 7

Symptomatic relief: 50 mmoL with KCl 10 mmol

Treatment of ketoacidosis Clinical measures

Gastric stasis: NG suction in drowsy pts Infection:

Usual signs lacking Hyperglycaemia increases risk of sepsis Use broad spectrum antibiotics after cultures

Risk of thrombosis Prophylactic SC Heparin 5000 units q6-8hrly in the

unconscious, elderly, hyperosmolar Hypotension: use plasma expanders Clinical monitoring

Complications of treatment ARDS

Sudden dyspnoea, hypoxaemia, diffuse pulmonary infiltrates

Younger pts, fatal Mechanisms:

Use of crystalloids Alveolar defect caused by acidosis snf hyperventilation

Cerebral oedema High mortality Use of hypotonic replacement fluids

Abdominal pain Can mimic acute abdomen

Hyperosmolar Non-ketotic Hyperglycaemia

Accounts for 5-10% of hyperglycemic comas

Mortality 30-50%, usually from arterial or venous thrombosis

Occurs mainly in elderly persons with type 2 diabetes

When compared with DKA, it has: Higher mortality Higher hyperglycemia More severe dehydration

HONK: Treatment Rehydration is the most important

treatment Is performed under close observation

of circulatory status

Insulin concentration is usually low Blood glucose will drop in parallel

with rehydration

Patients should be monitored in a special intensive care unit

HypoglycaemiaHypoglycaemia

Defined as blood glucose below 3 mmol/l Some people with diabetes develop

hypoglycaemic symptoms even when BG > 3 mmol/l

Some persons with diabetes do not have symptoms even at very low BG Hypoglycaemic unawareness

Causes of HypoglycaemiaCauses of Hypoglycaemia

Administration of too much insulin. Insufficient intake of carbohydrate. Delay or omission of a snack or main meal. Performing more exercise than usual. Overdosing of sulphonylureas. Over-indulgence in alcohol.

Hypoglycaemia : Symptoms and SignsHypoglycaemia : Symptoms and Signs

Autonomic Neurologic Nonspecific

Sweating Diminished psychomotor skills

Headache

Tremor Irrational and aggressive behavior

Dizziness

Palpitations Confusion Generalized weakness

Hunger Altered

salivation

Convulsions Coma

Paraesthesia

Hypoglycaemia : ClassificationHypoglycaemia : Classification Mild hypoglycaemia

Activation of the autonomic nervous system Symptoms: tremors, palpitations, sweating, hunger The patients are able to treat themselves

Severe hypoglycaemia Very low blood glucose level Symptoms : confusion, drowsiness, coma, seizure Help is needed from others or consciousness is lost Acute professional assistance may be needed

Nocturnal HypoglycaemiaNocturnal Hypoglycaemia Usually occurs between 2 and 4 am Diagnosis through :

Symptoms in the night and next morning Blood glucose testing at the time of occurrence

Treatment Add a snack before bedtime Reduce dose of insulin Adjust timing of insulin injection Change the type of insulin

Hypoglycaemia Caused by Sulphonylureas

Hypoglycaemia Caused by Sulphonylureas

More common with longer acting sulphonylureas Chlorpropamide Glibenclamide

Treatment with glucose Hospitalisation with severe

hypoglycaemia Alternative diabetic treatment

Shorter acting sulphonylureas Metformin

Hypoglycaemic UnawarenessHypoglycaemic Unawareness

Low blood glucose without symptoms

Associated with Long duration of diabetes

Condition requires frequent blood glucose monitoring

Treatment of Mild HypoglycaemiaTreatment of Mild Hypoglycaemia

Relieved by 1 glass of fruit juice or soft drink 3 heaped teaspoon of sugar, honey or 3-5 sweets Dextrose tablets of 5 g

Repeat if symptoms are not relieved after 5 to 10 minutes

If next meal not immediately due, take 30 g of complex carbohydrate i.e. an apple or a slice of bread after recovery

Treatment of Severe HypoglycaemiaTreatment of Severe Hypoglycaemia Confirm diagnosis with a portable meter Administer 1 mg of glucagon intramuscularly for

adults and for children >25 kg (children < 25kg, give 0.5 mg or 0.02 mg/kg body weight)

If next meal not immediately available, give 30 g complex carbohydrate

If the patient does not recover consciousness within 5-10 minutes, admit to hospital

Thyroid Storm Life threatening exacerbation of

hyperthyroid state with evidence of decompensation in one or more organ systems.

Incidence : 10% of patient hospitalized for thyrotoxicosis

Fatal if not treated Mortality 20-30%

Pathophysiology:

Levels of thyroid hormones Rate of rise of thyroid hormone Development of tissue

intolerance Role of adrenergic activation

PathophysiologyLevels of thyroid hormones Most older studies found no

difference in thyroid hormone levels

Newer studies measuring free hormone levels showed higher levels of free T4 in thyroid storm

PathophysiologyRate of rise of thyroid hormone Related to the change in levels of

binding proteins noted in systemic illness and postoperatively

Production of T4 binding inhibitors resulting in decreased binding affinity of T4 and increase free T4 levels

Rapid release of T4 into the circulation could saturate binding capacity

Pathophysiology Development of tissue intolerance

Homeostatic decompensation despite similar hormone levels.

Role of adrenergic activation Normal plasma levels of adrenaline

noted But T4 causes increased receptors in

some tissues Post receptor action to alter

responsiveness to catecholamine

Clinical presentation All of usual features of thyrotoxicosis -

usually exaggerated and severe History of previous thyroid disease

partially treated or a history of symptoms suggestive of thyrotoxicosis

Fever typically present Sweating profuse initially, later dry

when become dehydrated Pulse pressure widened

Atrial arrhythmias Nausea, vomiting, diarrhea Increase motor and psychic

restlessness confusion, delirium, agitation

Unusual presentation reported acute abdomen status epilepticus, coma stroke

Clinical presentation

Clinical Presentation Occasionally few or no thyrotoxic

features GI, cardiovascular or neurologic features predominate

May be impossible to distinguish between severe hyperthyroidism with concurrent illness and thyroid storm.

Usually thyroid storm, the fever and tachycardia tends to be out of proportion to the illness

Precipitating events Infection Surgery Radioactive iodine Withdrawal of anti-thyroid drugs Amiodarone, thyroid hormone ingestion DKA, CCF, Hypoglycemia PET, parturition Vigorous palpation of the thyroid gland

Diagnosis

Temperature99 - 99.9 5100 -100.9 10101 - 101.9 15102 -102.9 20103 - 103.9 25> 104 30

Mainly clinical Diagnostic criteria to aid clinical

diagnosis Thermoregulatory Dysfunction

Diagnosis Central Nervous system

Effects Absent 0

Mild (Agitation) 10

Moderate Delirium Psychosis Extreme lethargy

20

Severe Seizure Coma

30

Diagnosis Gastrointestinal-hepatic

Dysfunction Absent 0

Moderate Diarrhea Nausea/vomiting Abdominal pain

10

Severe Unexplained jaundice

20

Diagnosis Cardiovascular dysfunction

Tachycardia Congestive Cardiac Failure 99-109 5 Absent 0 110-119 10 Mild

Pedal edema5

120-129 15 Moderate Basal crepitations

10

130-139 20 Severe Pulmonary edema

15

>140 25 Atrial fibrillation

Absent 0 Present 10

Diagnosis Precipitant history

Negative 0

Positive 10

Clinical Diagnostic CriteriaA score of 45 or more is highly suggestive of a stormA score of 25-44 is suggestive of impending stormA score below 25 is unlikely to represent storm

Laboratory Criteria No lab criteria for a storm

Biochemical evidence of thyrotoxicosis i.e. T3, T4, TSH

Free T4 tends to be higher but no criteria as yet

Do not wait for lab confirmation If diagnosis not clear and no known history of

hyperthyroidism, 2 hour RAI uptake useful Other suggestive features include

hyperglycemia, leukocytosis, hypercalcemia, AST, LDH.

Treatment Correct hyperthyroidism

Block synthesis of additional hormones Block release of thyroid hormones Inhibit peripheral conversion Direct measures to reduce levels of

hormones Definitive treatment

Normalizing homeostatic decompensation

Treat precipitating event

Treatment Correct hyperthyroidism

Block synthesis of additional hormones PTU, carbimazole orally, NG. Block iodine incorporation within 1 hour PTU loading dose 600-1000 mg, then 200-250

mg q4hr Carbimazole 20 mg Q4H

Block release of thyroid hormones Inorganic iodine only after carbimazole. Orally

or nasogastric. Lugol’s iodine 30 drops daily Ipodate (Oragrafin) 1 g tds. Also inhibit T4

conversion Lithium only if allergic to iodine

Treatment Inhibit peripheral conversion

PTU Ipodate blockers with MSA e.g. propanolol steroids

Direct measures to reduce levels of hormones Plasmapheresis, PD, exchange transfusion

Definitive treatment Radioiodine must be delayed 6 months as

iodine can inhibit uptake

TreatmentNormalizing homeostatic

decompensation IV Fluids to rehydrate Glucose for calories and restore

glycogen storage Multivitamins Treatment of arrhythmias, CCF. Pressors/invasive monitoring if indicated Supplemental oxygen

Treatment Treat hyperthermia

Central thermoregulation Paracetamol. Aspirin can displace T4 from binding proteins

Peripheral measures icepacks, cooling blanket

Glucocorticoids Relative adrenal insufficiency due to increased

degradation of cortisol Absolute adrenal insufficiency associated with

Graves Disease Inhibit T4 to T3 conversion

Treatment Cardiac failure

CCF usual treatment Arrhythmias: most common AF Large doses of digoxin needed Significant risk of embolism: anticoagulate

if no contraindications Anti adrenergic agents

Propanolol result in dramatic improvement 20-40 mg Q6h

1 selective, esmolol (short acting during perioperative period).

Treatment Treat precipitating event

Identify and treat aggressively Infections

Treatment Response

Clinical response within 12-24 hours - defervesence, reduced pulse.

Full recovery in 7-8 days Mental status good marker for

recovery.