ENDOCRINE EMERGENCIES

February 2011

ENDOCRINE EMERGENCIES

A. Tuthill

INTRODUCTION (1)

Endocrine emergencies comprise approx. 1.5% of all hospital admissions in the UK

Diabetes mellitus is by far the most common endocrine disorder encountered in clinical practice

- Type 2 diabetes affects 5% population

- Type 1 diabetes affects 0.5 – 1% population

INTRODUCTION (2)

The most common endocrine emergencies therefore relate to diabetes and are

1. Hypoglycaemia

2. Diabetic Ketoacidosis

3. Hyperosmolar Hyperglycaemic State

INTRODUCTION (3)

The other emergencies which are life-threatening and frequently overlooked

- Acute adrenal insufficiency

- Pituitary apoplexy

- Phaeochromocytoma hypertensive crisis

- Thyroid storm

- Myxoedema coma

- Hypo / hypercalcaemia

HYPOGLYCAEMIA

In 2004-5 there were approx. 8,000 hospital admissions related to hypoglycaemia

However there can be up to 90,000 ambulance callouts per year for this condition

ALL UNCONSCIOUS PATIENTS SHOULD BE ASSUMED TO BE HYPOGLYCAEMIC UNTIL PROVEN OTHERWISE

HYPOGLYCAEMIA (1)

Causes :

1. Drugs

- insulin/oral hypoglycaemics

- alcohol

- salicylates

- quinine

- beta-blockers, pentamidine, disopyramide

- prescription errors e.g. chlorpropamide for chlorpromazine

HYPOGLYCAEMIA (2)

Causes :2. Tumours

- Insulinoma- Retroperitoneal sarcomas

3. Miscellaneous- Liver dysfunction

- adrenal insufficiency / hypopituitarism - renal failure - myxoedema

HYPOGLYCAEMIA (3)

Presentation :

1. Autonomic (Blood glucose 3.3 – 3.6 mmol/l)

- diaphoresis

- anxiety

- palpitations / tachycardia

- tremor

- warm feeling

HYPOGLYCAEMIA (4)

Presentation :2. Neuroglycopenic (Blood glucose <2.6 mmol/l) - confusion - slurred speech

- visual disturbances - being uncoordinated

- tiredness - focal neurological defects

- coma / seizures (usually with glucose <1.5 mmol/l)

HYPOGLYCAEMIA (5)

Hypoglycaemia unawareness occurs in up to 1/3 patients with type 1 diabetes

Conversely, some patients have hypoglycaemic symptoms when their glucose is above the target range (> 7.0 mmol/l)

Patients post total pancreatectomy have more frequent and severe episodes because they have also lost their glucagon producing cells

HYPOGLYCAEMIA (6)

Diagnosis :

- Blood glucose

- U and E, liver profile

- Insulin and C-peptide levels

- Sulphonylurea screen

- IGF-2

HYPOGLYCAEMIA (7)

Treatment :

- If the patient is conscious, treat orally

- If unconscious, give 50ml 50% dextrose IV

- Glucagon 1mg i.m.

- Infusion of 10% glucose

- Consider thiamine

- Vigilance, Re-education, Support

LOWS

HIGHS

DIABETIC KETOACIDOSIS

DKA is a triad of hyperglycaemia, ketosis and acidaemia

Diagnostic criteria (ADA) :

- Blood glucose > 13.8 mmol/l

- pH < 7.3

- Serum bicarbonate < 18mmol/l,

- Anion gap > 10

- Ketonaemia

DIABETIC KETOACIDOSIS (1)

EURODIAB study reported an incidence of DKA in type 1 diabetes of 8.6%

It is the most common cause of death in young people with diabetes and in those > 65 years of age

Precipitants include infection, MI, trauma, drugs (steroids, cocaine, antipsychotics), non-compliance.

It may also be the presenting feature of type 1 diabetes


Pathogenesis :

- insulin deficiency

- increased counter-regulatory hormones (glucagon, catecholamines, cortisol and GH)

This leads to increased glucose production by the liver and decreased utilisation in peripheral tissues. Lipolysis results in ketone body production and acidosis.


Clinical Features :

- Polyuria

- Polydipsia

- Weight loss

- Vomiting / abdominal pain

- Dehydration

- Tachypnoea

- Altered mental status


Laboratory Findings :

- Hyperglycaemia (> 13.8 mmol/l)

- Hyperosmolality [2x(Na+K) + Urea + Glucose]

- Ketones

- Widened anion gap metabolic acidosis (pH < 7.3)

- Elevated urea and creatinine

- Hyperkalaemia

- Leucocytosis


Management :

- FLUIDS

- Fluids

- Fluids

- INSULIN

- POTASSIUM

- ± ICU admission

- Search for precipitant

- Education

HYPEROSMOLAR HYPERGLYCAEMIC STATE

Hyperosmolar hyperglycaemic state (HHS) is caused by deficiency of insulin usually in elderly patients; 2/3 have previously undiagnosed diabetes

Mortality up to 50% Diagnostic criteria:

- Blood glucose > 33.3 mmol/l

- pH > 7.3

- Serum bicarbonate > 15 mmol/l,

- Serum Osmolality > 320mOsm/Kg

HYPEROSMOLAR HYPERGLYCAEMIC STATE

Precipitants :

- Infection

- Myocardial infarction / cerebrovascular accident

- Inadequate insulin treatment / noncompliance

- High sugar intake

- Other endocrine disorders e.g. acromegaly

- Drugs e.g. glucocorticoids, thiazides, loop diuretics, phenytoin

HHS (2)

Clinical Features :

- Similar to DKA but history often several days to weeks

- As the degree of hyperglycaemia and hyperosmolarity progresses neurologic symptoms are more common including lethargy, focal signs, obtundation and coma

- Severe dehydration

HHS (3)


- Hyperglycaemia

- Hyperosmolarity [2x(Na+K) + Urea + Glucose]

- Hypo or hypernatraemia

- Hyperkalaemia

HHS (4)

Management :

- FLUIDS

- Fluids

- INSULIN

- POTASSIUM

- Anticoagulation

- ± ICU admission

- Search for precipitant

- Education

ACUTE ADRENAL INSUFFICIENCY

Life-threatening emergency Causes :

- Autoimmune

- Adrenal TB / haemorrhage / metastases

- Hypopituitarism

- Drugs e.g. metyrapone, ketoconazole, rifampicin

- Interruption of adrenal replacement therapy

- Adrenoleucodystrophy

ACUTE ADRENAL INSUFFICIENCY(1)

Clinical Features :

- Hypotension (mineralocorticoid deficiency)

- Postural hypotension

- Nausea and vomiting, weight loss, fatigue

- Hypoglycaemia

- Hyperpigmentation


Laboratory Findings: - Hyponatraemia (90%) / hyperkalaemia (65%) - Elevated Urea

- Hypoglycaemia - Anaemia (normal MCV) - Metabolic acidosis

- Hypocortisolaemia / Failure to respond adequately to synthetic ACTH

- ACTH or - Plasma renin


Management :

- Intravenous fluids (Saline)

- Steroids

- Dextrose

- Evaluate cause (antibodies, imaging, VLCFA)

- Investigate for other endocrinopathies

- Steroid alert card / bracelet

- Education

PHAEOCHROMOCYTOMA / CATECHOLAMINE CRISIS

Phaeochromocytomas are catecholamine secreting tumours of the adrenal medulla

< 0.1% Hypertension, but may cause hypertensive emergencies (SBP > 220mmHg or DBP > 120 mmHg)

10% bilateral 10% extra-adrenal 10% malignant 10% familial (Neurofibromatosis, Von Hippel Lindau,

MEN 2, SDHD/SDHB mutations)

PHAEOCHROMOCYTOMA / CATECHOLAMINE CRISIS(1)

Secretory Products:

- Noradrenaline / normetanephrines

- Adrenaline / metanephrines

- Dopamine


Clinical Features :

- Hypertension

- Anxiety attacks

- Sweating and heat intolerance

- Flushing / Pallor, palpitations, pounding headaches, pyrexia

- Tachycardia / arrhythmias


Crisis Precipitants :

- Straining

- Exercise

- Pressure on abdomen

- Surgery

- Drugs



- Hyperglycaemia

- Hypokalaemia

Investigations :

- Urinary catecholamines

- Chromogranin A, B

- MRI / MIBG


Management :

- Rehydration

- Alpha blockade (Phentolamine / phenoxybenzamine)

- LATER, Beta blockade

- Surgical resection

- Screening for associated conditions

PITUITARY APOPLEXY

Apoplexy refers to infarction of the pituitary gland due either to haemorrhage or ischaemia

Causes : - Spontaneous haemorrhage - Anticoagulant therapy - Head trauma - Radiation therapy - Drugs (Bromocriptine) - Pituitary function testing

PITUITARY APOPLEXY(1)

Rare 0.6 – 25% cases of treated pituitary adenoma

Clinical Features :

- Headaches

- Nausea, vomiting

- Visual disturbance

- Cranial nerve palsy

- Meningism


Diagnosis :

- High degree of suspicion

- Brain imaging

- Hypo / hypernatraemia may occur

- Baseline pituitary function tests

- Visual fields


Management :

- Stabilise the patients (A, B, C)

- Hydrocortisone

- Fluid balance

- Early neurosurgical intervention particularly if significant visual involvement

- Reassess pituitary function once acute apoplexy resolved

HYPOCALCAEMIA

Usually the result of failure of PTH secretion or inability to release calcium from bone

Causes : - Hypoparathyroidism (autoimmune, surgical,

radiation, infiltration) - Failure of parathyroid development - Failure of PTH secretion (Magnesium deficiency) - Failure of parathyroid action

(Pseudohypoparathyroidism)

HYPOCALCAEMIA(1)

Causes : (contd.)

- Failure of 1,25 (OH)2D levels (drugs, pancreatitis)

- Failure of calcium release from bone (osteomalacia, renal failure, hungry bone syndrome)

- Complexing of calcium from the circulation (multiple blood transfusion, pancreatitis)

HYPOCALCAEMIA(2)

Clinical Features :

- Tingling and numbness espec. of fingers, toes or lips

- Cramps

- Carpopedal spasm

- Tetanic contractions (may include laryngospasm)

- Seizures

- Hypotension, bradycardia, arrhythmias, CCF

Trousseau’s Sign

HYPOCALCAEMIA(3)

Investigations :

- Plasma calcium, albumin and phosphate

- Magnesium

- U and E’s

- PTH

- ECG

- 25 (OH) Vit D

HYPOCALCAEMIA(4)

Management :

- Patients with tetany or seizures require urgent intravenous treatment with calcium gluconate followed by an infusion for maintenance

- Chronic hypocalcaemia is best managed with oral calcium and vitamin D

HYPERCALCAEMIA

Found in 5% hospital patients but only 0.5% general population

Frequently picked up by routine biochemical screen in an asymptomatic patient

HYPERCALCAEMIA(1)

Causes :

- Hyperparathyroidism

- Malignancy

- Hyperthyroidism

- Sarcoidosis

- Drug related (thiazides, vitamin D, lithium)

- Immobilisation

- Miscellaneous (Benign Familial Hypocalciuric Hypercalcaemia)

HYPERCALCAEMIA(2)

Clinical Features :

- Polyuria, polydipsia, dehydration

- Tiredness, weakness, anorexia, malaise, nausea

- Abdominal pain, constipation

- Confusion, lethargy, depression

- Renal calculi, renal failure

- Sudden cardiac arrest

HYPERCALCAEMIA(3)

Investigations : - Plasma Calcium (corrected for albumin) - Phosphate, Magnesium - U and E’s - LFT’s - PTH - 24 hr urine Calcium - ECG

HYPERCALCAEMIA(4)

Additional Investigations :

- Myeloma screen

- TFT’s

- Short synacthen test

- Renal US

- DEXA

HYPERCALCAEMIA(5)

Management :

- Rehydration (Saline)

- ± Loop diuretic

- IV Bisphosphonate

- Salmon calcitonin

- Steroids

SUMMARY

Most endocrine emergencies encountered by general physicians relate to hyperglycaemia and hypoglycaemia in diabetes

The remaining endocrine emergencies are very rare

Treatment should never be delayed for a confirmatory test

CONSIDER THE DIAGNOSIS

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ENDOCRINE EMERGENCIES