ENDOCRINE EMERGENCIES

Rural SIG Meeting Uluru 2018

Dr Judy Lynch

ENDOCRINE EMERGENCIES

• Thyroid emergencies

– Thyroid storm

– Thyrotoxic periodic paralysis

• Apudomas

– Phaeochromocytoma

– Carcinoid tumour/syndrome

• Diabetes Mellitus

– Euglycaemic ketoacidosis

Thyroid Storm

• Rare severe complication of hyperthyroidism

• Hyperthyroidism: treatment stopped or incomplete or intercurrent illness

• Unrecognised thyrotoxicosis with exposure to iodine containing meds/infection/labour

• Death may occur despite treatment ( 20-30%)

Thyroid Storm: Pathophysiology

• HighT3 & T4 (free/serum)

• Low TBG/ TSH

• Increased SNS activation: C.O/ HR/SV

• Increased BSL/ LFTs/ calcium/WBC

Thyroid Storm: Signs & Symptoms

• High fever, tachycardia, vomiting, diarrhoea, agitation, mental state changes, hypertension

• Cardiac: LVF, ischaemia/ infarction, arrhythmias. Hypotension (onset of shock)

• Organ dysfunction: eg liver

Thyroid Storm : Management

• Reduce production and release of thyroid hormones

• Reduce effects of thyroid hormones on tissues

• Replace fluid losses

• Controlling temperature

• Prompt treatment/ ICU admission

Thyroid Storm : Treatment

• Anti thyroid medication eg Propylthiouracil or Neomercazole

• Reduce synthesis and release of thyroid hormones

• Iodine : Lugols Iodine

Reduces synthesis/release of T3/4

Thyroid Storm :Treatment

• Beta blockers : Metoprolol or Atenolol

• Reduce effect of circulating thyroid hormones on end organs

Thyroid Storm : Supportive Measures

• Temperature control eg Paracetamol, external cooling

• Dehydration: (sweating/ diarrhoea/vomiting)

– Fluid replacement, electrolytes

• Treat any underlying cause

Thyrotoxic Periodic Paralysis

• Acute onset of episodes of profound proximal lower limb muscle weakness, secondary to hyperthyroidism

• Incidence 2% in hyperthyroidism

• Associated with severe hypokalaemia

• Occurs in male Asians 20-50 yrs

Thyrotoxic Periodic ParalysisPresentation

• Acute proximal symmetrical flaccid lower limb muscle weakness in early am/after strenuous exertion or high CHO meal

• Acute episodes preceded by muscle aches/stiffness/cramps

• Paralysis up to 3-6 hours

• Thyrotoxic symptoms

• Triggers: cold, trauma, infection, drugs

Thyrotoxic Periodic ParalysisPathology

• Fall in serum K+ (intracellular shift)

• Hypokalaemia: hyperpolarisation of muscle cells, decreased muscle contractility

• Increased B receptor number/sensitivity

• Exaggerated insulin response (to strenuous exercise/high carbohydrate intake)

Thyrotoxic Periodic Paralysis:ECG Findings

• Sinus tachycardia

• High P wave, long PR interval, wide QRS, low T wave, U wave

• May develop AF, AV block, VEBs, VF

Thyrotoxic Periodic ParalysisManagement

• Correct hypokalaemia : oral/IV, total dose

< 50 mmol KCL over several hours

• Propanolol : 3mg/kg oral/IV (prevents intracellular shift K+). Normalises serum K+ within 2 hours

• Manage hyperthyroid state

Thyrotoxic Periodic ParalysisDifferential Diagnosis

• Thyrotoxic myopathy

• Drugs eg diuretics,

• Renal causes (hypoK+)

• GIT loss K+ eg severe diarrhoea

• Familial periodic paralysis

Thyrotoxic Periodic ParalysisLaboratory Findings

• Increased CK (mild)

• Low serum K+/Mg/P04

• TSH very low, high T3 & T4

• No acid base disturbance

TPP: Case Study

• 22 yrs female, for hysteroscopy.

• Previous GAs OK

• History: Graves disease, poorly managed

• Preop: HR 84/min SR, resting tremor, on Neomercazole

• Uneventful surgery, LMA Fentanyl, Propofol, Midazolam

TPP Case Study

• Very slow emergence, twitching/ muscle weakness in lower limbs

• Haemodynamically stable

• Flumazenil given, no effect

• Calcium gluconate 2.2mmol, mild improvement

• UEC NAD

• TFTs: TSH < 0.2 T4 :439 T3: 10

• Given KCL 20 mmol IV over several hours, good effect

Apudomas

• Tumours of amine precursor uptake and decarcarboxylation (APUD) cells

• APUD cells occur in anterior pituitary, thyroid, adrenal medulla, pancreas, GIT, and lungs

• Classification: phaeochromocytoma, carcinoidtumour, gastrinoma, VIPomas and insulinoma

Phaeochromocytoma

• Tumour of chromaffin cells in adrenal medulla (90%) orSNS chain (10%)

• Bilateral 10% cases

• 90% benign

• 35% of extra-adrenal tumours malignant

• Occur in all age groups (rare in children)

• 30% occur as part of hereditary syndromes egmultiple endocrine neoplasia (MEN), neurofibromatosis, Von Hippel Lindau syndrome

Phaeochromocytoma

• Tumours secrete:Noradrenaline ( commonest)

Adrenaline

Dopamine

• Signs and SymptomsEpisodic headaches/ palpitations/diaphoresis/ severe

hypertension. Lasts seconds to hours

Frequency of symptoms: several times daily to monthly Frequency/ severity increases with tumour growth

PhaeochromocytomaClinical Signs and Manifestations

• Tremor, nausea, weakness, anxiety, epigastricand/or flank pain

• Hypertension – paroxsymal in 50% cases

• Postural hypotension (volume contraction)

• Weight loss, pallor, fever, ileus, constipation

• Tachyarrhythmias, cardiomyopathy

• Specific syndrome signs eg neurofibroma,

café au lait spots

PhaeochromocytomaAcute Presentations

• Acute pulmonary oedema

• CVA, AMI, tachyarrhythmias

• May present perioperatively. Inadequate treatment up to 50% mortality

PhaeochromocytomaManagement

• SNS blockade: a1 block before B block

• Long acting a1 : Phenoxybenzamine 7-10 days

• Short acting a1: Prazosin

• B blockade eg Atenolol, Metoprolol

• Other antihypertensives eg Ca channel blockers eg Nifedipine, Diltiazem

PhaeochromocytomaAnaesthetic Considerations

• Consider diagnosis: severe unexpected hypertension and SNS signs

• Control of BP: Prazosin,magnesium

• Treat arrhythmias eg Adenosine, Verapamil, Esmolol (once a1 blocker given) ? Amiodarone

• Fluid replacement once vasoconstriction managed

• ICU admission/ transfer elsewhere !

Carcinoid Tumour

• Derived from argentaffin cells

• Occur in GIT (75%), lung, pancreas, gonads

• Usually benign

• Vasoactive mediators metabolised in the liver

• Less than 25% carcinoid tumours produce carcinoid syndrome

• Vasoactive substances: serotonin, bradykinin, histamine (gastric tumours), PGs, VIP, Substance P

Carcinoid TumourSymptoms

• Primary tumour: intestinal obstruction or pulmonary symptoms eg haemoptysis

• Vasoactive substances– Flushing (90%) on head/neck/torso: bradykinin

– Diarrhoea (80%) +/- dehydration, electrolyte disturbances: serotonin

– Bronchospasm (20%) : histamine, bradykinin

– Hypotension/ hypertension/ tachycardia: serotonin

– Right heart failure (endocardial fibrosis in tricuspid and pulmonary valves)

Carcinoid TumoursInvvestigations & Complications

• Investigations

– ECG, echo (cardiac involvement)

– LFTs and clotting profile (hepatic metastases)

– Imaging eg CT/ CXR

• Perioperative Complications

– Severe hypertension/hypotension

– Fluid and electrolyte shift

– Bronchospasm

Carcinoid TumoursPreoperative Management

• Treat symptoms– Diarrhoea, correct dehydration & electrolytes

– Bronchodilators

– Treat heart failure

• Prevent release of mediators– Octeotride 100mcg subcut tds for 2 weeks preop

• Avoid factors that may trigger carcinoid crises– Catecholamines, anxiety, histamine release eg

Morphine, Atracurium

Carcinoid TumourAnaesthetic Considerations

• Haemodynamic compromise most likely with induction/intubation/ tumour manipulation

• Premed: Octeotride 100mcg subcut 1 hour preop (if not already blocked) plus benzodiazepine

• Postoperatively: patients awaken slowly ( serotonin). ICU/HDU admission

Carcinoid Tumours

• Consider diagnosis with unexpected:

– Bradykinin release: severe hypotension/flushing/bronchospasm

– Serotonin release: Unexpected hypertension and tachycardia, increased gut motility and diarrhoea

Carcinoid TumoursManagement

• Induction: avoid pressor response to intubation eg Remifentanil

• Suxamethonium safe

• Avoid histamine releasing drugs eg Morphine, Atracurium

• Hypotension intraoperatively– Ensure optimal IV filling

– Octeotride 10-20mcg boluses IV

– Consider small doses of Phenylephrine/Vasopressin

Carcinoid TumoursManagement

• Hypertension intraoperatively

– Esmolol, Labetolol, calcium channel blockers

• High dose corticosteroids preoperatively to decrease kinin release

SEVERE EUGLYCAEMIC KETOACIDOSIS

• Sodium–glucose co transporter 2 inhibitor drugs (SGLT2)

• Single drugs eg Forxiga and Jardiance

• Combination (Metformin): Xigduo, Jardiamet

• Mechanism of action: – Reduce renal glucose reabsorption, increase

urinary glucose excretion

– Increase glucagon secretion/ ketone production and renal ketone reabsorption

Severe Euglycaemic KetoacidosisPossible triggers

• Fasting

• Surgery

• Dehydration

• Active infection especially UTI

• Renal impairment

• Lactic acidosis

• Insulin insufficiency HbA1C > 9.0 and blood ketones > 0.6

Severe Euglycaemic KetoacidosisClinical Features

• Drowsiness, nausea, vomiting, fatigue, unexplained acidosis/deterioration

• Metabolic acidosis (venous or arterial)

• Ketones or B hydroxybutyrate blood levels > 0.6 perioperatively

• Normal plasma glucose or urine ketone levels do not exclude diagnosis

• DD: lactic acidosis

Severe EuglycaemicKetoacidosisLaboratory features

• Acidaemia pH < 7.30

• Metabolic acidosis BXs < -5, Bicarb < 15 wide anion gap > 12

• BSL normal/ mild increase < 14 mmol

• Increased plasma ketones

• Urinary ketones normal or increased

Anaesthetic Considerations

• Major surgery: cease drug 3 days preop. Substitute Metformin,

• Routinely check blood glucose and ketonelevels if patient unwell or limited oral intake

• Day surgery: only restart drug if full oral intake

• Major surgery: restart drug only when eating and drinking/ close to discharge