Acute Endocrine Emergencies

Dr. M Malik

Consultant Endocrinologist

Clinical Lead Diabetes & Endocrinology NLAG

Objectives

• Acute Severe Hyponatraemia

• Acute Hypocalcaemia & hypercalcaemia

• Adrenal Insufficiency

• Pituitary emergencies

• Emergency thyroid disorders

Acute Severe Hyponatraemia

Na Case I

• 84 F Progressive confusion for 3 days

• General weakness over 2-3 weeks

• PH Ca breast 15 years ago, no evidence of recurrence

• Na 115 Normal K, eGFR but raised CRP

• CT brain NAD

• Clinically slow and obtunded but no focal neurology

Na case II

• 52 F Metastatic Ca breast on active oncology Rx.

• Reduced level of consciousness for 24 hours

• CT brain NAD and normal WCC & Neutrophil

• Na 107

• GCS 8/15

Clinical Practice Guideline on Diagnosis

and Treatment of Hyponatraemia

Spasovski G et al. Eur J Endocrinol 2014;170:G1-G47

6.1.2. Definition of hyponatraemia based on time of development:

• 6.1.2.1 We define ‘acute’ hyponatraemia as hyponatraemiathat is documented to exist <48h.

• 6.1.2.2 We define ‘chronic’ hyponatraemia as hyponatraemia that is documented to exist for at least 48h.

• 6.1.2.3 If hyponatraemia cannot be classified, we consider it being chronic, unless there is clinical or anamnestic evidence of the contrary.

6.1 Classification of hyponatraemia

6.1.1. Definition of hyponatraemia based on biochemical severity

• 6.1. Mild hyponatraemia between 130 and 135 mmol/l .

• 6.1. Moderate hyponatraemia between 125 and 129 mmol/l .

• 6.1. Profound hyponatraemia as serum sodium concentration <125 mmol/l./l.

6.1 Classification of

hyponatraemia

Severity Symptom

• Moderately severe Nausea without vomiting

Confusion

Headache

• Severe Vomiting

Cardiorespiratory distress

Abnormal and deep somnolence

Seizures

Coma (Glasgow Coma Scale ≤8)

Classification of Symptoms of hyponatraemia

THINK SALT

Are there any symptoms of

cerebral oedema?

Coma (GCS ≤8)

Seizures

Abnormally deep somnolence

Cardiorespiratory distress

Projectile vomiting

Hyponatraemia <135mmol/L

-Consider immediate

treatment with hypertonic

saline (Protocol DCG05)

-Discuss with Consultant

A/E or Medical registrar

1. Assess and record

patient’s volaemic status

2. Order essential

investigations within

24hours of admission

a. Serum osmolality

b. Urine osmolality

c. Urine electrolytes

3. Order supplementary

investigations

a. Urea and creatinine

b. TSH

c. Random cortisol

d. Uric acid

4. Commence appropriate

treatment

5. Discuss with Senior A&E

Officer or Medical

Registrar if needed

YES

NO

If Na ≤ 125

-Laboratory will alert A&E Officer

-Send appropriate samples

-Discuss management with

Senior A&E officer or Medical

Registrar If Na 126 - 135

Management of Hyponatraemia

with severe symptoms

• 1. First-hour management, regardless of whether hyponatraemia is acute (<48 hours) or chronic (>48 hours or unknown duration).

• # Prompt i.v. infusion of 150ml 3% hypertonic saline over 20min#

(1D).

• Check the serum sodium concentration after 20min while repeating an infusion of 150ml 3% hypertonic saline for the next 20min (2D).

• Repeat therapeutic recommendations 1.1 and 1.2 twice or until a target of 5mmol/l increase in serum sodium concentration is achieved (2D).

• Manage patients with severely symptomatic hyponatraemia in an environment where close biochemical and clinical monitoring can be provided (HDU or ICU).

•

Follow-up management in case of improvement of symptoms after a

5mmol/l increase in serum sodium

• 2.1 Stop the infusion of hypertonic saline (1D).

• 2.2 Keep the i.v. line open by infusing the smallest feasible volume of 0.9% saline until cause-specific treatment is started (1D).

• 2.3 Start a diagnosis-specific treatment if available, aiming at least to stabilisesodium concentration (1D).

• 2.4 Limit the increase in serum sodium concentration to a total of 10mmol/l during the first 24h and an additional 8mmol/l during every 24h thereafter until the serum sodium concentration reaches 130mmol/l (1D).

• 2.5 Check the serum sodium concentration after 6 and 12h and daily afterwards until the serum sodium concentration has stabilised under stable treatment (2D).

3. Follow-up management in case of no improvement of symptoms after a 5mmol/l

increase in serum sodium concentration

• Continue i.v. infusion of 3% hypertonic saline or equivalent aiming for an additional 1mmol/l per h increase in serum sodium concentration (1D).

• Stop the infusion of 3% hypertonic saline or equivalent when the symptoms improve, the serum sodium concentration increases 10mmol/l in total or the serum sodium concentration reaches 130mmol/l, whichever occurs first (1D).

• Additional diagnostic exploration for other causes of the symptoms than hyponatraemia (1D).

• Check the serum sodium concentration every 4h as long as an i.v.infusion of 3% hypertonic saline or equivalent is continued (2D).

70kg person, Na 125 given 0.9% NaCl

[Na] per litre

of 0.9% NaCl

(contains

155mmol Na)

=

[Na]infusate – [Na]serum

155 - 125

Total body water + 1L

(70x0.6) + 1

Estimated change: 30 42+1 = 0.69 mmol/L

70kg person, Na 115 given 3.0% NaCl

[Na] per litre

of 3.0 % NaCl

(513mmol Na)

=

[Na]infusate – [Na]serum

513 - 115

Total body water + 1L

(70x0.6) + 1

Estimated change: 398 42+1 = 9.3 mmol

Acute Calcium Disorders

Calcium Case I

• 29 F Recent total thyroidectomy for resistant Grave’s

• Severe carpo-pedal spasm and peripheral tingling.

• Adjusted Ca 1.42 (N 2.2-2.6) Po4 1.79 (N 0.5-1.5)

Emergency management of acute hypocalcaemia in

adult patients

‘Mild’ hypocalcaemia: asymptomatic; serum calcium >1.9 mmol/L.

• Oral therapy with Calcium salts ± Vit D ± Mg

• Adjust treatment aiming for 2.1 – 2.4 mmol/L.

J Turner et al; http://www.endocrineconnections.orgDOI: 10.1530/EC-16-0056

Emergency management of

acute hypocalcaemia in adult patients

Severe hypocalcaemia: serum calcium <1.9 mmol/L and/or symptomatic at any level below reference range.

• Peri-oral and digital paraesthesiae

• Positive Trousseau’s and Chvostek’s signs

• Tetany and carpopedal spasm

• Laryngospasm

• ECG changes (prolonged QT interval) and

• Arrhythmia

• SeizureJ Turner et al; http://www.endocrineconnections.orgDOI: 10.1530/EC-16-0056

Emergency management of

acute hypocalcaemia in adult patients

• Medical Emergency:

• Iv Calcium Gluconate Boluses

• Iv calcium infusion

• Iv Magnesium

• 1-alpha hydroxylated Vit D (Alfacalcidol or Calcitriol)

Under ECG Monitoring

Caution in ESRF

J Turner et al; http://www.endocrineconnections.orgDOI: 10.1530/EC-16-0056

Management of Symptomatic Hypocalcaemia Post Thyroidectomy Infusion of intravenous calcium must be through a central line to avoid subcutaneous Calcification. Liaise with the endocrine team and clinical biochemists early 1. IV Calcium Infusion

20 mls of 10% calcium gluconate iv stat

iv infusion of 100 mls of 10% calcium gluconate in 1000 ml N/saline rate 100 mls/hr

Check Adj Ca 6 hourly and adjust Ca infusion as follows:-

Adj Ca < 1.8 increase calcium infusion to 200 ml/hour

Adj Ca 1.9 - 2.1 continue infusion at 100 ml/hour

Adj Ca 2.2 - 2.4 reduce infusion to 50 ml/hour

Adj Ca 2.45 - 2.65 reduce infusion to 25 ml/hour

Adj Ca > 2.65 stop Ca infusion

2. IV Magnesium 1 gram/ hr dilution = 50 gram MG in 1000 ml N/ saline rate 20 mls/hr for 48 hours 3. Oral Calcium Calcit 500 effervescent 4 tablets tid OR Sandocal 1000 2 tablets tid 4. Oral Magnesium Glycerophosphate (97 mg or 4 mmol per tablet) 2 tablets 4 times a day 5. Alphacalcidol 1 mcg po od 6. Bendrofluazide 2.5 mg po od 7. STRICTLY 6 HOURLY

1. Adj Ca 2. Phosphate 3. U&E’s

Dr M Malik 2008

Practical Points

• Iv calcium infusion should be through large or central venous access to avoid cutaneous calcinosis.

• Target adjusted calcium at or just below normal range.

• Oral supplements should be administered concomitantly.

• Monitor to avoid over-replacement

Calcium II

• 82 M Past history of COPD, IHD and DM

• Weight loss and general deterioration

• Adj Ca 3.4 Po4 0.9 urea 18.2 Creat 180

• Clinically dehydrated

Symptomatic Hypercalcaemia

• Obtain blood samples for PTH, Mg and if possible urine calcium before commencing calcium lowering therapy.

• Rest of work-up can wait

• Management:

1. Volume expansion to break down the nephrogenic DI cycle and encourage calcium excretion.

2. IV Bisphosphonate

3. S/C or IM Calcitonin 100 Units tds/qds

4. ? Calcium receptor memetic therapy

Resistant Hypercalcaemia

1. IV Calcitonin infusion 10 units over 6 hours

2. Haemofiltration.

3. Steroids only for Granulomatous hypercalcaemia & Hypervitaminosis D

Adrenal Emergencies

Adrenal Case I

• 78 F Reduced level of consciousness? CVA

• CT and MRI brain normal

• GCS 5/15 Na 125, K 5.4, Urea 11.0, BP 88/54

• CRP normal, but covered with BS antibiotics

• RA on long-term steroid maintenance.

• Previously independent

Relative biologic potencies

Steroids Anti-inflam

properties

HPA

suppression

Salt

retention

Cortisol 1 1 1

prednisolone 3 4 0.75

Methyl pred 6.2 4 0.5

Fludrocort 12 12 125

Dexametha 26 17 0

Chronic steroid therapy

• Any dose <3/52 – no problems.

• ?exception: frequent short term courses

• At 5mg /day – defects in HPA axis.

• Alternate day doses – less suppression

Chronic steroid therapy

• All pts treated chronically – similar to pts

with ACTH deficiency.

• Intercurrent illness – cover with

hydrocortisone 100-150mg/day.

N= 36

Answer N %

Take same dose 6 10.7%

Double the dose 12 22.6%

Triple the dose 10 18.8%

Seek medical help 19 35.8%

I don’t know 1 2%

Answer missing 5 9.4%

N = 53

0

2

4

6

8

10

12

14

16

18

Omit doseTake same

doseTake extra

doseTake extra

dose and

use

injection

Use steroid

injectionDON’T

KNOWMISSING

6

12

8

3

18

1

5

N = 53

Adrenal Case II

45 yr F Haematemesis, melena .

• ALD suspected

• Found to be in septic shock

• Resuscitated, antibiotics and “liver regimen”

• Slow response to rx

• 3/7 post admission: hypotensive

• SST: 0 min 85nmol/L, 30 min 285 nmol/L 60 min 394 nmol/L

1 µg/dl = 27.59 nmol/Lendomemo.com

critical illness-related corticosteroid insufficiency

(CIRCI)

• We suggest that intravenous corticosteroid therapy (200 to 300 mg per day) be administered to adult patients with severe septic shock (defined as a systolic blood pressure <90 mmHg for more than one hour despite both adequate fluid resuscitation and vasopressor administration) (Grade 2C).

• We suggest NOT administering corticosteroid therapy to patients without shock, or patients with less severe septic shock (defined as those in whom fluid resuscitation and pressor therapy have restored hemodynamic stability) (Grade 2B).

http://www.uptodate.com/contents/corticosteroid-therapy-in-septic-shock

critical illness-related corticosteroid insufficiency

(CIRCI)

• Response to ACTH testing should not be used to select patients for corticosteroid therapy.

• We typically administer hydrocortisone for five to seven days and taper the dose as guided by the clinical response. Close observation of those patients whose steroid therapy is stopped without being tapered is warranted. We do not add fludrocortisone to our regimen.

http://www.uptodate.com/contents/corticosteroid-therapy-in-septic-shock

ADRENAL Trial

• N= 3680

• Septic shock requiring ventilation

• 200 mg iv hydrocortisone V Placebo

• No difference in 90 days mortality; P 0.05

• Faster resolution of shock and shorter initial episode of ventilation; P <0.001

N Engl J Med 2018; 378:797-808

B Venkatesh et al. N Engl J Med 2018;378:797-808.

Rate of Survival and the Risk of Death at 90 Days, According to Subgroup.

APROCCHSS trial

• N = 1241

• Septic shock requiring ventilation

• Hydrocortisone 50-mg iv bolus every 6 hours, and fludrocortisone 50-μg tablet od via NG.

• RR of death in 90 days was 0.88 (95% CI, 0.78 to 0.99) in favour of HC+FC group. P0.03

• Mortality at discharge and 180 days was significantly lower, as shorter weaning of ventilation and vasopressors.

N Engl J Med 2018; 378:809-818

D Annane et al. N Engl J Med 2018;378:809-818.

Trial Outcomes.*

D Annane et al. N Engl J Med 2018;378:809-818.

90-Day Survival Distributions.

Pituitary Emergencies

Pituitary Case I

• 58 yr male. Extensive craniotomy for Large olfactory grove meningioma

• Post-op Poor memory, Mild speech difficulty & Transferring with 2

• Hypotensive & Moribund

• SST: 0 min 30nmol/L , 119 min. Panhypopit .

Post Brain Surgery/Trauma

Hypopituitarism

• Hypopituitarism has long been reported as a complication of head injury.

Escamilla RF, et al. J Clin Endo 1942

• Recently as complication of neurosurgery for non-pituitary brain tumours

Schneider HJ, et al. Eur J Endo. 2006

Post Brain Surgery/Trauma

Hypopituitarism

Schneider HJ, et al.

• N = 68 (28 female, age 45.0 ± 1.8 years).

• 17 Neurosurgery (NS) only.

• 51 NS in combination with radiotherapy (RT) and/or chemotherapy (CT).

Eur J Endocrinol. 2006 Oct;155(4):559-66

Percentages of hypopituitarism according to treatment (A) and regional distribution of tumours (B).

Aetiology

• Multifactorial:

• Direct damage to the pituitary or hypothalamus.

• Infarction and/or necrosis due to impaired circulation as a result of brain oedema.

• Secondary to the release of inflammatory mediators (such as cytokines, and free radicals).

Pituitary case II

• 49 M Hypertensive & incidental none functioning pituitary adenoma.

• Eupituitarism on serial MRI surveillance.

• Acute severe headache & blurring of vision.

• Mild diplopia & early meningism, but no other focal neurology, BP 165/95.

• Normal biochemistry

Case courtesy of Dr Frank Gaillard, Radiopaedia.org, rID: 17664

Case courtesy of Dr Frank Gaillard, Radiopaedia.org, rID: 17664

Pituitary Apoplexy

Randeva HS, et al.

• N=35

• Retrospective study 1985-96

• Headache (97%), nausea (80%) and a reduction of visual fields (71%). Hypertension26% of patients

• MRI correctly identified pituitary haemorrhage in 88% (n = 7), but CT scanning Identified haemorrhage in only 21% (n = 6).

Randeva HS, et al. Classical pituitary apoplexy: clinical feat.Clin Endocrinol (Oxf). 1999;51(2):181.

Pituitary Apoplexy

• Complete restoration of visual acuity occurred in all patients operated on within 8 days but only in 46% of patients operated on after this time (9-34 days).

• Long-term steroid or thyroid hormone replacement was necessary in 58% and 45% of patients, respectively. Of the male patients, 43% required testosterone

• high doses of corticosteroids and, for patients with a prolactinoma, administration of a dopamine agonist to reduce tumor size

Randeva HS, et.al. Classical pituitary apoplexy: clinical feat.Clin Endocrinol (Oxf). 1999;51(2):181.

Thyroid Emergencies

Thyroid Emergencies

• Acute hyperthyroidism with deranged LFTs and relative neutropenia

• ATD induced Agranylocytosis

• Thyroid storm

• Acute hypothyroidism with adrenal insufficiency

Case 1 Thyroid

• 26 F, 11/12 post-partum. Progressive thyrotoxic symptoms.

• TSH<0.01 T4 39.4 T3 19.6 TPO 340

• WCC 2.7 Neutrophil 0.6

• ALT 87 (N 0-37) GGT 200 AlkPh 228 Bilirubin 6

HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS: MANAGEMENT GUIDELINES OF THE

AMERICAN THYROID ASSOCIATION AND AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS

• RECOMMENDATION 15

• Prior to initiating antithyroid drug therapy for GD, we suggest that patients have a baseline complete blood count, including white count with differential, and a liver Function test.

• low white cell counts are common in patients with autoimmune diseases and in African Americans, and abnormal liver enzymes are frequently seen in patients with thyrotoxicosis

• baseline absolute neutrophil count <500/mm3 or liver transaminase enzyme levels elevated more than fivefold the upper limit of normal are contraindications to initiating antithyroid drug therapy.

Hyperthyroidism Management Guidelines, Endocr Pract. 2011;17(No. 3) e15

Case II Thyroid

• 29 F on Carbimazole 20mg bd for Graves hyperthyroidism.

• Seen her GP with sore throat two weeks after comencingATD therapy.

• Routine FBC revealed WCC 1.2 Nuetr 0.32.

HYPERTHYROIDISM AND OTHER CAUSES OF THYROTOXICOSIS: MANAGEMENT GUIDELINES OF THE

AMERICAN THYROID ASSOCIATION AND AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS

• RECOMMENDATION 16

• A differential white blood cell count should be obtained during febrile illness and at the onset of pharyngitis in all patients taking antithyroid medication. Routine monitoring of white blood counts is not recommended. 1/+00

• In a patient developing agranulocytosis or other serious side effects while taking either MMI or PTU, use of the other medication is absolutely contraindicated owing to risk of cross-reactivity between the two medications (101).

• Frequency of agranulocytosis is quite low 0.2-0.5%, and the condition is of sudden onset.

Hyperthyroidism Management Guidelines, Endocr Pract. 2011;17(No. 3) e15

Thyroid Case III

• 24 F Admitted with pyrexia of 38.5, severe agitation and confusion .

• Clinically tremulous, dehydrated, fast AF, hypotensive and tachyponic.

• Smooth moderate size goitre and mild proptosis.

• Tender abdomen with guarding and positive PR for blood.

• Treated as severe sepsis bending shock.

• T4 > 100 T3 37 Adj Ca 3.13

Thyroid Storm

• The incidence of thyroid storm currently may currently be as low as 0.2 cases/100,000 population (3) .

• most commonly following infection (1), which seems to induce an escape from control of thyrotoxicosis.

• Death may be caused by cardiac arrhythmia, congestive heart failure, hyperthermia, or other unidentified factors.

http://www.thyroidmanager.org/chapter/graves-disease-complications/

Thyroid Storm

• Supportive Measures:

1. Rest

2. Mild sedation

3. Fluid and electrolyte replacement

4. Nutritional support and vitamins as needed

5. Oxygen therapy

6. Nonspecific therapy as indicated

7. Antibiotics

8. Cardio-supportive

9. Cooling

Thyroid Storm

• Specific therapy

1. Propranolol (20 to 200 mg orally every 6 hours, or 1 to 3 mg intravenously every 4 to 6 hours)

2. Antithyroid drugs (150 to 250 mg PTU or 15 to 25 mg methimazole, every 6 hours)

3. Potassium iodide (one hour after first dose of antithyroiddrugs): 100 mg KI every 12 hours

4. Dexamethasone (2 mg every 6 hours)

• Possibly useful therapy

1. Ipodate (Oragrafin) or other iodinated contrast agents

2. Plasmapheresis or exchange

3. Oral T4 and T3 binding resins

4. Dialysis

Case IV Thyroid

• 37 F recent diagnosis with symptomatic hypothyroidism. Worsening symptoms despite increasing thyroxine dose. Admitted with collapse.

• TSH 22.4 T4 18.6 T3 3.6 TPO >1000

• FSH 58 LH 36

• Na 131 K 5.5 Adj Ca 1.98

• SST: 0 min 45 30 min 52 nmol/L

Hypoadrenalism n=52/740

50%

15%

8%

21%2% 4% Addison's (11)

Surgical HypoAD (4)

Primary Hypopit (8)

Post-op Hypopit (26)

AD Others (1)

Pit Others (2)

Addison’s Disease (n=11)Associated Condition Number of Patients

Grave’s Disease 4

Schmidt’s Syndrome 2

Hyperparathyroidism 1

APS I 1

APS II 1

No autoimmune disease 2

Thank you..