This document discusses thyroid emergencies including thyroid storm and myxedema coma. It provides details on the synthesis and effects of thyroid hormones, diagnosis of thyroid storm using the Burch-Wartofsky Point Scale and Japan Thyroid Association criteria, and management principles for thyroid storm including beta blockers, antithyroid medications, corticosteroids, iodine, and definitive therapy. Precipitating factors and management of myxedema coma are also summarized.

1. Endocrine Emergency
1. Thyroid storm
2. Myxedema coma
3. Adrenal Insufficiency

4. Pituitary hormones

5. Topic today..

6. 1. Synthesis of thyroxine
2. Effects of thyroid hormone
3. Diagnosis of thyroid storm
4. Principle of management and prevention

7. • Thyroglobulin is synthesized by follicular
cells and precursor for triiodothyronine (T3)
and thyroxine (T4)
• Only the small amounts of free T3 and T4 in
plasma can readily cross the cell membranes
to bind to thyroid hormone receptors as
majority bound to proteins.
• Hypothalamus produces TRH > pituitary
gland produces TSH >thyroid gland
Thyroxine

8. Physiological Effects of Thyroid Hormones
• Basic levels of thyroid hormone release are
essential to maintain a normal metabolic rate.
• Physiological effects of thyroid hormones include
• Heat production (thermogenesis)
• Increased basal metabolic rate
• Metabolic effects
• Increase in protein turnover (both synthesis and
degradation are increased, although overall effect is
catabolic)
• Increase in lipolysis
• Increase in glycogenolysis and gluconeogenesis
• Enhanced catecholamine effect
• Increase in heart rate, stroke volume and thus cardiac
output
• Important role in growth and development

10. Diagnosis of thyroid storm
• made clinically in a thyrotoxic patient with evidence of
decompensation.
• mortality rates in the range of 11%–25%
• presence of severe and life-threatening symptoms (hyperpyrexia,
cardiovascular dysfunction, altered mentation) in a patient with
biochemical evidence of hyperthyroidism
• Diagnostic tool
• Burch–Wartofsky Point Scale (BWPS)
• Japan Thyroid Association (JTA)

12. Difference between hyperthyroidism and
thyrotoxicosis
• Hyperthyroidism is a set of disorders that involve excess synthesis and
secretion of thyroid hormones by the thyroid gland which leads to the
hypermetabolic condition of thyrotoxicosis
• thyrotoxicosis, thyroid hormone levels are elevated with or without
increased thyroid hormone synthesis. Eg excess intake of the thyroid
medication levothyroxine or temporary excess release of thyroid
hormone due to thyroiditis.

13. Precipitating condition
• Non-compliance or discontinuation of anti-thyroid drugs
• Severe infection
• Cardiac event
• Thyroidal and non-thyroidal surgery
• Trauma
• Administration of iodinated contrast and radioactive iodine (RAI)
• Adrenal insufficiency
• Diabetic ketoacidosis

14. • In patients with severe thyrotoxicosis, points are
assigned to the highest weighted description
applicable in each category and scores totaled.
• When it is not possible to distinguish the effects
from those of the severe thyrotoxicosis per se,
points are awarded such as to favour the
diagnosis of storm and hence, empiric therapy.
• score of >45 or greater is highly suggestive of
thyroid storm;
• a score of 25–44 is suggestive of impending storm,
and a score,
• below 25 is unlikely to represent thyroid storm.
• BWPS of 25–44 represent a group in whom the
decision to use aggressive therapy should be
based on sound clinical judgment and not based
solely on diagnostic category in order to avoid
overtreatment and the resultant risk of drug
toxicity.

16. Comparison between BWPS and JTA
• Retrospective audits comparing the BWPS versus JTA generally show agreement
between the two methods, but there was a tendency for underdiagnosis with the
JTA.
• If the clinician is unsure whether the symptoms are due to thyroid storm or an
underlying disease, symptoms should be regarded as due to thyroid storm.
Although measurement of fT4, fT3, and TSH are required, these values may not
correlate with the severity of clinical presentation.

17. INVESTIGATION
•Urgent TFT
•FBC
•RP
•BLOOD GAS
•SEPSIS WORKUP IF INDICATED
•ECG and CXR

18. Principle of management of thyroid storm
a) Inhibiting synthesis and release of thyroid
hormone
b) Inhibiting peripheral action of thyroid hormone
c) Reversing systemic decompensation
d) Treating precipitating event
e) Addressing definitive therapy

19. Beta blocker
• Beta-adrenergic receptor antagonists are key to control heart rate and inhibit
other peripheral actions of thyroid hormones in thyroid storm.
• Caution should be exercised with patients in decompensated heart failure.
• If there are contraindications to b-blockers, such as in patients with obstructive
airway disease cardio selective calcium-channel blockers such as diltiazem or
short acting intravenous esmolol.
• IV PROPRANOLOL 1mg every 5 mins until severe tachycardia is controlled
• Intravenous esmolol infusions are given at a loading dose of 250–500 mcg/kg,
and thereafter at 50–100 mcg/kg/min of infusion, titrated to heart rate and blood
pressure.(not available in hdok)
• T .Propranolol 60mg 4 hourly or 80mg 8hourly
• When hemodynamics is impaired rapidly because of atrial fibrillation,
cardioversion is recommended when left atrial thrombus has been ruled out.

20. Why Propranolol Is Preferred to Other Beta-
Blockers in Thyrotoxicosis or Thyroid Storm ?
• Control heart rate.
• Block conversion of T4 to more
potent T3.
• Reverse reduced systemic
vascular resistance thus reduce
risk of developing high output
cardiac failure.

21. Management high output cardiac failure due
to thyroid storm
• Thyroid storm is a severe hypermetabolic condition resulting in increased
sensitivity and expression of beta-adrenergic receptors, leading to a higher
response to endogenous catecholamines.
• Hyperthyroidism causes high-output HF
• Pathophysiology
• create a hyperdynamic circulatory state via positive chronotropic and inotropic
effects
• reduction in systemic vascular resistance.
• the increased cardiac output is greater than the metabolic demand.
Patients will present with an increased stroke volume, increased
myocardial contractility, increased ejection fraction, atrial arrhythmia and
systolic hypertension with an associated wide pulse pressure

22. Principle management high output cardiac
failure due to thyroid storm
• Non invasive ventilation (NIV) ,for intubation if condition worsens.
• IV Frusemide
• Avoid non selective beta blocker
• Initiate inotrope if needed

23. Summary
Sinus tachycardia Fast Atrial fibrilation AF in failure Unstable AF
IV Propranolol 1mg every
5-10 mins until HR
controlled
IV Propranolol 1mg every
5-10 mins until HR
controlled
selective b-1 blockade
bisoprolol, landiolol, and
esmolol.
cardioversion is
recommended when left
atrial thrombus has been
ruled out.
If contraindicated to beta
blocker due to obstructive
airway disease calcium-
channel
blockers such as diltiazem
or intravenous esmolol can
be used to control
heart rate.
If contraindicated to beta
blocker due to obstructive
airway disease calcium-
channel
blockers such as diltiazem
or intravenous esmolol can
be used to control
heart rate.
IV Digoxin
IV Digoxin

25. Thionamides
• Propylthiouracil (PTU)
• Function : inhibiting the synthesis and release of thyroid hormones.
• no effect on the release of preformed hormone from the thyroid gland
• loading of 500–1000 mg, then 250 mg four-hourly
• Alternative to PTU
• methimazole (MMI) 60–80mg/day (not available in HDOK)
• PTU is preferentially used in comparison to MMI in thyroid storm, as it will inhibit type I deiodinase activity
in the thyroid gland and other peripheral organs, therefore reducing the conversion of T4 to T3. T3 levels
drop by 45% within one hour of PTU administration, but only about 10%–15% after starting MMI.
• In conditions where the absorption of oral PTU or MMI is compromised, such as in ventilated patients or in
those with conditions that impair absorption, rectal PTU or MMI can be used. (not available in HDOK)

26. Corticosteroid
• Hydrocortisone 100mg stat and TDS
• inhibit both thyroid hormone synthesis and peripheral conversion of
T4 to T3
• direct effect on the underlying autoimmune process, if the thyroid
storm is due to Graves' disease.
• also given as prophylaxis for relative adrenal insufficiency caused by a
hypermetabolic state in thyroid storm.

27. Iodine
• rapidly decrease T4 levels by inhibition of iodide oxidation and
organification and inhibits release of thyroid hormone.
• 10 drops of Lugol’s iodine 8 hourly
• Should only be given at least after one hour of antithyroid drug
administration, to prevent the use of iodine as a substrate for thyroid
hormone synthesis.
• Surgery should not be delayed for more than 8 to 10 days, because of
a phenomenon called escape from the Wolff-Chaikoff effect.
Wolff-Chaikoff effect
Large doses of exogenous iodine inhibit the organification of iodine and synthesis of thyroid in the thyroid
gland.

28. Early Definitive Therapy And Prevention
• All patients with thyroid storm should have early definitive therapy
with RAI.
• In patients with large obstructing goiter, early thyroidectomy should
be considered instead.
• However, these patients should be rendered close to euthyroid prior
to minimize risk of thyroid storm.
• Patient education is precipitating event is non compliance to Anti-
thyroid drugs.

30. Myxedema coma

31. Clinical manifestation
• Systemic condition that can affect every
organ and system.
• Rare condition which is diagnosed clinically in
patients
• Thyroid function test will be consistent with
hypothyroidism. Diagnostic scoring systems
have been designed but are not well
validated as the incidence is low.
• Hypothermia
• Neurological
• Psychosis
• Seizures
• altered consciousness
• metabolic decompensation
• hypoglycaemia
• Hyponatraemia
• cardiovascular
• Bradycardia
• hypotension
• pericardial effusion
• heart failure
• Respiratory
• Hypoventilation
• Hypercapnia
• sleep apnea
• renal failure
• Anaemia

32. Precipitating condition
• Non-compliance to meds
• Infection
• Cardiac event
• Trauma
• Drugs
• Amiodarone : Related to Wolff-
Chaikoff effect as amiodarone
contains iodine and closely
resemble T4.
• Lithium : inhibits thyroid hormone
release.

33. INVESTIGATION
•Urgent TFT
•FBC
•RP
•BLOOD GAS , DXT
•SERUM CORTISOL
•SEPSIS WORKUP IF INDICATED
•ECG and CXR

34. Management
• ABCD assessment and management
• Passive rewarming with a blanket is preferred for correction of hypothermia.
• Intravenous hydrocortisone 200 mg stat then 100 mg 8 hourly should be administered prior to levothyroxine
• Why?
• Hypothyroidism may associate with adrenal insufficiency, either due to pituitary disease or as a multifocal autoimmune disorder.
• Giving thyroid hormone without steroid can precipitate adrenal crisis.
• Initial intravenous levothyroxine of 200–400 mcg followed by 1.6 mcg/kg/day (75% if administered
intravenously) should be given thereafter.
• If intravenous levothyroxine is not available, oral levothyroxine can be given as 500 mcg loading followed by
maintenance dose.
• Intravenous liothyronine (when available) may be given in addition to thyroxine. Loading dose
recommended is 5–20 mcg followed by 2.5–10 mcg every 8 hours till patient regains consciousness.
• Improvements can be seen within one week of treatment. Thyroid function test can be monitored every 2
days.

35. 1. Effects and Regulation of cortisol
2. Types of adrenal insufficiency
3. Presentation of adrenal crisis
4. Management of adrenal insufficiency
5. IV Glucocorticoids in ill/septic patient ?cover for adrenal
insufficiency
ADRENAL CRISIS

36. Adrenal glands
• located on the superior pole of each kidney and retroperitoneal
• divided into two functionally distinct regions;
• Larger outer region (comprising about 90% of the gland) called the adrenal
cortex
• Inner, much smaller region called the adrenal medulla

37. Cortisol
• Cortisol and its analogues have
powerful effects on glucose
metabolism and all collectively
classified as glucocorticoids .
• Regulation of Cortisol Secretion
• Cortisol has a negative feedback
effect on the hypothalamus and the
anterior pituitary gland, inhibiting
release of CRH and ACTH
respectively.
• Cortisol is released in a pulsatile
pattern and displays a circadian
rhythm, highest during morning.

38. Effects of Cortisol
• raise plasma glucose by stimulating
glycolysis and gluconeogenesis in the
liver and inhibiting peripheral glucose
uptake into storage tissues.
• increase protein breakdown in skeletal
muscle, skin and bone to release amino
acids
• increase lipolysis from adipose tissues to
release fatty acids
• increase vasoconstrictive response of the
arterioles to catecholamines and plays
part in regulation of blood pressure.
• And at higher levels:
• mimic the actions of aldosterone on the
kidney to retain Na+ and water and lose K+
ions
• suppress the action of immune cells

39. Primary adrenal
insufficiency
Secondary AI Tertiary AI
Addison’s disease is due
to the inability of the
adrenal gland to produce
steroid hormones even
when the stimulus by the
pituitary gland via
corticotropin.
• due to low production
of adrenocorticotropic
hormone (ACTH) by
pituitary gland which in
turns causes low level
cortisol
• Occurs in patients
receiving chronic
exogenous
glucocorticoid
is the inability of the
hypothalamus to produce
sufficient amount of
corticotropin-releasing
hormone

42. • IV corticotropin stimulation
250microgram
• Peak cortisol levels below< 500
nmol/L at 30 or 60 minutes
indicate adrenal insufficiency
• If a corticotropin stimulation test
is not feasible, we suggest using
a morning cortisol <140 nmol/L
(5 microgram/dL) in
combination with ACTH >
100pg/ml as a preliminary test
suggestive of adrenal
insufficiency (until confirmatory
testing with corticotropin
stimulation is available)
• measurement of plasma ACTH
to establish PAI

44. Acute Adrenal insufficiency /Addisonian crisis
• Life threatening results from insufficient cortisol production.
• Symptoms are non specific and high mortality if left untreated.
• Need to consider adrenal crisis in acutely ill patients with otherwise
unexplained symptoms or signs suggestive of PAI (volume depletion,
hypotension, hyponatremia, hyperkalemia, fever, abdominal pain,
hyperpigmentation or, hypoglycaemia)

45. • Mineralocorticoid deficiency:
• mineralocorticoids stimulate Na reabsorption and K excretion,
• deficiency results in increased excretion of Na and decreased excretion of K, chiefly in urine but also in
sweat, saliva, and the GI tract.

47. Precipitating factors
• Stress
• Fever
• Recent surgery or trauma
• Cardiac event

48. INVESTIGATION
•FBC
•RP and electrolytes
•BLOOD GAS , DXT
•SERUM CORTISOL
•SEPSIS WORKUP IF INDICATED
•ECG and CXR

49. Management
• ABCD assessment and management
• Large IV access
• Correct hypoglycaemia and electrolyte abnormality
• Administer fluids if hypotensive and initiate vasopressor
• IV Hydrocortisone 100mg stat and 8 hourly
• Treat precipitating cause

50. GLUCOCORTICOID THERAPY IN ILL PATIENT
• Critical illness — Usual assumption
is critical illness (eg, due to sepsis)
would be a stressful situation and
that ACTH secretion would be
increased leading to large increases
in cortisol. However, critically ill
patients have reduced cortisol
metabolic clearance leading to
suppression of ACTH subsequently
reduce in cortisol production.
• The purpose of administering
glucocorticoids to patients with
sepsis is to restore balance to the
altered hypothalamic-pituitary-
adrenal (HPA) axis.

51. GLUCOCORTICOID THERAPY IN ILL PATIENT
• the major challenge associated with the administration of
glucocorticoids to patients with sepsis is to select those who are likely
to benefit.
• Patient selection — When considering patients with sepsis and septic
shock for glucocorticoid therapy, we generally use the following
guidelines:
• For most septic shock pt, suggest not routinely using intravenous
glucocorticoid therapy as part of initial therapy.
• use glucocorticoid therapy on a case-by-case basis with refractory shock (SBP
<90 mmHg despite adequate fluid resuscitation and vasopressor
administration)
with other parameters supportive of adrenal crisis

52. Evidence
• 2018 meta-analysis of 42 trials including 10,194 patients.
• While higher rates of shock reversal were reported compared with placebo
corticosteroids resulted in minimal or no reduction in the risk of death. Also
reported was a possible reduction in the length of hospital stay and a slight
increase in the risk of hypernatremia hyperglycemia and neuromuscular
weakness.

53. References
• Management of Thyroid disorders, Clinical Practice guidelines 2019,
MOH
• Diagnosis and Treatment of Primary Adrenal Insufficiency, Clinical
Practice Guideline 2016 Endocrine Society.
• Uptodate

54. Thank you