1. Thyroid Emergencies
Robina Rana
28th August, 2013

2. Objectives Discuss common thyroid problems: Thyroid Emergencies:
Thyroid Storm
Myxedema Coma
Thyrotoxic Periodic Paralysis
Epidemiology
Presentation
Diagnosis
Management

5. Relationship between serum-free thyroxine by dialysis (FT4) ng/dL and log10 TSH in euthyroid, hyperthyroid, hypothyroid, and T4-suppressed euthyroid individuals.

6. Spectrum of autoimmune disease of the thyroid gland
Spectrum of autoimmune disease of the thyroid gland. The clinical manifestations of autoimmune disease of the thyroid gland range from idiopathic myxedema, through nontoxic goiter, to diffuse toxic goiter, or Graves disease. Progression of autoimmune disease from one form to another in the same patient can occasionally occur.

7. Spectrum of autoimmune disease of the thyroid gland
Spectrum of autoimmune disease of the thyroid gland. The clinical manifestations of autoimmune disease of the thyroid gland range from idiopathic myxedema, through nontoxic goiter, to diffuse toxic goiter, or Graves disease. Progression of autoimmune disease from one form to another in the same patient can occasionally occur.

9. Hypothryoidism:

12. “End stage of untreated or inadequately treated hypothyroidism”
Myxedema Coma:

13. Myxedema Coma The clinical picture is often that of
an elderly obese female
who has become increasingly withdrawn,
lethargic, sleepy, and confused.
The history from the patient may be inadequate, but the family may report that
the patient has had thyroid surgery or
radioiodine treatment in the past or
that the patient has previously been receiving thyroid hormone therapy.

14. The presentation is one of severe hypothyroidism, with or without coma
(the term myxedema coma may, therefore, be a misnomer).
Myxedema coma may be precipitated by an
illness such as a cerebrovascular accident, myocardial infarction, or
an infection such as a urinary tract infection or pneumonia.
gastrointestinal hemorrhage;
acute trauma;
excessive dehydration; or
administration of a sedative, narcotic, or potent diuretic drug.

15. A schematic representation of the changes in serum thyroid hormone values with increasing severity of non thyroidal illness. A rapidly rising mortality rate accompanies the fall in serum total T4 (TT4) and free T4 (FT4) values.

16. Pathogenesis of myxedema coma
The decrease in serum T4 results in a lowering of intracellular T3. This can directly affect central nervous system function with altered mental status. The decrease in intracellular T3 causes decreased thermogenesis, resulting in hypothermia, which in turn causes decreased central nervous system sensitivity to hypercapnia and hypoxia. The resulting respiratory insufficiency induces cerebral anoxia and coma. At the same time, the decreased intracellular T3 results in decreased cardiac inotropism and chronotropism, decreased sensitivity to adrenergic stimuli, decreased cardiac output, and generalized vasoconstriction. This leads to a low-output state which, if untreated, culminates in decreased blood pressure and eventually shock and death. Finally, there is a change in fluid balance with increased water retention due to impaired renal perfusion as well as increased vascular permeability. These changes result in effusions and hyponatremia, which in turn contribute to the coma.

17. The physical findings are not specific. The patient may be
semi comatose or comatose
with dry, coarse skin,
hoarse voice,
thin scalp and eyebrow hair,
possibly a scar on the neck, and
slow reflex relaxation time.
Marked hypothermia, with body temperature sometimes falling to as low as 24°C (75°F), particularly in the winter months.
Precipitating factors such as pneumonia, urinary tract infection, ileus, anemia, hypoglycemia, or seizures.
Fever may be masked by coexistent hypothermia.
Often there are pericardial, pleural, or peritoneal effusions.

20. Remember the Basics; High index of suspicion  Adherence to ABCs 
clinical features
Adherence to ABCs 
LOC, Vitals (temp, arrhythmia ), IV access, IV fluids,
Order confirmatory tests 
Thyroid function tests
Other pituitary function tests
Institute early treatment
Cortisol
Levothyroxine
Identify and manage precipitant

21. Management of Myxedema Coma.
Admit to ICU for
ventilatory support and
for intravenous medications.{Oral medications may be poorly absorbed (due to gastric atony or ileus), and medications should be given intravenously if possible}.
(2) Parenteral thyroxine:
Give a loading dose of mcg IV, then maintainance mcg IV daily.
(May also give small doses of T3 (liothyronine) , 10 mcg IV every 8 h for the first 48 h if necessary. but this is usually not necessary, and it may contribute to untoward cardiovascular events.)
(3) Electrolytes:
Water restriction for hyponatremia. Avoid fluid overload.
(4) Limit sedation.
Appropriate reduction in drug dosage.
(5) Glucocorticoids:
Controversial but necessary in hypopituitarism or polyglandular failure.
Dosage: Hydrocortisone, mg every 6 h initially and tapered downward over 1 wk. (If initial serum cortisol was >30 mcg/dL (827.7 nmol/L) corticosteroids are unnecessary.)
(6) Hypothermia:
Do not externally rewarm. (Once myxedema coma is suspected in a hypothermic patient, external rewarming should be avoided, because this may cause redistribution of blood flow to subcutaneous tissues and cardiovascular collapse.)
(7) Treat the precipitating illness (eg, pneumonia or urinary tract infection).
The use of hydrocortisone is prudent because patients may have hypopituitarism or autoimmune polyglandular failure. Glucocorticoids are generally given in high doses until baseline cortisol or the results of rapid adrenocorticotropic hormone (ACTH) testing are available.
If the initial serum cortisol is more than 30 g/dL, steroid support is probably unnecessary.
However, if serum cortisol is less than 30 g/dL, hydrocortisone should be given intravenously in a dosage of 50 to 100 mg every 6 hours for the first 48 hours and the dose then tapered over the next 5 to 7 days while the pituitary-adrenal axis undergoes formal testing.

23. Mortality from myxedema coma was about 80%.
Prior to the recognition of the need for intravenous T4 and for respiratory support, Currently, the mortality is about 20%
Predictors of acute mortality include
level of consciousness,
lower Glasgow scores, and
higher APACHE II (acute physiology and chronic health evaluation) scores
Higher mortality is also associated with
increased age,
cardiac complications,
and high-dose thyroid hormone replacement (500 g/d of L-T4 or–75 g/d of L-T3). The latter presumably reflects the increased metabolic demand attendant to high dose replacement in the setting of limited physiologic reserve.
Persistent hypothermia and bradycardia, despite therapy, are associated with a poor prognosis.

28. Laboratory tests useful in the differential diagnosis of hyperthyroidism

29. Thyroid Storm / Thyroid Crisis:
An acute life-threatening exacerbation of thyrotoxicosis.
Thyroid Storm / Thyroid Crisis:

30. Thyroid Storm:
It accounts for 1% to 2% of hospital admissions for thyrotoxicosis.
It occurs in a patient with
Predisposition to hyperthyroidism
a history of Graves disease who has discontinued anti thyroid medication or
in a patient with previously undiagnosed hyperthyroidism.
Precipitants
Non thyroid related

31. Thyroid Storm—Precipitating Factors.
Withdrawal of antithyroid drugs
Severe infection
Diabetic ketoacidosis
Myocardial infarction
Cerebrovascular accident
Cardiac failure
Surgery
Parturition
Trauma (eg, hip fracture)
Radioiodine (rare)
Drug reaction
Iodinated contrast medium

32. “apathetic without the restlessness and agitation”,
The clinical picture is that of ;
an acute onset of hyperpyrexia (with temperature >40°C [104°F]),
sweating,
marked tachycardia often with atrial fibrillation,
nausea,
vomiting,
diarrhea,
agitation,
tremulousness, and
delirium.
The presence of jaundice is considered a poor prognostic sign.
Occasionally, the presentation is
“apathetic without the restlessness and agitation”,
but with symptoms of weakness, confusion, cardiovascular and gastrointestinal dysfunction, and hyperpyrexia.

33. Diagnosis is largely based on the clinical findings;
Serum T4, free T4, T3, and free T3 are all elevated, and TSH is suppressed.
These findings are not different from what is seen in other patients with hyperthyroidism, but the difference is in the setting.
It is thought that thyroid storm represents an exacerbation of thyrotoxicosis associated with
a shift of T4 from the bound to the free compartment with an increase in free T3 and T4, as well as
an exaggerated response to a surge of catecholamines that results from the stress of the precipitating event.
The cause of death is usually cardiac arrhythmia and failure.
Liver function abnormalities are often seen, as is leukocytosis, even in the absence of infection.

36. Remember the Basics; High index of suspicion  Adherence to ABCs 
clinical features
Adherence to ABCs 
LOC, Vitals (temp, arrhythmia ), IV access, IV fluids,
Order confirmatory tests 
Thyroid function tests
Other pituitary function tests
Institute early treatment
Identify and manage precipitant

37. An iodinated radiocontrast agent (if available) Glucocorticoids
The therapeutic regimen typically consists of multiple medications, each of which has a different mechanism of action:
A beta-blocker
to control the symptoms and signs induced by increased adrenergic tone
A thionamide
to block new hormone synthesis
An iodine solution
to block the release of thyroid hormone
An iodinated radiocontrast agent (if available)
to inhibit the peripheral conversion of T4 to T3
Glucocorticoids
to reduce T4-to-T3 conversion,
promote vasomotor stability, and
possibly treat an associated relative adrenal insufficiency

38. Cooper DS. N Engl J Med 2005;352:905-917.
Effects of Antithyroid Drugs.
(THIONAMIDES)
Propylthiouracil(PTU)
Methimazole(Tapazole)
Inhibition of thyroid hormone synthesis
a reduction in intrathyroidal immune dysregulation
Reduction of the peripheral conversion of thyroxine to triiodothyronine (in the case of propylthiouracil)
*Tyrosine-Tg denotes tyrosine residues in thyroglobulin, I+ the iodinating intermediate, and TPO thyroid peroxidase.
Figure 3. Effects of Antithyroid Drugs. The multiple effects of antithyroid drugs include inhibition of thyroid hormone synthesis and a reduction in both intrathyroidal immune dysregulation and (in the case of propylthiouracil) the peripheral conversion of thyroxine to triiodothyronine. Tyrosine-Tg denotes tyrosine residues in thyroglobulin, I+ the iodinating intermediate, and TPO thyroid peroxidase.
Cooper DS. N Engl J Med 2005;352:

39. Management of Thyroid Storm.
Supportive care 
Fluids
Oxygen
Cooling blanket
Acetaminophen (Aspirin should be avoided, because it will displace T4 from thyroid hormone—binding globulin, resulting in an increase in FT4
Multivitamins
If indicated, antibiotics, digoxin to treat a-fib and heart failure
Specific measures 
Propranolol, mg orally every 6 h ( adrenergic blockade)
Propylthiouracil, 150 mg every 6 h, or methimazole, 20 mg every 8 h; may be administered per rectum if oral route is unavailable
INORGANIC IODINE: inhibit thyroid hormone synthesis but also block the conversion of T4 to T3,.
Saturated solution of potassium iodide, 5 drops (250 mg) orally twice daily; or
iopanoic acid, 0.5 g IV or orally twice daily; or
iohexol, 0.6 g (2 mL of Omnipaque 300) IV twice daily
Dexamethasone, 2 mg every 6 h ( for adrenal support and decrease FT4 FT3 )
Cholestyramine or colestipol, g/d ( interferes with enterohepatic circulation of T4)

40. Thyrotoxic Periodic Paralysis:
Thyrotoxic periodic paralysis (TPP) is a rare but frightening thyroid emergency.
Thyrotoxic Periodic Paralysis:

41. Thyrotoxic Periodic Paralysis
The usual clinical presentation is of an
Asian male (male:female ratio approximately 17:1)
with symptoms of untreated hyperthyroidism
who awakens at night or in the morning with flaccid ascending paralysis.
Typically, there is a history of vigorous exercise and/or a large high-carbohydrate meal before retiring.
There is usually no family history of periodic paralysis, but there may be a family history of autoimmune thyroid disease.
The acute episode may be complicated by cardiac arrhythmias due to the concomitant presence of hypokalemia.
The illness has also been reported to occur in Native Americans, African Americans, and in individuals of Mexican or South American descent, but these ethnic groups are affected rarely.

42. The paralysis initially
involves the lower extremities but
progresses to the girdle muscles,
followed by the upper extremities.
Proximal muscle groups are affected to a greater extent than distal.
Facial and respiratory muscles are usually spared.
Sensory function, bowel and bladder function are not affected.
Deep tendon reflexes are depressed or absent.

43. Pathogenesis of thyrotoxic periodic paralysis;
The pathogenesis is summarized in Figure 24–2. Thyrotoxicosis, increased -adrenergic activity, and an assumed genetic predisposition, perhaps involving the potassium channel Kir2.6, which together with increased Na+-K+ ATPase activity leads to increased intracellular potassium concentrations. A high-carbohydrate meal with increased insulin secretion and glycogen deposition, vigorous exercise high salt intake, and the normal nocturnal potassium flux serve to drive serum potassium levels even lower, resulting in flaccid neuromuscular paralysis

44. The differential diagnosis of TPP includes
familial periodic paralysis,
Guillain-Barré syndrome, and
acute intermittent porphyria.
The diagnosis is based on the
absence of a family history,
the characteristic presentation,
the presence of hyperthyroidism due either to Graves disease or toxic nodular goiter (other types of hyperthyroidism have been implicated as well), and
usually a low serum potassium level.
The electromyogram, performed while the patient is experiencing weakness,
shows myopathic changes with reduced amplitude of compound muscle action potentials. These do not change in amplitude after administration of intra-arterial low-dose epinephrine (distinguishes from familial periodic paralysis).
Electrocardiograms show changes associated with
hypokalemia,
tachycardia,
increased QRS voltage,
first-degree heart block, and,
on occasion, serious ventricular arrhythmias.

45. Management of Thyrotoxic Periodic Paralysis.
With appropriate treatment, recovery is rapid, and once the thyrotoxicosis is controlled, the paralysis will not recur
(1) Oral potassium supplement cautiously (if needed); monitor serum K+
(2) Oral propranolol (60 mg every 6 h) blocks the -adrenergic stimulation of Na+-K+ ATPase.
(3) Antithyroid drug therapy should be started immediately, even though it takes time to bring the patient into a euthyroid state.
Avoid: 
IV potassium (important to be cautious if administering intravenous potassium, which may raise total body potassium to toxic levels as the episode resolves.
IV glucose which stimulates insulin secretion and worsens hypokalemia,
(ie, crystalloid fluid replacement only)
Adrenergic agonists (eg, isoproterenol) which promote movement of potassium into the intracellular compartment and exacerbate the problem
Acetazolamide, which has been shown to reduce frequency of attacks in familial periodic paralysis, may worsen attacks of thyrotoxic periodic paralysis and should be avoided.

46. Conclusion Thyrotoxic Periodic Paralysis: Myxedema coma:
With appropriate treatment, recovery is rapid, and once the thyrotoxicosis is controlled, the paralysis will not recur
Myxedema coma:
Passive warming
Load Synthroid
Daily IV
Start Hydrocortisone
Look for inciting event
Thyroid storm:
Control heart rate
B-blockade
Calcium channel blockade
Thionamide therapy
Look for inciting event

47. Thank You