Thyroid storm, or thyrotoxic crisis, is a life-threatening complication of hyperthyroidism characterized by multisystem involvement. It occurs when a precipitating event causes a sudden increase in thyroid hormone levels in a patient with hyperthyroidism. Common precipitants include discontinuing antithyroid medication or thyroid surgery. Thyroid storm requires prompt treatment with beta-blockers, antithyroid drugs, iodine, glucocorticoids, and supportive care to reduce mortality, which is estimated at 8-25% without treatment. Symptoms include fever, tachycardia, heart failure, neurological changes, and gastrointestinal issues. Diagnosis is clinical based on symptoms and elevated thyroid hormone levels

1. THYROID CRISIS
Presentation by : Faith Cherotich
NAME :BCM /K/0047/2021

3. Introduction
Thyroid storm, also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism.
It is an exaggerated presentation of thyrotoxicosis. It comes with sudden multisystem involvement. The
mortality associated with thyroid storm is estimated to be 8-25% despite modern advancements in its
treatment and supportive measures. [1] Thus, it is very important to recognize it early and start aggressive
treatment to reduce mortality. The diagnosis of thyroid storm is clinical.

4. Etiology
Superimposed precipitating factors cause thyroid storm in patients with diagnosed or undiagnosed
hyperthyroidism. It is more common with Graves’ disease but can occur with other etiologies of
hyperthyroidism, for example, toxic multinodular goiter and toxic adenoma of the thyroid.[2] The
precipitating factors are: Abrupt discontinuation of antithyroid medicine Thyroid surgery Non-
thyroid surgery Trauma Acute illness like infections, diabetic ketoacidosis, acute myocardial
infarction, cardiovascular accident, cardiac failure, drug reaction Parturition Recent use of Iodinated
contrast medium Radioiodine therapy (rare) Burns Stroke Medication side effect e.g. amiodarone,
anesthetics, salicylates.

5. Epidemiology
It is a rare presentation of hyperthyroidism. Thyroid storm accounts for about 1% to 2% of admissions
for hyperthyroidism. As per the United States survey, the incidence of storm ranged from 0.57 t0 0.76
cases per 100,000 per year in the normal population, and 4.8 to 5.6 cases/100,000 per year in
hospitalized patients.[3] As per the Japanese National Survey, the incidence of thyroid storm was 0.2
per 100,000 population per year, about 0.22% of all thyrotoxicosis patients and 5.4% of hospitalized
thyrotoxicosis patients. The average age of people with thyroid storm was 42 to 43 years, which was
similar to people with thyrotoxicosis without thyroid storm. The male to female ratio for the incidence
of thyroid storm was about 1:3, similar to thyrotoxicosis without storm group.[4]

6. Pathophysiology
The pathophysiological basis for precipitation of thyroid storm in patients with
thyrotoxicosis is not clear. But, a precipitating factor, as mentioned above, is always
required to cause thyroid storm. Several hypotheses have been purposed. One
hypothesis suggests the incidence of thyroid storm is due to the rapid increase in
thyroid hormone levels, rather than the absolute hormone level that occurs during
thyroid surgery, following radioactive iodine treatment, after sudden
discontinuation of the antithyroid drug, or after administration of the large dose of
iodine in contrast studies. The hyperactivity of the sympathetic nervous system with
increased response to catecholamine along with an increased cellular response to
thyroid hormone during acute stress or infections, causing cytokines release and
altered immunological disturbances, are other possible mechanisms of thyroid
storm. Most studies have failed to relate higher thyroid hormone levels as a cause
of thyroid storm, except for the study by Brooks and others, reported higher free
thyroid hormone among the patients with thyroid storm.[5] In other words, the
degree of thyroid hormone level is not directly related to a higher incidence of
thyroid storm.[2] The clinical features are due to the exaggerated effects of the
thyroid hormone. There is intense metabolic activity which increases oxygen
requirements. The resulting tachycardia to meet the oxygen requirements can
induce heart failure and predisposes the patient to arrhythmias. Similarly, the CNS
symptoms include irritability, seizures, delirium, and eventually coma.

7. Histopathology
Histopathology depends on the cause of the thyroid storm. The most
common cause Grave's disease shows diffuse follicular hyperplasia
along with increased thyroid receptor antibodies and increased
vascularization to the tissue. If it is a tumor causing storm, malignant
cells infiltrate and destroy the thyroid tissue freely, and rupture the
follicles

9. History and Physical
Presentation of thyroid storm is an exaggerated manifestation of
hyperthyroidism, with the presence of an acute precipitating factor. Fever,
cardiovascular involvement (including tachycardia, heart failure, arrhythmia),
central nervous system (CNS) manifestations, and gastrointestinal symptoms are
common. Fever of 104 F to 106 F with diaphoresis is a key presenting feature.
Cardiovascular manifestations include tachycardia more than 140 HR/minute,
heart failure with pulmonary edema and peripheral edema, hypotension,
arrhythmia, and death from cardiac arrest. CNS involvement includes agitation,
delirium, anxiety, psychosis, or coma. Gastrointestinal (GI) symptoms include
nausea, vomiting, diarrhea, abdominal pain, intestinal obstruction, and acute
hepatic failure. A Japanese study found the CNS involvement to be a poor
prognostic factor for increased mortality.Physical examination findings may
include high temperature, tachycardia, orbitopathy, goiter, hand tremors, moist
and warm skin, hyperreflexia, systolic hypertension, and jaundice.

10. Evaluation
The diagnosis of thyroid storm needs clinical suspicion based on the
presentation mentioned above in a patient with hyperthyroidism or
suspected hyperthyroidism. One should not wait for lab results before
starting treatment. Thyroid function tests can be obtained which
usually show high FT4/FT3 and low TSH. It is not necessary to have a
very high level of thyroid hormone to cause thyroid storm. Other lab
abnormalities may include hypercalcemia, hyperglycemia (due to
inhibition of insulin release and increased glycogenolysis), abnormal
LFTs, high or low white blood cell (WBC) count.

11. Diagnosis
Definite Thyroid Storm (TS1): Thyrotoxicosis (elevated FT3 and/or FT4) plus At least
one CNS manifestation plus one or more other symptoms (fever, tachycardia, CHF,
GI/Hepatic) ‘OR’ A combination of at least three features among fever, GI/Hepatic, CHF,
or tachycardia Suspected Thyroid Storm (TS2): Thyrotoxicosis (elevated FT3 and/or
FT4) .
A combination of at least two features among tachycardia, CHF, GI/Hepatic, Fever ‘OR’
A patient with h/o thyroid disease, presence of goiter and exophthalmos who meets
criteria for TS1 but TFTs not available These scoring systems are just guidelines. The
actual diagnosis is based on clinical judgment. Based on the BWPS scoring system, a
score of 45 or more is more sensitive but less specific than JTA scoring systems TS1 or
TS2 to detect thyroid storm cases.
BWPS score of 25 to 45 may suggest an impending storm. A chest x-ray may be done
to assess heart failure. Head CT may help exclude a neurological cause in some
patients. An ECG is often done to monitor for arrhythmias

12. Treatment
Treatment of thyroid storm consists of supportive measures like intravenous (IV) fluids, oxygen, cooling
blankets, acetaminophen, as well as specific measures to treat hyperthyroidism. If any precipitating
factors, for example, infection, are present, that needs to be taken care of. Patients with thyroid storm
must be admitted to the intensive care unit with close cardiac monitoring and ventilatory support if
needed.Specific Strategic Steps for Treatment
1.Therapy to control increased adrenergic tone: Beta-blocker
2. Therapy to reduce thyroid hormone synthesis: Thionamide
3. Therapy to reduce the release of thyroid hormone: Iodine solution
4. Therapy to block peripheral conversion of T4 to T3: Iodinated radiocontrast agent, glucocorticoid,
PTU, propranolol
5. Therapy to reduce enterohepatic recycling of thyroid hormone: Bile acid sequestrant After initial
supportive measures, a beta-blocker should be started for any case of suspected thyroid storm.
Typically, propranolol 40 mg to 80 mg is given every 4 to 6 hours. Then, either a loading dose of
propylthiouracil (PTU) 500 mg to 1000 mg followed by 250 mg every 4 hours or Methimazole (MMI) 20
mg every 4 to 6 hours should be given. Propylthiouracil is favored because it has a small but additional
effect of blocking the peripheral conversion of T4 to T3. An hour after the administration of
propylthiouracil or Methimazole, give five drops of SSKI (supersaturated potassium iodide) by mouth
every 6 hours. Always administer thionamide before starting iodine solution (SSKI) therapy. This
prevents the imminent increase in thyroid hormone synthesis due to increased iodine load from super
saturated potassium iodide.

13. Treatment cont
Hydrocortisone 100 mg IV every eight hours (or Dexamethasone 2 mg every 6 hours) should also be started. If available, oral
cholestyramine 4 grams four times daily can be started for severe cases. One should look for precipitating factors and treat
them accordingly. The use of aspirin should be avoided due to its potential risk of increasing free thyroid hormone levels by
interfering with thyroid binding protein. In the first 24 hours of treatment, propylthiouracil decreases T3 level by 45%, but
Methimazole drops T3 level by only 10 % to 15%. Methimazole, whereas, causes more rapid normalization of serum T3 level
after a few weeks of treatment and it has less hepatotoxicity compared to propylthiouracil.
Therefore, after initial stabilization, we should treat with Methimazole (if propylthiouracil was started at the beginning, it
should be changed to Methimazole). For patients who cannot take oral antithyroid medicine, liquid preparation (pharmacist
may have to compound) can be given as enemas. Sometimes, pharmacists can prepare an IV form of antithyroid medicine by
dissolving the tablet. Esmolol, a short-acting beta-blocker, at a loading dose of 250 mcg/kg to 500 mcg/kg followed by 50
mcg/kg to -100 mcg/kg/minute can be given in ICU setting. For patients with reactive airway disease, cardioselective beta-
blockers like atenolol or metoprolol should be chosen. If there is a contraindication for the use of beta-blockers, diltiazem is
an alternative. If thionamide therapy is contraindicated because of an allergic reaction, thyroidectomy is needed after
treatment with a beta-blocker, hydrocortisone, cholestyramine, and iodine solution.
Plasmapheresis is the last resort if all other measures fail. Once patients’ clinical conditions improve, the iodine solution
should be stopped, glucocorticoids can be tapered and stop, and beta-blocker should be adjusted. Thionamide therapy
should be titrated, and if propylthiouracil is used initially, it should be switched to Methimazole. Patients should be
recommended for definitive treatment with radioiodine (RAI) therapy or thyroidectomy. Surgery may be required in patients
with grave's disease for the treatment of hyperthyroidism. These patients need to be pretreated with beta-blockers,
glucocorticoids, and iodine formulas. Surgery is usually done after 5-7 day

14. Differential diagnosis
Thyroid storm should be differentiated from other diseases of similar
symptoms and signs.[16] As fever is the most common presentation of
multiple diseases, so it can be misdiagnosed. The differential diagnosis are:
• Sepsis
• Infection
• Psychosis
• Cocaine use
• Pheochromocytoma
• Neuroleptic malignant syndrome
• Hyperthermia

15. Surgical Oncology
If toxic adenoma or multinodular goiter is causing this disease, then
surgical resection and radioactive iodine ablation are the mainstay of
treatment. Thyroidectomy is preferred if a patient has compressive
symptoms. Patients who refuse ablation or have contraindications to
surgery can be treated with long-term antithyroid medicines. Grave's
disease with intrathoracic mass causes severe compressive symptoms
and thyroidectomy is preferred in these cases. Thyroidectomy has
other adverse effects like recurrent laryngeal nerve damage and
hypoparathyroidism.

16. Radiation Oncology
If toxic adenoma or multinodular goiter is causing this disease, then
surgical resection and radioactive iodine ablation are the mainstay of
treatment. Thyroidectomy is preferred if a patient has compressive
symptoms. Patients who refuse ablation or have contraindications to
surgery can be treated with long-term antithyroid medicines.Grave's
disease with intrathoracic mass causes severe compressive symptoms
and thyroidectomy is preferred in these cases. Thyroidectomy has
other adverse effects like
• Recurrent laryngeal nerve damage
• Hypoparathyroidism

17. Pertinent Studies and Ongoing Trials
Randomized trials are still under process for efficacies and safety of
more medicines

18. Toxicity and Side Effect Management
Complete surgical resection of thyroid and radioiodine ablation can
cause hypothyroidism. So these patients need lifetime exogenous
thyroxine therapy and should be monitored for hyperthyroidism. Dose
adjustments by endocrinologists are crucial as the patient is at the risk
of both hypothyroidism and hyperthyroidism.
Antithyroid drugs, MMI and PTU, causes agranulocytosis. Patients on
these drugs should be monitored with CBCs especially white cell count.
If white cell count starts decreasing, these drugs should be
discontinued due to the increased risk of infection. Other toxicities are
hepatic failure, cholestasis, rash, gastrointestinal toxicity, and
musculoskeletal pains.

19. Prognosis
• Thyroid storm is a real medical emergency which is fatal if left
untreated. Cause of death may be heart failure, arrhythmias or
multiple organ failure. However, with treatment, most patients see an
improvement within 24 hours. Risk factors for poor prognosis include:
Advanced age
• Neurological deficits on admission
• Failure to use beta-blockers
• Antithyroid medications
• Need for dialysis and/or mechanical ventilation

20. Complications
If left untreated, thyroid storm can lead to the following complications:
• Arrhythmias
• High output cardiac failure Seizures
• Delirium
• Coma
• Elevated liver enzymes
• Jaundice Abdominal cramps
• Vomiting
• Diarrhea
• Atrial fibrillation and thromboembolism