Thyroid Storm

Context

Thyroid storm is a rare but life threatening endocrine condition that should be considered, recognised and treated quickly. It is often caused by inadequate therapy or by a physiological stress, particularly infection.

Definition

Thyroid storm is an acute, severe, life-threatening hypermetabolic state of thyrotoxicosis caused either by excessive release of thyroid hormones (causing adrenergic hyperactivity) or altered peripheral response to thyroid hormone following the presence of one of more precipitants.[13]

Introduction

The thyroid gland produces and excretes two groups of hormones: thyroid hormones and calcitonin. Thyroid stimulating hormone (TSH) is secreted from the anterior pituitary gland and is responsible for the synthesis and secretion of thyroid hormones. The secretion of TSH is in turn controlled by two mechanisms:

• A negative feedback loop from plasma levels of thyroid hormones
• Thyrotropin releasing hormone (TRH) secreted from the hypothalamus. This TRH level is also related to a negative feedback loop, forming the hypothalamic pituitary thyroid axis.

Hypothalamus to anterior pituitary is regulated by thyroid releasing hormone (TRH). T3/4 inhibits the release of TSH and TRH.

Thyroid Hormone Synthesis

Thyroid hormone synthesis requires the ingestion of iodine (about 1mg per week). Sources include iodized table salt, seafood, seaweed, and vegetables.

After absorption from the gastrointestinal tract, it is removed as required from the blood and moved into the thyroid follicular cell colloid. Here, the iodine is oxidised and combined with thyroglobulin in a process called organification.

After several more combinations with aminoacids T3 and T4 are formed ready for secretion.

Thyroid Hormone Secretion

Over 90% of the active hormone secreted by the thyroid gland is thyroxine (T4) and the rest is triiodothyronine (T3). The functions of these two hormones are essentially the same however there is a difference in their intensity of action (T3 is approximately four times more active). Most of the T4 is converted into T3 within the tissues although both are functional.

The Action of T3 and T4 Within The Body

Within the blood plasma, over 99% of the T3 and T4 are bound to proteins e.g. thyroid binding globulin and albumin.

This is metabolically inactive and only the small unbound component is able to have any clinical effects. Free (unbound T3, T4) hormone level measurements are preferred as they are not influenced by concentrations of binding proteins.

At the cells, T4 is a prohormone whereas T3 is active. Both are taken into the cells where the T4 can be converted in to T3. The T3 can bind onto receptors on the nucleus influencing the activities of the mitochondria and gene transcription [2].

Actions of T3 and T4

The actions of T3 and T4:

• Maintain normal sensitivity of respiratory centres to change in oxygen and carbon dioxide concentration
• Maintain normal cell oxygen use
• Maintain a normal basal metabolic rate
• Promote calorigenesis (heat production) by increasing metabolic rate of cells
• Enhance the effects of the sympathetic nervous system
• Promote glucose metabolism, fat mobilisation and protein synthesis
• Maintain normal adult nervous system function
• Promote normal cardiac function to include rate and force of contraction
• Promote normal muscle development and function, skeletal growth and maturation
• Promote normal gastrointestinal motility, tone, enzyme secretion
• Maintain hydration and secretory function of the skin

These effects, when magnified lead to clinical signs and symptoms experienced by patients.

Learning bite

Thyrotoxic crisis typically occurs in patients in whom pre-existing hyperthyroidism has not been diagnosed or has been treated insufficiently.[4]

The Onset of Thyrotoxic Crisis

Hyperthyroidism A clinical state induced by excessive production and secretion of thyroid hormones by an overactive thyroid gland.

Thyrotoxicosis a condition associated with excess circulating thyroid hormones. It has many causes including Graves disease, drug induced (e.g. Lithium, amiodarone) and gestational thyrotoxicosis [14].

Thyroid storm Is an acute and life-threatening complication of thyrotoxicosis.

Thyroid storm or thyrotoxic crisis has an abrupt onset and is usually started by a precipitating factor [4].

The exact mechanism is unclear but it may be due to a change in the amount of unbound thyroid hormone [5] as the overall total thyroid hormone level can be unchanged.

However, thyroid storm may be caused by thyroid hormone or TSH releasing tumours that raise the total hormone levels.

The Causes of Thyrotoxic Crisis

There are many causes of thyrotoxic crisis. These include:

• Sepsis
• Surgery/anaesthesia induction
• Radioactive Iodine therapy
• Drugs (e.g. NSAIDs, chemotherapy, anticholinergic drugs, salicyclates)
• Diabetic ketoacidosis
• Pregnancy
• Hypoglycaemia
• Trauma
• Burns
• CVA
• PE
• Thyroid surgery
• Thyroid carcinoma

In some cases no cause is found. Cocaine use, paracetamol overdose and thyroxine overdose have not been found to be a cause.

Introduction

The diagnosis of thyroid storm is a clinical one. The clinical state resembles that of a hyperadrenergic state. There is no cut off for thyroid hormone levels which defines thyroid storm or differentiates it from severe thyrotoxicosis.

The scoring system (below) can be used to aid diagnosis but if a patient exhibits signs of severe thyrotoxicosis it is safer to assume that thyroid storm may be imminent and manage the patient aggressively.

Scoring system for thyroid crisis by Burch and Wartofsky [4]

This uses a numerical score to predict the presence of thyroid storm with categories of unlikely, impending and diagnostic. Five features are assessed to give an overall score:

Thermoregulatory dysfunction

Cardiovascular Dysfunction

Central Nervous System Effects

Gastrointestinal effects

Precipitant history

Likelihood of thyroid storm

Signs and Symptoms of Thyroid Storm:

• High fever
• Sweating
• Tachycardia
• Atrial Fibrillation/supraventricular tachycardia
• CCF
• Confusion
• Restlessness
• Coma
• Hypotension
• Dehydration
• Tremors
• Jaundice
• Vomiting
• Diarrhoea

Investigations

The diagnosis is made on clinical grounds and confirmed with biochemical tests.

The pattern of thyroid storm is similar to that of thyrotoxicosis: a very suppressed TSH concentration and elevation of unbound T4 and T3. No specific level distinguishes the two. Systemic illness compromises the ability to convert T4 to T3, so T3 levels may only be slightly elevated or normal.

There may also be hyperglycaemia and hypercalcaemia with hepatic enzyme abnormalities.

ECG will often show a tachycardia arrhythmias may be present with atrial fibrillation being most common. These arrhythmias should be treated in the standard manner. It is important to be aware of the cardiac effects of some thyroid storm treatments e.g. beta-blockers [1].

General Management

The mortality rate for thyroid storm is high. Reports vary but it is estimated to be 8-25% and much higher if unrecognised and untreated [15].

Consequently, the patient should be treated early and aggressively.

• Initial Assessment: Start with airway and ventilatory status. Apply oxygen. Thyrotoxicosis itself is unlikely to cause an airway or breathing problem but underlying conditions such as pneumonia or sepsis may affect either.
• Check haemodynamics; HR and BP.
• ECG assess is any arrhythmia is present
• IV access patients are likely markedly dehydrated consider volume replacement with crystalloid [caution in elderly]
• Send bloods including urea, electrolytes, full blood count, thyroid function tests and calcium. A venous gas can be helpful and a bedside glucose should be checked.
• Urinary catheter
• Cooling measures antipyretics and standard cooling measures.
• Chest X-Ray: may be useful in evaluating for an infective focus or provide evidence of cardiac failure.

Note: Aspirin should be avoided as it increases unbound thyroxine levels.

Specific Management

Specific management aims to stop the peripheral effects of thyroid hormones and reduce hormone levels.

As the condition is rare, has a high mortality, and is part of a spectrum of disease, discussion with an endocrinologist is advised. Thyroid hormone levels do not define thyroid storm but normal levels should prompt a search for other diseases.

Strategies to stop peripheral effects

• A high index of suspicion should be maintained to ensure thyroid storm (a rare condition) is considered early and treatment instituted quickly.
• Tachycardia in this setting is multifactorial; hormonal stimulation, dehydration, infection/sepsis. Consequently, interpreting response to treatment can be challenging.

1. Pimentel L, Hansen KN. Thyroid disease in the emergency department: a clinical and laboratory review. J Emerg Med. 2005 Feb;28(2):201-9.
2. Guyton AC, Hall JE. Textbook of Medical Physiology. 10th Ed, Saunders, 2000.
3. Mistovich JJ, Krost WS, Limmer DD. Beyond the basics: endocrine emergencies. Part 1: Hyperthyroidism and thyroid storm. EMS Mag. 2007 Oct;36(10):123-7; quiz 128-9.
4. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am. 1993 Jun;22(2):263-77. PMID: 8325286.
5. Rennie D. Thyroid storm. JAMA. 1997 Apr 16;277(15):1238-43. PMID: 9103350.
6. Migneco A, Ojetti V, Testa A, et al. Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):69-74.
7. McGugan EA. Hyperpyrexia in the emergency department. Emerg Med (Fremantle). 2001 Mar;13(1):116-20.
8. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006 Dec;35(4):663-86, vii.
9. Duggal J, Singh S, Kuchinic P, et al. Utility of esmolol in thyroid crisis. Can J Clin Pharmacol. 2006 Fall;13(3):e292-5. Epub 2006 Nov 26.
10. Kearney T, Dang C. Diabetic and endocrine emergencies. Postgrad Med J. 2007 Feb;83(976):79-86.
11. Kannan CR, Seshadri KG. Thyrotoxicosis. Dis Mon. 1997 Sep;43(9):601-77. PMID: 9301645.
12. Dillmann WH. Thyroid storm. Curr Ther Endocrinol Metab. 1997;6:81-5. PMID: 9174709.
13. Idrose A. Hyperthyroidism. In: Tintinalli JE, Stapczynski J, Ma O, Yealy DM, Meckler GD, Cline DM. eds. Tintinallis Emergency Medicine: A Comprehensive Study Guide, 8e. McGraw Hill; 2016.
14. Vaidya B, Pearce S H S. Diagnosis and management of thyrotoxicosis. BMJ 2014; 349 :g5128.
15. Ross DS, Burch HB, Cooper DS, Greenlee MC, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421.
16. Milner MR, Gelman KM, Phillips RA, et al. Double-blind crossover trial of diltiazem versus propranolol in the management of thyrotoxic symptoms. Pharmacotherapy 1990; 10:100.