Introduction

A thyroid storm, or thyrotoxic crisis, is a rare, life-threatening complication of hyperthyroidism. Hyperthyroidism is a condition where the ‘thyroid gland’ produces too much thyroid hormone. A thyroid storm can occur in people with hyperthyroidism, when the thyroid gland releases a large amount of thyroid hormone very quickly. Despite modern treatments, the death rate following a thyroid storm is around 8-25%. Therefore, recognising symptoms early for quick treatment, and understanding the risk factors for early identification and prevention, is vital to minimise the risk of a thyroid storm.¹ This article will focus on understanding conditions and situations that increase the likelihood of thyroid storm.

What is a thyroid storm?

A thyroid storm is an ‘acute’ (fast onset) complication of hyperthyroidism in which the thyroid is overactive.¹ The thyroid is a small ‘butterfly shaped’ gland located in the front of your neck that produces hormones that affect heart rate and body temperature. An increased amount of thyroid hormones results in the symptoms of hyperthyroidism.² Thyroid storms are rare and account for only 1-2% of admissions for hyperthyroidism.¹ 

While the causes of a thyroid storm are not fully understood, theories suggest thyroid storms occur due to a rapid increase in thyroid hormone levels; this rapid increase can occur due to situations including following thyroid surgery, a large dose of iodide, or sudden discontinuation of an antithyroid drug. Alternatively, changes in response to thyroid hormone following short term stresses or infections are other possible mechanisms by which a thyroid storm could develop.¹ 

The clinical features of a thyroid storm (how the complication presents) are linked to over-exaggerated effects of thyroid hormone. In a thyroid storm, the increased effects of thyroid hormone lead to increased metabolic activity (increased energy usage in the body). Increased metabolic activity can affect temperature regulation an lead to dysfunction of multiple systems including the heart, liver, intestines, and central nervous system.³ If left untreated, consequences of a thyroid storm include organ failure and death.¹ 

The causes of thyroid storm

Hyperthyroidism is the primary underlying cause of thyroid storm. Hyperthyroidism can result in an overactive thyroid and increase the risk of experiencing a thyroid storm. The most common condition linked with thyroid storm is Graves' disease, however, a thyroid storm can occur as a complication of other conditions that cause hyperthyroidism.¹ 

Long term undertreated or untreated hyperthyroidism can lead to a thyroid storm. However, a thyroid storm is more often attributed to a sudden and intense event or situation. Therefore, these causative events could trigger a thyroid storm in individuals with hyperthyroidism include:¹ 

• Sudden discontinuation of antithyroid medicine
• Thyroid surgery
• Non-thyroid surgery
• Trauma (sudden injury)
• Short term illnesses,s uch as infections including influenza (flu), COVID-19, diabetic ketoacidosis (DKA), heart attack and failure
• Childbirth
• Recent use of iodinated contrast medium (ICM), which are drugs containing iodine, used to help improve contrast in medical images, such as CT scans
• Radioiodine therapy is used to treat thyroid cancer
• Burns
• Stroke
• Traumatic brain injury
• Side effects of some medications including: amiodarone, anesthesia, salicylates.
• Hyperemesis gravidarum in pregnancy

Pre-existing thyroid conditions as risk factors

Graves' disease

Graves’ disease (GD) is an autoimmune condition that affects the thyroid gland. GD arises when the body's own immune system attacks healthy tissue in the thyroid. The attack causes the thyroid to produce too much thyroid hormone.⁴ GD is the most common cause of hyperthyroidism in developed countries, such as the United states with an annual incidence of around 20 cases per 100,000 people.⁵ The condition is more common in women between 30-60 years old.⁵ Symptoms of GD can be divided into those common to hyperthyroidism and those specific GD, the most common symptoms seen are nervousness, fatigue, a rapid heartbeat, palpitations, weight loss, and heat intolerance.⁴ 

Toxic multinodular goiter (Plummer’s disease)

‘Multinodular goiter’ is a term used to describe an enlarged thyroid gland with multiple areas of nodularity (areas with visible ‘nodules’, also referred to as ‘growths’ or ‘lumps’). Goiter refers to enlargement of the thyroid gland and comprises a variety of different conditions that can be classified as toxic or non-toxic. Multinodular goiter is the most common endocrine disorder globally, affecting an estimated 500 to 600 million people. The condition usually arises due to iodine deficiency; iodine deficiency can lead to hypothyroidism (under active thyroid), causing an increase in thyroid stimulating hormone (TSH), which stimulates growth of the thyroid gland and leads to nodule formation. These nodulated areas of increased size and functioning can progress to hyperthyroidism if they produce too much thyroid hormone. When ‘thyrotoxicosis’ (too much thyroid hormone in the body) results from multinodular goiter, it is referred to as toxic multinodular goiter or plummer’s disease. Symptoms are common to any type of hyperthyroidism.⁶ 

Thyroid adenoma

A thyroid adenoma is a benign tumour of the thyroid gland, which develops as an overgrowth of normal thyroid tissue. These adenomas could be inactive or active in producing thyroid hormones, and if active, they are sometimes referred to as toxic thyroid adenomas. While most cases result in no symptoms, a toxic adenoma can cause hyperthyroidism. Thyroid adenoma typically presents as a solitary nodule thus are differentiable from other conditions, including multinodular goiter or carcinomas.⁷ 

Situations increasing susceptibility

Whilst untreated and unmanaged hyperthyroidism alone, stemming from some of the previously discussed thyroid conditions, could induce a thyroid storm. A thyroid storm is more commonly seen following a causative event. This section discusses some of the events/situations that could trigger a thyroid storm in individuals with hyperthyroidism. 

Thyroid surgery or radiation treatment

Sudden fluctuations in physical stress, such as stress experienced following trauma (sudden injury) or surgery, can provoke the onset of a thyroid storm in patients with hyperthyroidism. As such, it is common medical practice for patients with hyperthyroidism undergoing thyroid surgery to be treated prior to surgery to minimise the risk of a thyroid storm. Treatment options include antithyroid medication (thionamides) until an ‘euthyroid state’ (state in which ‘normal’ levels of thyroid function) is achieved, iodine therapy to reduce thyroid hormone production, medication to stabilize blood flow, or a combination of these medications.⁸ Historically, thyroid storms occured more frequently in patients following thyroid surgery (thyroidectomy) that were pre-treated with potassium iodide alone. However, these patients were not ‘euthyroid’ and would not be considered appropriately prepped for surgery by today's standards. 

Today, exacerbation of ‘thyrotoxicosis’ (excess thyroid hormone) is still seen in patients sent to surgery before appropriate preparation. However, following appropriate treatment, exacerbation of thyrotoxicosis and subsequent thyroid storm risk, is rare.⁹ 

Non-thyroid surgery could increase the risk of thyroid storm development in extremely thyrotoxic patients. Therefore, these patients could be pre-treated prior to surgery to achieve an euthyroid state.⁹ 

Radiation treatment with the radioisotope iodine-131 (131-I), which is prescribed to treat hyperthyroidism, rarely results in exacerbations of thyrotoxicosis. However, a small proportion of patients undergoing 131-I treatment have experienced exacerbations that could be defined as a thyroid storm.^9,3

Iodine exposure

A sudden, large dose of iodine in your body, for example, due to the use of iodine-based contrast agents (prescribed to aid in medical imaging including CT scans) or following excessive iodine intake (from taking a large amount of iodine supplements), can trigger a thyroid storm in susceptible individuals with hyperthyroidism ¹⁰

Thyroid hormone treatment errors

Overdose of thyroid medications or improper management, such as sudden cessation of anti-thyroid medication, could lead to loss of control of thyrotoxicosis and, therefore, can trigger a thyroid storm.¹ 

Pregnancy 

The incidence (frequency) of hyperthyroidism in pregnancy ranges between 0.2%-0.9% and is highest in the first trimester and the prevalence of thyroid storms is 2.97 per 1,000,000 pregnancies. Hyperthyroidism can develop during pregnancy from the same causes and conditions as the general population. Additionally, hyperthyroidism can develop from pregnancy-specific conditions, such as Human chorionic gonadotropin (hCG)-mediated hyperthyroidism, where the pregnancy hormone hCG can stimulate thyroid activity because it resembles TSH. Additionally, thyroid storms can arise in pregnancy following conditions like anemia, pre-eclampsia, placenta previa, induction of labor/C-section, and chorioamnionitis.¹¹

Infections

Thyroid storms can be triggered by infections because infections could lead to a loss of control of thyrotoxicosis. Examples of infections include pneumonia and upper respiratory tract infections, such as influenza or COVID-19. One theory is that an infection could prevent thyroid hormone binding, leading to higher free levels of thyroid hormones in the body that could cause a thyroid storm.⁹

Other contributing factors

Age

The thyroid storm rate is approximately three-fold higher in older individuals (60+) compared to younger individuals. Additionally, the death rate following a thyroid storm is much higher in older individuals.¹² Furthermore, many of the thyroid conditions linked with thyroid storm development are more common in older individuals. 

Gender

The thyroid storm rate is approximately two-fold higher in females compared to males.¹² There are numerous factors that mean women have a higher risk of developing a thyroid storm, such as experiencing pregnancy and having an increased risk of having hyperthyroidism due to Graves disease, which is 5-10 fold more frequent in women.⁵

Undiagnosed or poorly managed thyroid disease

Delayed diagnosis or lack of treatment increases the susceptibility of unmanaged hyperthyroidism and subsequent thyrotoxicosis, which if untreated, could trigger a thyroid storm, or make individuals susceptible to a thyroid storm following a causative event.⁹

Summary 

A thyroid storm is a serious life-threatening exacerbation of thyrotoxicosis (excess thyroid hormone in the body) that stems from hyperthyroidism (an overactive thyroid gland). Individuals with hyperthyroidism are susceptible to a thyroid storm. Common conditions that lead to hyperthyroidism and, therefore, increase thyroid storm risk include Graves’ disease and plummer's disease. Rarely, unmanaged hyperthyroidism alone could cause a thyroid storm. However, it is more common that a thyroid storm occurs following a causative event or situation. Situations linked to thyroid storm development include infections, excess iodine exposure, sudden cessation of antithyroid drugs, and surgery.