Introduction

If you or someone you love is experiencing sudden confusion, seizures or sudden changes in mental clarity, it can be extremely overwhelming. These neurological symptoms, when manifest in combination with whole-body symptoms like fever, high blood pressure/rate and jaundice, then it may be indicative of a thyroid storm. This is a rare, life-threatening complication of untreated or severe hyperthyroidism that is capable of affecting the brain in profound ways. 

In this article, we will explore how the neurological symptoms of thyroid storm arise and present. Read on to gain an understanding of the biology of thyroid storm and how rapid medical care can make all the difference. 

Understanding Thyroid Storm 

Thyroid storm is a severe, potentially fatal complication that can occur when hyperthyroidism, especially if left untreated or poorly controlled, becomes extreme. It most often affects individuals with underlying  Graves’ disease. It requires a triggering event (sometimes referred to as a precipitating factor), which can be things like:

• The abrupt stopping of medications for hyperthyroidism
• Thyroid or non-thyroid surgeries
• Trauma
• Illness or infection such as COVID-19 or a heart attack
• Childbirth
• Stroke

Thyroid storm is considered a medical emergency, as it is associated with a death rate of up to 90% if left untreated.¹ This is because it affects multiple organ systems, being responsible for symptoms like sudden high blood pressure, a high fever and yellowing of the skin and eyes (a symptom indicative of liver problems). 

Unfortunately, there is no specific laboratory test that can accurately confirm the diagnosis; hence, the knowledge and understanding of the range of symptoms of thyroid storm are crucial in prompt and accurate treatment. Many diagnostic manuals require at least one symptom associated with the central nervous system in the diagnosis of thyroid storm. These include:¹ 

• Agitation
• Delirium and psychosis
• Extreme lethargy (tiredness)
• Seizures
• Coma

The relationship between the brain and thyroid

The thyroid is a gland that produces hormones essential for regulating the body’s metabolism.. These hormones are crucial in metabolism, growth and development, as well as the function of many organs. The thyroid and central nervous system (brain and spine) are closely linked. Signals are constantly sent back and forth between an area of the brain called the hypothalamus, a gland in the brain called the pituitary gland and the thyroid, to strictly control the production of hormones in accordance with the body's needs.² Thyroid hormones are considered critical in the development of the brain, with their disruption being associated with the disruption of brain signalling, leading to neurological symptoms.³ 

Although the exact role and function of thyroid hormones in the brain of adult humans are not yet fully understood, we have an idea of where these hormones are present. In the central nervous system, thyroid hormones are activated in cells that promote the function of neurons.⁴ Research has also shown that thyroid hormones can alter neuronal signalling by changing the function of specific ion channels.⁵ 

The biology of thyroid storm

Thyroid storm is a collection of symptoms thought to be caused more so by the sudden increase in thyroid hormone levels following a precipitating event, rather than the actual hormone levels during the symptoms. In other words, the whole-body symptoms of thyroid storm are associated with the knock-on effects of the surge in thyroid hormone rather than high levels of the hormone. This is why it cannot be diagnosed solely by laboratory testing. 

A surge in thyroid hormone can alter:⁶

• Neurotransmission (the way that nerves communicate with each other)—Thyroid hormones interact with neurotransmitters (chemicals that are responsible for brain signalling)
• Metabolism—Thyroid hormones increase basal metabolic rate. A surge in thyroid hormone increases oxygen and glucose demand
• The way genes are expressed—Leading to different proteins being made
• Oxidative stress—Thyroid hormones increase oxidative stress, which can cause tissue damage

The neurological symptoms of thyroid storm

In this section, we will explore more about the neurological symptoms of thyroid storm and their prevalence, presentations and possible biological mechanisms. 

Seizures 

Seizures are caused by increased excitability of neurones in the brain, leading to uncontrolled brain activity. They are a less common neurological symptom of thyroid storm and are considered to be a severe central nervous system disturbance.⁷ 

Possible mechanisms

Little is known about the exact cause of seizures in thyroid storm. Some research suggests that high levels of thyroid hormone can cause imbalances of electrolytes (different minerals and ions) in the brain.⁸ Studies have also shown that seizures can develop as a consequence of oxidative stress, which can occur in a thyroid storm.⁸ 

Delirium

Delirium refers to a rapid onset of confusion. This can generally present as:⁷

• The inability to think or speak clearly or quickly
• Disorientation—The individual might be unaware of their location or surroundings
• Struggling to focus or maintain attention
• Struggling to remember things
• Hallucinations—Seeing or hearing things that are not present

Delirium can be categorised as hyperactive or hypoactive. Hyperactive delirium often presents as restlessness or agitation, whereas hypoactive delirium presents as social withdrawal or unusual drowsiness. 

The prevalence of delirium in patients with thyroid storm is unknown; however, it is considered a moderate disturbance of the central nervous system.⁷ 

Possible mechanisms 

The exact biological mechanisms underlying delirium in any case are not well-characterised in research. Some studies suggest that it is caused by dysfunction in the function of the chemicals responsible for signalling in the brain (neurotransmitters).⁹ Others state that the cause of delirium is inflammation.⁹ It is most likely a combination of the two and other, not yet characterised mechanisms. 

Thyroid storm has been shown to alter the communication of neurones (neurotransmission) and metabolism, hence providing a possible mechanism for delirium in this condition.⁶ 

Altered mental status 

Altered mental status is an umbrella term for a range of neurological symptoms that imply a change in mental capacity or function. This can range from mild confusion to coma and may be used by professionals if they cannot identify a specific cognitive change. As we have previously discussed delirium, this section will focus on other thyroid storm-induced altered cognitive functions. 

Coma 

Coma is a state in which a person is unconscious with minimal brain activity. It is a severe manifestation of thyroid storm, associated with an almost 40% death rate.^7,10 The prevalence of coma as a symptom of thyroid storm is low, which is why little is known about the biology underlying it. 

Research suggests that a coma can occur due to a deficit of oxygen or glucose to the brain. In thyroid storm, an increase in metabolism can lead to oxygen and glucose being used up too fast, thus providing a possible mechanism for coma. 

Other presentations

Other forms of altered mental status in thyroid storm (confusion or agitation without delirium and extreme tiredness) are milder than coma. These can be explained by the general consequence of thyroid storm on the brain: differences in neurotransmission, metabolism, gene expression and oxidative stress.⁶ 

Management of neurological symptoms in thyroid storm

Whilst neurological symptoms are required in the diagnosis of thyroid storm, they are not necessarily treated alone. Due to the life-threatening nature of the condition, treatment focuses on restoring heart function to normal and dealing with thyroid hormone levels as well as resolving any precipitating factors. This can look like:

• Intravenous fluids, oxygen administration, and cooling blankets 
• Treating infections with antibiotics 
• Administering drugs called beta blockers to slow down the heart
• Administering drugs to decrease levels of thyroid hormone if they are too high. This can be done by decreasing the making, release, conversion or recycling of the hormone

Neurological symptoms should subside following treatment.¹¹

Summary

Thyroid storm is a medical emergency that is caused by a sudden surge in thyroid hormones, leading to whole-body complications. This surge can occur as a consequence of untreated or poorly managed hyperthyroidism or Graves’ disease and requires a triggering event like surgery, infection or stroke. Diagnosis of this condition is not easy, as its life-threatening nature means that clinicians must rely on clinical presentations rather than laboratory tests. One required presentation is the presence of neurological symptoms, such as seizures, delirium and mental state alterations. It is thought that the cause of the neurological symptoms is a disruption of brain signalling, increased metabolism, oxidative stress and changes in gene expression. Early recognition and treatment are crucial for the survival of thyroid storm. Treatments include treating triggering events, decreasing thyroid hormone concentration and administering drugs to slow down the heart rate.