Thyrotoxicosis: Symptoms and signs

Much confusion exists about the value of symptoms and signs in the diagnosis of thyrotoxicosis. The most common view is to dismiss symptoms entirely because each, considered separately, is “nonspecific” to thyrotoxicosis. However, there is no such thing as a “thyroid-specific” symptom because thyroid hormones have their effects in every organ and system of the body. 

What’s do the experts recommend? Look for several symptoms manifesting at once.

Braverman & Cooper’s 2013 chapter in Werner & Ingbar’s The Thyroid, 10th edition, says “it is usually the combination of several that suggests the possibility of the disorder.”

Their chapter divides a list into “symptoms” and “signs.”

Basically, a symptom is a phenomenon that is experienced by the individual affected by the disease, while a sign is a phenomenon that can be detected by someone other than the individual affected by the disease.

I’ve put an asterisk (*) on symptoms that require further commentary below the list.

Symptoms listed by Braverman & Cooper include “Hyperactivity; Tachycardia [fast heart rate]; atrial arrhythmia*; Systolic hypertension; Warm, moist, smooth skin; Stare and eyelid retraction*; Tremor; Hyperreflexia [over-responsive tendon reflex]; Muscle weakness*”

Signs may include “Nervousness; Fatigue*; Weakness*; Increased perspiration; Heat intolerance*; Tremor; Hyperactivity; Palpitations*; Appetite change (usually increase)
Weight change (usually weight loss)*; Menstrual disturbances*

Comments:

In general, their division between “symptoms” and “signs” is arbitrary and misleading.

Any doctor can measure the “symptoms” of systolic hypertension and heart rate in the office, and all “signs” listed are symptoms that the patient can assess as well.

This textbook chapter should have referred to the literature providing research-validated clinical symptom and sign scoring systems for thyrotoxicosis, like Wayne’s Index, which I cite below.

Cardiovascular symptoms: A too common misconception is that all cardiovascular signs and symptoms, such as atrial arrhythmia, hypertension, and palpitations, are only found in thyrotoxicosis and never in the opposite state of hypothyroidism. This is simply false. Patients with isolated low T3 can and do present with cardiac and cardiovascular distress, especially in the context of heart failure and ischemic heart disease (Kannan et al, 2018; von Hafe et al, 2019)

According to “Wayne’s index,” a clinical scoring system for hyperthyroidism, a sign of thyrotoxicosis is an elevated resting heart rate over 90. (Kalra, et al, 2011).  A heart rate elevated by constantly elevated thyroid hormone will likely be sustained, not occasional. 

Atrial arrythmia (atrial fibrillation): This sign is often found in patients with high Free T4, even within the upper part of reference range, much more than in patients with high Free T3. (Anderson et al, 2018; Baumgartner et al, 2017; Kannan et al, 2018) 

Stare and eyelid retraction: Excess thyroid hormones are NOT the cause of Graves’ eye disease. This should not be listed here unless it is identified as a sign of the Graves disease antibody.

I have heard patients say that their doctor missed their diagnosis because “my eyes were not bugged out.”  The syndrome of Graves’ eye disease, which presents like Rodney Dangerfield, an actor with the syndrome, can present with or without thyrotoxicosis. TSH-Receptor antibodies may or may not attack the eyes along with the thyroid gland.

If a doctor is looking for eye signs to diagnose Graves’ disease or thyrotoxicosis, the absence of this sign can mislead them into thinking a person does not have the antibody at all, or doesn’t have thyrotoxicosis.

Fatigue and weakness: Both hyperthyroid and hypothyroid patients can suffer from fatigue. However, the type of fatigue found in thyrotoxicosis is from an overconsumption of metabolic resources and inability to rebuild them. In patients’ experience, muscle weakness may be felt as legs shaking or giving way when descending stairs or tremors appearing when repeatedly lifting a heavy object. In contrast, hypothyroidism more often manifests with continual drowsiness, slower motion and thought, and the need for very long naps during the day. 

Menstrual disturbances: It is a misconception that menstrual disturbances are common in thyrotoxicosis. Instead, lighter and irregular periods may occur in some cases of thyrotoxicosis, while heavy menstrual bleeding and irregular periods are more often found in severe hypothyroidism. (Krassas et al, 1994, 1999)

HOW TO USE DISCERNMENT WITH SYMPTOMS

Expect symptoms and signs to be very individualized.

Braverman & Cooper write “The frequency and severity of these symptoms and signs vary considerably among patients; some patients have only a few symptoms or signs and others many, and their severity varies widely.”

Excess and deficiency of thyroid hormone will often manifest in parts of the individual’s body that are already weakened by other health conditions or may simply be due to genetic individuality. A chain will break at its weakest link.

Age also gives clues as to how thyrotoxicosis may manifest. Braverman & Cooper explain “For example, as compared with younger patients, older patients have fewer symptoms and signs of sympathetic activation, such as anxiety, hyperactivity, and tremor, and more symptoms and signs of cardiovascular dysfunction, such as congestive failure and atrial fibrillation, and they are more likely to lose weight.”

PUT TSH AND THYROID LAB RESULTS IN CONTEXT

Braverman & Cooper explain that “The extent and severity of the clinical manifestations of thyrotoxicosis are not strongly correlated with its biochemical severity.”

The “biochemicical” severity they are referring to is “biochemical confirmation of thyrotoxicosis by measurements of serum TSH and direct or indirect measurements of the serum total T4, free T4, total T3, free T3, or all.” 

Notice they did not say “TSH or” thyroid hormone measurements, but “TSH and.”

TSH is not enough as a sole indicator.

This is consistent with their definition of thyrotoxicosis, which does not mention TSH at its core.

Lab results and symptoms “are not strongly correlated” in their severity because each person’s homeostatic “set point” for thyroid hormone may be located in a different portion of the reference range.

Each thyroid patient on hormone therapy will convert T4 into T3 at a different rate within and beyond their bloodstream. One person may require Free T4 in the middle of reference and Free T3 in the upper third; another may require Free T4 at the bottom of reference and Free T3 near the top.

However, one thing is clear in research: it is a dangerous pattern for almost any human being to have free T4 hovering near top of reference and Free T3 near the bottom of reference range. A very low T3:T4 ratio most often yields the worst prognosis in critical illness and in elderly people, especially for people with cardiovascular conditions and risk of stroke. In contrast, a T3-dominant profile is generally safer. (Ataoglu et al, 2018; Jiang et al, 2017; Visser et al, 2005; van Vliet et al, 2017)

Another reason why the “biochemical severity” of thyrotoxicosis often does not manifest is that the human body is protected from mild excursions above reference range.

Excess T3 and T4 can be quickly cleared by the thyroid-hormone-converting enzyme Deiodinase Type 3, whose preferred substrate is T3 hormone. It converts T3 to T2 as well as T4 to Reverse T3. The DIO3 gene is responsive to the presence of excess thyroid hormone above one’s metabolic setpoint, appearing when triggered by critical illness, fasting, and in depression. (Charlamboux & Hernandez, 2013; Galecka et al, 2017)

Braverman and Cooper caution that the “easy” availability of the TSH, Free T3 and Free T4 tests can lead to mistaken overreliance on this complete set of tests when obtaining “biochemical confirmation of thyrotoxicosis.”

“Fortunately,” they conclude, “the etiology [causes of thyrotoxicosis] can often be determined by physical examination, and tests to determine the cause are not routinely necessary.”

Their word is “Fortunately.”

The main reason that Braverman and Cooper offer for testing is to “obtain biochemical confirmation” of a diagnosis of a syndrome whose existence can readily be discerned by physical examination.

Thyroid hormone tests may assist in helping categorize a patient as subclinical or overt, but they are not the only judge.

It’s fortunate for the doctor that a physical examination is the foundation, since their medical training and discernment can be utilized.

It’s ultimately fortunate for the patient, whose syndrome is not likely to be misdiagnosed or overlooked due to arbitrary population reference range cutoffs or policies that forbid direct thyroid hormone testing.

It is unfortunate, on the other hand, that TSH-monotesting policies and the literature supporting them continually overlooks the many reasons why a low TSH can never by itself be a proof of thyrotoxicosis or hyperthyroidism.

Free T3 and Free T4 testing and the signs and symptoms of thyrotoxicosis are always going to be the at the heart of correct diagnosis and therapy, no matter what cost-saving policy-promoters tell you.

REFERENCES

See References for Thyrotoxicosis vs. Low TSH series