Hypothyroid patients describe what brain fog feels like

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Hypothyroid patients describe what brain fog feels like

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Hypothyroid Patients Describe What Brain Fog Feels Like
Review of: Ettleson MD, Raine A, Batistuzzo A, Batista SP, McAninch E, Teixeira MCTV, Jonklaas J, Laiteerapong N, Ribeiro MO, Bianco AC 2021 Brain fog in hypothyroidism: Understanding the patient's perspective. Endocr Pract. Epub 2021 Dec 8. PMID: 34890786

SUMMARY
Background

Patients often report brain fog, described as a state of cognitive dysfunction associated with lack of energy, forgetfulness, sleepiness, and mood disturbances. This symptom is common in patients with hypothyroidism, but it has also been associated with menopause, chemotherapy, celiac disease, lupus, chronic fatigue syndrome, COVID-19, depression, and sleep apnea (1–5). The nonspecificity of the brain fog terminology poses a diagnostic and therapeutic challenge to clinicians in caring for their patients.

This study aimed to determine the specific symptoms associated with brain fog, identify the patient-reported factors that modify these symptoms, and identify the patient concerns related to brain fog that are not included in thyroid-specific questionnaires.

Methods
A survey on brain fog symptoms, adapted from the Thyroid-Specific Patient-Reported Outcome (ThyPRO) questionnaire, was approved by the American Thyroid Association (ATA) and distributed online to patients within the ATA patient database (September 2020–October 2020) and through hypothyroid support websites and social media groups.

Participants ≥16 years of age who reported having brain fog despite treatment for hypothyroidism were included. Other information included sex, cause of hypothyroidism, onset, frequency, and daily duration of brain fog and its frequency of association with specific symptoms. Answering two open-ended questions, participants noted factors that improved or worsened brain fog symptoms and provided additional comments to help researchers better understand brain fog. Textual data analysis was performed to identify common areas of concern.

Categorical variables were presented as proportions and numerical variables as mean and standard deviation. In the subgroup analysis based on an age cutoff of 50 years, categorical variables were compared using a χ2 test and numeric variables using a t-test. Multivariable logistic-regression analysis was used to calculate the odds ratio of the association of brain fog with each symptom and in the analyses of factors modifying brain fog symptoms and classification of the open-ended responses.

Results
A total of 5170 participants reporting brain fog while being treated for hypothyroidism were included in the analysis. The mean participant age was 51 years, and 96% of the participants were women. Hashimoto disease was the most common cause of hypothyroidism (45%), although 32% reported hypothyroidism of unknown cause. Most participants (79%) experienced brain fog symptoms frequently or all the time and 47% reported symptom onset prior to the diagnosis of hypothyroidism.

Of the symptoms listed, >95% of the participants associated fatigue, forgetfulness, sleepiness, and difficulty focusing most frequently with brain fog, with a mean negative impact score of 3.1/4. More rest, adjustment of thyroid hormone, and more exercise were the most common factors provided for improving symptoms (51.7%, 28.3%, and 10.4% respectively). Thyroid hormone adjustments improved symptoms in only 28% of patients. Patients ≥50 years old reported more frequently that the addition of liothyronine (LT3) improved symptoms (9.2%, vs. 7.2% for patients < 50 years old; P = 0.009) and that levothyroxine (LT4) alone worsened symptoms (5.5% vs. 3.9% for patients < 50 years old; P = 0.007). The textual data analysis identified areas of concern that are not often included in thyroid-specific quality-of-life questionnaires, including a focus on the diagnosis of hypothyroidism, the medications, and the patient–doctor relationship. Multivariable logistic-regression analysis showed similar results.

Conclusions
Brain fog in treated hypothyroid patients was associated most frequently with fatigue and cognitive symptoms and negatively impacted the participants’ lives. Patient–doctor relationship and other areas of patient concern were found to be associated with brain fog, and these are not typically addressed in thyroid-specific questionnaires for quality of life.

COMMENTARY
Brain fog is a nonspecific term and is often related to cognitive decline with aging (6). Okosieme et al (7) found that up to 37% of patients with hypothyroidism remain inadequately treated despite frequent laboratory monitoring and LT4 dose adjustments and it is hypothesized that this could account for brain fog symptoms. For patients with persistent symptoms of hypothyroidism despite adequate LT4 treatment and after exclusion of other comorbidities, a potential benefit of a physiologic thyroid hormone replacement trial with a combination of LT4 and LT3 therapy was proposed (8) and is supported by a recent consensus statement from the American, British, and European Thyroid Associations (9) with a focused assessment based on patient-centered outcomes.

The study by Ettleson et al. (1) has several limitations, notably a significant selection bias, lack of confirmation of the diagnosis of hypothyroidism or other comorbid conditions, and lack of information regarding the treatment method and control of the hypothyroidism. Based on the study design, the prevalence of brain fog in hypothyroid patients or the actual impact of hypothyroidism on brain fog could not be determined. However, this study describes what constitutes brain fog from the patients’ perspective. It also provides valuable information regarding lifestyle factors that can alleviate symptoms and the extent to which LT3, desiccated thyroid extract, or adjustment of thyroid hormone can improve symptoms. Finally, the patient–doctor relationship emerged as an important focus of concern for hypothyroid patients struggling with brain fog, a research area that has been overlooked when assessing thyroid-related quality of life.

Brain fog has a negative impact on quality of life. Clearly, more research is needed to assess the relationship between brain fog and hypothyroidism. In the meantime, clinicians ought to ask patients about related symptoms, validate their concerns, optimize treatment for hypothyroidism, and address underlying comorbidities.
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