What hormone workup is recommended for a 43-year-old female presenting with brain fog, anxiety, and insomnia?

Hormone Workup for 43-Year-Old Female with Brain Fog, Anxiety, and Insomnia

A comprehensive thyroid function assessment is the primary recommended hormone workup for a 43-year-old female presenting with brain fog, anxiety, and insomnia, as these symptoms could indicate thyroid dysfunction which is particularly common in perimenopausal women.

Initial Hormone Workup

Thyroid Function Tests

• TSH (Thyroid Stimulating Hormone) - First-line screening test
• Free T4 (Thyroxine) - To evaluate thyroid hormone levels
• Free T3 (Triiodothyronine) - Particularly if TSH is abnormal
• Thyroid antibodies (TPO and Tg) - To assess for autoimmune thyroid disease 1

Adrenal Function Assessment

• Morning cortisol with paired ACTH - To evaluate adrenal function
• Consider ACTH stimulation test if morning cortisol is between 85-275 nmol/L 2

Sex Hormone Evaluation

• FSH and LH - To assess menopausal status
• Estradiol - To evaluate estrogen levels
• Progesterone - Particularly if patient has irregular menstrual cycles

Rationale for Thyroid Testing

Thyroid dysfunction is particularly relevant for this patient for several reasons:

1. Age-related risk: There is an increasing prevalence of elevated TSH levels in perimenopausal women 3
2. Symptom overlap: Thyroid disorders can present with symptoms identical to those described - brain fog (cognitive impairment), anxiety, and sleep disturbances 1, 3
3. High prevalence: Subclinical thyroid disease affects approximately 23.2% of postmenopausal women, with subclinical hypothyroidism being most common (73.8% of subclinical cases) 3

Importance of Thyroid Function Testing

• Even mild thyroid dysfunction can cause depression, memory loss, cognitive impairment, and sleep disturbances 3
• Studies show significant differences in neurocognitive index (NCI), executive functions, psychomotor speed, reaction time, complex attention, and cognitive flexibility based on TSH levels 4
• Women with FT3 at the lower limit of normal range and FT4 below standard showed poorer cognitive performance 4

Adrenal Assessment Considerations

• Adrenal insufficiency can present with fatigue, anxiety, and sleep disturbances
• Morning cortisol with paired ACTH can distinguish between primary and secondary adrenal insufficiency 2
• A cortisol level <275 nmol/L with elevated ACTH suggests primary adrenal insufficiency 2
• A cortisol level <275 nmol/L with low/normal ACTH suggests secondary adrenal insufficiency (hypophysitis) 2

Hormonal Connections to Symptoms

Brain Fog

• Thyroid dysfunction strongly correlates with cognitive impairment 3, 4
• Estrogen fluctuations during perimenopause can affect cognitive function 5
• Cortisol abnormalities (both high and low) can impair cognitive performance

Anxiety

• Anxiety disorders have been associated with thyroid dysfunction in multiple studies 1
• Hormonal fluctuations during perimenopause can trigger new-onset anxiety 6
• Within-woman changes in FSH, LH, and estradiol variability are significantly associated with mood changes 6

Insomnia

• Thyroid disorders (both hypo- and hyperthyroidism) can disrupt sleep patterns 1
• Hormonal fluctuations during perimenopause commonly cause sleep disturbances 6
• Cortisol dysregulation can lead to sleep-wake cycle disruption

Clinical Approach Algorithm

1. Start with thyroid function panel (TSH, Free T4, Free T3, TPO antibodies)
2. If thyroid normal, proceed to adrenal assessment (morning cortisol with ACTH)
3. Assess menopausal status with FSH, LH, and estradiol
4. Consider additional factors that may contribute to symptoms:
   • Medication effects (review current medications for sleep-disrupting potential) 1
   • Caffeine, alcohol consumption (document in sleep log) 1
   • Sleep environment and patterns (document in sleep log) 1

Important Considerations

• Timing matters: Collect hormone samples in the morning (before 9 AM for cortisol)
• Medication interference: Note that oral estrogen therapy can increase thyroxine-binding globulin (TBG), potentially affecting thyroid function test interpretation 7
• Subclinical disease: Even thyroid values at the upper or lower limits of normal range can be associated with cognitive symptoms 4
• Perimenopause transition: Women with no history of depression are 4 times more likely to develop depressive symptoms during menopausal transition 6

By systematically evaluating these hormone systems, you can identify potential underlying causes of the patient's brain fog, anxiety, and insomnia, leading to targeted treatment approaches that address the root hormonal imbalances.