What labs should be ordered to evaluate low libido, weight gain, and fatigue?

Laboratory Evaluation for Low Libido, Weight Gain, and Fatigue

Order a morning total testosterone level, TSH, free T4, morning cortisol, ACTH, and comprehensive metabolic panel as the initial laboratory workup for this symptom triad. 1

Essential Hormone Testing

Testosterone Assessment

• Measure morning total testosterone in all patients presenting with decreased libido, as this is the recommended screening test per the American Diabetes Association guidelines 1
• If total testosterone is borderline (near lower limit of normal), obtain free testosterone either by equilibrium dialysis or calculated using total testosterone, sex hormone-binding globulin (SHBG), and albumin 1
• Add LH and FSH levels to distinguish primary hypogonadism (high LH/FSH with low testosterone) from secondary hypogonadism (low or normal LH/FSH with low testosterone) 1

Thyroid Function

• TSH and free T4 are essential, as hypothyroidism commonly presents with this exact triad of symptoms 1
• Free T4 is particularly important because TSH alone may miss central hypothyroidism 1

Adrenal Function

• Morning cortisol and ACTH should be obtained simultaneously to evaluate for adrenal insufficiency, which presents with fatigue, weight changes, and can affect libido 1
• The relationship between ACTH and cortisol distinguishes primary adrenal insufficiency (high ACTH, low cortisol) from secondary/central adrenal insufficiency (low ACTH, low cortisol) 1
• If morning cortisol is indeterminate (between 3-15 mcg/dL), consider ACTH stimulation testing 1

Additional Metabolic Screening

Basic Metabolic Panel

• Comprehensive metabolic panel including electrolytes to screen for metabolic causes and assess for diabetes insipidus (hypernatremia) if pituitary pathology is suspected 1
• Fasting glucose or HbA1c should be included, as diabetes is associated with lower testosterone levels and sexual dysfunction 1, 2

Lipid Assessment

• Consider lipid panel, as dyslipidemia is associated with hypogonadism and metabolic syndrome 1

Sex-Specific Considerations

For Males

• The testosterone-libido relationship is well-established, though individual variation exists 3
• Morning sampling is critical as testosterone levels follow a diurnal pattern 1

For Females

• Consider testosterone, DHEA-S, LH, FSH, and estradiol in premenopausal women with fatigue, loss of libido, and mood changes 1
• DHEA replacement may be considered in women with documented deficiency and low libido who are otherwise adequately replaced on other hormones 1
• Both low and high testosterone can cause symptoms in women, with optimal free testosterone around 0.4-0.6 ng/mL 4

Clinical Pitfalls to Avoid

• Do not check testosterone in patients currently on corticosteroids for other conditions, as this causes iatrogenic secondary adrenal insufficiency and will confound results 1
• Always start corticosteroid replacement before thyroid hormone if both deficiencies are present, to prevent precipitating adrenal crisis 1
• Oral estrogen therapy increases SHBG, which lowers free testosterone and can worsen symptoms despite normal total testosterone 5
• Obesity is a major confounder in testosterone interpretation, as it independently lowers testosterone levels 1, 2

When to Consider Advanced Imaging

• MRI brain with pituitary cuts should be obtained if multiple hormonal deficiencies are identified, suggesting hypophysitis or pituitary pathology 1
• This is particularly important if accompanied by severe headaches or vision changes 1