What are the differential diagnoses for a 43-year-old female presenting with alopecia (hair loss), nocturnal diaphoresis (night sweats), and fatigue (low energy)?

Differential Diagnoses for Hair Loss, Night Sweats, and Low Energy in a 43-Year-Old Female

The most critical differential to consider is thyroid disease (hypothyroidism or hyperthyroidism), as it commonly presents with this triad of symptoms and is readily treatable, followed by iron deficiency anemia, perimenopause, and autoimmune conditions including alopecia areata with associated autoimmune thyroiditis. 1, 2

Primary Endocrine Differentials

Thyroid Dysfunction

• Hypothyroidism is a leading cause of diffuse hair loss, fatigue, and can cause night sweats, requiring TSH screening as first-line testing 1, 2
• If TSH is elevated, complete evaluation with free T4 and thyroid peroxidase (TPO) antibodies to confirm autoimmune thyroiditis 1
• Hyperthyroidism can also cause hair loss, fatigue, and night sweats with heat intolerance 2
• Alopecia areata associates with autoimmune thyroid disease in approximately 20% of cases 1

Perimenopause/Menopause

• At age 43, perimenopausal transition commonly causes night sweats (vasomotor symptoms), fatigue, and hair thinning 3
• Declining estrogen levels affect hair follicle cycling and can unmask androgenetic alopecia 3
• Associated symptoms include irregular menstrual cycles and mood changes

Nutritional Deficiencies

Iron Deficiency Anemia

• Ferritin <60 ng/mL indicates iron deficiency requiring supplementation, and is the most common nutritional deficiency worldwide causing chronic diffuse telogen hair loss 1, 4
• Iron deficiency causes profound fatigue and can contribute to temperature dysregulation 5
• Check complete blood count and serum ferritin as first-line testing 1, 4

Vitamin D Deficiency

• 70% of alopecia areata patients have vitamin D levels <20 ng/mL versus 25% of controls, with inverse correlation to disease severity 1
• Vitamin D deficiency associates with fatigue and may contribute to autoimmune conditions 1

Zinc and Folate Deficiency

• Serum zinc levels tend to be lower in patients with alopecia areata, particularly those with resistant disease >6 months duration 1
• Folate deficiency may contribute to hair loss and fatigue 1

Autoimmune Conditions

Alopecia Areata

• T lymphocyte-mediated autoimmune attack on hair follicles causing patchy, non-scarring hair loss 1
• 20% have family history and strong association with other autoimmune diseases including thyroid disease, lupus, and vitiligo 1
• Typically does not cause systemic symptoms like night sweats or fatigue unless associated with another autoimmune condition 1

Systemic Lupus Erythematosus

• Can cause both scarring and non-scarring alopecia, fatigue, and constitutional symptoms including night sweats 1
• Consider serology for lupus when systemic symptoms are prominent 1

Autoimmune Polyglandular Syndrome Type 2

• Rare but important differential combining Addison's disease, autoimmune thyroiditis, and can include alopecia universalis 6
• Presents with severe fatigue, hypotension, hyperpigmentation, and hair loss 6

Hormonal Disorders

Polycystic Ovary Syndrome (PCOS)

• Causes androgenetic alopecia in women with androgen excess 1, 3
• Associated features include irregular periods, acne, hirsutism, and metabolic dysfunction 1
• Check total or free testosterone, SHBG, and consider 2-hour oral glucose tolerance test 1

Hyperprolactinemia

• Can contribute to hair loss and menstrual irregularities 1
• Check prolactin level if suspected based on menstrual history 1

Stress-Related Conditions

Telogen Effluvium

• Physiologic or emotional stressors push hair follicles prematurely into resting phase, causing diffuse shedding 1, 5
• Psychological stress and iron deficiency are the most common underlying factors (statistically significant, p<0.05) 5
• Can be triggered by illness, surgery, severe emotional stress, rapid weight loss, or nutritional deficiencies 1
• Resolves spontaneously in 80% of cases <1 year duration once precipitating cause is eliminated 4

Infectious/Inflammatory Causes

Chronic Infections

• Tuberculosis, HIV, or other chronic infections can cause night sweats, fatigue, and hair loss
• Secondary syphilis presents with patchy "moth-eaten" hair loss and systemic symptoms 1
• Consider serology for syphilis when appropriate 1

Tinea Capitis

• Fungal scalp infection causing patchy hair loss with inflammation and scaling 1
• Requires fungal culture for diagnosis and oral antifungal treatment 1

Malignancy/Hematologic Disorders

Lymphoma or Other Malignancies

• Night sweats (especially drenching), fatigue, and hair loss can indicate underlying malignancy
• Consider if constitutional symptoms are prominent with unintentional weight loss

Recommended Diagnostic Algorithm

First-Line Laboratory Testing

• Complete blood count and serum ferritin (target >60 ng/mL) 1, 4, 5
• TSH (if abnormal, add free T4 and TPO antibodies) 1, 4
• Vitamin D level (deficiency <20 ng/mL) 1, 4
• Serum zinc and folate levels 1, 4

Second-Line Testing (If First-Line Normal or Clinical Suspicion)

• If signs of androgen excess: total or free testosterone, SHBG, consider PCOS workup 1, 3
• If menstrual irregularities: prolactin level 1
• If systemic symptoms prominent: ANA, ESR, CRP for lupus or other autoimmune conditions 1
• If risk factors present: syphilis serology, HIV testing

When to Consider Biopsy

• Diagnosis remains uncertain after initial workup 1
• Scarring alopecia suspected 1
• Diffuse alopecia areata that is challenging to diagnose clinically 1

Common Pitfalls to Avoid

• Failing to check ferritin levels, as iron deficiency is the most common nutritional cause and requires levels >60 ng/mL for optimal hair growth 1, 4
• Ordering excessive laboratory tests when diagnosis is clinically evident 1
• Overlooking thyroid disease, which commonly presents with this symptom triad 1, 2
• Missing perimenopause as a diagnosis in this age group, which is a common cause of all three symptoms
• Failing to assess psychological impact, as hair loss causes considerable psychological disability warranting evaluation for anxiety and depression 1
• Not considering that multiple etiologies often coexist (67.2% of patients with hair loss have abnormalities in two or more parameters) 3