What laboratory tests should a 34-year-old male with a Body Mass Index (BMI) of 30 undergo to investigate symptoms of fatigue, stress, mood swings, depression, elation, hair loss, insomnia, dry eyes, and cracked fingers and nails?

Laboratory Workup for a 34-Year-Old Male with Fatigue, Mood Instability, Hair Loss, Insomnia, and Dry Eyes

This patient requires comprehensive thyroid function testing (TSH, free T4), morning cortisol/ACTH, complete blood count, comprehensive metabolic panel, vitamin D, and fasting glucose as the essential initial laboratory evaluation. 1

Primary Laboratory Tests

The constellation of fatigue, mood swings (depression alternating with elation), hair loss, insomnia, and dry eyes strongly suggests potential endocrine dysfunction, particularly thyroid disease or hypophysitis, which must be ruled out systematically.

Essential Endocrine Evaluation

• Thyroid function tests (TSH, free T4): Hypothyroidism commonly presents with fatigue, weight changes, hair loss, cold intolerance, constipation, and depression, while thyrotoxicosis can cause anxiety, palpitations, heat intolerance, and mood lability 1
• Morning cortisol and ACTH (ideally around 8 AM): Adrenal insufficiency presents with fatigue, mood changes, and can be associated with other endocrine abnormalities 1
• Fasting glucose and hemoglobin A1C: To evaluate for diabetes mellitus, which can cause fatigue, mood changes, and polyuria 1

Hematologic and Nutritional Assessment

• Complete blood count (CBC): Anemia is a treatable cause of fatigue and must be identified 1
• Comprehensive metabolic panel: To assess renal function, electrolytes, and liver function, as these organ dysfunctions contribute to fatigue 1
• Serum 25-hydroxyvitamin D: Vitamin D deficiency is associated with fatigue, mood disturbances, and hair loss 2

Secondary Laboratory Tests Based on Initial Findings

If Thyroid Dysfunction Suspected

• Thyroid peroxidase (TPO) antibody: If hypothyroidism is confirmed, to identify autoimmune thyroiditis 1
• Thyroid stimulating immunoglobulin (TSI) or TRAb: If thyrotoxicosis is present, to differentiate Graves' disease from thyroiditis 1

If Hypophysitis or Multiple Hormone Deficiencies Suspected

• Gonadal hormones (testosterone in men, FSH, LH): Hypophysitis can cause multiple pituitary hormone deficiencies 1
• Consider MRI of the sella with pituitary cuts: If ≥1 pituitary hormone deficiency is found (particularly TSH or ACTH deficiency) combined with headache symptoms 1

For Dry Eye Evaluation

• Anti-Sjögren syndrome A antibody (SSA/anti-Ro), anti-Sjögren syndrome B antibody (SSB/anti-La), rheumatoid factor, and antinuclear antibody: Clinically significant dry eyes with systemic symptoms warrant evaluation for Sjögren syndrome 1
• Point-of-care testing including salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP) may be considered if available 1

Additional Considerations

Inflammatory Markers

• C-reactive protein: Can be considered as part of the evaluation for systemic inflammation contributing to fatigue 1

Lipid and Cardiovascular Assessment

• Fasting lipid panel: Given BMI of 30 and age, cardiovascular risk assessment is appropriate 1

Critical Clinical Caveats

The timing of cortisol/ACTH testing is crucial—these must be drawn in the morning around 8 AM before any steroid administration, as physiologic cortisol levels vary throughout the day 1. If adrenal insufficiency and hypothyroidism coexist, steroids must always be started before thyroid hormone replacement to avoid precipitating an adrenal crisis 1.

Mood instability warrants psychiatric screening: While laboratory tests are being obtained, use the two-question depression screen: (1) "In the last month, have you often felt dejected, sad, depressed or hopeless?" and (2) "In the last month, did you experience significantly less pleasure than usual with the things you normally like to do?" 1. If positive, consider PHQ-9 for depression severity assessment 1.

Hair loss combined with fatigue and mood symptoms has been associated with depression in multiple studies, but also represents a cardinal feature of thyroid disease 1, 3. The combination of symptoms makes endocrine evaluation the priority.

Insomnia evaluation: While polysomnography is not routinely indicated for chronic insomnia, other laboratory testing is not indicated unless there is suspicion for comorbid disorders—which this patient clearly has 1. The laboratory workup above addresses the suspected comorbidities.

Dry, cracked fingers and nails may represent dermatologic manifestations of thyroid disease, nutritional deficiencies, or autoimmune conditions, making the above laboratory evaluation even more pertinent 1.