What is the diagnosis and treatment for a 25-year-old female experiencing weakness, fatigue, bloating, acne, mood swings, and poor sleep?

Differential Diagnosis and Systematic Evaluation

This constellation of symptoms—weakness, fatigue, bloating, acne, mood swings, and poor sleep—in a 25-year-old female most likely represents either polycystic ovary syndrome (PCOS), thyroid dysfunction (particularly hypothyroidism), or a primary mood disorder with secondary physical manifestations, and requires immediate thyroid function testing, complete blood count, and comprehensive metabolic panel as the essential first steps. 1

Priority Laboratory Evaluation

The following tests are essential and should be ordered immediately:

• Thyroid function tests (TSH, free T4) - Hypothyroidism frequently presents with this exact symptom cluster and is one of the most important treatable causes to investigate first 1, 2
• Complete blood count - Anemia occurs in approximately 2.8% of patients with fatigue and is a common, easily treatable cause 1
• Comprehensive metabolic panel - To assess for electrolyte imbalances (sodium, potassium, calcium, magnesium) that contribute to fatigue 3, 1
• Fasting glucose and hemoglobin A1c - To evaluate for diabetes or insulin resistance, particularly given the bloating and acne 3
• Vitamin D, B12, folate, and ferritin levels - Specific nutritional deficiencies directly linked to fatigue 1, 2

Hormonal Assessment

Given the patient's age, sex, and symptom pattern (acne, mood swings, bloating):

• Consider PCOS evaluation with total testosterone, DHEA-S, LH/FSH ratio, and pelvic ultrasound if menstrual irregularities are present 4
• Assess for premenstrual symptoms - Document timing of symptoms relative to menstrual cycle 4

Sleep Disorder Evaluation

Sleep disturbances affect 30-75% of patients with fatigue and must be systematically addressed 3:

• Screen for insomnia - Difficulty falling or staying asleep at least 3 times per week for at least 4 weeks 3
• Assess for obstructive sleep apnea risk factors - Particularly important as OSA can develop in young women and cause this symptom complex 3, 2
• Evaluate sleep hygiene behaviors - Irregular sleep schedules, daytime napping, pre-bedtime caffeine/alcohol/high-sugar food intake, late-night screen use 3, 2
• Consider formal polysomnography if history suggests OSA or if fatigue persists despite treatment of other factors 3

Psychological Assessment

Depression and anxiety are critical contributors that are frequently overlooked:

• Screen for depression using validated tools (PHQ-2 or PHQ-9) - Depression affects 18.5% of patients with tiredness and is strongly associated with fatigue 1, 2
• Assess for anxiety - Anxiety frequently accompanies fatigue and acne, with studies showing higher State-Trait Anxiety scores in patients with acne 5, 2
• Note the bidirectional relationship - Acne itself is associated with increased stress (18% report daily stress vs 13.9% in controls), poor sleep quality, and reduced sexual activity 5, 6

Medication and Substance Review

• Systematically review all medications including over-the-counter drugs, herbal supplements, and vitamins for sedating side effects 3, 1, 2
• Assess caffeine and alcohol intake - Both can perpetuate sleep disturbances and fatigue 3, 2

Physical Activity Assessment

• Document current exercise patterns - Decreased physical activity worsens fatigue, while regular physical activity reduces fatigue in those without organic causes 1, 3
• Assess for deconditioning - Determine if the patient has modified activity patterns since symptom onset 3

Management Algorithm

Step 1: Treat Identified Organic Causes

• If hypothyroidism - Initiate levothyroxine replacement 1, 2
• If anemia - Treat based on etiology (iron supplementation, B12 replacement, etc.) 3, 1
• If nutritional deficiencies - Supplement vitamin D, B12, folate, magnesium, or other identified deficiencies 1, 2
• If electrolyte imbalances - Correct with appropriate supplementation 3, 2

Step 2: Address Sleep Disturbances

• Implement sleep hygiene education - Dark, quiet, comfortable sleep environment; regular sleep schedule; avoid screens/caffeine/alcohol before bed 3, 2
• Treat underlying sleep disorders - CPAP for OSA if diagnosed; cognitive behavioral therapy for insomnia (CBT-I) is highly effective 3
• Avoid routine use of hypnotics - Rarely needed when underlying conditions are treated 3

Step 3: Manage Mood Symptoms

• If depression or anxiety present - Offer in-office counseling and/or pharmacotherapy (SSRIs are first-line) and/or refer to mental health resources 3
• Consider duloxetine if neuropathic symptoms coexist 3
• Cognitive behavioral therapy is effective for both fatigue and mood symptoms 3

Step 4: Lifestyle Interventions

• Prescribe regular physical activity - This is evidence-based for reducing fatigue even without identifiable organic cause 3, 1
• Start gradually if deconditioned - Begin with low-level activities and increase over time 3
• Dietary counseling - Address bloating through dietary modifications; ensure adequate caloric intake 3

Step 5: Dermatologic Management

• Treat acne appropriately - Standard acne treatments (topical retinoids, benzoyl peroxide, antibiotics, or hormonal therapy for PCOS-related acne) 5
• Recognize psychological impact - Acne is strongly associated with poor sleep quality (PSQI score 5.2 vs 4.1 in controls), increased anxiety, and fatigue upon waking (65.4% vs 58.4%) 5, 6
• Improvements in sleep and mood may benefit acne treatment 5

Critical Clinical Pitfalls to Avoid

• Do not overlook thyroid dysfunction - It is one of the first and most important causes to investigate 1, 2
• Do not dismiss psychological causes - Depression and anxiety lead to inadequate treatment when missed 1, 2
• Do not ignore medication side effects - These perpetuate fatigue and are easily modifiable 1, 2
• Do not skip sleep disorder assessment - This results in incomplete management 1, 2
• Do not assume laboratory results will be diagnostic - They affect management in only 5% of cases, but core testing remains essential to rule out treatable causes 1
• Do not underestimate the bidirectional relationship between acne and quality of life - Acne causes stress, fatigue, and mood disturbances, which in turn may worsen acne 5, 6

Expected Outcomes

When organic causes are identified and treated, combined with sleep hygiene optimization, mood disorder management, and regular physical activity, most patients experience significant improvement in fatigue, mood, and overall quality of life 3, 1. The interconnected nature of these symptoms means that addressing one component (e.g., improving sleep) often leads to improvements in others (e.g., reduced fatigue and better mood) 3.