Differential Diagnosis for Unintentional Weight Gain, Insomnia, Hair Loss, Sweating, and Elevated Blood Pressure
The constellation of unintentional weight gain, insomnia, hair loss, sweating, and hypertension most strongly suggests Cushing's syndrome, though medication-induced causes, thyroid disorders (both hypo- and hyperthyroidism), and heart failure with fluid retention must be systematically excluded. 1
Immediate Priority Assessment
Rapid weight gain (>2 kg in 3 days) indicates fluid retention and requires urgent evaluation for heart failure, which carries significant mortality risk if missed. 1, 2 Assess immediately for:
If heart failure is identified, initiate diuretic therapy and sodium restriction immediately. 2
Primary Differential Diagnoses
1. Cushing's Syndrome (Most Likely Given Full Constellation)
Central obesity, facial plethora, proximal muscle weakness, and wide purple striae are the key physical findings that distinguish Cushing's syndrome. 3
- Thin, atrophic skin with striae is highly indicative 1
- Central obesity with facial rounding and easy bruisability 3
- Hypertension is a cardinal feature 3
- Hair loss and insomnia can occur with hypercortisolism 1
- Sweating may result from metabolic effects 1
Diagnostic workup: Order 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test. 1
2. Medication-Induced Weight Gain
Review all medications systematically, as this is the most commonly overlooked reversible cause. 1
Weight-promoting medications include:
- Antipsychotics (clozapine, olanzapine, risperidone) cause significant weight gain 1
- Corticosteroids (both systemic and high-dose topical) 1
- Diabetes medications: insulin and sulfonylureas cause 4-5 kg gain when combined with thiazolidinediones 1
- Thiazolidinediones (rosiglitazone, pioglitazone) cause dose-dependent weight gain of 2-5 kg 1
Medications causing insomnia:
- SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), venlafaxine, duloxetine 3
- Stimulants: caffeine, methylphenidate, amphetamine derivatives 3
- Decongestants: pseudoephedrine, phenylephrine 3
Medications causing hypertension:
3. Hypothyroidism
Hypothyroidism causes weight gain, hair loss, and can contribute to hypertension, but typically presents with fatigue rather than insomnia. 1
- Weight gain is gradual over weeks to months 1
- Hair loss is a classic feature 1
- Check TSH as initial screening test 3, 1
4. Hyperthyroidism (Paradoxical Presentation)
While hyperthyroidism typically causes weight loss, some patients experience weight gain from increased appetite, and it classically causes insomnia, sweating, and hypertension. 3, 4
Levothyroxine overdosage causes:
- Insomnia 4
- Excessive sweating 4
- Hair loss 4
- Increased blood pressure 4
- Increased appetite (which can lead to weight gain) 4
5. Obstructive Sleep Apnea
Large neck circumference, snoring, and hypersomnolence are clinical clues, though insomnia can also occur. 3
- Strongly associated with resistant hypertension (20% prevalence) 3
- Weight gain is both a cause and consequence 3
- Non-restorative sleep and daytime sleepiness are key features 3
6. Primary Aldosteronism
Consider when hypertension is accompanied by unprovoked or excessive hypokalemia and muscle weakness. 3
- Prevalence approximately 20% in resistant hypertension 3
- Muscle cramps and weakness from hypokalemia 3
- Check serum potassium 3
7. Pheochromocytoma
Episodic symptoms are the hallmark: BP lability, episodic pallor, dizziness, and sweating. 3
- Sweating is a cardinal feature 3
- Weight loss is more typical than weight gain 3
- Consider if symptoms are paroxysmal 3
Essential Diagnostic Workup
Initial laboratory evaluation:
- Complete blood count and comprehensive metabolic panel 1
- TSH (thyroid-stimulating hormone) 3, 1
- Fasting glucose and HbA1c 3, 1
- Serum sodium, potassium, calcium 3
- Lipid profile 3, 1
- Serum creatinine with eGFR 3
- Urinalysis 3
If Cushing's syndrome suspected: 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test. 1
Physical examination must document:
- Height, weight, BMI, and waist circumference 1
- Blood pressure (seated and standing to detect orthostatic changes) 3
- Neck circumference (for sleep apnea assessment) 1
- Skin examination for striae, thinning, acanthosis nigricans 1
- Signs of fluid retention 1, 2
Critical Clinical Pitfalls to Avoid
Do not attribute all symptoms to lifestyle choices without investigating medical and medication causes. 1 This is the most common error leading to delayed diagnosis.
Failing to recognize medication-induced weight gain leads to unnecessary testing and patient frustration. 1 Always review the medication list first.
Missing fluid retention in heart failure can result in preventable hospitalizations and mortality. 2 Always assess volume status when weight gain is present.
Overlooking Cushing's syndrome when the full constellation of symptoms is present delays critical diagnosis. 1 The combination of central obesity, hypertension, and characteristic skin changes should trigger immediate screening.
Not addressing insomnia as a potential medication side effect (SSRIs, stimulants, decongestants) perpetuates the problem. 3
Management Approach Algorithm
- Assess for heart failure urgently if rapid weight gain (>2 kg in 3 days) 1, 2
- Review and discontinue weight-promoting medications when possible 1
- Screen for Cushing's syndrome if characteristic physical findings present 1
- Check TSH to evaluate thyroid function 3, 1
- Evaluate for sleep apnea if large neck circumference or snoring 3
- Check serum potassium if muscle weakness present (primary aldosteronism) 3
- Consider pheochromocytoma if episodic symptoms 3
Treat identified underlying causes first before attributing symptoms to primary hypertension or lifestyle factors. 1