What are the secondary causes of obesity?

Secondary Causes of Obesity

Screen for secondary causes of obesity when history or physical examination findings are suggestive, focusing on hormonal abnormalities (hypothyroidism, hypercortisolism), psychiatric diagnoses (binge eating disorder), iatrogenic causes (medications), and genetic syndromes. 1

Endocrine and Hormonal Causes

The most important hormonal causes to evaluate include:

• Hypothyroidism: Screen with thyroid function tests as part of basic laboratory evaluation in all patients with obesity 1
• Cushing's disease/hypercortisolism: Look for thin, atrophic skin on physical examination as a key clinical clue 1
• Polycystic ovarian syndrome (PCOS): Examine for hirsutism and acanthosis nigricans, which suggest insulin resistance and PCOS 1

Iatrogenic Causes

Medications are a critical and often overlooked cause of secondary weight gain. 1

• Review all current medications for weight-promoting effects 1
• Common culprits include antidepressants and anticonvulsants 2
• When possible, substitute with weight-neutral or weight-loss promoting alternatives 1

Psychiatric and Behavioral Causes

• Binge eating disorder: This psychiatric diagnosis is a recognized secondary cause requiring specific evaluation 1
• Depression: There is a bidirectional association between depression and obesity, where each increases risk of developing the other 1
• Disordered eating patterns should be systematically assessed 1

Genetic Syndromes

• Rare genetic causes include proopiomelanocortin deficiency and other monogenic obesity syndromes 1
• Consider genetic evaluation when obesity presents in childhood with normal height, though a secondary cause is unlikely in children of normal stature 1
• Family history of obesity should be documented as part of the evaluation 1

Sleep Disorders

Obstructive sleep apnea is both a complication and contributor to obesity, particularly in severe obesity. 1

• Screen using the Epworth Sleepiness Scale and STOPBANG questionnaire 1
• Look for large neck circumference on physical examination as a clinical indicator 1
• Insufficient sleep duration is an independent risk factor for obesity 1

Physical Examination Clues

Key physical findings that suggest specific secondary causes:

• Acanthosis nigricans: Indicates insulin resistance 1
• Hirsutism: Suggests PCOS 1
• Thin, atrophic skin: Points toward Cushing's disease 1
• Large neck circumference: Associated with obstructive sleep apnea 1

Laboratory Evaluation

Basic screening should include comprehensive metabolic panel, fasting lipid profile, and thyroid function tests in all patients. 1

• Additional testing should be guided by history and physical examination findings 1
• Screen for abnormal blood glucose in adults aged 40-70 years with obesity as part of cardiovascular risk assessment 1
• Order specific tests when Cushing's syndrome, thyroid disorders, or other endocrine abnormalities are suspected 1

Clinical Pitfalls

• Do not assume obesity is purely lifestyle-related without screening for secondary causes when clinical features are suggestive 1
• Medication review is frequently overlooked but represents a modifiable cause of weight gain 1
• Sleep disorders are commonly missed despite being highly prevalent in obesity 1
• In children with obesity and normal height, secondary causes are unlikely and extensive workup is not warranted 1