What endocrine and hormone labs should be tested in a patient with excessive appetite, considering age, sex, and potential underlying conditions like polycystic ovary syndrome (PCOS) or hypogonadism?

Endocrine and Hormone Laboratory Testing for Excessive Appetite

Order thyroid-stimulating hormone (TSH), morning cortisol with consideration for 24-hour urinary free cortisol or late-night salivary cortisol if Cushing's syndrome is suspected, morning total and free testosterone (especially in men), prolactin, fasting glucose with insulin (to calculate glucose/insulin ratio), and leptin levels as the core endocrine workup for excessive appetite. 1, 2

Core Endocrine Panel

Thyroid Function

• Measure TSH to exclude thyroid disease, as both hyperthyroidism and hypothyroidism can alter appetite regulation 2
• Thyroid dysfunction is a common reversible cause of appetite changes and must be ruled out early 1

Adrenal Function and Cushing's Syndrome Screening

• Screen for Cushing's syndrome if the patient exhibits: buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies 1, 2
• Initial screening tests include: late-night salivary cortisol (≥2 tests), 24-hour urinary free cortisol (≥2 collections), or overnight 1 mg dexamethasone suppression test 1
• Cushing's syndrome causes pathological hypercortisolism that directly increases appetite and leads to central obesity 1

Sex Hormones - Critical for Both Sexes

In Men:

• Measure morning total testosterone (8-10 AM) and free testosterone by equilibrium dialysis to assess for hypogonadism, which is associated with energy imbalance, increased abdominal fat mass, and altered appetite regulation 1
• Normal total testosterone range is 300-800 ng/dL; levels <300 ng/dL warrant further evaluation 1
• Also measure sex hormone-binding globulin (SHBG) since obesity-related testosterone decreases are frequently due to low SHBG concentrations 1
• If testosterone is low, repeat the test and measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 1

In Women:

• Measure total testosterone or free testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the preferred method, with pooled sensitivity of 74% and specificity of 86% 2
• Measure LH and FSH between cycle days 3-6 to calculate LH/FSH ratio, with ratio >2 suggesting polycystic ovary syndrome (PCOS) 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia, with levels >20 μg/L considered abnormal 2
• PCOS is strongly associated with insulin resistance, central obesity, and altered appetite regulation 3, 4

Metabolic and Appetite-Regulating Hormones

Insulin and Glucose Metabolism

• Measure fasting glucose and fasting insulin levels to calculate the glucose/insulin ratio, with ratio >4 suggesting reduced insulin sensitivity 2
• Consider 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes, particularly if PCOS or obesity is present 2
• Insulin resistance and hyperinsulinemia are directly linked to increased appetite and weight gain 3, 4

Ghrelin Assessment

• Consider measuring fasting ghrelin levels in patients with suspected binge eating or excessive appetite, as ghrelin is a key orexigenic (appetite-stimulating) hormone 5, 6
• Paradoxically, ghrelin may be lower in chronic overeating states due to down-regulation, but measurement can help characterize the appetite dysregulation 6

Leptin Levels

• Measure leptin levels to assess for leptin resistance, which is common in obesity and associated with continued excessive appetite despite adequate energy stores 5
• Leptin is involved in appetite regulation, and altered leptin signaling is demonstrated in conditions like anorexia nervosa (low) and obesity (high with resistance) 5

Additional Hormones Based on Clinical Context

Growth Hormone Axis

• Measure insulin-like growth factor 1 (IGF-1) if acromegaly is suspected based on coarse facial features, enlarged hands/feet, or excessive appetite with weight gain 1
• Growth hormone excess causes increased appetite and metabolic changes 1

Prolactin

• Measure morning prolactin levels to exclude prolactinoma, which can present with weight gain and metabolic changes 1, 2
• If prolactin is elevated, confirm with 2-3 samples at 20-60 minute intervals to exclude stress-related spurious elevation 2

Age and Sex-Specific Considerations

Premenopausal Women

• Prioritize PCOS workup with total/free testosterone, LH, FSH, and metabolic screening (fasting glucose, insulin, lipid panel) 2, 3
• PCOS affects up to 10% of reproductive-age women and is characterized by hyperandrogenism, insulin resistance, and central obesity with increased appetite 3, 4

Men with Obesity

• Prioritize testosterone assessment including morning total testosterone, free testosterone by equilibrium dialysis, and SHBG 1
• Testosterone deficiency is associated with increased abdominal fat mass, impaired glucose control, and energy imbalance 1

Adolescents

• Exercise caution with PCOS diagnosis and avoid ultrasound in those with gynecological age <8 years due to high incidence of multifollicular ovaries 2
• Measure 17-hydroxyprogesterone if premature pubarche or severe hirsutism is present to exclude non-classic congenital adrenal hyperplasia 7

Critical Pitfalls to Avoid

• Do not rely solely on clinical assessment for Cushing's syndrome; biochemical confirmation is mandatory given the significant overlap with simple obesity 1
• Do not use direct immunoassays for testosterone in women, as they have lower specificity (78%) compared to LC-MS/MS (92%) and may lead to false positives 2
• Do not assume PCOS without excluding other causes of hyperandrogenism, including non-classic congenital adrenal hyperplasia, Cushing's syndrome, and androgen-secreting tumors 2, 7
• Do not overlook hypogonadism in obese men, as it is frequently present and contributes to metabolic dysfunction and altered appetite regulation 1

Practical Laboratory Algorithm

1. First-tier tests for all patients: TSH, fasting glucose, fasting insulin, morning cortisol 1, 2
2. Second-tier based on sex:
   • Men: morning total and free testosterone, SHBG 1
   • Women: total/free testosterone (LC-MS/MS), LH, FSH, prolactin 2
3. Third-tier if clinical suspicion warrants:
   • Cushing's screening: 24-hour urinary free cortisol or late-night salivary cortisol 1
   • Acromegaly screening: IGF-1 1
   • Appetite hormone assessment: ghrelin, leptin 5, 6