Which hormonal and metabolic laboratory tests should be obtained to evaluate pituitary function in an adult with an incidentally identified partially empty sella?

Laboratory Evaluation for Partially Empty Sella

All adults with an incidentally identified partially empty sella should undergo comprehensive hormonal screening regardless of symptoms, as approximately 30-40% demonstrate hypopituitarism upon testing, with affected-axis rates often exceeding 10% and potentially reaching 50%. 1, 2, 3, 4

Mandatory Hormonal Panel

The following laboratory tests should be obtained to evaluate pituitary function:

Thyroid Axis

• Thyroid-stimulating hormone (TSH) 5, 3
• Free thyroxine (fT4) 5, 3
• Thyroid deficiencies occur in 8-81% of patients with sellar pathology, with up to 48% showing abnormalities in empty sella cases 5, 6

Adrenal Axis

• Morning cortisol (8 AM) 5, 3, 7
• Adrenocorticotropic hormone (ACTH) 5, 3
• Secondary adrenal insufficiency affects 14.7-62% of patients and is significantly more common in complete versus partial empty sella 6, 3, 4

Gonadal Axis

• Follicle-stimulating hormone (FSH) 3, 7
• Luteinizing hormone (LH) 3, 7
• Estradiol (in females) 3
• Total testosterone (in males) 3, 7
• Hypogonadism occurs in 20-96% of patients with pituitary pathology, with higher rates in complete empty sella 6, 3, 4

Prolactin

• Serum prolactin 5, 3, 7
• Hyperprolactinemia occurs in approximately 6.5-28% of empty sella cases 5, 4, 8

Growth Hormone Axis

• Insulin-like growth factor-1 (IGF-1) 3, 7
• Growth hormone (GH) if IGF-1 is low 3
• GH deficiency is the most commonly affected axis (12.5-100% of cases) 6, 4, 7

Clinical Context and Testing Rationale

Why Screen Asymptomatic Patients

• Hormonal abnormalities are diagnosed in 29% of incidentally discovered empty sella cases, even without symptoms 4
• The high prevalence of endocrine dysfunction (19-50% across studies) mandates routine evaluation to detect deficiencies early and institute appropriate replacement therapy 3, 4, 9, 7

Partial vs. Complete Empty Sella

• Complete empty sella (≥50% CSF filling, pituitary <2mm) has significantly higher rates of secondary adrenal insufficiency and hypogonadism compared to partial empty sella 3
• Multiple pituitary axis deficiencies are more common in complete empty sella 3
• However, both types require full hormonal screening as affected-axis rates exceed 10% in both categories 2, 3

Additional Considerations

Dynamic Testing

• Perform appropriate stimulation tests (such as ACTH stimulation test or insulin tolerance test) when baseline results suggest hypopituitarism or when clinical suspicion is high despite normal baseline values 8

Follow-Up Timing

• If initial hormonal evaluation is normal, careful reassessment at 24-36 months is suggested given the low but present risk of progression 9
• Hormonal deterioration occurs in approximately 3% of patients during follow-up, particularly when partial empty sella progresses to complete empty sella 4

Critical Pitfalls to Avoid

• Do not skip hormonal screening in asymptomatic patients with incidental findings, as 29% will have abnormalities despite lack of symptoms 4
• Do not assume partial empty sella is benign without testing, as 40-50% of patients have at least one hormonal deficiency 4, 7
• Do not attribute headache directly to empty sella, as it is usually an incidental finding unrelated to headache symptoms and more common primary headache disorders should be considered 5, 2, 6
• Do not overlook idiopathic intracranial hypertension (IIH) in patients presenting with headache and papilledema, as partially empty sella is a typical neuroimaging feature of raised intracranial pressure 2

When to Refer to Endocrinology

• Any detected hormonal abnormalities on screening 5, 2
• Symptoms suggestive of pituitary dysfunction including fatigue, cold intolerance, sexual dysfunction, or visual changes 5, 2
• Complete empty sella given higher risk of multiple axis involvement 3