What is the next best step in evaluating a 62-year-old man with syncope, normal complete blood count (CBC), normal comprehensive metabolic panel (CMP), normal plasma morning (a.m.) cortisol and adrenocorticotropic hormone (ACTH) levels, and an empty sella on brain magnetic resonance imaging (MRI)?

Evaluation of Empty Sella in a Patient with Syncope

Serum thyroid stimulating hormone, free thyroxine, and prolactin levels should be ordered as the next step in this 62-year-old man with syncope and empty sella on brain MRI.

Rationale for Endocrine Evaluation

The finding of an empty sella on brain MRI in a patient with syncope warrants a focused endocrine evaluation, even with normal morning cortisol and ACTH levels already documented. According to clinical guidelines, empty sella can be associated with various hormonal abnormalities that may contribute to syncope 1.

Hormonal Abnormalities in Empty Sella

• Primary empty sella (PES) is defined as herniation of the subarachnoid space into the sella turcica
• PES can be associated with various degrees of pituitary dysfunction
• While the patient has normal cortisol and ACTH levels, other pituitary axes may be affected

Diagnostic Approach for Empty Sella

When empty sella is identified on MRI, a complete evaluation of pituitary function is indicated, particularly when presenting with symptoms like syncope that could be related to hormonal deficiencies 2, 3:

1. Thyroid function assessment: Central hypothyroidism (low TSH with low free T4) is one of the most common pituitary hormone deficiencies in empty sella syndrome 2, 3

   • Hypothyroidism can cause bradycardia and decreased cardiac output, contributing to syncope

2. Prolactin measurement: Important to evaluate for both hyperprolactinemia and hypoprolactinemia, which can occur in empty sella 2

3. Gonadal axis assessment: Secondary hypogonadism is significantly more common in complete empty sella 3

Why Not Other Options?

A. Cosyntropin stimulation test

• Not indicated as first-line testing since morning cortisol and ACTH levels are already normal
• While isolated ACTH deficiency has been reported with empty sella 4, the normal morning cortisol and ACTH levels make this less likely
• Could be considered later if clinical suspicion remains despite normal baseline values

B. Neurosurgical referral

• Not indicated at this time as empty sella is often an incidental finding
• No evidence of mass, hemorrhage, or other acute neurosurgical issues on MRI
• Management should first focus on identifying potential hormonal abnormalities

Syncope Evaluation Context

The patient's syncope requires a systematic approach. According to ACC/AHA guidelines 2:

1. The initial evaluation should include history, physical examination, and ECG
2. Targeted testing based on clinical suspicion is recommended
3. The finding of empty sella on MRI warrants specific endocrine evaluation

Clinical Pearls and Pitfalls

• Pearl: Empty sella is present in approximately 20% of the general population based on autopsy studies 5, but when symptomatic requires endocrine evaluation
• Pitfall: Assuming normal cortisol and ACTH levels rule out all pituitary dysfunction; multiple hormonal axes can be affected independently
• Pearl: Complete empty sella (≥50% CSF filling with pituitary <2mm) has higher rates of hormonal abnormalities than partial empty sella 3
• Pitfall: Overlooking thyroid dysfunction as a potential cause of syncope, particularly in older adults 1

In conclusion, while the patient has normal cortisol and ACTH levels, evaluation of other pituitary hormones is essential given the finding of empty sella on MRI and the presentation with syncope. Thyroid function tests and prolactin measurement represent the appropriate next step in evaluation.