What are the diagnostic and treatment approaches for a patient with suspected pituitary dysfunction?

Diagnostic and Treatment Approaches for Suspected Pituitary Dysfunction

For patients with suspected pituitary dysfunction, obtain dedicated pituitary MRI with pre- and post-contrast sequences (T1, T2, and volumetric gradient echo) as the primary diagnostic imaging, combined with comprehensive hormonal assessment of all pituitary axes coordinated by an endocrinologist, followed by treatment tailored to whether the dysfunction is due to hormone hypersecretion (adenoma) or hyposecretion (hypopituitarism). 1

Initial Diagnostic Workup

Hormonal Assessment

Systematically evaluate all pituitary axes with the following specific tests 2:

• Morning (9 AM) cortisol for secondary adrenal insufficiency (if <250 nmol/L with symptoms or <150 nmol/L random, indicates deficiency) 1
• TSH and free T4 for central hypothyroidism 2
• LH, FSH, and sex steroids (testosterone in men, estradiol in premenopausal women) for hypogonadotropic hypogonadism 2
• IGF-1 for growth hormone deficiency 2
• Prolactin level to assess for prolactinoma or stalk effect 2

Neuroimaging Protocol

Obtain dedicated pituitary MRI with the following specifications 1:

• Pre-contrast T1 and T2 sequences (2 mm thin slices)
• Post-contrast T1 sequences with gadolinium
• Post-contrast volumetric gradient (recalled) echo sequences for increased adenoma detection sensitivity 1
• Images must be interpreted by a neuroradiologist 1

Consider 3-Tesla MRI for enhanced anatomical definition when surgical planning is anticipated 1

Visual Assessment

For any patient with macroadenoma or visual symptoms, perform 1:

• Visual acuity testing (logarithm of minimum angle of resolution measurement preferred)
• Visual field testing (Goldmann perimetry preferred)
• Fundoscopy with or without color vision assessment

Treatment Algorithms Based on Etiology

For Hormone Hypersecretion (Pituitary Adenomas)

Prolactinomas

Medical therapy is first-line treatment, even for macroadenomas with visual compromise 3:

• Dopamine agonists achieve control in 80-90% of microprolactinomas and 60-75% of macroprolactinomas 4
• Cabergoline is preferred over bromocriptine due to better efficacy and tolerability 5, 6
• Surgery reserved only for dopamine agonist resistance or intolerance 3

Critical caveat: Cabergoline requires cardiac monitoring—obtain baseline echocardiogram and repeat every 6-12 months to assess for valvular disease, particularly at doses >2 mg/day 6

Growth Hormone-Secreting Adenomas (Acromegaly)

Transsphenoidal surgery is first-line therapy 3, 7, 4:

• Surgical resection as primary treatment except for giant macroadenomas or surgical contraindications 3
• Post-operative medical therapy with somatostatin analogs, cabergoline, or pegvisomant for residual disease 3
• Radiation therapy reserved for incomplete surgical and medical response 7

Nonfunctioning Macroadenomas

Transsphenoidal surgery for symptomatic lesions causing mass effects 3, 7:

• Surgery improves visual function in 75-91% and hypopituitarism in 35-50% 7
• Residual tumor rates of 10-36% 7
• Asymptomatic microadenomas can be observed with MRI surveillance 3

Post-surgical surveillance: MRI at 3 months, 6 months, then 1,2,3, and 5 years 7

ACTH-Secreting Adenomas (Cushing's Disease)

Transsphenoidal adenomectomy is primary treatment 4:

• Steroidogenic inhibitors for patients not cured surgically or who relapse after surgery and radiotherapy 4

For Hormone Hyposecretion (Hypopituitarism)

Hormone Replacement Sequence

CRITICAL: Always initiate glucocorticoid replacement BEFORE thyroid hormone replacement to prevent precipitating adrenal crisis 2:

1. Cortisol replacement first (hydrocortisone 20/10/10 mg daily if 9 AM cortisol <250 nmol/L or random <150 nmol/L with symptoms) 1, 2
2. Thyroid hormone replacement second (only after 1 week of cortisol replacement) 1
3. Sex hormone replacement third (testosterone in men, estrogen/progesterone in women) 2
4. Growth hormone replacement (if indicated, remains controversial in adults) 8

Monitoring for Post-Surgical Complications

Water metabolism disturbances are common after pituitary surgery 1, 2:

• Monitor fluid input/output closely for diabetes insipidus (26% incidence) and SIADH (14% incidence) 1
• Patterns include transient/permanent AVP deficiency, biphasic response, or triphasic pattern 1, 2
• Risk factors: female sex, CSF leak, drain placement, posterior pituitary manipulation 1, 2

For Severe Presentations

Pituitary Apoplexy or Severe Mass Effect

Initiate IV methylprednisolone 1 mg/kg immediately after sending pituitary axis bloods 1:

• Provide analgesia for severe headache 1
• Withhold any causative medications (e.g., immune checkpoint inhibitors) 1
• Obtain formal visual field assessment 1
• Consider early surgery—pediatric pituitary apoplexy can be more severe than in adults 1

Moderate Symptoms

Oral prednisolone 0.5-1 mg/kg once daily after pituitary axis assessment 1:

• If no improvement in 48 hours, escalate to IV methylprednisolone as above 1
• Refer to endocrinologist 1

Radiotherapy Indications

Offer radiotherapy when tumor is symptomatic, growing, resistant to medical therapy, and surgically inaccessible 1:

• External beam fractionated radiotherapy at 45-50.4 Gy in 1.8 Gy daily fractions 1
• Proton beam therapy preferred where available, or highly conformal photon therapy 1
• Hypopituitarism develops in 20% at 5 years and 80% at 10-15 years post-radiotherapy, with GH axis most vulnerable 2

Long-Term Surveillance

Perform complete endocrine evaluation at 12-month intervals to detect progressive hormone deficiencies, particularly after radiation 2:

• Post-surgical patients: assess adrenal function at postoperative day 2,6 weeks, and 12 months 2
• Visual assessment within 3 months of first-line therapy for all macroadenomas 3
• Hormone-specific monitoring based on tumor type 3

Critical Pitfalls to Avoid

All patients with adrenal insufficiency must obtain and carry a medical alert bracelet 2

Never correct hyponatremia faster than 6 mmol/L over 6 hours or 8 mmol/L over 24 hours (maximum rate 1 mmol/L/hour) to prevent osmotic demyelination 2

Never initiate thyroid hormone replacement before cortisol replacement in patients with both deficiencies—this can precipitate life-threatening adrenal crisis 2

Educate all patients on "sick day rules" and provide prescription for IM steroid for emergency use 1

For pediatric patients, management requires a specialized multidisciplinary team with both pediatric and adult expertise, and genetic assessment should be offered to all children with pituitary adenomas due to higher likelihood of genetic etiology 1, 3