What is the recommended diagnostic workup and initial management for a patient suspected of having a pituitary disorder presenting with visual field loss, headaches, and endocrine abnormalities such as abnormal growth, menstrual irregularities, infertility, fatigue, weight changes, hypertension, hyperglycemia, or signs of hormone excess or deficiency?

Diagnostic Workup and Initial Management of Suspected Pituitary Disorders

For patients presenting with visual field loss, headaches, and endocrine abnormalities suggestive of a pituitary disorder, obtain MRI of the sella with pituitary cuts as the first-line imaging study, perform comprehensive hormonal evaluation including morning cortisol, ACTH, TSH, free T4, LH, FSH, sex steroids, IGF-1, and prolactin, and arrange formal ophthalmologic assessment with visual acuity and visual field testing—all before initiating any treatment. 1, 2, 3, 4

Immediate Clinical Assessment

Presenting Symptoms Requiring Urgent Evaluation

• Visual disturbances (field defects, decreased acuity, diplopia) indicate mass effect on the optic chiasm or cranial nerves and require urgent ophthalmologic consultation within days, not weeks 1, 3, 4
• Severe headache with visual changes or altered mental status raises concern for pituitary apoplexy—a neurosurgical emergency requiring immediate imaging and endocrine evaluation 2, 3
• Signs of acute adrenal insufficiency (hypotension, hyponatremia, hypoglycemia) mandate immediate stress-dose hydrocortisone 50-100 mg IV every 6-8 hours before any other hormonal testing or treatment 2, 5

Endocrine Manifestations by Tumor Type

• Prolactinomas (32-66% of adenomas): amenorrhea, galactorrhea, infertility in women; decreased libido, erectile dysfunction in men 3, 4, 6
• Growth hormone excess (8-16% of adenomas): acromegalic features including enlarged hands, feet, lips, tongue, nose; screen with IGF-1 level 3, 4, 6
• Cushing disease (2-6% of adenomas): central obesity, hypertension, hyperglycemia, proximal muscle weakness, easy bruising; screen with late-night salivary cortisol 3, 4, 6
• Hypopituitarism (34-89% of macroadenomas): fatigue, weight changes, cold intolerance, menstrual irregularities, decreased libido—symptoms overlap with primary hypothyroidism but TSH will be low or inappropriately normal with low free T4 1, 3, 4

Diagnostic Imaging Protocol

MRI Specifications

Order MRI of the sella with dedicated pituitary cuts using gadolinium-based contrast to identify adenoma size, suprasellar extension, cavernous sinus invasion, and optic chiasm compression 1, 2, 3, 4

• Macroadenomas (≥10 mm) comprise 48-50% of pituitary tumors and commonly cause mass effect 3, 4
• Microadenomas (<10 mm) comprise 50-52% of tumors and rarely cause visual symptoms but may produce hormonal excess 3, 4
• Key imaging findings include pituitary enlargement, stalk thickening, suprasellar convexity, heterogeneous enhancement, and hemorrhagic components in apoplexy 1, 2

When to Use Unenhanced Imaging

For pediatric patients or those with renal impairment (eGFR <30 mL/min/1.73 m²), consider unenhanced T1-weighted and T2-weighted sequences during follow-up to minimize gadolinium exposure, though initial diagnostic imaging typically requires contrast 1

Comprehensive Hormonal Evaluation

Morning Laboratory Panel (Ideally 8 AM)

Draw all baseline hormones before initiating any treatment, particularly before starting corticosteroids or thyroid hormone replacement 1, 2, 5, 3, 4

• Cortisol and ACTH: morning cortisol <5 mcg/dL indicates adrenal insufficiency; values 5-15 mcg/dL require cosyntropin stimulation test 1, 2, 5
• TSH and free T4: low TSH with low free T4 indicates central hypothyroidism (>90% of hypophysitis cases); never start thyroid hormone before ensuring adequate cortisol replacement 1, 2, 5
• LH, FSH, and sex steroids: testosterone in men, estradiol in premenopausal women; central hypogonadism occurs in ~50% of hypophysitis 1, 2, 5
• Prolactin: levels >200 ng/mL strongly suggest prolactinoma; levels 25-200 ng/mL may represent stalk effect from non-functioning adenoma 3, 4, 6
• IGF-1: elevated level screens for acromegaly; confirm with oral glucose tolerance test showing failure to suppress GH <1 ng/mL 3, 4, 6

Critical Sequencing Rule

If both adrenal insufficiency and central hypothyroidism are present, always start hydrocortisone at least one week before initiating levothyroxine to prevent life-threatening adrenal crisis 1, 2, 5

Ophthalmologic Assessment

Required Visual Testing

Refer all patients with macroadenomas or visual symptoms for formal ophthalmologic evaluation within one week 1

• Visual acuity: measure with logarithm of the minimum angle of resolution (logMAR) testing, not qualitative Snellen charts 1
• Visual fields: Goldmann perimetry is ideal; automated static perimetry detects subtle bitemporal hemianopsia even when patients are asymptomatic 1
• Fundoscopy: assess for optic disc pallor indicating chronic compression 1
• Optical coherence tomography: consider baseline measurement in patients with severe deficits to document retinal nerve fiber layer thickness 1

Prognostic Factors for Visual Recovery

Patients with age <6 years, symptom duration >4 months, or pre-existing optic atrophy have reduced chance of post-operative vision improvement and should be counseled accordingly 1

Initial Management Strategy

Hormone Replacement Protocol

For confirmed hypopituitarism, initiate physiologic hormone replacement immediately—this is the cornerstone of management, not high-dose steroids 2, 5

• Hydrocortisone 20 mg morning, 10 mg afternoon for adrenal insufficiency; increase to stress doses (50-100 mg IV q6-8h) for severe illness or surgery 2, 5
• Levothyroxine 50-100 mcg daily for central hypothyroidism, but only after at least one week of adequate cortisol replacement 1, 2, 5
• Testosterone or estradiol replacement for hypogonadism after addressing cortisol and thyroid deficiencies 1, 2, 5

When to Use High-Dose Corticosteroids

Reserve high-dose steroids (prednisone 1 mg/kg/day) exclusively for severe neurological symptoms from mass effect, such as rapidly progressive visual loss or altered consciousness—not for routine hypopituitarism management 2, 5

Indications for Urgent Surgical Intervention

Absolute Indications for Transsphenoidal Surgery

Proceed with urgent endoscopic transsphenoidal decompression when any of the following are present 2, 3, 4:

• Progressive visual deterioration despite medical management
• Severe mass effect threatening the optic chiasm on imaging
• Pituitary apoplexy with neurological decline
• Acute visual field defects or decreased acuity
• Altered level of consciousness or focal neurological deficits

Medical Management as Primary Therapy

Prolactinomas are the exception—treat with dopamine agonists (cabergoline 0.25-1 mg twice weekly or bromocriptine 2.5-15 mg daily) as first-line therapy, even for macroadenomas with chiasmatic compression 3, 4, 6

• Visual improvement often occurs within hours to days of starting dopamine agonists 7, 3, 4
• Tumor shrinkage is usually significant, avoiding surgery in most cases 3, 4, 6
• Reserve surgery for dopamine agonist-resistant prolactinomas or intolerance to medications 3, 4, 6

Tumor-Specific Treatment Algorithms

Growth Hormone-Secreting Adenomas

Transsphenoidal surgery is first-line therapy unless the macroadenoma is giant or surgery is contraindicated 7, 3, 4

• Post-operative somatostatin analogs (octreotide LAR 20-40 mg IM monthly or lanreotide 90-120 mg SC monthly) for persistent elevation 7, 3, 4
• Pegvisomant (GH receptor antagonist) for somatostatin analog resistance 7, 3, 4
• Radiotherapy for partially resected tumors or persistent disease 7, 3, 4

ACTH-Secreting Adenomas (Cushing Disease)

Primary therapy is transsphenoidal surgery by an experienced pituitary surgeon, whether or not a microadenoma is visible on MRI 7, 3, 4

• Screen with late-night salivary cortisol (most sensitive test) 4
• Petrosal sinus sampling may be necessary to distinguish pituitary from ectopic ACTH source 4
• Medical therapy (ketoconazole, mifepristone, pasireotide) for surgical failures or while awaiting radiotherapy effects 7, 4
• Bilateral adrenalectomy as last resort for refractory cases 7, 4

Clinically Non-Functioning Adenomas

Transsphenoidal surgery with or without post-operative radiotherapy for symptomatic macroadenomas causing mass effect 7, 3, 4, 6

• Small, incidentally discovered microadenomas may be observed with serial MRI every 6-12 months 7, 6, 8
• Surgery indicated for growth on surveillance imaging or development of visual symptoms 6, 8
• Most are gonadotropin-secreting on immunocytochemistry despite being clinically silent 7, 6

Post-Operative Monitoring

Fluid and Electrolyte Management

Monitor serum sodium and osmolality every 4-6 hours initially to detect diabetes insipidus or SIADH, which occur in 26% and 14% of post-operative patients respectively 2

• Diabetes insipidus: polyuria (>3 L/day), hypernatremia, dilute urine; treat with desmopressin 2
• SIADH: oliguria, hyponatremia, concentrated urine; manage with fluid restriction 2
• Triphasic pattern: initial DI → SIADH → permanent DI may occur after pituitary surgery 2

Risk Factors for Post-Operative Complications

Female sex, CSF leak during surgery, drain placement, and posterior pituitary manipulation increase risk of DI and SIADH 2

Patient Safety Measures

Essential Patient Education

All patients with adrenal insufficiency must obtain and wear a medical alert bracelet, receive education on "sick day" rules, and have a prescription for emergency intramuscular hydrocortisone 1, 2, 5

• Double or triple oral hydrocortisone dose for fever, vomiting, or significant illness 2, 5
• Administer emergency IM hydrocortisone 100 mg and seek immediate medical attention for severe illness or inability to take oral medications 2, 5

Common Diagnostic Pitfalls

Distinguishing Central from Primary Hypothyroidism

Low or inappropriately normal TSH with low free T4 indicates central hypothyroidism from pituitary disease—do not mistake this for primary hypothyroidism where TSH would be elevated 1, 5, 3

Recognizing Stalk Effect Hyperprolactinemia

Prolactin levels 25-200 ng/mL in a patient with a large non-functioning adenoma likely represent stalk compression ("stalk effect"), not a prolactinoma—do not treat with dopamine agonists 3, 4, 6

Avoiding Premature Thyroid Hormone Replacement

Never initiate levothyroxine before confirming adequate cortisol levels—accelerated cortisol metabolism from thyroid hormone can precipitate fatal adrenal crisis in unrecognized adrenal insufficiency 1, 2, 5