What is the diagnosis and management for a patient with hypocortisolism and hyperprolactinemia?

Diagnosis: Pituitary Adenoma with Secondary Adrenal Insufficiency and Hyperprolactinemia

This patient has secondary adrenal insufficiency (cortisol 3.7 µg/dL) with concurrent hyperprolactinemia (prolactin 150 ng/mL), most likely from a pituitary adenoma causing both ACTH deficiency and prolactin excess, or from primary hypothyroidism causing pituitary hyperplasia.

Immediate Diagnostic Workup

Confirm Hypocortisolism and Determine Etiology

• Measure morning (8-9 AM) plasma ACTH to differentiate between primary adrenal insufficiency (high ACTH) and secondary/central adrenal insufficiency (low or inappropriately normal ACTH) 1, 2
• A cortisol of 3.7 µg/dL is clearly subnormal and diagnostic of adrenal insufficiency 3
• If ACTH is low or inappropriately normal (<5-10 pg/mL) with low cortisol, this confirms secondary (central) adrenal insufficiency from pituitary or hypothalamic disease 3
• If ACTH is elevated (>20 pg/mL), this indicates primary adrenal insufficiency (Addison's disease) 3

Evaluate the Hyperprolactinemia

• Check TSH and free T4 immediately to rule out primary hypothyroidism, which is a critical and reversible cause of both pituitary hyperplasia and hyperprolactinemia 4
• Severe primary hypothyroidism (TSH >500 mU/L, low FT4) can cause pituitary hyperplasia mimicking a pituitary adenoma, with moderate hyperprolactinemia (typically <200 ng/mL) and secondary adrenal insufficiency 4
• Obtain pituitary MRI with contrast to evaluate for pituitary adenoma, looking specifically for mass effect, stalk compression, and size of any lesion 1, 2
• Prolactin levels >150 ng/mL suggest either a prolactinoma, stalk compression from a non-functioning adenoma, or severe primary hypothyroidism 5, 4

Additional Pituitary Function Testing

• Measure LH, FSH, and sex hormones (testosterone in males, estradiol in females) to assess for hypogonadotropic hypogonadism, which commonly accompanies hyperprolactinemia 6, 4
• Check IGF-1 to screen for growth hormone deficiency, which may coexist with other pituitary hormone deficiencies 4
• These tests establish the full extent of hypopituitarism and guide replacement therapy 6, 4

Immediate Management

Glucocorticoid Replacement (Life-Saving Priority)

• Start hydrocortisone replacement immediately at 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon, 5 mg evening) to prevent adrenal crisis 7, 3
• Do not delay glucocorticoid replacement while awaiting diagnostic workup, as untreated adrenal insufficiency is life-threatening 3
• Patients with hypocortisolism are vulnerable to adrenal crisis during any stressful situation and may die without treatment 3
• Educate the patient on stress dosing: double or triple the dose during illness, injury, or surgery 7

Thyroid Hormone Replacement (If Primary Hypothyroidism Confirmed)

• If TSH is markedly elevated and FT4 is low, start levothyroxine replacement at 1.6 µg/kg/day (typically 100-125 µg daily in adults) 4
• Thyroid hormone replacement must be started after or concurrent with glucocorticoid replacement to avoid precipitating adrenal crisis 4
• In cases of pituitary hyperplasia from primary hypothyroidism, thyroid hormone replacement alone will normalize prolactin, resolve pituitary enlargement, and restore adrenal function within 3 months 4

Differential Diagnosis and Treatment Algorithm

Scenario 1: Primary Hypothyroidism with Pituitary Hyperplasia

• If TSH >100 mU/L with low FT4, moderate hyperprolactinemia (<200 ng/mL), and pituitary enlargement on MRI, this strongly suggests pituitary hyperplasia from primary hypothyroidism 4
• Treatment: Start hydrocortisone and levothyroxine replacement 4
• Repeat MRI in 3 months to confirm regression of pituitary enlargement, which definitively establishes the diagnosis 4
• Galactorrhea, amenorrhea, and secondary adrenal insufficiency should all resolve with thyroid hormone replacement 4

Scenario 2: Prolactinoma

• If prolactin >200 ng/mL with normal thyroid function and a pituitary adenoma on MRI, this suggests a prolactinoma 5, 4
• Treatment: Start hydrocortisone replacement immediately, then initiate cabergoline 0.25-0.5 mg twice weekly, titrating based on prolactin levels 8
• Cabergoline normalizes prolactin in most patients and shrinks prolactinomas in 80-90% of cases 8
• Monitor prolactin levels and repeat MRI at 3-6 months to assess tumor response 8

Scenario 3: Non-Functioning Pituitary Adenoma with Stalk Compression

• If prolactin 100-200 ng/mL with a large pituitary mass (>1 cm) causing stalk compression, this suggests "stalk effect" hyperprolactinemia from a non-functioning adenoma 5, 4
• Treatment: Start hydrocortisone replacement and consider transsphenoidal surgery for mass effect, visual field defects, or progressive hypopituitarism 8
• Prolactin levels typically normalize after surgical decompression of the stalk 5

Critical Pitfalls to Avoid

• Never start thyroid hormone replacement before or without glucocorticoid replacement in patients with suspected hypopituitarism, as this can precipitate life-threatening adrenal crisis 4
• Do not assume every pituitary mass with hyperprolactinemia is a prolactinoma—always check TSH to rule out primary hypothyroidism causing pituitary hyperplasia 4
• Do not perform pituitary surgery for presumed prolactinoma without first treating primary hypothyroidism if present, as the pituitary enlargement will regress with thyroid hormone replacement alone 4
• Do not attribute hyperprolactinemia to medications without first excluding structural pituitary lesions and primary hypothyroidism with MRI and thyroid function tests 5

Long-Term Monitoring

• Lifelong glucocorticoid replacement is required for permanent secondary adrenal insufficiency 7, 3
• Annual monitoring of pituitary function (ACTH, TSH, LH/FSH, prolactin, IGF-1) to detect progression or new hormone deficiencies 8
• Serial MRI every 6-12 months initially, then annually if stable, to monitor for tumor growth or regression 8, 4
• If pituitary hyperplasia from hypothyroidism, adrenal function may recover after 3-6 months of thyroid hormone replacement, allowing gradual withdrawal of hydrocortisone under close supervision 4