How to manage metabolic acidosis in a patient with a growth hormone (GH) secreting tumor?

Management of Metabolic Acidosis in Growth Hormone-Secreting Tumors

Direct Answer

Metabolic acidosis in patients with GH-secreting tumors should be managed by treating the underlying tumor with transsphenoidal surgery as first-line therapy, while simultaneously correcting the acidosis with alkali therapy (sodium bicarbonate or citrate solutions), as the acidosis itself creates GH resistance that impairs treatment response. 1, 2

Understanding the Bidirectional Relationship

The relationship between GH excess and metabolic acidosis is complex and bidirectional:

• Metabolic acidosis causes GH resistance by decreasing hepatic GH receptor expression and IGF-1 mRNA production, creating a state where circulating GH cannot effectively stimulate IGF-1 synthesis 3, 4, 2
• Chronic metabolic acidosis significantly decreases serum IGF-1 concentration (from 45±6 to 33±6 nmol/L in studies) while paradoxically enhancing GH response to GH-releasing factor, indicating impaired negative feedback 2
• This GH resistance means that acidosis must be corrected to optimize treatment response to surgical or medical management of the GH-secreting tumor 1, 3

Primary Treatment Algorithm

Step 1: Immediate Tumor Management

Offer transsphenoidal surgery by an experienced pituitary neurosurgeon as the definitive treatment for the GH-secreting adenoma, even when complete surgical cure appears unlikely. 1, 5

• Surgery should be performed at centers conducting at least 50 pituitary operations annually to optimize outcomes 6
• Surgical success rates achieve approximately 50% remission in experienced centers 1, 5
• Even incomplete resection reduces circulating GH burden and facilitates subsequent medical therapy 1, 5

Step 2: Concurrent Acidosis Correction

Administer alkali therapy with sodium bicarbonate or citrate solutions to correct the metabolic acidosis while addressing the tumor. 1

• Target plasma bicarbonate normalization (>22 mmol/L) to restore GH receptor sensitivity 1, 2
• Critical pitfall: Medical noncompliance with alkali therapy is common due to unpleasant taste, leading to persistent acidosis, hypercalciuria, and increased nephrocalcinosis risk 4
• Monitor serum bicarbonate levels closely during treatment 1

Step 3: Pre-operative Medical Optimization (If Surgery Delayed)

Consider pre-operative medical therapy with somatostatin analogues and/or GH receptor antagonists to rapidly control symptoms and support perioperative management, particularly if surgery must be delayed. 1, 5

• This approach can reduce height velocity in children and facilitate airway management 1
• However, recognize that acidosis-induced GH resistance may blunt the response to these medications until acidosis is corrected 3, 2

Post-Operative Management

For Residual Disease

Offer monotherapy or combination medical therapy with somatostatin receptor ligands, GH receptor antagonist (pegvisomant), or dopamine agonists for post-operative residual disease. 1, 5

• Pegvisomant normalizes serum IGF-1 levels in adequate doses and suppresses growth velocity 5
• Cabergoline can be used alone for mild GH excess or combined with somatostatin analogues 1, 5
• Monitor for hypoglycemia: GH opposes insulin effects, so glucose tolerance may improve with GH reduction, requiring adjustment of anti-diabetic medications 7

Monitoring Requirements

Assess treatment efficacy using both auxological measurements (growth velocity, height) and biochemical markers (serum GH and IGF-1 levels). 1, 5

• Baseline and serial liver function tests (ALT, AST, total bilirubin, alkaline phosphatase) are mandatory before and during medical therapy 7
• Monthly liver tests for first 6 months, then quarterly, then bi-annually 7
• Regular MRI surveillance to monitor tumor size 5, 7

Special Considerations for Acidosis-Related Complications

Assess for Associated Metabolic Derangements

Evaluate and treat complications of both GH excess and metabolic acidosis, including glucose intolerance, hypertension, hypercalciuria, and hypocitraturia. 1, 4

• Metabolic acidosis increases nephrocalcinosis risk through hypercalciuria and hypocitraturia 4
• GH excess commonly causes glucose intolerance requiring monitoring 1

Evaluate for Syndromic Causes

Offer clinical evaluation and biochemical screening for syndromic causes of somatotrophinomas, including McCune-Albright syndrome, Carney complex, MEN1, and MEN1-like diseases. 1, 5

• GH-releasing hormone-secreting pancreatic tumors should be considered in MEN1 syndrome 1
• These syndromes require comprehensive pituitary hormone screening 1

Radiotherapy for Refractory Cases

Offer pituitary radiotherapy to patients with uncontrolled tumor growth despite incomplete surgical and medical response, except in patients with skull base fibrous dysplasia (McCune-Albright syndrome). 5

• Radiotherapy requires up to 10 years for full GH suppression effect, necessitating continued medical therapy 5
• Hypopituitarism develops in approximately 20% at 5 years and 80% at 10-15 years post-radiotherapy, requiring lifelong monitoring 5
• Periodically attempt dose reduction or withdrawal of medical therapy to assess radiation efficacy 5

Critical Clinical Pitfalls

• Do not assume GH/IGF-1 therapy will work effectively in the presence of uncorrected metabolic acidosis – the acidosis creates hepatic GH resistance that must be addressed first 3, 2
• Do not overlook medication compliance with alkali therapy – the unpleasant taste leads to frequent noncompliance and persistent complications 4
• Do not use pegvisomant without baseline and serial liver function monitoring – transaminase elevations up to 15 times upper limit of normal can occur 7
• Do not forget to adjust anti-diabetic medications when GH levels decrease, as improved insulin sensitivity may cause hypoglycemia 7
• Do not delay surgical referral to an experienced pituitary neurosurgeon, as surgical expertise significantly impacts outcomes 1, 5, 6