What are the management recommendations for a patient with an elevated IGF-1 level, specifically a Z-score of 1.3, who is taking tesamorelin (Growth Hormone-Releasing Hormone analogue) and has a history of HIV (Human Immunodeficiency Virus) and metabolic conditions?

Management of Elevated IGF-1 (Z-score 1.3) in HIV Patient on Tesamorelin

An IGF-1 Z-score of 1.3 is within the normal age-adjusted reference range (-2 to +2 standard deviations) and does not require dose reduction or discontinuation of tesamorelin at this time. 1

Understanding the IGF-1 Result

• The Z-score of 1.3 falls well below the threshold for concern, as the FDA label for tesamorelin (EGRIFTA SV) recommends considering discontinuation only when IGF-1 levels persistently exceed 3 standard deviation scores (SDS), particularly if the efficacy response is not robust 2

• Age-adjusted interpretation is critical—a single absolute IGF-1 value of 251 ng/mL may be normal for a younger patient but elevated for an older patient, which is why the Z-score standardization is essential 1

• The Endocrine Society emphasizes maintaining IGF-1 levels within the age-adjusted normal reference range, typically targeting the mid-to-upper portion to optimize therapeutic efficacy while minimizing adverse effects 1

Monitoring Strategy

Continue current tesamorelin therapy with routine IGF-1 monitoring every 3-6 months to ensure levels remain within the age-adjusted reference range 1

• During clinical trials, 47% of patients receiving tesamorelin for 26 weeks had IGF-1 levels greater than 2 SDS, and 36% had SDS >3, with this effect seen as early as 13 weeks of treatment 2

• Among patients who remained on tesamorelin for 52 weeks, 34% had IGF-1 SDS >2 and 23% had IGF-1 SDS >3 at the end of treatment 2

Assess for Confounding Factors

Before attributing any IGF-1 elevation solely to tesamorelin, evaluate for conditions that can spuriously affect IGF-1 measurements:

• Check glucose control: Poorly controlled diabetes mellitus can produce spuriously elevated IGF-1 levels—verify HbA1c and fasting glucose 1

  • This is particularly important given that tesamorelin treatment can result in glucose intolerance, with an increased risk of developing diabetes (HbA1c ≥6.5%) relative to placebo observed with a hazard odds ratio of 3.3 (CI 1.4,9.6) 2
  • HIV-infected patients already have a 4-fold increased risk of diabetes mellitus when receiving antiretroviral therapy 3

• Evaluate thyroid function: Severe hypothyroidism suppresses hepatic IGF-1 generation—check TSH and free T4 1

• Review medication list: Oral estrogen therapy reduces hepatic IGF-1 synthesis through first-pass hepatic metabolism 1

• Assess nutritional status: Malnutrition or energy deficiency directly suppresses IGF-1 production—evaluate body weight trends 1

• Rule out acute illness: Severe active infection suppresses the GH-IGF-1 axis 1

• Check organ function: Hepatic or renal failure may cause falsely elevated IGF-1 measurements—review liver and kidney function tests 1

Metabolic Monitoring Requirements

Evaluate glucose status and lipid parameters at baseline and within 4-6 weeks after starting antiretroviral therapy, then periodically 3

• Monitor fasting glucose and lipid levels to diagnose patients who develop impaired glucose tolerance or diabetes during tesamorelin therapy 2

• Patients with diabetes receiving tesamorelin should be monitored at regular intervals for potential development or worsening of retinopathy, as tesamorelin increases IGF-1 2

• HIV-infected patients have higher rates of insulin resistance (15-20% with impaired glucose tolerance) and dyslipidemia associated with traditional risk factors, HIV infection itself, and antiretroviral drugs 3

Efficacy Assessment

Verify that the patient is experiencing a robust therapeutic response to justify continued therapy:

• Tesamorelin reduces visceral adipose tissue (VAT) by approximately 15-24% compared to placebo over 26 weeks 4, 5

• Treatment effects include significant decreases in triglycerides (treatment effect -12.3%) and cholesterol to HDL ratio (treatment effect -7.2%) 4

• Improvements in body image parameters, including belly appearance distress and patient/physician rating of belly profile, should be evident 4

When to Consider Dose Adjustment or Discontinuation

Discontinue or reduce tesamorelin dose only if:

• IGF-1 levels persistently exceed 3 SDS (Z-score >3), particularly if the efficacy response is not robust 2

• Patient develops glucose intolerance or diabetes without a clear efficacy response 2

• Evidence of malignancy recurrence or new malignancy develops, as tesamorelin induces endogenous growth hormone release, a known growth factor 2

• Hypersensitivity reactions occur (pruritus, erythema, flushing, urticaria, rash), which occurred in 4% of patients in clinical trials 2

Common Pitfalls to Avoid

• Do not use a single universal IGF-1 cutoff value—always interpret results using age-adjusted Z-scores or standard deviation scores 1

• Do not compare values across different laboratory assays without understanding assay-specific reference ranges 1

• Do not assume all elevated IGF-1 values indicate overdosing without considering confounding factors like poorly controlled diabetes 1

• Do not discontinue effective therapy prematurely based on IGF-1 levels that remain within the acceptable range (Z-score <3) 2