Endocrine News Podcast Episode 94: Update on Acromegaly

Date: November 13, 2024
Host: Aaron Lohr (A)
Guest: Dr. Maria Fleseriu (B) – Professor of Medicine and Neurological Surgery, Director of the Pituitary Center, Oregon Health & Science University

Episode Overview

This episode provides a comprehensive update on acromegaly, featuring expert insights from Dr. Maria Fleseriu. The discussion covers the disease’s prevalence, challenges in timely and accurate diagnosis, traditional and evolving treatment paradigms, impacts of delayed care and comorbidities, exciting new therapies, and current gaps in research. Dr. Fleseriu emphasizes the need for early detection, personalized approaches, and ongoing research.

Main Discussion Points & Insights

1. What is Acromegaly? Prevalence and Challenges

• Definition & Etiology:

  • Acromegaly is caused in 98% of cases by a pituitary tumor secreting growth hormone.
  • Name comes from Greek, referring to enlargement of extremities—often a late sign.
  • Early symptoms: diabetes, hypertension, sweating, irregular periods in women.

• Prevalence & Underdiagnosis:

  • Exact prevalence in the U.S. is unknown due to insufficient studies; European registries estimate 2.8–13.8 per 100,000 (meta-analysis: ~6/100,000) ([01:20]).
  • Likely underdiagnosed: Many cases found incidentally or without overt symptoms. IGF1 testing often reveals additional cases.

• Delayed Diagnosis:

  • Average delay now ~5 years (was 11 years); women experience even longer delays, possibly due to symptom overlap with other conditions (e.g., PCOS) and estrogen’s effect on IGF1 ([01:20–04:58]).
  • Notable Quote:

    “The delay in diagnosis is still significant...studies show that while getting better every decade, it’s still a diagnosis delay of about five years now.”
    —Dr. Fleseriu [02:44]

2. Diagnosis: Methods and Barriers

• Main Diagnostic Test:

  • IGF1 (Insulin-like Growth Factor 1); elevated in acromegaly due to excess growth hormone.
  • OGTT (Oral Glucose Tolerance Test) once essential; now, guidelines increasingly recognize limitations—up to 30% of early cases have normal suppression on OGTT ([05:24–09:04]).

• Laboratory Challenges:

  • Variability in IGF1 assays, reliability across labs; up to 40% variability detected in Dr. Fleseriu’s experience.
  • Medications (e.g., estrogen), lab quality, and local protocols can interfere.

• Practical Diagnostic Steps:

  • Screen IGF1 in all pituitary adenomas before treatment to catch early cases, especially when adenomas are found incidentally.

• Notable Quote:

  “If a patient has signs and symptoms of growth hormone excess and high IGF1...then you don’t need the OGTT.”
  —Dr. Fleseriu [07:38]

3. Traditional and Current Treatments

• Surgical First-Line:

  • Surgery is primary, with 80-90% remission in specialized centers when tumors are small. Larger tumors (cavernous sinus invasion) have lower cure rates, requiring adjunctive medication ([09:11]).

• Medical Therapy:

  • Pituitary-Directed Drugs: Somatostatin receptor ligands (e.g., octreotide, lanreotide, pasireotide).
  • Growth Hormone Receptor Blockers: Pegvisomant.
  • Combination Therapy: Used for difficult cases and improved outcomes.
  • Individualized Approach: Tumor pathology, receptor subtype (especially SSTR2A absence), and patient factors guide therapy selection.

• Challenges:

  • Insurance barriers to individualized therapy; monthly injections (adherence issues); need to go to medical centers for injections.
  • Newer options like oral octreotide (capsule) and combination therapies increasing flexibility ([11:09–14:13]).

• Notable Quote:

  “With individualized treatment, you can get to normal IGF1 in half of the time...very important to look at the patient as a whole.”
  —Dr. Fleseriu [11:35]

4. Treatment Adherence & Patient Experience

• Persistence & Adherence:

  • Long-term adherence is a major challenge with monthly injections.
  • Radiation is third-line; may induce panhypopituitarism, requiring lifelong hormone replacements.
  • Quality of life is a persistent concern—joint pain, cognitive effects, and ongoing comorbidities often remain even with treatment ([14:23–19:35]).

• Comorbidity Management:

  • Screening for colon polyps, sleep apnea, bone fractures, diabetes, and cardiovascular issues is routine but can be overwhelming.

• Patient-centered Care:

  • Emphasis on patient preference, comorbidities, and personalized, sequenced information to support adherence.
  • Telemedicine is improving follow-up and decreasing patient burden.

• Notable Quote:

  “We...tell them, you need screening for colonic polyps, an echo, a sleep study, a colonoscopy, a dexascan, x-rays to rule out vertebral fracture...it’s a huge change overall and has to be approached [carefully]...”
  —Dr. Fleseriu [17:32]

5. Personalized & Precision Approaches

• Personalized Treatment Considerations:

  • Tumor size, patient age, and cavernous sinus invasion predict response to surgery.
  • Tumor granulation pattern and SSTR2A receptor expression predict response to somatostatin analogs.
  • Prioritize patient goals and preferences (oral vs. injectable, frequency, comorbidities).

• Adverse Events & Dosage:

  • Monitoring side effects to guide dosage titration or combination therapy.
  • Some drugs, e.g., pasireotide, can worsen diabetes; adjust therapy accordingly.

• “Notable Quote:”

  “Patient preference should move up in the personalized treatment...some patients want injections, some want oral; we need to think about all these overall.”
  —Dr. Fleseriu [16:28]

6. Novel Therapies and Trials (as of ENDO 2024)

• Non-peptide SST2 Receptor Agonist (Piltuzatide):

  • Oral, once daily, promising results in symptom and IGF1 control for both previously treated and therapy-naive patients ([22:41–28:34]).
  • Over 50% response rate in trials for naive patients; higher than historical data for other therapies.

• Novel Subcutaneous Depot Octreotide:

  • Patient-administered, pre-filled syringe (monthly). Easier than requiring doctor visits.
  • Five times higher bioavailability than regular octreotide; improved symptoms reported.

• Longer-acting Growth Hormone Receptor Antagonists:

  • Drugs in preclinical and phase 1 studies—potential for less frequent injections.

• Research Takeaway:

  • Earlier diagnosis allows more patients access to new, less burdensome therapies.

• Notable Quote:

  “With all these new medications ... we have observed over time that control doesn’t mean just numbers. The symptoms are important.”
  —Dr. Fleseriu [26:56]

7. Gaps and Directions for Future Research

• Laboratory & Assay Improvement:

  • Need standardized, accurate IGF1 testing (“big challenge”).

• Physiological Questions:

  • Why do 30% of patients have discordant GH and IGF1? What’s the effect of tumor/assay variability and paradoxical glucose response?

• Genetics and Biomarkers:

  • Existing knowledge of AIP and MEN1 mutations—need to identify other genetic contributors, tumor-specific biomarkers, and their clinical applications.

• Bone Health and Comorbidities:

  • “Building bad bones”: patients suffer fractures even with normal bone density; need more clarity on mechanism and prevention.

• Patient-Reported Outcomes:

  • Need validated, unified tools to measure symptoms, therapy satisfaction, and quality of life.

• Cost-Effectiveness:

  • Need more studies showing whether individualized/personalized treatments reduce long-term complications and costs.

• Notable Quote:

  “We have a long list, and I hope in several years...I will just report to you that: check, check, check to all these, so we can actually improve the outcomes in these patients with rare disorders, and acromegaly especially.”
  —Dr. Fleseriu [33:14]

Notable Quotes & Memorable Moments

• On Diagnosis Delay (02:44):

  “The delay in diagnosis is still significant... studies show... a diagnosis delay of about five years now.”

• On Limitations of OGTT (07:38):

  “If a patient has signs and symptoms of growth hormone excess and high IGF1... then you don’t need the OGTT.”

• On Individualized Therapy (11:35):

  “With individualized treatment, you can get to normal IGF1 in half of the time... very important to look at the patient as a whole.”

• On Managing Patient Expectations (19:57):

  “What I can strongly recommend is the tumor size, age of the patient, and cavernous sinus invasions are very good proven predictors for response to surgery.”

• On Novel Therapies (26:56):

  “With all these new medications ... we have observed over time that control doesn’t mean just numbers. The symptoms are important.”

• On Research Needs (33:14):

  “We have a long list, and I hope in several years...I will just report to you that: check, check, check to all these, so we can actually improve the outcomes in these patients with rare disorders, and acromegaly especially.”

Timestamps for Important Segments

• [01:20] - Prevalence of Acromegaly and factors in delayed diagnosis.
• [05:24] - Diagnostic challenges and limitations of current tests.
• [09:11] - Traditional and current treatment strategies.
• [14:23] - Adherence, persistence, and patient quality-of-life issues.
• [19:57] - Personalized medicine in acromegaly.
• [22:41] - Overview of novel therapies and recent research (ENDO 2024).
• [28:51] - Gaps in understanding and future research needs.

Conclusion

This episode of the Endocrine News Podcast provides an expert deep dive into the challenges and advances in acromegaly care. Early detection, individualized treatment informed by tumor and patient characteristics, and ongoing research into novel therapies and underlying mechanisms are key to improving outcomes. Dr. Fleseriu advocates for more research, better diagnostic tools, inclusion of quality of life in disease management, and a patient-centered, personalized approach to therapy.