Algorithms and recommendations in the management of Acromegaly

1. Lewis S. Blevins, Jr., M.D.
Algorithms and recommendations
in the management of patients
with Acromegaly

3. Acromegaly
Patients deserve….
Individualized care
Based on evidence
The art of medicine
The most appropriate drug for their situation
To participate in decisions regarding their care
A swift resolution of their disease process
The very best health care team and center available

4. Guidelines and Algorithms in Acromegaly
My impressions
Treat a population and not the individual
Biased by those who write and sponsor them
Change every 2 years or so
Based on trial information which does not often apply to practice
Do not consider individual caveats of therapy
Do not consider third party payor mandates
Do not consider third party payor ramifications
Do not consider medicolegal ramifications
Too evidenced-based…eliminate the “art of medicine”
Assays vary
Efficacy of drugs not as touted
Time consuming and arduous
There never really is a consensus!

5. Acromegaly
AACE 2011
Rating scheme for strength of evidence
Rating scheme for strength of recommendations
based on publications
Executive summary of recommendations
Four of 6 members received support from Pharm
companies
2 of 3 reviewers received support from Pharm and one
now works for Pharm company
A total of 119 recommendations!

6. Acromegaly
AACE 2011: Are these helpful?
R7- blood pressure should be measured, and
appropriate therapy should be administered if
hypertension is present.
R19- visual field testing should be performed if there
is optic chiasmal compression noted on the MRI or if
the patient has complaints of reduced peripheral
vision.
R21- all patient should undergo a comprehensive
medical history, physical examination, and
appropriate laboratory testing.
Katznelson at al. Endocr Pract 17:1-44,2011.

7. Acromegaly
AACE 2011: Essentials
R47-fasting GH level measured early postoperatively,
postoperative day one GH level less than 2 ng/mL
correlates with long-term remission
R48- a serum IGF 1 level should be remeasured at 12
weeks; a normal IGF one value is consistent with surgical
remission
R49- a repeated OGTT maybe performed at 12 weeks; a
GH less than 1 ng/mL consistent with surgical remission
R50- this panel suggest that the serum GH nadir after
glucose administration be lowered to 0.4 ng/mL…

8. Acromegaly
AACE 2011: Essentials
R60-dopamine agonist may be considered as first-line
medical therapy…..
R68- SSA’s are effective in normalizing IGF-I and GH
levels in approximately 55% of patients.
R74- Pegvisomant is highly effective in normalizing IGF-I
values (>90%), including patients who are partially or
completely resistant to other medical therapies.
R84- pituitary radiation therapy and acromegaly should be
considered an adjunctive treatment in patients not fully
responding to surgical or medical treatments ( or both).

9. Acromegaly
Acromegaly Consensus Group 2009
Six reports since 2000.
Similar rating and grading schemes.
Sixty-eight pituitary specialists reconvened in 2007.
Developed a consensus on approach to managing
acromegaly including appropriate roles for
neurosurgery, medical therapy, and radiation therapy
in the management of these patients.
Melmed et al. J Clin Endocrinol Metab 94:1509-1517, 2009.

10. Acromegaly
Acromegaly Consensus Group 2009
In patients with intrasellar microadenomas, surgical
removal provides biochemical control with normalization
of IGF 1 in 75-95% of patients. Control rates are lower in
patients with noninvasive macroadenomas, but even in
these cases surgical removal provides all chemical control
with normalization of IGF 1 and 40-68% of patients.
Expertise in surgical management of acromegaly is very
important-the control rates outlined above can only be
achieved with surgeries performed by a dedicated and
experienced pituitary neurosurgeon conducting at least 50
pituitary operations per year.

11. Acromegaly
Acromegaly Consensus Group 2009
Long-term studies indicate that approximately 70% of
patients receiving SRLs have GH levels below 2.5 ng/ml
and normalized IGF-I. In unselected populations, SRLs
reduce GH to less than 2.5 ng per milligram normalize
IGF-I and 44 and 34% of patients, respectively.
Patient should remain on the same dose for 3 months….
“The use of SRLs is most appropriate”…. potential first-line
therapy with low probability for surgical cure, after
surgery has failed to achieve control, for surgery to
improve comorbidities, to provide disease control or
partial control… radiotherapy…..

12. Acromegaly
Acromegaly Consensus Group 2009
Growth hormone receptor antagonist not really
recommended but indications were discussed.
“Clinical situations in which cabergoline may be useful
include”….preference for oral medication, after surgery in
selected patients such as those with elevated prolactin or
modest elevations of growth hormone and IGF 1, as an
additive therapy to SRL.

13. Acromegaly
Acromegaly Consensus Group 2009
“Radiation therapy should generally be reserved for
third-line treatment, and occasionally a second-line
treatment, but rarely as first-line treatment.”
Medical therapy with a SRL is usually required….

14. Acromegaly
Acromegaly Consensus Group 2009
Goal of treatment is growth hormone less than 2.5
ng/mL or a normal age and sex adjusted IGF 1 level.
Recommended GH < 1.0 ng/mL during OGTT three
months after surgery. Using a sensitive assay, GH of
<0.4 ng/mL would be consistent with remission.
No recommendations regarding IGF-I assay.

16. Acromegaly
Acromegaly Consensus Group

17. Clemmons et al. J Clin Endocrinol Metab 88:4759-4767,2003

18. Acromegaly
Acromegaly Consensus Group 2010
A consensus on criteria for cure of acromegaly
Discussed the inherent limitations of immunoassay is for
growth hormone and IGF 1.
Recommended WHO international standards for growth
hormone and IGF 1.
Anticipated that development of mass spectroscopy based
technology may overcome limitations.
Recognized and discusseddiscordance between growth
hormone and IGF 1 levels in 30% of patients with
acromegaly after treatment.
Giustina et al. J Clin Endocrinol Metab 95:3141-3148, 2010.

19. Acromegaly
Acromegaly Consensus Group 2012
Diagnosis and treatment of Acromegaly complications
First publication 2003. Second publication 2012.
“Required” EKG, echocardiogram, blood pressure
determination, sleep study for sleep apnea, assessment of
peripheral arterial system.
Suggested treatment of diabetes.
Suggested evaluation and treatmentfor hypogonadism.
Suggested consideration of quality of life assessments.
Recommended evaluation for osteoporosis risk factors.
Recommended screening colonoscopy at time of diagnosis
and then screening similar to general population.
Melmed at al. Pituitary 18 August 2012

20. Acromegaly
Acromegaly Consensus Group 2014
Maintaining the same GH and IGF-1 assay throughout
management
Against the use of routine preoperative medical
therapy in attempt to improve surgical outcomes
Use SRL or Pegvisomant for moderate to severe
residual disease
Try cabergoline for mild residual disease

21. Acromegaly
A survey of management practices
Aim was to determine whether consensus statements changed clinical
practice.
Surveyed 65 acromegaly experts who participated in the consensus
workshop!
98% of respondents stated that primary treatment with SRLs was
indicated at least sometime during the management of acromegaly
patients.
96% of centers stated the use of Pegvisomant monotherapy was
restricted to patients who had failed to achieve biochemical control
with SRL therapy.
Concluded that most centers followed the consensus statement
recommendations and that this encouraged the future utility of
workshops!!
Giustina et al. Pituitary 14:125-133, 2011.

22. Acromegaly
Factors to consider/ What the guidelines and
algorithms omit
Age
Overall health
Education and understanding
Willingness to accept side-effects
Ability to accept, implement, and monitor treatment
Tumor size and character
Small vs large
Noninvasive vs invasive
Co-secreting

23. Acromegaly
Factors to consider/ What the algorithms omit
Prior interventions and responses coupled with
tumor character and expertise of treating physicians
Co-morbidities
DM? May prefer pegvisomant
Cardiomyopathy? May choose to avoid DA agonists
Radiotherapy is beneficial to many patients
Financial constraints
Insurance coverage
Co-pays

24. Acromegaly
IGF-I data and treatment history
TSATSA
&
CPK
Start-Sandostatin LAR-Stop
Start-Somavert-Stop
Cabergoline

25. Acromegaly Management
Individualize therapy
Address specific needs
Patient preference
Dovetail strategic use of surgery and radiotherapy as
well as specific medical therapy
Don’t give up on a patient!!!
Growth and change is inevitable!