LETTER OF MEDICAL NECESSITY FOR HEREDITARY PANCREATITIS GENETIC TESTING
Date:
Date of service/claim
To:
Utilization Review Department
Insurance Company Name, Address, City, State
Re:
Patient Name, DOB, ID #
ICD-9 Codes: (list codes)
This letter is in regards to my patient and your subscriber, First, Last Name to request full coverage of
medically-indicated genetic testing for hereditary pancreatitis predisposition to be performed by Ambry
Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-approved and CLIA-certified laboratory
located at 15 Argonaut, Aliso Viejo, CA 92656. Significant aspects of my patient’s personal and/or family
medical history are below:
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

Based on my patient’s recurrent attacks of acute pancreatitis, an underlying genetic cause is
suspected. Additionally, results of routine tests already performed suggest a diagnosis of hereditary
pancreatitis. However, the only way to confirm this diagnosis is to perform genetic testing on my patient.
There are currently at least 4 genes that have been identified as significant risk factors in recurrent acute
and/or chronic pancreatitis. These include: the cystic fibrosis transmembrane conductance regulator gene,
CFTR; the cationic trypsinogen gene, PRSS1; the pancreatic secretory trypsin inhibitor gene, SPINK1; and
the chymotrypsin C gene, CTRC.
Confirmation of the diagnosis through molecular genetic testing will directly impact my patient’s care and
management. An accurate diagnosis of the underlying cause of the pancreatitis will identify the most
appropriate medical management, based on the gene mutations that are identified. Mutations in different
genes will indicate a different course of treatment as follows:
PRSS1 mutations that alter either of the calcium regulatory regions markedly increase sensitivity to
calcium-mediated activation or enzyme survival. Therefore, strategies to minimize the rise in intra-acinar
cell calcium concentrations are warranted. These include minimizing stimulation of the acinar cells by
giving digestive enzymes and possibly gastric acid suppression and optimizing acinar cell calcium
regulation by reducing intracellular stress with antioxidants, alcohol avoidance, and attention to metabolic
factors like serum calcium levels. Additionally, individuals with PRSS1 mutations can develop an
inflammatory milieu at high risk for the accumulation of oncogenic mutations, causing an increased lifetime
risk to develop pancreatic cancer. Identifying these mutations could allow for an aggressive cancer
surveillance plan to be implemented [1].
CFTR mutations markedly reduce the ability to flush digestive enzymes out of the pancreatic duct.
Therefore, strategies to reduce the risk of damage within the pancreatic duct focus on maximizing fluid
flow through the duct. This may include avoiding gastric acid suppression in order to increase release of
secretin, and using high-quality, acid-resistant digestive enzyme supplements such as Creon®.
Utilizing this testing, a significant number of patients will actually be diagnosed with a form of cystic
fibrosis (CF); it is then unlikely that these strategies will be effective. However, these patients should be
triaged immediately for CF care, which would change medical management regarding pulmonary functions.
Heterozygous mutations in SPINK1 and CTRC have been linked to worsening of the pancreatitis phenotype,
and to markedly increasing the risk of pancreatitis with most CFTR mutations. Strategies to minimize the
effects of these mutations must therefore be linked to limiting the effect of trypsinogen mutations or CFTR
mutations.
Additionally, symptoms of pancreatitis may be due to sphincter of Oddi dysfunction, typically diagnosed by
endoscopic sphincterotomy. Unfortunately, this invasive and costly procedure may actually induce
pancreatitis in up to 20% of individuals [2, 3]. Confirming an inherited cause for my patient’s pancreatitis
through genetic testing would help eliminate this likelihood by sparing my patient this procedure.
A positive test result would provide a definitive cause for my patient’s pancreatitis and would ensure this
patient is being treated appropriately, depending on the gene involved. As such, I am ordering this
genetic test as medically necessary care, and affirm that my patient has provided informed consent
for genetic testing. I am specifying Ambry Genetics because this laboratory has highly sensitive and costeffective testing for hereditary pancreatitis, along with the largest database of tested patients to ensure the
most accurate and informative test interpretation.
I recommend that you support this request for coverage of diagnostic genetic testing for hereditary
pancreatitis predisposition for my patient. Genetic testing can take up to five weeks to complete and the
laboratory will not bill until testing is concluded. Therefore, we are requesting that the authorization be
valid for 2 months.
Thank you for your time and please don’t hesitate to contact me with any questions.
Sincerely,
Ordering Clinician Name (Signature Provided on Test Requisition Form)
(MD/DO, Clinical Nurse Specialist, Nurse-Midwives, Nurse Practitioner, Physician Assistant, Genetic
Counselor*)
*Authorized clinician requirements vary by state
Test Details
CPT codes:
81223x1, 81224x1, 81404x2, 81479x1, 81222x1
Laboratory:
Ambry Genetics Corporation (TIN 33-0892453 / NPI 1861568784), a CAP-accredited and
CLIA-certified laboratory located at 15 Argonaut, Aliso Viejo, CA 92656
References:
1.
2.
3.
Weiss, F.U., Pancreatic cancer risk in hereditary pancreatitis. Front Physiol, 2014. 5: p. 70.
Fogel, E.L., et al., Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic
stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone. Endoscopy, 2002.
34(4): p. 280-5.
Cotton, P.B., et al., Risk factors for complications after ERCP: a multivariate analysis of 11,497
procedures over 12 years. Gastrointest Endosc, 2009. 70(1): p. 80-8.