CAM 099

Diagnostic Testing of Iron Homeostasis & Metabolism

Category:Laboratory   Last Reviewed:January 2020
Department(s):Medical Affairs   Next Review:January 2021
Original Date:January 2016    

Description/Background
Iron deficiency is considered to be the most common nutritional deficiency in the world, and is the most common cause of anemia in the United States. Prevalence of iron deficiency varies by age, sex and race. The Centers for Disease Control and Prevention estimates that 14% - 16% of children age 1 - 2 years; 4% - 5% of children age 3 - 5 years; and 9% - 10% of females age 12 - 49 years in the United States are iron deficient. Blacks and Mexican-Americans are at higher risk than Caucasians. Additionally, socioeconomic factors impact risk for iron deficiency.

Iron deficiency is caused by increased iron needs and/or decreased iron intake or absorption. Rapidly growing infants and young children need more iron than do older children. Pregnant women require more iron than non-pregnant individuals, and those with frequent or excessive blood loss require additional iron to replace that which is lost. Iron is obtained from various foods, such as meat, poultry, fish, beans and fortified cereals. Iron supplements, such as those present in multivitamins, are also a common source of iron.

Prolonged iron deficiency can lead to iron deficiency anemia, although most people with iron deficiency do not develop anemia. Regardless, iron deficiency, with or without associated anemia, is considered to cause developmental, neurological and physical impairment of varying degrees. Iron deficiency during pregnancy can result in small and/or pre-term babies, and iron deficiency in infants can cause developmental delays in motor or mental function. In teens, iron deficiency is associated with deficits in memory and mental function, and in adults iron deficiency can cause fatigue, which impacts quality of life and work productivity.

Iron deficiency is readily detectable with testing, and treatable through improved nutrition and supplementation. The Healthy People 2020 objectives for "improving the health of all Americans" include reductions in iron deficiency among young children and females of childbearing age, and among pregnant women.

Policy

  1. Measurement of serum ferritin levels is considered MEDICALLY NECESSARY in any of the following situations:
    • In the evaluation of an individual with abnormal hemoglobin and/or hematocrit levels.
    • In the evaluation and monitoring of iron overload disorders.
    • In individual with symptoms of hemochromatosis * (See Note 1)
    • In individual with first-degree relatives with confirmed hereditary hemochromatosis (HH)
    • In the evaluation of individuals with liver disease.
    • In the evaluation and monitoring of patients with chronic kidney disease who are being considered for, or are receiving treatment for, anemia at a frequency of every 1 to 3 months.
    • In the evaluation of hemophagocytic lymphohistiocytosis (HLH) and Still’s Disease.
    • For individuals on iron therapy, at a frequency of every 1 to 3 months.
    • In males with secondary hypogonadism.
  2. The use of ferritin or transfemin measurement, including transferrin saturation, as a screening test in asymptomatic patients is considered NOT MEDICALLY NECESSARY.
  3. Serum transferrin saturation (using serum iron and serum iron binding capacity measurements) MEETS COVERAGE CRITERIA in the following:
    • For the evaluation of iron overload in individuals with symptoms of hemochromatosis (See Note 1).
    • For the evaluation of iron overload in individuals with first-degree relatives with confirmed hereditary hemochromatosis (HH).
    • For the evaluation of iron deficiency anemia
  4. Serum hepcidin testing, including immunoassays, is considered investigational and/ or unproven and is therefore considered NOT MEDICALLY NECESSARY.
  5. The use of GlycA testing to measure or monitor transferrin or other glycosylated proteins is considered investigational and/or unproven and is therefore considered NOT MEDICALLY NECESSARY.

NOTE 1: Symptoms of hemochromatosis, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, include the following (NIDDK, 2014):

  • Joint pain
  • Fatigue
  • Unexplained weight loss
  • Abnormal bronze or gray skin color
  • Abdominal pain
  • Loss of sex drive

Rationale
While there are guidelines and recommendations related to screening for anemia in certain populations, none of them recommend use of ferritin as a first-line test in asymptomatic individuals. Use of ferritin is recommended as a follow-up to abnormal hemoglobin or hematocrit screening results.

The National Kidney Foundation’s KDOQI guidelines recommend use of ferritin testing as part of the evaluation of iron status in individuals with chronic kidney disease who are being treated for anemia. They recommend testing prior to initiation of treatment, once per month during initial treatment and at least every 3 months after a stable hemoglobin level is reached.

The American Association for the Study of Liver Diseases recommends use of ferritin testing as part of the workup of individuals with suspected iron overload, those with a family history of hereditary hemochromatosis and those with liver disease. (See Hereditary Hemochromatosis medical policy for additional details.)

References 

  1. "Screening for Iron Deficiency Anemia in Childhood and Pregnancy; Update of the 1996 U.S. Preventive Task Force Review." Evidence Syntheses, No. 40 Agency for Healthcare Research and Quality (US); April 21, 2006. Report No.: 06-0590-EF-1. Accessed 1.2014 at http://www.ncbi.nlm.nih.gov/books/NBK33399/
  2. Shersten Killip, John M. Bennett, Mara D. Chambers, "Iron Deficiency Anemia" Am Fam Physician 2007;75:671-8.
  3. "Recommendations to Prevent and Control Iron Deficiency in the United States," MMWR 1998; 47 (No. RR-3) p. 5. Accessed 1.2014 at http://www.cdc.gov/nutrition/everyone/basics/vitamins/iron.html
  4. "Screening for Iron Deficiency Anemia--Including Iron Supplementation for Children and Pregnant Women." Retrieved on 1.17.2014 from http://www.uspreventiveservicestaskforce.org/uspstf06/ironsc/ironscr.pdf
  5. "Anemia or Iron Deficiency." FastStats, Centers for Disease Control and Prevention. Accessed 1.2014 at http://www.cdc.gov/nchs/fastats/anemia.htm
  6. "Iron Deficiency Anemia" National Heart Lung and Blood Institute. Accessed 1.2014 at http://www.nhlbi.nih.gov/health/health-topics/topics/ida/
  7. "Ferritin" LabTestsOnline, Accessed 1.2014 at http://labtestsonline.org/understanding/analytes/ferritin/tab/sample/
  8. "KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease." National Kidney Foundation. Accessed 1.2014 at http://www.kidney.org/professionals/kdoqi/guidelines_anemia/cpr12.htm
  9. Bruce R. Bacon, Paul C. Adams, Kris V. Kowdley, Lawrie W. Powell, and Anthony S. Tavill "Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases" Hepatology, Vol. 54, No. 1, 2011  
  10. SCA Meijvis, H Endeman, ABM Geers, EJ ter Borg. "Extremely high serum ferritin levels as diagnostic tool in adult-onset still’s disease" The Netherlands Journal of Medicine, vol. 65, no. 6, June 2007.CE
  11. Allen , X Yu, CA Kozinetz, KL McClain. "Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis," Pediatr Blood Cancer. 2008 Jun;50(6):1227-35

Coding Section 

Codes Number Description
CPT  82728  Ferritin 
  83540  Iron 
  83550  Iron binding capacity 
  84466 Transferrin
  84999  Unlisted chemistry procedure (Hepcidin) 
  0024U  Glycosylated acute phase proteins (GlycA), nuclear magnetic resonance spectroscopy, quantitative 
ICD-10-CM  

E29.1

Testicular hypofunction/Testicular hypogonadism NOS
 

E89.5 

Postprocedural testicular hypofunction 
  F50.89 Pica in adults
 

F98.3

Pica of infancy and childhood
  G25.81 Restless legs syndrome
  K72.90  Hepatic failure, unspecified without coma 
  K72.91  Hepatic failure, unspecified with coma 
  M25.50 Pain in unspecified joint
  M25.511 Pain in right shoulder
  M25.12 Pain in left shoulder
  M25.519 Pain in unspecified shoulder
  M25.521 Pain in right elbow
  M25.522 Pain in left elbow
  M25.529 Pain in unspecified elbow
  M25.531 Pain in right wrist
  M25.532 Pain in left wrist
  M25.539 Pain in unspecified wrist
  M25.551 Pain in right hip
  M25.552 Pain in left hip
  M25.559 Pain in unspecified hip
  M25.561 Pain in right knee
  M25.562 Pain in left knee
  M25.569 Pain in unspecified knee
  M25.571 Pain in right ankle and joints of right foot
  M25.572 Pain in left ankle and joints of left foot
  M25.579 Pain in unspecified ankle and joints of unspecified foot
 

R10.0

Abdominal pain
  R10.81 Upper abdominal pain
  R10.811 Right upper quadrant abdominal tenderness
  R10.812 Left upper quadrant abdominal tenderness
  R10.813 Right lower quadrant abdominal tenderness
  R10.814 Left lower quadrant abdominal tenderness
  R10.815 Periumbilic abdominal tenderness
  R10.816 Epigastric abdominal tenderness
  R10.817 Generalized abdominal tenderness
  R10.819 Abdominal tenderness, unspecified site
  R10.82 Rebound abdominal tenderness
  R10.821 Right upper quadrant rebound abdominal tenderness
  R10.822 Left upper quadrant rebound abdominal tenderness
  R10.823 Right lower quadrant rebound abdominal tenderness
  R10.824 Left lower quadrant rebound abdominal tenderness
  R10.825 Periumbilic rebound abdominal tenderness
  R10.826 Epigastric rebound abdominal tenderness
  R10.827 Generalized rebound abdominal tenderness
  R10.829 Rebound abdominal tenderness, unspecified site
  R10.83 Colic
  R10.84 Generalized abdominal pain
  R10.9 Unspecified abdominal pain
  R23.8 Other skin changes
  R53.83 Fatigue NOS
  R63.4 Abnormal weight loss
  R68.82 Decreased libido
  Z83.49 Family history of other endocrine, nutritional and metabolic diseases

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2016 Forward     

01/06/2020 

Annual review, no change to policy intent. Updating coding. 

04/02/2019 

Interim review updating coding. No change to policy intent. 

01/10/2019 

Annual review, updating policy title to enlarge scope of policy to include Iron Homeostasis and Metabolism. Adding additional criteria for medical necessity, adding investigational testing statements. Updating ICD coding. Adding "Note 1." 

01/17/2018 

Annual review, no change to policy intent. 

04/26/2017 

Updated category to Laboratory. No other changes. 

01/03/2017 

Annual review, no change to policy intent. 

01/07/2016

NEW POLICY


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