Elevated levels of AST, ALT, and CPK • no family history of liver disease • Dx?

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Case Reports

Elevated levels of AST, ALT, and CPK • no family history of liver disease • Dx?

J Fam Pract. 2017 July;66(7):450-452

By

Mitesh B. Patel, MD

Haripriya Maddur, MD

► Elevated levels of AST, ALT, and CPK
► No family history of liver disease

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References

1. Shonle HA, Rohrmann E, inventors; Eli Lilly and Company, assignee. Aminoalkanes. Patent US2350318A. May 30, 1944.

2. Shonle HA, Rohrmann E, inventors; Eli Lilly and Company, assignee. Carbonates of 1-R-1 aminoethanes. Patent US2386273. October 9, 1945.

3. Eli Lilly and Company. Forthane. Registration 0925396, February 1, 1971. United States Patent and Trademark Office.

4. Federal Register. Vol. 48, No. 218/Notices. November 9, 1983.

5. Shipley A. Chemist’s new product contains hidden substance. Washington Post. May 8, 2006:Sports. Available at: http://www.washingtonpost.com/wp-dyn/content/article/2006/05/07/AR2006050700913.html. Accessed June 5, 2017.

6. Gregory PJ. Availability of DMAA supplements despite US Food and Drug Administration action. JAMA Intern Med. 2013;173:164-165.

7. Gee P, Jackson S, Easton J. Another bitter pill: a case of toxicity from DMAA party pills. N Z Med J. 2010;123:124-127.

8. Gee P, Tallon C, Long N, et al. Use of recreational drug 1,3 Dimethylamylamine (DMAA) [corrected] associated with cerebral hemorrhage. Ann Emerg Med. 2012;60:431-434.

9. Ping Z, Jun Q, Qing L. A study on the chemical constituents of geranium oil. Journal of Guizhou Institute of Technology. 1996;25:82-85.

10. Lisi A, Hasick N, Kazlauskas R, et al. Studies of methylhexaneamine in supplements and geranium oil. Drug Test Anal. 2011;3:873-876.

11. Elsohly MA, Gul W, Elsohly KM, et al. Pelargonium oil and methyl hexaneamine (MHA): analytical approaches supporting the absence of MHA in authenticated Pelargonium graveolens plant material and oil. J Anal Toxicol. 2012;36:457-471.

12. Charlier R. [Pharmacology of 2-amino-4-methylhexane]. Arch Int Pharmacodyn Ther. 1950;83:573-584.

13. Ahlquist R. A contribution to the pharmacology of the aliphatic amines. J Pharmacol Exp Ther. 1944;81:235-239.

14. Swanson EE, Chen KK. Comparison of pressor action of aliphatic amines. J Pharmacol Exp Ther. 1946;88:10-13.

15. Swanson EE, Chen KK. Comparison of pressor action of alicyclic derivatives of aliphatic amines. J Pharmacol Exp Ther. 1948;93:423-429.

16. Marsh DF, Howard A, Herring DA. The comparative pharmacology of the isomeric nitrogen methyl substituted heptylamines. J Pharmacol Exp Ther. 1951;103:325-329.

17. Venhuis BJ, Kaste D. Scientific opinion on the regulatory status of 1,3-dimethylamylamine (DMAA). European Journal of Food Research and Review. 2012;2:93-100.

18. Eliason MJ, Eichner A, Cancio A, et al. Case reports: Death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA). Mil Med. 2012;177:1455-1459.

19. Young C, Oladipo O, Frasier S, et al. Hemorrhagic stroke in young healthy male following use of sports supplement Jack3d. Mil Med. 2012;177:1450-1454.

20. Salinger L, Daniels B, Sangalli B, et al. Recreational use of a bodybuilding supplement resulting in severe cardiotoxicity. Clin Toxicol (Philadelphia). 2011;49:573-574.

21. Lee GY, Lee H, Kim YJ. Rhabdomyolysis recognized after elevation of liver enzymes following prolonged urologic surgery with lateral decubitus position: a case report. Korean J Anesthesiol. 2011;61:341-343.

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THE CASE

A 26-year-old healthy male veteran with bipolar disorder and post-traumatic stress disorder was referred for a gastroenterology consultation after a routine laboratory evaluation revealed elevated levels of aspartate aminotransferase (AST), 1040 IU/L (normal range, 10-40 IU/L), and alanine aminotransferase (ALT), 334 IU/L (normal range, 7-56 IU/L). He had been taking divalproex and ziprasidone for the previous 2 years, during which time liver test results had been normal.

The patient reported no symptoms in the course of a detailed history. He had no family history of liver disease, drank alcohol infrequently, and didn’t use tobacco. He hadn’t received any blood transfusions and didn’t have tattoos.

The patient indicated that he had recently returned from military deployment and that a week before his laboratory tests, he’d resumed weight training. To boost his workout, he’d begun taking a nutritional supplement supplied by a friend. Further questioning revealed that the supplement was MuscleMeds’ Code Red, which contains 1,3-dimethylamylamine (DMAA). He denied using any other dietary supplements.

The physical examination was unremarkable and additional lab work was unrevealing. Lab results included normal levels of ceruloplasmin, alpha-1 antitrypsin, ferritin, iron, and transferrin. Viral hepatitis serologies revealed immunity to the hepatitis A and B virus. The patient tested negative for Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human immunodeficiency virus, antinuclear antibody, anti-smooth muscle antibody, and antimitochondrial antibody. A toxicology screen was remarkable for cannabinoids. The remainder of the basic metabolic panel and complete blood count were within normal limits.

THE DIAGNOSIS

The patient’s AST and ALT levels prompted measurement of creatine phosphokinase (CPK), which was elevated at 34,270 IU/L (normal range, 22-198 IU/L). We diagnosed rhabdomyolysis in this patient, which can be associated with elevated levels of AST and ALT. When we contacted the patient about the diagnosis, he reported no muscle aches or pains, or other symptoms.

We instructed the patient to increase his fluid intake and refrain from further use of Code Red. Repeat liver tests one month after the initial consultation revealed significant improvement in AST (29 IU/L) and ALT (68 IU/L), as well as a decline in CPK to 743 IU/L.

DISCUSSION

Much debate has surrounded the safety and use of DMAA, also known as methylhexamine or Geranamine, in dietary supplements such as Code Red. Eli Lilly and Company developed and patented DMAA in the 1940s, then trademarked it under the name Forthane as an inhaled nasal decongestant in 1971.^1-3 United States Food and Drug Administration (FDA) approval for Forthane was withdrawn in 1983 at Lilly’s request.⁴ DMAA was reintroduced as a dietary supplement more than a decade ago after the FDA, in 2004, banned supplements containing ephedrine alkaloids, which have effects similar to DMAA.⁵

DMAA has been used to increase muscle mass, promote weight loss, and improve physical performance; it’s also been used as a recreational drug.^6-8 Several case reports have described poor outcomes in patients who consumed DMAA products. In 2012, the deaths of 2 military personnel who used DMAA prompted the FDA to warn manufacturers of DMAA-containing supplements to stop production, but such supplements remain easily available in the United States.⁶

DMAA’s validity as a dietary supplement is controversial. The claim that DMAA is naturally present in geraniums hasn’t been verified, leading some to question whether an inaccurate description of DMAA as a natural substance was employed to justify its use as a nutritional supplement.⁹ No published evidence exists to establish DMAA as a dietary ingredient.^10,11