Category: Adrenal Disorders
We present a case in which a patient with known adrenal insufficiency and epilepsy, managed with corticosteroids and phenytoin, developed worsening of his adrenal insufficiency when his phenytoin level became supratherapeutic.
Methods : Case presentation and literature review.
Results : A 69 year old male presented to the emergency department from his assisted living facility after several days of weakness, weight loss and falls. He had history of primary adrenal insufficiency and secondary hypothyroidism as well as epilepsy. He was on Levothyroxine 100mcg/d, hydrocortisone 30mg in the morning and 10mg in the evening, fludrocortisone 0.2mg/d and phenytoin 350mg/d. In the emergency department he was hypotensive with a blood pressure of 90/52mmHg. He was hyponatremic with a sodium of 119mEq/L. Potassium was 4.3mEq/L. His phenytoin level was elevated at 35.6 mcg/mL (reference 10-20mcg/mL). A serum cortisol level shortly after admission was low at 0.6 mcg/dL with an adrenocorticotropic hormone (ACTH) elevated at 835 pg/mL. His Free T4 was 1.01 (normal 0.58-1.64 ng/dL). During his admission, his dose of hydrocortisone was increased and his phenytoin dosage was reduced. His morning serum cortisol level improved but was still low at 2.9 mcg/dL. His ACTH level improved to 99 pg/mL. His sodium improved too. Neurology discontinued his phenytoin and started him on Keppra. One month from his hospitalization laboratory tests showed normalization of cortisol to 18.9 mcg/dL with ACTH of 352 pg/mL. Clinically the patient improved.
Several factors could have contributed to worsening control of his adrenal insufficiency. Noncompliance with medical therapy was considered, however the patient had been living in an assisted living facility for several months prior to his hospitalization and had his medications provided by staff. Stressor such as infection were considered, however workup during his hospitalization failed to reveal obvious signs of infection or other significant stressors. He was euthyroid on levothyroxine and his FT4 was mid normal range. Drugs can alter the bioavailability of corticosteroids by induction of the cytochrome P450 pathway. Phenytoin is a strong CYP3A4 inducer. CYP3A4 catalyzes hydroxylation of cortisol in the liver. Reviewing his case, we found that several months before his hospitalization his phenytoin level had been 14.7 mcg/mL. His prior cortisol level while on his baseline dose of hydrocortisone was 28.4 mcg/dL. His weight loss may have contributed to his phenytoin toxicity.
In patients with worsening adrenal insufficiency while on replacement therapy, inducers of the cytochrome P450 pathway should be considered as a precipitator.
Christopher Barnes– Fellow, Division of Endocrinology and Metabolism, Arnot-Ogden Medical Center, Lake Erie College of Osteopathic Medicine, Horseheads, New York
Ahmet Can– Program Director and Faculty, Arnot-Ogden Medical Center, Lake Erie School of Osteopathic Medicine, Horseheads, New York
Tahir Haytoglu– Endocrinologist, Arnot Health, Horseheads, New York
Yusef Hazimeh– Endocrinology fellowship program director, LECOM , Arnot Health, Arnot Ogden Health System
Division of Endocrinology and Metabolism, Arnot-Ogden Medical Center, Lake Erie College of Osteopathic Medicine
Horseheads, New York
Dr. Barnes graduated from Lake Erie College of Osteopathic Medicine in 2014. He completed residency in Internal Medicine at the Arnot Ogden Medical Center and remains there for fellowship in Endocrinology.
Program Director and Faculty
Arnot-Ogden Medical Center, Lake Erie School of Osteopathic Medicine
Horseheads, New York
Ahmet Selcuk Can, MD went to medical school in Istanbul Faculty of Medicine and graduated in 1989. He did his internship and residency in internal medicine in Cabrini Medical Center affiliated with New York Medical College, in New York City between 1994 and 1996. He completed his Endocrinology Fellowship in Weill Cornell Medicine and Memorial Sloan-Kettering Cancer Center combined program. During his fellowship, he worked in inborn errors of steroid metabolism and published a paper about molecular genetics of 5 alpha reductase deficiency. After fellowship, he worked in various Hospitals and Universities in Turkey. He published about prevalence of the metabolic syndrome and on the sensitivity and specificity of the thyroid fine needle aspiration biopsies. Before joining to Arnot-Ogden Medical Center in Elmira, New York, he worked in a private practice and had affiliations in the Community Medical Center, in Toms River and Ocean Medical Center in Brick, New Jersey and after that worked as a Professor of Medicine in Termal Vocational School in Yalova, Turkey. He has 20 publications in peer-reviewed journals. He serves as the Program Director for Endocrinology, Diabetes and Metabolism Fellowship at Arnot-Ogden Medical Center in Elmira, NY, affiliated with Lake Erie School of Osteopathic Medicine.
Horseheads, New York
Graduated 1996 HACETTEPE University School of Medicine in ANKARA, TURKEY
Internal Medicine Residency:
1997 – 2000 St. Barnabas Hospital (Affiliated with Cornell Medical School) in BRONX, NY
200 -2002 University of California, Davis, Medical Center in SACRAMENTO, CA
Preventive Cardiology Fellowship:
2002-2003 VA Boston Healthcare System / Brigham and Women’s Hospital (Affiliated with Harvard Medical School) in Boston, MA
09/2003 – 06/2018 American Hospital of Istanbul, Turkey. Practicing Endocrinologist and served as Vice Chief and Chief of the Endocrinology Division
07/2018 – Current ARNOT HEALTH Endocrinologist
ABIM Board Certified in Endocrinology and Internal Medicine in 2002 and 2000 and re-certified from both in 2017.