A 25-year-old woman comes to the physician with 2 months of progressively increasing pain in both lower extremities. The pain is localized over both shins and is worse with ambulation. She reports a 2-kg (4.5-lb) weight loss, but no fever, night sweats, chest pain, or abdominal pain. Her past medical history is unremarkable and she is currently on no medications. Family history is significant for a mother and sister with hypothyroidism. The patient has a 5-pack-year smoking history and drinks 2 glasses of beer on weekends. She has a nutritious diet with regular intake of vegetables, meats, whole-grain foods, and dairy products. Examination shows tenderness at both shins and vitiligo over her back. Laboratory results are as follows:
The red blood cells are hypochromic and microcytic. Basic metabolic chemistry panel is otherwise normal. The serum ferritin level is low. Plasma 25-hydroxy vitamin D level is undetectable. Which of the following blood tests is likely to indicate the diagnosis?

Question

A 25-year-old woman comes to the physician with 2 months of progressively increasing pain in both lower extremities.  The pain is localized over both shins and is worse with ambulation.  She reports a 2-kg (4.5-lb) weight loss, but no fever, night sweats, chest pain, or abdominal pain.  Her past medical history is unremarkable and she is currently on no medications.  Family history is significant for a mother and sister with hypothyroidism.  The patient has a 5-pack-year smoking history and drinks 2 glasses of beer on weekends.  She has a nutritious diet with regular intake of vegetables, meats, whole-grain foods, and dairy products.  Examination shows tenderness at both shins and vitiligo over her back. Laboratory results are as follows:
 The red blood cells are hypochromic and microcytic.  Basic metabolic chemistry panel is otherwise normal.  The serum ferritin level is low.  Plasma 25-hydroxy vitamin D level is undetectable.  Which of the following blood tests is likely to indicate the diagnosis?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c14f_6962_8f63_29b9df9b167d_MD0005_00 This patient has iron and vitamin D deficiencies despite consuming a nutritious diet, suggesting a malabsorption disorder. In a young patient with multi-nutrient malabsorption, the most likely explanation is celiac disease (gluten-sensitive enteropathy). The likelihood of celiac disease is even higher in this patient with vitiligo and a family history of hypothyroidism (associated autoimmune disorders). Although celiac disease is classically associated with prominent gastrointestinal symptoms such as diarrhea, a substantial subset of patients develops malabsorption with minimal or no gastrointestinal symptoms. Screening for celiac disease is performed by checking the anti-endomysial antibody and anti-tissue transglutaminase antibody levels. Simultaneously checking both antibody levels increases the sensitivity for diagnosing the disease. The gold standard for diagnosis is small intestinal biopsy. (Choice B) Alkaline phosphatase is a marker of bone turnover (bone fraction) as well as biliary tract disease (liver fraction). In the setting of vitamin D deficiency, the elevated serum alkaline phosphatase level is most likely related to high bone turnover. In the absence of other features suggesting concurrent liver disease, fractionation of alkaline phosphatase is not needed. (Choice C) Circulating 25-hydroxyvitamin D is converted to the active form, 1,25-hydroxyvitamin D, primarily in response to parathyroid hormone. Although 25-hydroxyvitamin D levels are very sensitive markers for vitamin D intake, 1,25-dihydroxy-vitamin D levels may remain normal until late stages of vitamin D deficiency due to upregulation of 1-alpha-hydroxylase in the kidneys. In this patient with vitamin D deficiency confirmed by a low 25-hydroxyvitamin D level, measuring 1,25-hydroxyvitamin D would be unlikely to add any additional useful information. (Choice D) Hypocalcemia in hypoparathyroidism is associated with increased serum phosphorus levels. This patient has hypophosphatemia, making hypoparathyroidism unlikely. In addition, bone pain is not a typical feature of hypoparathyroidism. Parathyroid hormone level in this patient may be elevated due to secondary hyperparathyroidism; however, measurement will not be helpful in delineating the diagnosis. (Choice E) Multiple myeloma (MM) is a potential cause of bone pain in older patients. Patients with MM can also show anemia, hypercalcemia, and renal insufficiency as well as systemic symptoms such as fatigue and weight loss. It is strongly suggested by a monoclonal protein on serum or urine protein electrophoresis. However, MM is unlikely in young patients such as this. In addition, alkaline phosphatase is not usually elevated in MM as the lytic bone lesions are characterized by bone resorption rather than bone turnover with new bone formation. Educational objective: Celiac disease is a common cause of multi-nutrient malabsorption. Iron deficiency anemia and vitamin D deficiency can develop even in the absence of classic gastrointestinal malabsorption symptoms such as diarrhea. References: Metabolic and nutritional features in adult celiac patients. (http://www.ncbi.nlm.nih.gov/pubmed/18431062)

A 25-Year-Old Woman Comes to the Physician with 2 Months