A 35-year-old woman comes to the office with malaise and generalized weakness. Her other medical problems include type 1 diabetes mellitus and hypothyroidism for which she takes insulin and levothyroxine. She eats a balanced, diabetic diet and exercises 5 times per week. Physical examination shows mild conjunctival pallor.Laboratory results are as follows: Further evaluation shows a very low vitamin B₁₂ level and a normal folate level. Which of the following sets of physiologic alterations is most likely to be present in this patient?

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11ec160b_3ae9_6bb9_9249_4f115043d0f0_MD0001_00 This patient's vitamin B₁₂ (cobalamin) deficiency in the setting of preexisting autoimmune disease (eg, type 1 diabetes mellitus, Hashimoto thyroiditis) is suggestive of pernicious anemia. This condition occurs as a result of a CD4+ cell-mediated immune response against parietal cells found in the body and fundus of the stomach (autoantibodies against parietal cell components are also produced and are useful for diagnosis but not significantly involved in the pathogenesis). Progressive destruction of oxyntic (acid-producing) mucosa leads to loss of parietal cell mass, causing the following effects: Decreased intrinsic factor secretion impairs absorption of dietary vitamin B₁₂ by the terminal ileum, resulting in vitamin B₁₂ deficiency and the development of megaloblastic anemia. Decreased secretion of hydrochloric acid (achlorhydria) causes an elevated intraluminal pH that stimulates gastrin secretion by gastric G cells. (Choice B) Proton pump inhibitors result in elevated intraluminal pH, causing upregulation of gastrin secretion. Prolonged use may result in secondary hypertrophy and hyperplasia of parietal cells. (Choice C) Gastrinomas are gastrin-secreting tumors commonly located in the pancreas and duodenum. Excess gastrin production leads to parietal cell hypertrophy and hydrochloric acid hypersecretion. (Choices D and E) In patients with pernicious anemia, autoimmune destruction of parietal cells results in excess gastrin production (not decreased production). This increases the risk of neuroendocrine (carcinoid) tumors. Educational objective: Pernicious anemia is an autoimmune disease characterized by CD4+ cell-mediated destruction of parietal cells. As parietal cells are destroyed, their ability to secrete hydrochloric acid decreases, resulting in an elevated intraluminal pH that leads to upregulation of gastrin secretion. Patients also develop vitamin B₁₂ deficiency as a result of decreased intrinsic factor secretion. __________ References: Diagnosis and management of pernicious anemia. (http://www.ncbi.nlm.nih.gov/pubmed/21947876)

A 35-Year-Old Woman Comes to the Office with Malaise and Generalized