79-Year-Old Woman With Forgetfulness

A 79-year-old woman presented to the clinic because she had experienced forgetfulness over the previous 6 months. She had no trouble completing her daily activities or paying her own bills, but she was having increased difficulty remembering people's names. She had no other symptoms. She was exercising daily without any chest pain or shortness of breath noted. She denied experiencing any fever, changes in weight, light-headedness, changes in urine or stool, nausea, vomiting, or any gastroesophageal reflux symptoms. She had not had any focal neurologic deficits or changes in her gait. Her medical history was remarkable for chronic low back pain due to osteoarthritis, essential hypertension, and gastroesophageal reflux disease. She was taking ramapril, tramadol, and vitamin D supplements. Her surgical history was notable for several knee arthroscopies and a hysterectomy. She had a 10-pack-year history of tobacco use but had quit smoking more than 10 years ago. She was up-to-date on her yearly mammogram and immunizations but was due for a colonoscopy later in the year. She denied any use of illicit drugs or excessive use of alcohol. Her family history included breast cancer in her maternal aunt. The patient's cardiac and respiratory examination findings were normal, including S1 and S2 without murmur or gallop and clear lung sounds bilaterally with no evidence of wheezing. Abdominal examination revealed a soft, nontender, nondistended abdomen with normal bowel sounds and no hepatosplenomegaly. Neurologic examination elicited grossly intact responses. Other findings on physical examination were unremarkable. Results of laboratory testing, including complete blood cell count and electrolyte panel, were all within normal limits except for microcytosis (mean corpuscular volume, 78 fL). Electrocardiography showed sinus rhythm with first-degree atrioventricular block. Chest radiography showed no consolidation or abnormalities other than degenerative spinal changes. Further serum analysis revealed a ferritin level of 9 ng/mL and an undetectably low vitamin B12 level. 1 To determine the cause of the vitamin B12 deficiency, which one of the following is the most appropriate diagnostic test at this time? a Schilling test b Metabolites of methylmalonate (MMA) measurement c Stool studies for ova and parasites d Determination of serum iron level and total iron-binding capacity (TIBC) e Electromyelography Although the Schilling test was once commonly used in the work-up of vitamin B12 deficiency, most laboratories have stopped performing it because production of the cobalt radioisotopes and labeled vitamin B12 test substances is lacking. The level of MMA is elevated in more than 90% of patients with vitamin B12 deficiency. However, MMA tends to have a relatively high false-positive rate in elderly persons, with as many as 25% of patients over the age of 70 years having elevated levels of MMA and up to one-third of these patients having normal vitamin B12 levels.1 Stool studies to evaluate whether tapeworms could be causing vitamin B12 deficiency have very low yield in patients who have no history of recent international travel or weight loss. In light of the microcytosis, measurement of the serum iron level and TIBC would be appropriate to determine whether blood loss is occurring. Electomyelography can be useful in diagnosing peripheral neurologic changes from vitamin B12 deficiency but would not be the next step in an asymptomatic patient. Low serum ferritin levels are highly sensitive for iron deficiency and are the mainstay of initial testing. Serum iron levels and TIBC were low and high, respectively, in this patient, providing further evidence of iron deficiency. In the presence of the vitamin B12 deficiency, oral iron supplementation and vitamin B12 subcutaneous replacement therapy were initiated. Serum anti-intrinsic factor antibody testing was considered but was not performed. 2 Which one of the following procedures is the most appropriate next diagnostic test? a Tagged red blood cell scan b Upper and lower endoscopy c Measurement of gastric acid secretion d Endoscopic ultrasonography e Computed tomographic (CT) angiography Tagged red blood cell imaging is useful to evaluate for bleeding of the small intestine but should be done only after upper and lower endoscopy, if these are available. Endoscopy allows for gross evaluation of the alimentary canal to assess whether signs of blood loss or atrophic gastritis exist, as well as allowing for biopsies of the gastric and duodenal mucosa. Measurement of gastric acid secretion is a cumbersome and invasive test that would be appropriate only if other testing did not yield a diagnosis. Endoscopic ultrasonography would be used to perform biopsy or to assess the homogeneity of a mass suspected of causing blood loss. Computed tomographic angiography would show vessels supplying the gastric and intestinal tissues, but it has a very low sensitivity for detecting small vessel bleeds. Upper endoscopy revealed multiple gastric polyps, including one actively bleeding pyloric polyp protruding into the duodenum. Histologic examination of the biopsy specimens showed evidence of atrophic gastritis and multiple carcinoid polyps. Because these findings explained both the iron deficiency anemia and pernicious anemia, colonoscopy was not performed. 3 In view of the endoscopic findings, which one of the following tests is the most appropriate next step? a Chest radiography b Genetic testing for familial adenomatous polyposis c CT of the head d Measurement of 24-hour urinary serotonin excretion e Determination of serum gastrin and chromogranin A levels Although a chest x-ray may identify a suspicious lesion in the chest that could represent a carcinoid tumor, this finding is highly nonspecific. Genetic testing for familial adenomatous polyposis would not be necessary because this disease manifests with adenomatous polyps in the large intestine. A CT scan of the head, which could identify a pituitary mass suggesting multiple endocrine neoplasia type 1, would not be the next test ordered. Measurement of 24-hour urinary secretion of serotonin would be an appropriate test for metastatic carcinoids; however, serum gastrin and chromogranin A levels would be important to establish whether atrophic gastritis was the cause of the gastric carcinoids. On serum analysis, the gastrin level was found to be very elevated at more than1800 pg/mL (reference range, <100 pg/mL), and the chromogranin A level was also elevated at more than 1300 ng/mL (reference range, ≤225 ng/mL). 4 Which one of the following procedures is most appropriate at this time? a Observation b Barium swallow study c Wireless pH study d Confocal endoscopy e Upper endoscopy with endoscopic ultrasonography Observation would not be appropriate in this case, nor would a barium swallow study because it is not highly sensitive for gastric lesions. Because it would not lead to a definitive diagnosis, a wireless pH study would not be the procedure of choice in this case. Confocal endoscopy, used to assess histologic features of alimentary masses, would not be appropriate. Upper endoscopy with endoscopic ultrasonography would be prudent to assess the depth and the homogeneity of the polyps. This would also allow for fine-needle biopsy of the lesions. Upper endoscopy with endoscopic ultrasonography was performed to categorize the depth and the density of the polyps, which were found to be smaller than 1 cm each. For staging, CT scan of the abdomen and pelvis was done following the identification of the gastric polyps, which showed no evidence of regional lymph node involvement or distant metastasis. 5 On the basis of the endoscopic and CT findings, which one of the following procedures is the most appropriate next step? a Endoscopic mucosal resection (EMR) b Total gastrectomy c Gastric vagotomy d Helicobacter pylori stool testing e Parietal cell antibody testing Because the lesions are smaller than 1 cm each, EMR is the next step in treatment of this patient. Total gastrectomy would not be necessary at this time because of the absence of distant metastasis. Gastric vagotomy would not be the definitive treatment. H pylori testing would be important in the management of a patient who did not undergo an upper endoscopy with tissue biopsy. A serum test for pernicious anemia or parietal cell antibody testing would not lead to a diagnosis of the underlying tissue disorder. Endoscopic mucosal resection was performed with successful removal of the largest gastric carcinoids and the large benign pyloric polyp. These procedures were done as both treatment of the iron deficiency anemia and prevention of further progression of the gastric carcinoid. Repeated serum laboratory testing at 3 months indicated resolution of both vitamin B12 and iron deficiencies, as well as normalization of her previous anemia. Further, the patient's memory difficulties greatly improved, suggesting that vitamin B12 deficiency was contributing to her cognitive impairment. The patient will be monitored with screening endoscopy every 6 months and will continue vitamin B12 and iron supplementation.