Diagnosing the Treatment

A 70-year-old man presented to the emergency department with 5 days of decreased appetite, frequent urination, tremors, and memory difficulties. He also reported 9 months of malaise, generalized weakness, and weight loss. There was no history of fever, chills, nausea, diarrhea, constipation, pain, or focal neurologic complaints.

This patient exemplifies a common clinical challenge: an older adult with several possibly unrelated concerns. In many patients, a new presentation is usually either a different manifestation of a known condition (eg, a complication of an established malignancy) or the emergence of something they are at risk for based on health behavior or other characteristics (eg, lung cancer in a smoker). The diagnostic process in older adults can be complicated because many have, or are at risk for, multiple chronic conditions.

After reviewing the timeline of symptoms, the presence of 9 months of symptoms suggests a chronic and progressive underlying process, perhaps with subsequent superimposition of an acute problem. Although it is not certain whether chronic and acute symptoms are caused by the same process, this assumption is reasonable. The superimposition of acute symptoms on a chronic process may represent progression of the underlying condition or an acute complication of the underlying disease. However, the patient’s chronic symptoms of malaise, weakness, and weight loss are nonspecific.

Although malignancy is a consideration given the age of the patient and time course of symptoms, attributing the symptoms to a specific pattern of disease or building a cogent differential diagnosis is difficult until additional information is obtained. One strategy is to try to localize the findings to 1 or more organ systems; for example, given that tremors and memory difficulties localize to the central nervous system, neurodegenerative disorders, such as “Parkinson plus” syndromes, and cerebellar disease are possible. However, this tactic still leaves a relatively broad set of symptoms without an immediate and clear unifying cause.

The patient’s medical history included hyperlipidemia, peripheral neuropathy, prostate cancer, and papillary bladder cancer. The patient was admitted to the hospital 4 months earlier for severe sepsis presumed secondary to a urinary tract infection, although bacterial cultures were sterile. His social history was notable for a 50 pack-year smoking history. Outpatient medications included alfuzosin, gabapentin, simvastatin, hydrocodone, and cholecalciferol. He used a Bright Light Therapy lamp for 1 hour per week and occasionally used calcium carbonate for indigestion. The patient’s sister had a history of throat cancer.

On examination, the patient was detected with blood pressure of 104/56 mm Hg, pulse of 85 beats per minute, temperature of 98.2 °F, oxygen saturation of 97% on ambient air, and body mass index of 18 kg/m². The patient appeared frail with mildly decreased strength in the upper and lower extremities bilaterally. The remainder of the physical examination was normal. Reflexes were symmetric, no tremors or rigidity was noted, sensation was intact to light touch, and the response to the Romberg maneuver was normal.

Past medical history is the cornerstone of the diagnostic process. The history of 2 different malignancies is the most striking element in this case. Papillary bladder cancer is usually a local process, but additional information is needed regarding its stage and previous treatment, including whether or not the patient received Bacille Calmette Guerin (BCG) vaccine, which can rarely be associated with infectious and inflammatory complications. Metastatic prostate cancer could certainly account for his symptomatology, and bladder outlet obstruction could explain the history of urinary frequency and probable urosepsis. His medication list suggested no obvious causes to explain his presentation, except that cholecalciferol and calcium carbonate, which when taken in excess, can cause hypercalcemia. This finding is of particular importance given that many of the patient’s symptoms, including polyuria, malaise, weakness, tremor, memory difficulties, anorexia, acute kidney injury and (indirectly) hypotension and weight loss, are also seen in patients with hypercalcemia. The relatively normal result of the neurologic examination decreases the probability of a primary neurologic disorder and increases the likelihood that his neurologic symptoms are due to a global systemic process. The relative hypotension and weight loss similarly support the possibility that the patient is experiencing a chronic and progressive process.