A Complex Medical Case: Understanding Unexplained Weight Loss and Neurological Symptoms

Table of Contents

• Case Presentation
• Medical History and Medications
• Physical Examination Findings
• Laboratory Test Results
• Imaging Studies
• Diagnostic Process
• Final Diagnosis
• Clinical Implications
• Limitations
• Patient Recommendations
• Source Information

Case Presentation

A 70-year-old man arrived at the emergency department with a 6-week history of concerning symptoms. He had experienced complete loss of appetite (anorexia), significant weakness, and unintentional weight loss. His psychiatrist had initially increased his depression medication (bupropion) due to progressive fatigue, but when his symptoms worsened, the medication was reduced and then stopped entirely.

Just eight days before this hospital visit, the patient had come to the same emergency department with muscle weakness, headache, and ongoing appetite loss. Doctors performed imaging studies at that time which revealed some abnormalities that required further investigation.

Despite initial treatment with medications for nausea and headache, his condition continued to deteriorate. He returned to the hospital seven days later with severe fatigue, taste disturbances (dysgeusia), and reported losing 13.6 kg (approximately 30 pounds) over the previous six weeks.

Medical History and Medications

The patient had several significant medical conditions in his history. He had been treated for hairy-cell leukemia (a type of blood cancer) that had been in remission for seven years. He also had major depressive disorder that required multiple psychiatric hospitalizations and treatments including electroconvulsive therapy and a vagus nerve stimulator implant.

Other conditions included obesity treated with gastric bypass surgery, high blood pressure (hypertension), and enlarged prostate (benign prostatic hyperplasia). His medication regimen included bupropion, escitalopram, gabapentin, risperidone, tamsulosin, and lisinopril.

The patient lived alone in an urban area and was mostly homebound due to his declining health, requiring assistance with daily activities. He did not smoke, drink alcohol, or use recreational drugs, and had no recent travel or exposure to sick individuals.

Physical Examination Findings

On examination, doctors noted several abnormal findings. His temperature was normal at 36.3°C, but he had elevated blood pressure (136/81 mm Hg), rapid heart rate (100 beats per minute), and fast breathing (24 breaths per minute) despite normal oxygen levels.

Notable physical findings included scattered bruises and thinning of the skin, though there was no rash or small bleeding spots (petechiae). The patient remained alert and could perform mental tasks like reciting the days of the week backward without difficulty during the initial exam.

Laboratory Test Results

Blood tests revealed several significant abnormalities. The patient had low potassium levels (3.1 mmol/L, normal range 3.4-5.0) and high blood sugar (225 mg/dL, normal range 70-110). His blood count showed low platelets (91,000 per microliter, normal range 150,000-400,000) which was a chronic condition from his cancer treatment, and low lymphocyte count (570 per microliter, normal range 1000-4800).

Other notable findings included low carbon dioxide levels (16 mmol/L, normal range 23-32), elevated blood urea nitrogen (28 mg/dL, normal range 8-25), and abnormal blood gas readings showing respiratory alkalosis (pH 7.48 with low carbon dioxide pressure). His hemoglobin A1c (a measure of long-term blood sugar control) was 7.2%, up from 6.2% a year earlier.

Testing for HIV, syphilis, hepatitis B, and hepatitis C all returned negative results. Vitamin B12, copper, and thyroid function tests were normal.

Imaging Studies

CT scans of the abdomen and pelvis revealed a small growth (nodule) on the left adrenal gland measuring 1.9 cm in diameter. This lesion was indeterminate, meaning doctors couldn't determine if it was benign or concerning based on the imaging characteristics alone.

Scans of the head and neck showed no acute abnormalities initially. However, when repeated five days later after the patient's condition worsened, new areas of concern appeared in the brain. These showed areas of decreased density in the right caudate and anterior limb of the internal capsule, and the left lateral thalamus, suggesting possible small strokes (lacunar infarcts).

Diagnostic Process

The medical team used a systematic approach they called "jigsaw heuristics" to solve this complex case. They began by laying out all available information, then identified key timelines and boundaries of the problem.

They identified several pivot points for their diagnostic thinking. The patient showed numerous features suggesting Cushing's syndrome (hypercortisolism), including fatigue, hypertension, skin changes, low potassium, and high blood sugar. However, he lacked typical features like weight gain and facial fullness.

The dramatically abnormal spinal fluid findings provided crucial clues. The cerebrospinal fluid showed elevated white blood cells (67 cells/μL, normal 0-5), low glucose (2 mg/dL, normal 50-75), high protein (92 mg/dL, normal 5-55), and extremely high opening pressure (≥58 cm water). These findings pointed strongly toward meningoencephalitis, particularly of fungal origin.

The team recognized that Cushing's syndrome suppresses the immune system, making patients vulnerable to opportunistic infections like fungal meningitis. The combination of hormonal imbalance and immune suppression created the perfect conditions for a severe infection to develop.

Final Diagnosis

The final diagnosis was cryptococcal meningitis caused by Cryptococcus neoformans infection occurring in the context of undiagnosed Cushing's syndrome. Blood cultures eventually grew yeast organisms, confirming the fungal infection.

Cushing's syndrome explained many of the patient's initial symptoms including skin thinning, bruising, high blood pressure, low potassium, and high blood sugar. The adrenal nodule found on imaging was likely the source of excess cortisol production.

The cryptococcal meningitis explained the neurological deterioration, headaches, and abnormal spinal fluid findings. The immune suppression caused by excess cortisol allowed this typically opportunistic infection to take hold and progress rapidly.

Clinical Implications

This case demonstrates several important clinical implications for patients. First, it shows how hormonal disorders like Cushing's syndrome can have wide-ranging effects throughout the body, including weakening the immune system and making patients vulnerable to serious infections.

Second, it illustrates that weight loss isn't always positive - when unintended and accompanied by other symptoms, it can signal serious underlying medical conditions. The patient's 13.6 kg weight loss over six weeks was a crucial red flag that prompted further investigation.

Third, the case highlights how patients with complex medical histories require careful coordination between specialists. This patient's cancer history, mental health treatment, and surgical history all contributed to the diagnostic challenge.

Finally, it shows the importance of considering rare but serious infections in patients with unexplained neurological symptoms, especially when they have conditions or treatments that affect immune function.

Limitations

This case report has several limitations that patients should understand. As a single case study, it represents one patient's experience and may not apply to everyone with similar symptoms. The diagnostic process took time, and the patient's condition deteriorated significantly before the final diagnosis was confirmed.

The presence of the vagus nerve stimulator prevented MRI imaging, which might have provided additional information earlier in the diagnostic process. Additionally, the patient's multiple medical conditions and medications created a complex clinical picture that made isolating individual contributing factors challenging.

Finally, the report doesn't provide long-term follow-up information, so we don't know how the patient responded to treatment or what his ultimate outcome was.

Patient Recommendations

Based on this case, patients should consider several important recommendations. If you experience unexplained weight loss (especially rapid loss of 10+ pounds without trying), persistent fatigue, or changes in mental function, seek medical attention promptly.

Patients with complex medical histories should ensure all their doctors are aware of all their conditions and medications. This is particularly important for patients with:

• History of cancer or cancer treatments
• Mental health conditions and treatments
• Previous weight loss surgery
• Multiple chronic conditions

If you have conditions or take medications that affect your immune system, be vigilant for signs of infection including persistent headaches, fever, or changes in mental status. Don't assume symptoms are just side effects of your existing conditions or medications.

Finally, advocate for thorough evaluation when symptoms don't make sense or don't improve with initial treatments. Complex cases often require time, multiple tests, and specialist collaboration to reach the correct diagnosis.

Source Information

Original Article Title: Case 13-2025: A 70-Year-Old Man with Weight Loss, Weakness, and Anorexia

Authors: Matthew G. Gartland, Anthony R. Russo, Samuel C.D. Cartmell, John S. Albin, Daniel Restrepo

Publication: The New England Journal of Medicine, May 8, 2025

DOI: 10.1056/NEJMcpc2412518

This patient-friendly article is based on peer-reviewed research from the Case Records of the Massachusetts General Hospital series.