A 72-year-old man comes to the office due to progressive weakness, fatigue, anorexia, and a 10-kg (22-lb) weight loss over the past 4 months. He says that food doesn't taste as good as it once did, and he feels full after eating only a small amount. The patient has had a morning cough for the past several years and had streaks of blood in his sputum 2 weeks ago. He has a 50-pack-year smoking history. On examination, the patient appears frail with a sunken face and bitemporal wasting. His arms are thin with notable muscle wasting. Lung examination reveals wheezing on the right side. Chest x-ray reveals an irregular right perihilar mass. Which of the following is most likely contributing to this patient's muscle wasting?

Question

A 72-year-old man comes to the office due to progressive weakness, fatigue, anorexia, and a 10-kg (22-lb) weight loss over the past 4 months.  He says that food doesn't taste as good as it once did, and he feels full after eating only a small amount.  The patient has had a morning cough for the past several years and had streaks of blood in his sputum 2 weeks ago.  He has a 50-pack-year smoking history.  On examination, the patient appears frail with a sunken face and bitemporal wasting.  His arms are thin with notable muscle wasting.  Lung examination reveals wheezing on the right side.  Chest x-ray reveals an irregular right perihilar mass.  Which of the following is most likely contributing to this patient's muscle wasting?

Quizplus · Accepted Answer

Cachexia is a syndrome that encompasses anorexia, malaise, anemia, weight loss, and generalized wasting due to underlying systemic disease. Cachexia in this patient is likely a manifestation of the lung neoplasm revealed on his chest x-ray. Tumor necrosis factor-α (TNF-α) is a cytokine that causes necrosis of some tumors in vitro and produces symptoms of cachexia in experimental animals. TNF-α is also called cachectin and is considered a main mediator of paraneoplastic cachexia (along with interleukin [IL]-1β, and IL-6). TNF-α is produced by macrophages in response to infection as well as by some neoplastic cells. Its role in cachexia is explained by its influence on the hypothalamus, leading to appetite suppression. It also increases basal metabolic rate. In bacterial infections, TNF-α produces fever (along with IL-1), mediates many of the symptoms of septic shock, and causes hepatic release of acute-phase reactants (eg, C-reactive protein and fibrinogen). (Choice A) Eaton-Lambert syndrome is a paraneoplastic condition that manifests as progressive, symmetric proximal muscle weakness (rather than wasting) along with ocular and autonomic symptoms. It is due to autoantibodies to voltage-gated calcium channels. (Choice B) Interferon-α is synthesized by leukocytes and has antiviral as well as anti-tumor activity. (Choice C) IL-3 is produced by activated CD4+ T_H cells. It stimulates growth and differentiation of myeloid cells. (Choice D) The main function of transforming growth factor-β is inhibition of the inflammatory response. It decreases T cell proliferation and cytokine production. (Choice F) Production of vasopressin by some tumors (eg, small cell lung cancer) results in the syndrome of inappropriate antidiuretic hormone secretion. Educational objective: Tumor necrosis factor-α is thought to mediate paraneoplastic cachexia in humans by suppressing appetite and increasing basal metabolic rate.

A 72-Year-Old Man Comes to the Office Due to Progressive