Prolonged and Recurrent Hypoglycemia Induced by Trimethoprim-Sulfamethoxazole in a Hodgkin Lymphoma Patient with Pneumocystis carinii Pneumonia
This case report describes a 64-year-old Chinese male patient with Hodgkin lymphoma who developed prolonged and recurrent hypoglycemia following treatment with trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis carinii pneumonia (PCP). The patient’s clinical course, diagnostic challenges, and management strategies highlight the rare but potentially life-threatening adverse effects of TMP-SMX, particularly in patients with renal dysfunction.
Patient Presentation and Initial Diagnosis
The patient was admitted to the hematology department of Peking University First Hospital with a history of intermittent fever lasting three months and the recent discovery of enlarged cervical lymph nodes. A lymph node biopsy confirmed the diagnosis of nodular sclerosis, a subtype of classical Hodgkin lymphoma. Positron emission tomography/computed tomography (PET/CT) revealed widespread lymph node enlargement with high fructose diphosphate (FDG) uptake, increased glucose metabolism in the L2 vertebra, right sacrum, sciatica, and femoral neck, and low-density foci in the right lobe of the liver. Bone marrow aspiration and biopsy showed no signs of lymphoma infiltration, leading to a diagnosis of classical Hodgkin lymphoma, nodular sclerosis subtype, stage IV, group B.
Chemotherapy and Complications
The patient was started on the ABVD chemotherapy regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine). After two cycles, PET/CT showed complete remission, and the chemotherapy regimen was continued. However, one week after the third cycle, the patient developed hyperthermia, abdominal pain, and diarrhea. Laboratory tests revealed severe pancytopenia: white blood cell count was 1.31 × 10⁹/L (reference range: 3.5–9.5 × 10⁹/L), hemoglobin was 66 g/L (reference range: 130–175 g/L), and platelet count was 17 × 10⁹/L (reference range: 125–350 × 10⁹/L). The patient was diagnosed with a gastrointestinal tract infection and treated with meropenem, granulocyte-colony stimulating factor, and platelet infusion. His symptoms improved, and his body temperature normalized.
Development of Pneumocystis carinii Pneumonia
Two weeks later, the patient developed mild to moderate fever and dyspnea. Arterial blood gas analysis showed a pH of 7.461 (reference range: 7.35–7.45), partial pressure of oxygen of 36.6 mmHg (reference range: 80–100 mmHg), partial pressure of carbon dioxide of 41.3 mmHg (reference range: 35–45 mmHg), bicarbonate level of 28.2 mmol/L (reference range: 22–27 mmol/L), and oxygen saturation of 62.2% (reference range: 92.0%–98.5%). Thoracic CT revealed diffuse ground-glass opacities (Figure 1A). A presumptive diagnosis of PCP was made, as the patient refused bronchoscopy for alveolar lavage.
Treatment with Trimethoprim-Sulfamethoxazole
Given the patient’s normal estimated glomerular filtration rate (eGFR) of 70.97 mL/min/1.73 m², he was started on oral TMP-SMX at a dose of 1920 mg four times daily. His brain natriuretic peptide levels were elevated, so torsemide 10 mg/day was also prescribed. Two days later, his pulse oxygen saturation improved to 95% in room air, and his body temperature remained normal. However, on day 5, his eGFR decreased to 49.67 mL/min/1.73 m², and he suddenly became delirious, speaking nonsense and displaying involuntary arm movements. Neurological examination was unremarkable, but his blood glucose level was critically low at 1.7 mmol/L (reference range: 3.9–6.0 mmol/L).
Management of Hypoglycemia
The patient was immediately treated with an intravenous bolus of 40 mL of 50% dextrose, followed by continuous infusion of 5% glucose in normal saline. He regained mental clarity but experienced recurrent hypoglycemic episodes despite continuous infusion of 10% dextrose. Laboratory tests during the hypoglycemic episodes showed elevated plasma insulin at 115.3 mU/mL (reference range: 2.6–24.9 mU/mL) and C-peptide at 19.55 ng/mL (reference range: 1.1–4.4 ng/mL). Morning cortisol, adrenocorticotropic hormone levels, and thyroid function were normal, indicating excessive endogenous insulin secretion as the cause of hypoglycemia.
Suspected Role of Trimethoprim-Sulfamethoxazole
TMP-SMX was suspected as the cause of hypoglycemia due to its structural similarity to sulfonylureas, which stimulate insulin secretion from pancreatic beta cells. TMP-SMX and torsemide were temporarily discontinued, leading to a decrease in plasma insulin and C-peptide levels to within the normal range. However, due to the lack of alternative treatments for severe PCP in mainland China, TMP-SMX was restarted at a reduced dose of 1920 mg/day, with close monitoring of blood glucose five times daily. No further hypoglycemic episodes occurred, and one month later, thoracic CT showed significant improvement in pulmonary lesions (Figure 1B).
Discussion
PCP is a life-threatening infection that commonly occurs in immunocompromised individuals. TMP-SMX is the first-line treatment for PCP, recommended for mild, moderate, and severe disease, with a treatment duration of 21 days. However, TMP-SMX can cause severe hypoglycemia, a rare but potentially fatal adverse effect. The mechanism of TMP-SMX-induced hypoglycemia is attributed to the sulfamethoxazole component, which shares a molecular structure with sulfonylureas and stimulates insulin oversecretion.
In patients with renal dysfunction, TMP-SMX can accumulate due to reduced renal clearance, increasing the risk of hypoglycemia. The half-life of TMP-SMX is 2 to 5 times longer in patients with renal impairment compared to those with normal renal function. Therefore, regular monitoring of blood glucose is essential in patients with renal dysfunction receiving TMP-SMX.
Clinical Implications
This case underscores the importance of recognizing TMP-SMX-induced hypoglycemia, particularly in patients with renal dysfunction. While discontinuation of TMP-SMX is the safest approach to eliminate the risk of recurrent hypoglycemia, in regions where alternative treatments for severe PCP are unavailable, dose-adjusted TMP-SMX therapy with close blood glucose monitoring may be considered. Clinicians should be vigilant for this rare but serious adverse effect, especially in patients with compromised renal function.
Conclusion
This case report highlights the potential for TMP-SMX to induce prolonged and recurrent hypoglycemia, particularly in patients with renal dysfunction. Although rare, this adverse effect can be life-threatening if not promptly recognized and managed. Clinicians should be aware of this risk and consider close monitoring of blood glucose in patients receiving TMP-SMX, especially those with renal impairment. Dose adjustment and careful monitoring can allow for the continued use of TMP-SMX in cases where alternative treatments are unavailable.
doi.org/10.1097/CM9.0000000000001285
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