Elevated serum LDH in patients with non‐Hodgkin's lymphoma: not always an ominous sign

Abstract

The serum level of lactate dehydrogenase (LDH) is commonly elevated in lymphoproliferative disorders. In patients with non-Hodgkin's lymphoma (NHL), LDH values have prognostic value and are commonly used to assess treatment response and monitor for tumour recurrence. LDH is widely distributed in mammalian tissues, and high concentrations are found in muscle and liver cells in addition to haemopoietic cells and their descendants (2). Because of this distribution, there are other causes of an elevated serum LDH in addition to malignancy. These include myocardial or pulmonary infarction, hepatic dysfunction, haemolysis, and myopathy. Elevated serum LDH levels in association with hypothyroidism have also been reported (1). When patients with treated non-Hodgkin's lymphoma develop other disorders that cause elevated serum LDH levels, anxiety and an unnecessary tumour hunt can result. This may be especially likely with hypothyroidism, which is asymptomatic in its early stages. We report three cases of elevated serum LDH due to hypothyroidism in patients who had been treated for non-Hodgkin's lymphoma. A 56-year-old man presented in July 1995 with a large-cell lymphoma of the soft tissue of the left neck. Initial serum LDH was 335 U/l (normal 104–236 U/l); serum levels of sensitive thyroid-stimulating hormone (sTSH) and total thyroxine (T4) were normal. The patient received radiation therapy to the left neck and mediastinum and chemotherapy. His serum LDH fell to 249 U/l following treatment, and his free-thyroxine index was normal. 4 months following the completion of treatment, a routine surveillance serum LDH was 469 U/l; on repeat testing it was 493 U/l. Extensive evaluation for recurrent lymphoma was unrevealing. His sTSH was found to be markedly elevated (57.2 mU/l; normal 0.30–5.0 mU/l), and levothyroxine was administered. 6 weeks later the patient's LDH had fallen to 188 U/l. 5 months later the sTSH and LDH were both within normal limits, and the patient remains free of lymphoma 3 years later. He continues to take levothyroxine daily. A 72-year-old woman presented in April 1990 with a left supraclavicular follicular mixed-cell non-Hodgkin's lymphoma. Initial serum LDH was normal. She was treated with radiation in a mini-mantle pattern and achieved a clinical complete remission. An intra-abdominal recurrence in 1992 was associated with an LDH of 541 U/l and was successfully treated with chemotherapy. Her LDH fell below 200 U/l. In January 1997 a routine surveillance LDH was found to be 521 U/l. Extensive evaluation for recurrent tumour was unrevealing. Her sTSH was elevated (9.2 mU/l); the T4 level was normal (83 nmol/l; normal 65–160 nmol/l). Her only previous thyroid study had been a normal T4 (87 nmol/l) in 1978. She started levothyroxine therapy. 6 weeks later her LDH had fallen to 125 U/l and her sTSH had normalized at 1.5 mU/l. 2 years later her LDH remains normal and she is lymphoma-free. A 64-year-old woman presented in July 1997 with retroperitoneal large-cell non-Hodgkin's lymphoma. The serum LDH was 562 U/l. The patient was also found to have an elevated sTSH (12.7 mU/l) with a normal free thyroxine (18 pmol/l; normal 10–24 pmol/l). She began oral levothyroxine. She then received chemotherapy and achieved a complete remission. Following chemotherapy, her sTSH was normal and LDH was 189 U/l. 3 months after completing chemotherapy the patient's LDH was found to have increased to 273 U/l. Evaluation for tumour recurrence was unrevealing. Her sTSH was checked and elevated (7.6 mU/l), so her levothyroxine dose was increased; 6 weeks later her LDH had fallen to 117 U/l and sTSH was 0.11 mU/l. In August 1998 the patient's LDH and sTSH were again found to be rising. She admitted to decreasing her levothyroxine dose because of insomnia. She began taking supplementary hog thyroid extract, and her sTSH and LDH returned to normal. Her lymphoma remains in remission. We report three cases of elevated serum LDH values due to hypothyroidism in patients previously treated for non-Hodgkin's lymphoma. To our knowledge, no previous cases of LDH elevation due to hypothyroidism in this subgroup of patients have been reported. In each case, treatment of non-Hodgkin's lymphoma resulted in normalization of a previously elevated LDH value. Subsequently the LDH was found to be elevated on routine surveillance testing, but no tumour recurrence could then be detected. Biochemical evidence of hypothyroidism was then identified (all three patients were asymptomatic), and the LDH values normalized after thyroid hormone replacement was initiated. These three cases demonstrate that an elevated serum LDH level may not always be due to tumour recurrence in patients previously treated for non-Hodgkin's lymphoma. Clinicians must keep the possibility of undiagnosed hypothyroidism in mind, especially in patients previously treated with thyroid radiation, a risk factor for hypothyroidism (3).