Acute Adrenal Insufficiency with Hypercalcemia: An Unusual Initial Presentation of Primary Adrenal Lymphoma

Primary Adrenal Lymphoma (PAL) is a very rare malignancy accounting for < 1% of non-Hodgkin's Lymphoma. We report, to our knowledge, the first case of PAL associated with adrenal insufficiency (AI) and hypercalcemia.

Case Description :

A 65-year-old healthy male presented to the hospital with confusion, weakness and weight loss for few months. On examination, vitals were normal, BMI 23(27.2 a few months ago). Labs showed AM Cortisol 3.94mcg/dl (6.02-18.4), ACTH 258 pg/mL (9-118), calcium 10.4mg/dL (8.6-10.4), negative adrenal antibodies and CBC, CMP, TSH were normal. CT showed bilateral adrenal masses left 4.5x1.6cm >right 4.1x1.6cm. The working diagnosis was reduced adrenal reserve due to mass effect and he was discharged on hydrocortisone 15mg am/5mg pm. He was admitted a few months later for fever and altered mentation, labs showed hypercalcemia 11.2mg/dL (8.6-10.4), Albumin 3.5g/dL (3.5-5.5), Vitamin D 29.3ng/mL (25-80), PTH 5pg/mL (9-76), PTHrP 0.5pmol/L ( < 4.2), Cr 1.2mg/dL (0.5-1.2), LDH 401 IU/L (125-220), quantiferon negative. CT abdomen showed increase in the size of the adrenal mass, abdominal lymphadenopathy and splenomegaly. FNA biopsy of the left adrenal mass showed diffuse large B-cell lymphoma (non-germinal center type). Hypercalcemia was treated with fluids and bisphosphonate. He achieved remission after R-CHOP chemotherapy.

Discussion :

PAL affects elderly males and involves both adrenal glands in 70% of cases. Clinical features of PAL include B symptoms, symptoms related to tumor mass, and AI. There is no clear definition of PAL, so most clinicians have adopted the following criteria: 1) biopsy confirmed adrenal lymphoma; 2) no other organ involvement after diagnosis for at least 6 months; 3) no evidence of leukemia. Adrenal biopsy may be a diagnostic option after excluding pheochromocytoma. Hypercalcemia can occur due to increased alpha hydroxylation. Treatment of PAL includes combination chemotherapy and surgery, followed by adjuvant chemo/radiation. Median survival ranges from 13-26 months and poor prognostic factors are advanced age, tumor size, elevated LDH, and germinal center phenotype. Bilateral involvement of the adrenals with AI worsens the prognosis.
Owing to lack of clear definition, rarity and non-specific symptoms, PAL poses a unique challenge. Complete evaluation on the etiology of the adrenal mass could have prevented the delay in the treatment and morbidity in our case. Hence, it is crucial to have a high index of suspicion for PAL in patients presenting with bilateral adrenal masses in the setting of rapid onset AI, hypercalcemia, and weight loss. Early diagnosis and intervention have a significant impact on clinical outcome.