The Adrenals Under Silent Siege: Diffuse Large B-Cell Lymphoma Presenting as Addisonian Crisis

Abstract

Primary adrenal insufficiency (Addison’s disease) is a potentially life-threatening disorder most commonly caused by autoimmune adrenalitis, though rare etiologies such as infiltrative malignancies must be considered, particularly when bilateral adrenal involvement leads to clinical manifestations. Diffuse large B-cell lymphoma (DLBCL), an aggressive subtype of non-Hodgkin lymphoma, may rarely involve the adrenal glands and precipitate adrenal crisis. We report a 58-year-old male patient who presented with giddiness, vomiting, fatigability, hyperpigmentation, weight loss, and hypotension. Laboratory evaluation revealed hyponatremia, bicytopenia, and markedly elevated adrenocorticotropic hormone (ACTH) levels, consistent with primary adrenal insufficiency. Imaging demonstrated bilateral adrenal masses with intra-abdominal lymphadenopathy, and histopathological examination of adrenal biopsy confirmed DLBCL. The patient was promptly treated with intravenous corticosteroids, resulting in hemodynamic stabilization while undergoing regular antidiabetic therapy. The patient was later referred to oncology for further management. This case highlights a rare presentation of DLBCL manifesting as Addisonian crisis due to bilateral adrenal infiltration. Given the nonspecific clinical features that often delay diagnosis, clinicians should maintain a high index of suspicion for malignant causes in patients presenting with adrenal insufficiency and bilateral adrenal masses, as early recognition and timely corticosteroid therapy are critical for improving outcomes.

Introduction

Addison’s disease, or primary adrenal insufficiency, is a disorder characterized by destruction or dysfunction of the adrenal cortex resulting in deficient production of glucocorticoids, mineralocorticoids, and adrenal androgens [1]. Cortisol deficiency impairs vascular tone, gluconeogenesis, and the physiologic stress response, while aldosterone deficiency leads to sodium wasting, volume depletion, hyperkalemia, and hypotension [2]. Chronic adrenocortical failure may present insidiously with fatigue, weight loss, anorexia, hyperpigmentation due to elevated adrenocorticotropic hormone (ACTH), and electrolyte abnormalities [2]. When unrecognized, it can culminate in Addisonian crisis, an acute, life-threatening state characterized by severe hypotension, shock, hyponatremia, hypoglycemia, and metabolic disturbances [3]. The nonspecific and protean nature of its early manifestations often delays diagnosis, increasing morbidity and mortality.

The etiopathogenesis of primary adrenal insufficiency most commonly involves autoimmune adrenalitis; however, infectious, infiltrative, metastatic, and hemorrhagic causes are also recognized [4]. Bilateral adrenal involvement is typically required before clinical insufficiency becomes evident, as the majority of cortical tissue must be destroyed before symptoms develop [1]. Among infiltrative causes, malignancies represent an uncommon but important etiology.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, arising from mature B lymphocytes and characterized by aggressive clinical behavior and rapid proliferation [5]. It commonly presents with nodal disease but may also involve extranodal sites including the gastrointestinal tract, central nervous system, bone marrow, and, less frequently, the adrenal glands [5]. Adrenal involvement may occur as part of disseminated disease or, rarely, as primary adrenal lymphoma. When bilateral, such infiltration can result in adrenal insufficiency.

We report a rare presentation of systemic DLBCL manifesting as an acute Addisonian crisis secondary to bilateral adrenal infiltration at the Rajiv Gandhi Government General Hospital. This case underscores the diagnostic challenge posed by vague constitutional symptoms and highlights the importance of considering malignant infiltration in the differential diagnosis of adrenal insufficiency.

Case presentation

A 58-year-old male patient presented with complaints of intermittent giddiness, generalized fatigability, and recurrent episodes of vomiting for 10 days. He reported an insidious onset of hyperpigmentation over the palms and soles, evening rise of temperature, progressive loss of appetite, and unintentional weight loss over the preceding weeks. Notably, he described an episode of syncope occurring during micturition. There was no significant past medical or family history. He was a former smoker and chronic alcohol consumer for over 40 years, having quit both two years prior to presentation.

On general examination, the patient was pale and hypotensive, with a blood pressure of 90/60 mmHg. Other vital parameters were within normal limits. Systemic examination did not reveal organomegaly, lymphadenopathy, or focal neurological deficits.

Laboratory investigations revealed bicytopenia with a hemoglobin of 6.1 g/dL and platelet count of 77,000/µL, while total leukocyte count was 4,200/µL (Table 1). Serum total protein (5.2 g/dL) and albumin (2.8 g/dL) were reduced. Arterial blood gas analysis showed alkalemia (pH of 7.524) with low pCO₂ (25.8 mm Hg). Serum sodium was 129 mEq/L. Random blood glucose was 346 mg/dL, with HbA1c of 8%. Coagulation parameters were within the low-normal range. Serum ACTH was markedly elevated at 240 pg/mL.

Table 1. Baseline laboratory parameters at presentation.

RBC: red blood cell; RDW: red cell distribution width; HbA1c: hemoglobin A1c; pCO₂: partial pressure of carbon dioxide; pO₂: partial pressure of oxygen; DM: diabetes mellitus; ACTH: adrenocorticotropic hormone

Investigation	Value	Reference range
Hemoglobin	6.1 g/dL	13-17 g/dL (male)
Packed cell volume (PCV)	18.8%	40-50%
RBC count	2.3 million/µL	4.5-5.9 million/µL
Platelet count	77,000/µL	150,000-450,000/µL
Total leukocyte count	4,200/µL	4,000-11,000/µL
RDW	18.3%	11.5-14.5%
Total protein	5.2 g/dL	6.0-8.3 g/dL
Albumin	2.8 g/dL	3.5-5.0 g/dL
Arterial pH	7.524	7.35-7.45
pCO₂	25.8 mmHg	35-45 mmHg
pO₂	78 mmHg	80-100 mmHg
Serum sodium	129 mEq/L	135-145 mEq/L
Random blood sugar	346 mg/dL	<140 mg/dL (random)
HbA1c	8%	<5.7% (normal); ≥6.5% diagnostic DM
Prothrombin time	12.1 sec	11-13.5 sec
Serum cortisol	3.02 mcg/dL	6.02-18.4 mcg/dL
Serum ACTH	240 pg/mL	10-60 pg/mL

Ultrasonography of the abdomen revealed a 5 × 4 cm right adrenal lesion and a 9 × 3 cm left adrenal lesion, along with enlarged celiac lymph nodes, the largest measuring 1.7 × 1.6 cm. Contrast-enhanced computed tomography (CECT) of the abdomen confirmed bilateral heterogeneous adrenal masses measuring 5.3 × 4.2 cm (right) and 7.3 × 4 cm (left), with absolute washout of 54% and relative washout of 26.6%. Multiple enlarged lymph nodes were noted in the para-aortic, retrocaval, aortocaval, and hepatoduodenal regions. The radiological images were not available for review/documentation during preparation of this manuscript. Differential considerations included adrenal lymphoma and infectious etiologies such as tuberculosis; however, sputum examination for acid-fast bacilli was negative (Table 2).

Table 2. Radiological and histopathological investigations of the patient.

CECT: contrast-enhanced computed tomography; AFB: acid-fast bacilli; USG: ultrasonography

Investigation	Finding	Reference/normal finding
Ultrasonography abdomen	Right adrenal lesion 5 × 4 cm; Left adrenal lesion 9 × 3 cm; enlarged celiac nodes (1.7 × 1.6 cm)	Normal adrenals not enlarged; no focal mass
CECT abdomen	Bilateral heterogeneous adrenal masses (5.3 × 4.2 cm right; 7.3 × 4 cm left); multiple enlarged para-aortic, retrocaval, aortocaval, hepatoduodenal nodes; absolute washout 54%, relative washout 26.6%	No adrenal mass; no pathological lymphadenopathy
Sputum AFB	Negative	Negative
USG-guided adrenal biopsy (HPE)	Diffuse large B-cell lymphoma; CD19+, CD20+, CD45+	No malignant infiltration

Serum ACTH was markedly elevated at 240 pg/mL, supporting primary adrenal insufficiency. Ultrasound-guided adrenal biopsy was performed, and histopathological examination demonstrated diffuse infiltration by atypical lymphoid cells (Figure 1). Immunohistochemistry was positive for CD19, CD20, and CD45, consistent with a diagnosis of DLBCL. 

Figure 1. Histopathological examination of adrenal biopsy showing diffuse infiltration by atypical lymphoid cells consistent with diffuse large B-cell lymphoma.

CECT imaging revealed direct invasion into segment VI of the liver, retroperitoneal lymphadenopathy, and adrenal masses (Figure 2). Based on the Ann Arbor staging, the patient is classified as stage IV.

Figure 2. CECT image depicting a bilateral adrenal gland infiltrate.

CECT: contrast-enhanced computed tomography

A final diagnosis of Addisonian crisis due to bilateral adrenal infiltration by stage IV DLBCL, with concomitant type 2 diabetes mellitus, was established. The patient was immediately resuscitated with intravenous hydrocortisone 200 mg stat at the time of presentation, followed by maintenance dosing of 50 mg intravenously four times daily. Hemodynamic parameters improved subsequently. The standard rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen was administered every 21 days for six cycles according to weight and body area, with 100 mg oral prednisolone on days 1-5. The patient was, however, lost to follow-up, and the authors aren't aware of his current status. 

Discussion

This case highlights a rare but life-threatening presentation of DLBCL manifesting as an acute Addisonian crisis. A 58-year-old male patient presented with nonspecific constitutional symptoms including fatigue, vomiting, weight loss, hyperpigmentation, and hypotension, ultimately found to have primary adrenal insufficiency with markedly elevated ACTH levels. Imaging revealed bilateral adrenal masses with associated lymphadenopathy, and histopathological evaluation confirmed DLBCL. Prompt recognition and treatment with intravenous corticosteroids led to initial hemodynamic stabilization, underscoring the importance of early diagnosis. This report emphasizes the need to consider infiltrative malignancies such as lymphoma in the differential diagnosis of adrenal insufficiency, particularly in cases with bilateral adrenal enlargement and systemic features.

The salient features of this case include the acute presentation as an Addisonian crisis, the presence of bilateral adrenal masses, and the absence of significant peripheral lymphadenopathy or organomegaly at presentation, which can obscure the underlying diagnosis. The patient’s constitutional symptoms-fever, weight loss, and anorexia-along with biochemical findings such as hyponatremia and markedly elevated ACTH, pointed toward primary adrenal insufficiency. The coexistence of bicytopenia and intra-abdominal lymphadenopathy further suggested a systemic process. Additionally, the co-existing diabetic state of the patient could make the signs and symptoms of hypoglycemia less pronounced. Importantly, this case illustrates the often late and severe presentation. The rapid clinical response to corticosteroid therapy reinforces the reversibility of acute adrenal crisis when managed promptly, even before definitive oncological treatment is initiated.

Similar cases have been described in the literature, highlighting the variable and often nonspecific presentation of primary adrenal lymphoma. A 68-year-old female patient [6] presented with prolonged fever of unknown origin, night sweats, and weight loss, reflecting the classic “B symptoms” of lymphoma. Another report [7] described a 63-year-old woman presenting with impending adrenal crisis in the setting of bilateral adrenal masses, where empiric steroid therapy was initiated prior to biochemical confirmation, emphasizing the importance of clinical suspicion. Similarly, a 78-year-old woman [8] presented with adrenal insufficiency and bilateral adrenal enlargement, later diagnosed as DLBCL following biopsy and treated with immunochemotherapy. In contrast, an 80-year-old man [9] initially improved with steroid replacement for Addison’s disease but was later found to have progressive bilateral adrenal lymphoma, ultimately with poor outcome despite chemotherapy. Other cases, such as a 57-year-old man [10], have demonstrated associated lumbar pain, palpable masses, and elevated lactate dehydrogenase levels, reflecting tumor burden. A study of 10 immunocompetent patients [11] with a median age of 68 years also highlighted the aggressive nature of this disease, particularly noting that BCL6 rearrangement is associated with poor prognosis. Collectively, these reports reinforce that adrenal lymphoma often presents late with adrenal insufficiency and carries a guarded prognosis.

Despite its clinical significance, primary adrenal lymphoma remains a rare entity, contributing to diagnostic challenges and limited standardized management protocols. The rarity of bilateral adrenal involvement leading to overt adrenal insufficiency further complicates early recognition. Additionally, the lack of follow-up and the nonspecific nature of presenting symptoms often leads to delays in diagnosis, as seen in many reported cases. Limitations of this report include its single-case design and lack of long-term follow-up data regarding oncological outcomes. Nevertheless, this case adds to the growing body of literature emphasizing the need for heightened clinical suspicion, especially in patients presenting with adrenal crisis and bilateral adrenal masses. Early imaging, timely biopsy, and prompt initiation of corticosteroid therapy are critical steps that can significantly influence patient outcomes in this otherwise aggressive and potentially fatal condition.

Conclusions

In this case, we report a rare presentation of DLBCL manifesting initially as an acute Addisonian crisis due to bilateral adrenal infiltration. This case highlights the diagnostic challenge associated with atypical clinical features and emphasizes the need to consider DLBCL in patients presenting with Addisonian crisis and bilateral adrenal masses. Early diagnosis, prompt fluid and electrolyte correction, and steroid replacement therapy, along with a targeted lymphoma regimen, are all essential in reducing morbidity and mortality.