Primary Adrenal Insufficiency Due to Recurrent Unilateral Adrenal Infarction in a Patient With Myelodysplastic Syndrome With Isolated del(5q)

Abstract

Background/Objective

Adrenal infarction is a rare cause of primary adrenal insufficiency (PAI), typically associated with hypercoagulable states. While PAI usually results from simultaneous bilateral adrenal involvement, progression from unilateral infarction to bilateral disease leading to PAI is rare. We report the first documented case of adrenal infarction in a patient with myelodysplastic syndrome (MDS) with isolated del(5q), who presented with recurrent unilateral adrenal infarction leading to bilateral involvement and PAI.

Case description

A 72-year-old woman with thrombocythemia secondary to MDS with isolated del(5q) on cilostazol therapy presented with left-sided lumbago. Imaging studies, including computed tomography and magnetic resonance imaging, revealed left adrenal infarction. A cosyntropin stimulation test revealed a normal cortisol response. Two months later, the patient developed a second infarction in the right adrenal gland. The patient was diagnosed with PAI confirmed by a low cortisol response to cosyntropin, and started glucocorticoid replacement. Four months later, the patient had a third infarction in the left adrenal gland. Intensifying prophylactic antithrombotic therapy for recurrent adrenal infarction was not considered necessary, as the clinical management would remain unchanged: glucocorticoid replacement for PAI is required regardless of recurrence.

Conclusion

We present the first case of recurrent unilateral adrenal infarctions associated with MDS with isolated del(5q), which progressively led to bilateral involvement and PAI. This case suggests the importance of assessing adrenal function and individualized consideration of prophylactic antithrombotic therapy in patients with adrenal infarction.

Highlights

• •The first case of adrenal infarction in myelodysplastic syndrome with isolated del(5q)
• •Recurrent unilateral infarctions can progressively lead to adrenal insufficiency
• •Sequential adrenal function testing revealed gradual adrenal deterioration
• •Antithrombotic therapy consideration differs between unilateral and bilateral cases

Clinical Relevance

The first case of recurrent adrenal infarctions associated with myelodysplastic syndrome with isolated del(5q) suggests the importance of serial adrenal function monitoring and individualized antithrombotic therapy in patients with recurrent adrenal infarction to prevent adrenal insufficiency due to bilateral involvement.

Introduction

Primary adrenal insufficiency (PAI) is defined by the inability of the adrenal cortex to produce enough glucocorticoids and mineralocorticoids, resulting in a severe and potentially life-threatening condition.¹ Accordingly, appropriate assessment of adrenal function, identification of the underlying cause, and replacement therapy are essential. The most common cause of PAI is autoimmunity, followed by infectious diseases such as tuberculosis, adrenalectomy, neoplasia, and various genetic disorders.¹

Adrenal infarction is a rare cause of PAI. Adrenal infarction usually occurs in hypercoagulable states, such as antiphospholipid antibody syndrome, essential thrombocythemia, polycythemia vera, Crohn’s disease, and pregnancy.2, 3, 4 The pathophysiology of adrenal infarction is not fully understood but is suspected to be based on its unique vascular anatomy, which consists of multiple arteries and a single draining vein, which form a vascular plexus called a “vascular dam.”⁵ This structure is believed to be associated with the formation of thrombosis,⁶ which can lead to hemorrhagic or nonhemorrhagic infarction.

As adrenal insufficiency appears when more than 90% of the cortex is destroyed,² bilateral adrenal infarction can lead to PAI. Indeed, most cases of adrenal infarction have been reported as bilateral cases leading to PAI,² whereas unilateral adrenal infarction has rarely been reported to cause PAI. Herein, we report a patient with myelodysplastic syndrome (MDS) who presented with PAI caused by recurrent unilateral infarction affecting both adrenal glands.

Case Description

A 72-year-old woman with MDS with isolated del(5q) presented with sudden-onset left-sided lumbago. The patient had been diagnosed with MDS with isolated del(5q) at the age of 70 when she developed anemia and thrombocythemia, and she had been taking lenalidomide for 13 months. Her medical history included cerebral infarction at the age of 56, for which she had been receiving cilostazol. Additionally, she had diabetes mellitus, dyslipidemia, and hypertension but no history of smoking.

Physical examination was not remarkable except for left-sided back pain. Hematological examination revealed anemia (hemoglobin, 5.0 g/dL) and thrombocytosis (platelet count, 591,000/μL). Laboratory findings were as follows: C-reactive protein, 26.3 mg/L; adrenocorticotropic hormone (ACTH) measured by electrochemiluminescence immunoassay (ECLIA) (Elecsys ACTH; Roche Diagnostics, Basel, Switzerland), 34.2 pg/mL (7.63 pmol/L) (reference range, 7.2–63.3 pg/mL [1.6–13.9 pmol/L]); cortisol measured by ECLIA (Elecsys cortisol II; Roche Diagnostics, Basel, Switzerland), 20.4 μg/dL (562.8 nmol/L) (reference range, 4.0–18.3 μg/dL [110.3–504.8 nmol/L]); lupus anticoagulant, 0.8; prothrombin time with International Normalized Ratio, 1.24; activated partial thromboplastin time, 30.2 s; D-dimer, 2.3 μg/mL; anti-cardiolipin antibodies, negative; protein C activity (reference range, 64% to 146%), 87%; protein S activity (reference range, 56% to 126%), 63%. Urinalysis showed no proteinuria or microscopic hematuria. Abdominal enhanced computed tomography (CT) revealed a left thickened adrenal gland surrounded by fat stranding and a lack of enhancement (Fig. 1A). Magnetic resonance imaging (MRI) showed a diffusion-weighted image (DWI)-hyperintense (Fig. 1B), apparent diffusion coefficient (ADC)-hypointense (Fig. 1C), and T2-weighted image-hyperintense (Fig. 1D) signals on the left adrenal gland. These image findings suggested the cause of lumbago was left adrenal infarction. The peak plasma cortisol level after intravenous administration of 250 μg of cosyntropin was 16.9 μg/dL (452.4 nmol/L) (Table). According to Japanese guidelines,⁷ this value did not meet the diagnostic criteria for PAI (peak cortisol <15 μg/dL [413.8 nmol/L]). Given the normal ACTH level, these results are consistent with normal adrenal function. Lenalidomide was stopped due to the risk of thrombosis.

Fig. 1.

Adrenal imaging at the first episode of adrenal infarction. Axial views of the left adrenal gland at the first episode of adrenal infarction. A, Early phase of contrast-enhanced computed tomography showing a thickened left adrenal gland without contrast enhancement (red arrow). B–D, Magnetic resonance imaging of the left adrenal gland. The gland appears hyperintense on a diffusion-weighted image (B). The infarcted area of the adrenal gland appears hypointense on an apparent diffusion coefficient image (C) and hyperintense on a T2-weighted image (D) (yellow arrows).

Table.

Plasma Cortisol Levels (μg/dL [nmol/L]) in Cosyntropin Stimulation Test After the First and Second Adrenal Infarction

Event	Baseline	30 min	60 min
First adrenal infarction (left)	6.3 (173.8)	14.3 (394.5)	16.9 (466.2)
Second adrenal infarction (right)	8.4 (231.7)	13.0 (358.6)	14.8 (408.3)

Reference ranges are as follows: basal cortisol, 4.0–18.3 μg/dL (110.3–504.8 nmol/L); peak cortisol after cosyntropin stimulation for diagnosing PAI,⁷ <15 μg/dL (413.8 nmol/L).

Two months later, the patient presented with sudden-onset right-sided lumbago and fatigue. Abdominal CT showed decreased contrast enhancement of the right adrenal gland (Fig. 2A). MRI revealed hyperintensity on a DWI (Fig. 2B), hypointensity on an ADC image (Fig. 2C), and isointensity on a T2-weighted image (Fig. 2 D), leading to the diagnosis of right adrenal infarction (the second episode). Glucocorticoid replacement with hydrocortisone was temporarily administered due to suspected adrenal insufficiency. Adrenal function was assessed 1 week after the onset of adrenal infarction, following discontinuation of the glucocorticoid replacement. The plasma ACTH level was 95.7 pg/mL (21.1 pmol/L), and the peak plasma cortisol response to cosyntropin was 14.8 μg/dL (408.3 nmol/L) (Table). The elevated ACTH level and reduced cortisol response to cosyntropin suggested adrenal insufficiency due to bilateral adrenal infarction. The patient was initiated on glucocorticoid supplementation therapy with 10 mg of hydrocortisone, which improved her fatigue, and the patient was subsequently discharged.

Fig. 2.

Adrenal computed tomography at the second episode of adrenal infarction. Axial views of the right adrenal gland at the second episode of adrenal infarction. A, Early phase of contrast-enhanced computed tomography. A part of the right adrenal gland shows no contrast enhancement (red arrow). B–D, Magnetic resonance imaging showing the ischemic adrenal gland, which appears hyperintense on a diffusion-weighted image (B), hypointense on an apparent diffusion coefficient image (C), and isointense on a T2-weighted image (D) (yellow arrows).

Four months later, the patient presented with sudden-onset left-sided lumbago, which was diagnosed as the third episode of adrenal infarction affecting the left adrenal gland. While dual antiplatelet therapy could theoretically provide more robust prevention of recurrent infarctions, there is no established evidence supporting its efficacy in adrenal infarction. The patient was concerned about the potentially increased bleeding risk associated with adding a second antiplatelet agent. Given the uncertain benefit and the patient's safety concerns, the patient declined dual antiplatelet therapy. Therefore, cilostazol monotherapy was continued. The patient had received glucocorticoid replacement and had not developed adrenal infarction for at least 6 months since the third episode of adrenal infarction.

Discussion

We report the first case of adrenal infarction in a patient with MDS with isolated del(5q) who developed PAI due to recurrent unilateral adrenal infarctions despite cilostazol therapy. The first infarction occurred in the left adrenal gland, the second in the right, and the third again in the left adrenal gland. Each episode was characterized by sudden-onset back pain, and imaging studies confirmed adrenal ischemia. After the second infarction, the patient developed PAI, confirmed by the elevated ACTH level and low cortisol response to cosyntropin, and subsequently treated with hydrocortisone.

Our case suggests that recurrent unilateral adrenal infarction can lead to progressive adrenal dysfunction, resulting in PAI. As adrenal insufficiency appears when most of the cortex is destroyed,² unilateral adrenal infarction alone usually does not cause adrenal insufficiency. Most reported cases of adrenal infarction involve bilateral lesions causing PAI,^8,9 but some cases with unilateral adrenal infarction have presented with PAI-like symptoms such as hypotension, weight loss, and nausea.² In our case, the initial left adrenal infarction did not impair adrenal function, but the subsequent right adrenal infarction led to PAI, suggesting that if unilateral adrenal infarction recurs, it may progressively affect both adrenal glands and cause PAI. Such progression has rarely been reported in the literature. Hypercoagulable states may be associated with the repeated development of adrenal infarction. This hypothesis highlights the underlying hypercoagulable state possibly affecting the risk of recurrent adrenal infarctions.

In our case, MDS with isolated del(5q) may be associated with the development of adrenal infarction. MDS with isolated del(5q) is characterized by anemia and normal or increased platelet counts.¹⁰ Patients with MDS with isolated del(5q) have an increased risk of thrombotic events, potentially due to lenalidomide use and normal-to-elevated platelet counts.¹¹ Adrenal infarction has also been reported in a patient with essential thrombocythemia.⁵ Our patient had thrombocythemia and developed unilateral adrenal infarction even after discontinuing lenalidomide, suggesting a possible association between MDS with isolated del(5q)-related thrombocythemia and adrenal infarction. To the best of our knowledge, this is the first report describing a case of adrenal infarction in patients with MDS with isolated del(5q). As our report lacks broader coagulation studies, such as factor V Leiden, further studies are needed to clarify the association between adrenal infarction and MDS with isolated del(5q).

Prophylactic antithrombotic therapy has been used for patients with an increased risk of thrombotic events. In our case, adrenal infarctions recur even on cilostazol therapy, suggesting that cilostazol alone may not be sufficient to prevent adrenal infarction. However, the patient experienced a second adrenal infarction, and intensifying antithrombotic therapy was not needed as recurrence would not affect the ongoing glucocorticoid replacement therapy. As a result, prophylactic antithrombotic therapy might be important for adrenal infarction risk only before developing PAI. While the role of antithrombotic therapy in preventing adrenal infarction remains unclear, it may be considered on a case-by-case basis in patients with potential thrombotic risk.

These findings suggest the importance of adrenal function assessment and possible prophylactic antithrombotic therapy. In patients with PAI receiving glucocorticoid replacement, prophylactic antithrombotic therapy may not be necessary, as recurrent adrenal infarction does not affect glucocorticoid replacement. In contrast, antithrombotic therapy may be considered in those patients without adrenal insufficiency, as recurrent adrenal infarction could lead to adrenal insufficiency. Therefore, assessing adrenal function may be essential in patients with adrenal infarction. The role of antithrombotic therapy in preventing adrenal infarction has been still unknown. Further studies are needed to clarify the risk of adrenal infarction and the role of prophylactic antithrombotic therapy.

Conclusion

We described a patient who had MDS with isolated del(5q), developing recurrent unilateral adrenal infarction, leading to bilateral adrenal involvement and PAI. This case suggests the importance of adrenal function assessment for appropriate glucocorticoid replacement and the potential consideration of prophylactic antithrombotic therapy, although further studies are needed to clarify the role of prophylactic antithrombotic therapy for adrenal infarction.

Informed Patient Consent

Signed informed consent for case report publication was obtained directly from the patient.

Disclosure

The authors have no conflicts of interest to disclose.