Bilateral Adrenal Infarction as an Uncommon Complication of Heparin-Induced Thrombocytopenia: A Case Report

Introduction

Adrenal insufficiency is a life-threatening condition that can result from bilateral adrenal hemorrhage, and less frequently from adrenal infarction (AI) [1,2]. While hemorrhage is often observed in critically ill patients or in association with trauma, septicemia, and coagulopathies, AI usually results from hypercoagulable states or venous thrombosis, leading to ischemia of the adrenal glands [3–5].

In the literature, an association of AI with heparin-induced thrombocytopenia (HIT) is recognized but remains an uncommon complication. HIT typically develops 5–14 days after heparin administration, which is commonly used postoperatively [6,7]. Although HIT causes thrombocytopenia, it paradoxically leads to a hypercoagulable state due to the presence of anti-PF4 antibodies. These antibodies lead to the overactivation of platelets and lead to thrombotic complications such as deep venous thrombosis (DVT), pulmonary embolism (PE), and stroke in up to 50% of patients with HIT [6,8]. While adrenal vein thrombosis has been reported in HIT, bilateral AI remains an underrecognized complication, with limited documentation [9].

Here, we present a case of HIT-associated bilateral AI in a postoperative patient, with rapid clinical improvement after prompt steroid replacement and anticoagulation. Early recognition and timely management are essential in avoiding progression to adrenal insufficiency and achieving better outcomes in patients.

Case Report

A 73-year-old woman with a past medical history of essential hypertension for 4 years, hypothyroidism for 40 years, and depression and anxiety for 4 years presented to the emergency department with a 6-day history of nausea, vomiting, abdominal pain, constipation, weakness, and postural dizziness. She also reported warm sensations and cold chills, but denied fever, shortness of breath, or chest pain. She had been discharged 1 week earlier after an uneventful cervical spine surgery. During her prior admission, she had hyponatremia with a baseline sodium level of 121–130 mmol/L and normal cortisol levels (Table 1). This was attributed to SSRI-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was managed with fluid restriction before discharge.

On presentation, her vital signs were notable for marked hypotension, with a blood pressure of 99/54 mmHg, heart rate of 94 bpm, respiratory rate of 16 breaths per minute, temperature of 36.6 °C, and oxygen saturation of 94% on room air. Physical examination revealed that she was alert and oriented to time, place, and person. Her skin was warm and dry. Abdominal examination revealed a soft, mildly distended abdomen that was tender to palpation, with decreased bowel sounds. No rebound tenderness or guarding was noted.

Initial laboratory workup revealed stable normocytic anemia with a hemoglobin level of 8.7 g/dL, mild neutrophilic leukocytosis at 10.3×109/L, and new-onset thrombocytopenia with a platelet count of 95×109/L, which was significantly decreased from her prior platelet count at the time of discharge. The metabolic panel showed marked hyponatremia, with a sodium level of 118 mmol/L, which was significantly lower than during her previous admission (Table 1).

This sudden drop raised concerns for worsening hyponatremia, which was initially suspected to be due to SSRI-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH).

A thorough workup was performed to identify the underlying cause. The differential diagnosis included acute adrenal insufficiency and hypovolemic states. As part of the evaluation, urine studies, including urine sodium, urine osmolality, and serum osmolality, were obtained (Table 1) and did not support the diagnosis of SIADH. Additionally, the absence of fluid overload excluded hypervolemic causes of hyponatremia, and normal levels of thyroid-stimulating hormone (TSH) ruled out hypothyroidism as a potential cause or contributing factor. Relevant lab values are summarized in Table 1.

Given the combination of marked hyponatremia, hypotension, and nonspecific gastrointestinal symptoms, acute adrenal insufficiency secondary to bilateral AI was suspected. The baseline serum cortisol level was markedly reduced (Table 1). Contrast-enhanced computed tomography (CT) of the abdomen was performed due to the patient’s presentation with nausea, vomiting, and abdominal pain. CT was remarkable for enlarged, non-enhancing adrenal glands with surrounding fat stranding, consistent with bilateral AIs, which were normal on prior imaging (Figure 1). Bilateral lower-extremity venous Doppler ultrasonography was also performed and was negative for thrombosis. There was no evidence of atrial fibrillation, hypercoagulable disorder, malignancy, or any signs of systemic infection or possible blood loss.

Endocrinology was consulted, and the patient was promptly started on intravenous hydrocortisone and fludrocortisone, along with hemodynamic support. This intervention led to progressive correction of the electrolyte imbalance and stabilization of the patient’s hemodynamic status. The patient demonstrated marked clinical improvement over the following 24 to 48 hours. Simultaneously, due to the new drop in platelet count and prior heparin exposure during hospitalization, a workup for HIT was initiated. Platelet factor 4 (PF4) antibody testing and serotonin release assay (SRA) returned positive, confirming the diagnosis of HIT.

Hematology was consulted, and prophylactic heparin was promptly discontinued. Anticoagulation was initiated with rivaroxaban for HIT-associated adrenal infarction. Rivaroxaban was chosen for its convenience as an oral agent, favorable safety profile, and coverage under the patient’s insurance plan. This resulted in a marked improvement in platelet count. As part of follow-up recommendations, rivaroxaban was continued for 3 months and then transitioned to lifelong aspirin. Heparin was documented as an allergy in her medical records, and she remained clinically stable with no recurrent thrombotic or adrenal events on follow-up.

Discussion

HIT is a well-known complication of heparin therapy, with adrenal infarction being an unusual and potentially fatal consequence [6,7]. This case is clinically important due to the development of adrenal insufficiency secondary to AI, which can progress to life-threatening adrenal crisis and increased mortality if not diagnosed and treated promptly [10,11]. With very limited data in the literature, this complication of HIT can easily be overlooked in clinical practice.

Across published reports, several patterns consistently emerge, many of which were also observed in our patient. Symptoms typically develop 5–10 days after heparin exposure, initially followed by thrombocytopenia, with adrenal dysfunction occurring later. The initial presentation is often nonspecific. Clinicians should therefore maintain vigilance for adrenal involvement in patients with recent heparin exposure who develop nonspecific symptoms such as abdominal or flank pain, hypotension, fever, or hyponatremia alongside decreasing platelet count levels. Early recognition of these red flags is critical, as delayed diagnosis can worsen adrenal damage and increase the risk of adrenal crisis [2,6,10,11].

The lack of specific standardized guidelines makes management of HIT-induced adrenal infarction challenging. Upon confirming that our patient was clinically stable and had no increased bleeding risk, we followed the American Society of Hematology (ASH) guidelines for patients with acute HIT complicated by thrombosis. These recommend immediate discontinuation of heparin and initiation of a non-heparin anticoagulant, such as fondaparinux or direct oral anticoagulants (DOACs), to reduce the risk of further thrombotic events and promote recovery [8,12]. In our patient, treatment with rivaroxaban was initiated alongside urgent glucocorticoid replacement therapy to prevent progression to adrenal crisis.

It is important to note that for patients with an increased bleeding risk, ASH guidelines recommend initiation of short-acting intravenous anticoagulants such as argatroban or bivalirudin instead. This allows close monitoring and dose adjustment if necessary to minimize bleeding complications. Anticoagulation is essential in all cases of HIT to reduce ongoing thrombosis; however, it is crucial to balance thrombosis prevention with each patient’s individual risk of hemorrhage or the potential conversion of AI to adrenal hemorrhage. Fortunately, our patient did not have such risk factors, and the chosen management led to stabilization of hemodynamics, correction of electrolyte abnormalities, and significant clinical improvement. Given the limited guidance for HIT-associated adrenal infarction and variations in bleeding risks, careful risk stratification and adherence to accepted HIT management recommendations are essential for safe and effective care [2,12,13].

Despite positive PF4 antibodies, a positive SRA, and thrombocytopenia confirming HIT, and CT imaging confirming AI, the direct causal link between them remained uncertain. Contrast-enhanced CT imaging demonstrated bilateral hypodense, non-enhancing adrenal enlargement with surrounding fat stranding, features highly suggestive of bilateral AI (Figure 1). Importantly, the scan also helped exclude alternative diagnoses; no hyperdense lesions were observed to indicate acute hemorrhage, and there were no discrete enhancing masses, nodularity or infiltrative changes to suggest infection, metastasis, or other adrenal pathology. Despite these findings, no direct evidence of venous thrombosis was visualized on abdominal CT or Doppler imaging, making it difficult to confirm the direct thrombotic pathogenesis of the AI in our patient. However, HIT has been reportedly associated with microvascular thrombosis, which may explain infarction in the small, difficult-to-assess adrenal veins, even without detectable thrombi on standard imaging [14]. As this report describes a single case, conclusions are inherently limited. This highlights the reliance of clinicians on clinical context, laboratory findings, and indirect imaging features when attributing AI to HIT.

Additionally, the patient’s prior diagnosis of SSRI-induced SIADH may have contributed to an initial anchoring bias when she re-presented with nonspecific features, including hyponatremia, hypotension, and gastrointestinal symptoms. However, due to prompt reevaluation of cortisol levels during the current admission, the clinicians were able to recognize adrenal involvement and diagnose AI with further imaging. This sequence suggests that, in our patient, early reliance on previous diagnoses may have delayed consideration of AI. More importantly, it highlights the need to assess adrenal function through cortisol levels in patients presenting with these nonspecific symptoms and with recent heparin exposure. This can guide clinicians to avoid diagnostic delays and further progression of AI to adrenal crisis [15,16].

When evaluating AI in the context of HIT, it is important to thoroughly and systematically exclude other potential causes and contributing factors. Differential diagnoses such as SIADH, hypothyroidism, and hypovolemic states were reconsidered and ruled out based on the laboratory findings and clinical presentation. The patient’s urine and serum osmolality were inconsistent with SIADH, thyroid function was normal, and the absence of fluid overload ruled out hypervolemic states. In addition, a coagulative workup, including serologic testing for lupus anticoagulant or cardiolipin antibodies, is essential to exclude antiphospholipid antibody syndrome (APS), a known cause of AI and subsequently adrenal insufficiency. In our case, precipitating factors like the patient’s recent cervical spine surgery could have led to vascular injury in the adrenal glands, due to increased inflammation and hormonal stress responses in hypercoagulable states such as APS [17,18]. Although cardiogenic embolism is unlikely in the absence of atrial fibrillation, other rare embolic sources, such as mural thrombi or patent foramen ovale, should be excluded via echocardiography and bubble study [19].

Conclusions

In summary, we report a case of adrenal insufficiency due to bilateral adrenal infarction in the setting of HIT, while emphasizing diagnostic and therapeutic challenges. Clinicians should remain vigilant for adrenal involvement in patients with recent heparin exposure, especially those with nonspecific symptoms like abdominal pain, hyponatremia, or hemodynamic instability on presentation. Prompt recognition and empirical corticosteroid therapy in suspected cases, combined with appropriate anticoagulation determined by bleeding risk, can improve patient outcomes and decrease mortality.