A case of adrenal insufficiency presenting with seizures, complicated by developmental cerebral venous anomaly and Takotsubo cardiomyopathy: a case report

Abstract

Background

Adrenal insufficiency is a potentially life-threatening condition that often presents with nonspecific symptoms. While fatigue, hypotension, and electrolyte disturbances are common features, seizures and stress-induced cardiomyopathy are rare initial manifestations. This case is reported for its atypical presentation and to highlight the diagnostic challenge it posed in the absence of classic biochemical findings.

Case Presentation

We report a case of a 68-year-old Hispanic woman with diabetes, hypertension, dyslipidemia, and hypopituitarism secondary to Sheehan syndrome, who presented with new-onset seizures after abruptly discontinuing chronic steroid therapy. Her symptoms included progressive weakness and behavioral changes over several weeks. Initial evaluation revealed hyperglycemia, mild hyponatremia, and no hyperkalemia—findings consistent with secondary adrenal insufficiency-associated seizures, although contributing to initial diagnostic uncertainty. Brain imaging incidentally identified a developmental cerebral venous anomaly, which was initially suspected as a potential cause of the seizures. In addition, echocardiographic findings were consistent with Takotsubo cardiomyopathy, likely precipitated by the stress of her medical condition. However, further evaluation confirmed adrenal insufficiency with low cortisol and adrenocorticotropic hormone levels, and subnormal response to cosyntropin stimulation. Management included hydrocortisone for adrenal insufficiency and levetiracetam for seizure prophylaxis, leading to symptom resolution and no recurrence of seizures.

Conclusion

This case emphasizes the importance of maintaining a high index of suspicion for adrenal insufficiency in patients with a suggestive history, even when classic electrolyte abnormalities are absent and neuroimaging reveals confounding findings. Recognizing rare presentations such as seizures and stress cardiomyopathy can prevent delays in diagnosis and improve outcomes.

Background

Adrenal insufficiency (AI) is a rare but potentially life-threatening condition characterized by inadequate cortisol production, leading to symptoms such as fatigue, weakness, hypotension, and, in unusual cases, seizures. AI can be classified as primary, secondary, or tertiary, depending on whether the underlying dysfunction lies within the adrenal glands, pituitary gland, or hypothalamus, respectively [1–4]. While autoimmune adrenalitis remains the most common cause of primary AI, secondary AI is often linked to hypopituitarism or chronic glucocorticoid therapy, where abrupt withdrawal can precipitate adrenal crisis, especially in individuals with underlying hypothalamic–pituitary dysfunction, as observed in our patient.

Seizures are an uncommon but reported manifestation of AI, sometimes occurring in the absence of typical electrolyte abnormalities. Diagnosis can be further complicated by coexisting neurological findings. Developmental venous anomalies (DVAs), the most frequent type of cerebral vascular malformation, are typically benign and asymptomatic [5–8] but can be misinterpreted as pathological when encountered incidentally on imaging.

This case report aims to describe a rare presentation of adrenal insufficiency manifesting as new-onset seizures in a patient with Sheehan syndrome and chronic steroid use. We also discuss the diagnostic complexities introduced by an incidental DVA and the subsequent development of Takotsubo cardiomyopathy, underscoring the importance of a comprehensive and multidisciplinary approach in evaluating patients with overlapping endocrine and neurologic features.

Case presentation

A 68-year-old Hispanic woman with a medical history of hypertension, diabetes (on glimepiride 4 mg daily and metformin 1000 mg daily), hypothyroidism (on levothyroxine 75 mcg daily), and Sheehan syndrome (secondary to postpartum hemorrhage and subsequent pituitary dysfunction, on long-term steroid therapy) presented with new-onset generalized tonic–clonic seizures following the abrupt discontinuation of her corticosteroid treatment. She had been receiving hydrocortisone therapy for several years owing to hypopituitarism. The patient denied smoking, alcohol consumption, use of over-the-counter medications or herbal supplements or any history of substance abuse.

In the days leading up to her presentation, the patient experienced behavioral changes, including increasing irritability, fatigue, and reduced appetite, which were out of character for her baseline. Family members noted confusion and forgetfulness, attributing these to stress. These symptoms raised concern for an endocrine imbalance.

Upon admission, the patient was alert but mildly confused. Vital signs were stable: blood pressure 120/78 mmHg, heart rate 88 beats per minute, respiratory rate 16 breaths per minute, and oxygen saturation 97% on room air. Notably, she did not exhibit hypotension, which is typically seen in AI, complicating the diagnosis.

Steroid therapy had been abruptly tapered off by her primary care physician (PCP) in the weeks prior to admission. The PCP questioned the diagnosis of Sheehan syndrome, citing insufficient evidence to justify ongoing steroid therapy, despite the patient’s history of hypopituitarism and prior steroid use.

Laboratory results (Table 1) revealed hyperglycemia (glucose = 241 mg/dL, (hemoglobin A1c) HbA1c = 11.5%), mild hyponatremia (Na = 130 mEq/L), and normal potassium levels (K = 3.8 mEq/L). These findings, along with her clinical symptoms, particularly the seizure and behavioral changes, and the recent steroid discontinuation, raised suspicion for AI. A urine toxicology screen was negative for recreational drugs. Her renal function was preserved (blood urea nitrogen (BUN) = 6 mg/dL, creatinine = 0.73 mg/dL), minimizing the likelihood of uremia or impaired drug clearance as contributing factors to her seizure. Thyroid-secreting hormone (TSH) and free thyroxine (FT4) levels were normal.

Table 1.

The patient’s laboratory values revealing findings suggestive of adrenal insufficiency

	Patient’s laboratory values	Reference range
Glucose level	241 mg/dL	70–110 mg/dL
HbA1c	11.5%	4–6%
Sodium level	130 mEq/L	135–145 mEq/L
Potassium level	3.8 mEq/L	3.5–5.0 mEq/L
BUN	6 mg/dL	7–23 mg/dL
Creatinine	0.73 mg/dL	0.60–1.30 mg/dL
A.m. cortisol level	1.1 mcg/dL	1.4–16.7 mcg/dL
Baseline cortisol level	1.4 mcg/dL	1.4–16.7 mcg/dL
Cortisol level 30 minutes after cosyntropin	4.1 mcg/dL	18–20 mcg/dL
Cortisol level 60 minutes after cosyntropin	4.0 mcg/dL	18–20 mcg/dL
ACTH	< 3.1 pg/mL	7.2–63.3 pg/mL
TSH	1.074 µIU/mL	0.450–5.330 µIU/mL
FT4	8.7 mcg/dL	4.5–10.9 mcg/dL

The low cortisol level is a strong indicator of adrenal insufficiency, and along with low adrenocorticotropic hormone (ACTH) and a subnormal cortisol increase after cosyntropin, reflects inadequate cortisol production. The hyponatremia is consistent with this diagnosis, as reduced aldosterone activity in adrenal insufficiency leads to impaired sodium retention and dilutional hyponatremia. The potassium level is normal. Mild hyponatremia and a normal potassium level are seen in secondary adrenal insufficiency. The elevated glucose level is notable, as adrenal insufficiency typically results in hypoglycemia owing to the lack of cortisol’s gluconeogenic effects. The elevated glucose here may reflect a concurrent stress response and her uncontrolled diabetes. ACTH, adrenocorticotropic hormone

Given the history of hypopituitarism, adrenal function testing was initiated. A baseline serum cortisol level was drawn at 5:00 a.m., consistent with an early morning (a.m.) cortisol measurement, and was found to be low at 1.1 mcg/dL. This was followed by a standard 250 mcg intramuscular (IM) cosyntropin stimulation test, with cortisol levels measured at 30 and 60 minutes (4.1 and 4.0 mcg/dL, respectively), confirming adrenal insufficiency. The patient’s adrenocorticotropic hormone (ACTH) level was also low (< 3.1 pg/mL). While a complete pituitary hormonal panel was not performed during this admission, the patient’s clinical presentation and past medical history of Sheehan syndrome supported the diagnosis of secondary adrenal insufficiency. She was started on intravenous hydrocortisone 25 mg every 8 hours, leading to gradual improvement. The seizures resolved, and she was transitioned to an oral hydrocortisone regimen: 10 mg in the morning at 7:00 a.m. and 5 mg in the afternoon at 4:00 p.m. In addition, levetiracetam 500 mg twice daily was initiated for seizure prophylaxis.

A head computed tomography (CT) scan (Fig. 1) revealed an incidental developmental venous anomaly (DVA) in the right frontal lobe. Further imaging with magnetic resonance imaging (MRI) and venography of the brain showed a left frontal DVA associated with cortical prominence, increased signal in the left frontal parasagittal region, and corresponding enhancement suggesting edema and venous congestion. There was no evidence of restricted diffusion indicating recent infarction or cerebritis. Although DVAs are usually benign and asymptomatic, this incidental finding raised questions about its potential role in the patient’s lowered seizure threshold. Magnetic resonance angiography showed no significant occlusion or aneurysm. The MRI also showed a partly empty sella turcica. Together with the patient’s remote history of postpartum hemorrhage and prolonged steroid therapy, this finding is consistent with Sheehan syndrome.

Fig. 1.

Computed tomography scan of the brain demonstrating a large developmental venous anomaly, also referred to as a venous angioma, located in the left parasagittal region. There is a prominent blush in this area (red arrow), which likely represents congestion of small veins that persists into the venous phase, consistent with the characteristic appearance of a developmental venous anomaly

Electroencephalography (EEG) showed abnormal patterns suggestive of focal cerebral dysfunction in the left hemisphere and mild diffuse encephalopathy, but no epileptiform discharges or seizures were observed. Neurology and neurosurgery were consulted. Both teams concluded that the DVA was unlikely to be the primary cause of the seizures and that no surgical intervention was warranted. Given the temporal association between steroid withdrawal and the seizure, along with the clinical course, the seizure was attributed primarily to adrenal insufficiency rather than the DVA.

Cardiovascular workup revealed sinus rhythm with prolonged QTc interval and electrocardiogram findings consistent with a prior inferior and anterolateral infarct. Elevated troponin levels (1369 ng/L, downtrending to 723 ng/L) prompted cardiology consultation. Initial echocardiography revealed a reduced ejection fraction (EF) of 35–40%, with abnormal mid and apical anterior septum, mid inferolateral segment, apical lateral segment, and apex. Thyroid function tests were within normal limits, ruling out thyrotoxicosis as a contributing factor to the cardiomyopathy. Given the patient’s uncontrolled diabetes, a formal ischemic workup was offered, but the patient declined for personal reasons. A repeat echocardiography showed improvement of the EF to 55–60% 9 days following corticosteroid therapy, with resolution of the left ventricular dysfunction. This significant improvement in the echocardiographic findings supports a diagnosis of Takotsubo cardiomyopathy rather than ischemic heart disease. Patient’s uncontrolled diabetes and prior infarcts seen on her electrocardiogram (EKG) warranted further investigation of ischemic heart disease. Cardiac stress tests were also offered, but the patient deferred them to be performed as an outpatient. The patient’s condition improved with supportive care, and she was discharged on a steroid regimen with close follow-up for adrenal insufficiency management.

The initial differential diagnosis included adrenal insufficiency, metabolic disturbances (hyponatremia and hypoglycemia), primary neurological causes (epilepsy, cerebrovascular event, or structural brain lesions), and toxic or infectious etiologies. The combination of laboratory findings and clinical history strongly suggested AI, which was confirmed by low cortisol levels and subnormal response to cosyntropin stimulation. Brain imaging revealed an incidental DVA, but given the clinical context and EEG findings, the seizure was most likely secondary to adrenal insufficiency.

Management included immediate intravenous hydrocortisone to address adrenal crisis, seizure prophylaxis with levetiracetam, and supportive care for Takotsubo cardiomyopathy. Once stabilized, the patient was transitioned to an oral steroid regimen mimicking physiological cortisol rhythms.

The patient showed significant clinical improvement following corticosteroid therapy. Her confusion resolved, and no further seizures occurred during her hospitalization. Follow-up echocardiography demonstrated complete resolution of left ventricular dysfunction associated with Takotsubo cardiomyopathy. She was discharged on an oral steroid regimen with instructions for adherence and stress-dose adjustments during illness. Endocrinology follow-up was arranged to reassess her long-term steroid needs, and neurology follow-up was recommended to monitor for any potential recurrence of seizures.

Discussion

Adrenal insufficiency (AI) is a life-threatening endocrine disorder resulting from inadequate production of glucocorticoids, with or without mineralocorticoid and androgen deficiency, depending on the etiology. AI is typically categorized as primary (Addison’s disease), secondary, or tertiary. Secondary and tertiary forms arise from impaired hypothalamic–pituitary signaling, as seen in this patient with Sheehan syndrome, where pituitary ischemia due to postpartum hemorrhage led to long-term adrenocorticotropic hormone deficiency and reliance on corticosteroid replacement [3, 9].

In this case, the abrupt discontinuation of corticosteroid therapy precipitated on adrenal crisis, manifesting as new-onset seizures and behavioral changes—atypical but recognized features of AI. While seizures are uncommon in AI, literature suggests that acute cortisol deficiency can lower the seizure threshold, particularly when compounded by stressors or withdrawal of chronic steroid use [10]. Interestingly, our patient exhibited only mild hyponatremia and normokalemia, and did not present with hypotension or hypoglycemia, which are classically associated with adrenal crisis. This highlights the variability of AI presentation and supports emerging evidence that not all patients follow the textbook profile, especially in cases of secondary or tertiary AI. The seizures in AI may occur owing to severe physiological stress induced by cortisol deficiency. Early diagnosis and treatment are critical to prevent adrenal crisis. With appropriate steroid replacement therapy, patients with AI generally have a favorable prognosis. However, delayed intervention can lead to significant morbidity and mortality [11].

The diagnosis of AI relies on clinical presentation, laboratory findings, and imaging. Initial laboratory tests such as serum cortisol levels with values < 5 mcg/dL are indicative of AI. The adrenocorticotropic hormone (ACTH) stimulation test is crucial for differentiating primary from secondary AI. In primary AI, cortisol levels do not respond adequately to ACTH stimulation, whereas in secondary AI, cortisol production increases. Measurement of serum ACTH is also helpful: elevated ACTH suggests primary AI, while normal or low ACTH levels indicate secondary AI. Other biochemical markers, such as hypoglycemia, hyponatremia, and hyperkalemia, can support the diagnosis. In cases of mineralocorticoid deficiency, elevated renin and low aldosterone levels may also be observed [10].

The diagnosis of adrenal insufficiency in this patient was confirmed by a low a.m. cortisol and a subnormal response to the high-dose cosyntropin stimulation test. Her baseline serum cortisol level at 5:00 a.m. was 1.1 mcg/dL, and cortisol levels at 30 and 60 minutes after administration of 250 mcg intramuscular cosyntropin were 4.1 mcg/dL and 4.0 mcg/dL, respectively. These values fall well below the expected threshold of 18–20 mcg/dL for a normal response, with minimal increment from baseline, indicating impaired adrenal reserve. In addition, her low serum ACTH level (< 3.1 pg/mL) supports the diagnosis of secondary (central) adrenal insufficiency, where pituitary dysfunction leads to insufficient ACTH production and subsequently inadequate adrenal stimulation. This fits the patient’s history of Sheehan syndrome, which results from pituitary infarction following postpartum hemorrhage and is a recognized cause of chronic hypopituitarism. Importantly, her biochemical profile also aligns with secondary AI: the patient exhibited mild hyponatremia (Na = 130 mEq/L) but normal potassium levels (K = 3. mEq/L), a pattern often seen in central AI due to preserved mineralocorticoid function. In secondary (central) AI, aldosterone secretion is typically preserved because it is primarily regulated by the renin–angiotensin system. Thus, hyperkalemia is not usually seen. In contrast, primary AI involves both glucocorticoid and mineralocorticoid deficiency, leading to both hyponatremia and hyperkalemia. The absence of hypotension or hypoglycemia, which are common in adrenal crisis, further underscores the variable and sometimes subtle presentation of secondary AI. Her preserved normal function and normal toxicology drug screen makes toxic or metabolic causes of her seizure less likely. Nevertheless, the neuropsychiatric symptoms, including behavioral changes and seizures, were ultimately attributed to cortisol deficiency, highlighting the importance of recognizing non-classical features in the appropriate clinical context.

The coexistence of a developmental venous anomaly (DVA) complicated the neurological evaluation. Although DVAs are typically benign and incidental on neuroimaging, there is increasing recognition that associated venous congestion or edema may contribute to seizure activity in certain individuals [12–14]. In this patient, the presence of a left frontal DVA with associated cortical signal changes raised the possibility of a multifactorial seizure etiology. Nonetheless, the temporal association with steroid withdrawal, the resolution of symptoms following corticosteroid replacement, and the absence of ongoing epileptiform discharges on EEG favored adrenal insufficiency as the primary cause.

Adding further complexity was the detection of Takotsubo cardiomyopathy, a stress-induced cardiomyopathy that can mimic myocardial infarction and is increasingly reported in patients with endocrine emergencies. Cortisol deficiency can contribute to exaggerated stress responses and myocardial dysfunction, making endocrine evaluation critical in such presentations [11, 15].

Current management guidelines for AI emphasize early recognition and prompt glucocorticoid replacement and patient education regarding stress-dose adjustments during illness or medical procedures [4, 12]. Our patient responded well to intravenous hydrocortisone followed by transition to a physiologic oral regimen, highlighting the reversibility of symptoms with timely intervention. The case reinforces the importance of cautious tapering of steroids under specialist supervision and the need for ongoing endocrinology follow-up in patients with hypopituitarism.

Conclusion

This case underscores the importance of considering adrenal insufficiency (AI) as a potential underlying cause of seizures, particularly in patients with chronic steroid therapy or known pituitary dysfunction. Although seizures are a rare manifestation of AI, this presentation—alongside mild electrolyte disturbances and a DVA—illustrates how nonspecific and overlapping features can obscure the diagnosis. Prompt recognition and steroid replacement led to rapid clinical improvement, avoiding further neurologic or cardiac complications.

Clinicians should maintain a high index of suspicion for AI in patients presenting with unexplained neuropsychiatric symptoms or seizures in the context of recent steroid withdrawal. In addition, this case highlights the diagnostic and therapeutic challenges posed by incidental findings such as DVAs and stress cardiomyopathy, emphasizing the need for a multidisciplinary approach. Greater awareness and individualized management of AI can reduce morbidity and improve outcomes in this vulnerable population.

Abbreviations

AI

Adrenal insufficiency

AM cortisol

Morning cortisol

ACTH

Adrenocorticotropic hormone

BUN

Blood urea nitrogen

CT

Computed tomography

DVA

Developmental venous anomaly

EEG

Electroencephalogram

FT₄

Free thyroxine

HbA1c

Hemoglobin A1c

IM

Intramuscular

MRI

Magnetic resonance imaging

TSH

Thyroid-secreting hormone

Author contributions

KV contributed to the conceptualization, supervision, visualization, and the writing of the original draft, as well as review and editing of the manuscript. BE, KJ, SA, AM, and AH contributed to the writing of the original draft, as well as review and editing of the manuscript. RT contributed to the conceptualization, supervision, and visualization of the manuscript.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Our institution does not require ethical approval for reporting individual cases.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.