Cardiac tamponade as a presentation of primary adrenal insufficiency

Abstract

Cardiac tamponade is an important and severe consequence of pericardial effusion. Patients with haemodynamically significant pericardial effusions present with signs and symptoms relating to the degree of their impaired cardiac function. Although autoimmune disease is a recognised cause of pericardial effusion, cardiac tamponade as a clinical presentation of primary adrenal insufficiency (PAI) is infrequently reported. We present a case of a woman, in her early 50s, who was admitted to the coronary care unit with cardiac tamponade caused by an acute adrenal crisis from unrecognised PAI. We hope to raise clinicians’ awareness of PAI as a rare but important cause of cardiac tamponade.

Background

Cardiac tamponade is an important and severe consequence of pericardial effusion. The clinical presentation of a pericardial effusion depends on its haemodynamic significance.¹ The degree of haemodynamic instability is related to the amount of fluid that accumulates within the pericardial space to impact the myocardium.²

Common causes of pericardial effusions and cardiac tamponade include viral infection, iatrogenesis, trauma, autoimmune diseases and malignancy.^2–4 Recognised autoimmune diseases include systemic lupus or scleroderma, but cardiac tamponade as a clinical presentation of primary adrenal insufficiency (PAI) is infrequently reported.²

We present a case of a woman, in her early 50s, who was admitted to the coronary care unit (CCU) with cardiac tamponade caused by unrecognised PAI.

Case presentation

A woman, in her early 50s, presented to the emergency department with pleuritic chest pain, shortness of breath and lethargy following a recent complicated appendicectomy. Her medical history included chronic lymphocytic leukaemia which is managed with imatinib.

On examination, she was hypotensive (85/62 mm Hg), tachycardic (130 beats per minute) and febrile (38.2°C) with a raised jugular venous pressure. The patient remained clinically shocked despite 3.5 L fluid resuscitation and broad-spectrum antibiotics. Her admission ECG showed low voltage complexes.

Her admission biochemistry revealed hyponatraemia (sodium 124 mmol/L) with a potassium towards the upper limit of normal (potassium 4.9 mmol/L). She also had a raised C reactive protein (see table 1).

Table 1.

Admission blood results

Test	Value	Reference
Hb	106 g/L	120–150
WCC	6.69 × 109/L	4.0–10.0
Neutrophils	4.52 × 109/L	2.0–7.0
Lymphocytes	1.01 × 109/L	1.0–3.0
Platelets	667 × 109/L	150–410
Sodium	124 mmol/L	135–145
Potassium	4.9 mmol/L	3.5–5.0
CRP	119 mg/L	<10
D-dimer	3.17 µgFEU/mL	<0.5

CRP, C-reactive Protein; Hb, Haemoglobin; WCC, White Cell Count.

Given the patient’s recent surgery, clinical presentation and haemodynamic instability, a pulmonary embolism was suspected. The patient scored 4 points using Wells' criteria for pulmonary embolism which prompted urgent CT pulmonary angiography (CTPA). A CT abdomen and pelvis was requested to investigate any postsurgical complications. The CTPA and CT abdomen were negative for pulmonary embolism and intra-abdominal collections respectively. The abdominal organs, including adrenal glands, were radiologically normal. However, a significantly large pericardial effusion was evident (figure 1).

Figure 1.

The CT pulmonary angiography demonstrates a large pericardial effusion with a depth of 20 mm and bilateral pleural effusions.

Investigations

Urgent transthoracic echocardiogram (TTE) confirmed a global pericardial effusion (depth 20 mm) with both right ventricular diastolic and right atrial systolic collapse. Left ventricular ejection fraction was >60%. Emergent pericardiocentesis was performed and 1800 mL of pericardial fluid was drained within 24 hours.

Fluid analysis confirmed a sterile effusion with mixed inflammatory cells. Despite successful pericardiocentesis, the patient remained haemodynamically shocked for the next 48 hours. Urine output was preserved and lactate concentration <2 mmol/L. Surgical, radiology and microbiology opinions were sought. No acute surgical pathology was identified on review of the patient and her imaging. Antimicrobial cover was broadened with meropenem until an infective cause was excluded.

The patient’s admission to hospital 28 days previously was reviewed. She required laparotomy for a gangrenous appendix causing proximal small bowel obstruction. She was admitted to the intensive care unit postoperatively for both inotropic support and intravenous fluid therapy due to profound hypotension (90/63 mm Hg) and acute kidney injury. Despite fluid resuscitation and gradual weaning of norepinephrine, the patient remained hypotensive, tachycardic and intermittently feverish. The patient’s sodium ranged between 119 and 136 mmol/L and potassium between 5.2 and 6.1 mmol/L. She reported intermittent chest discomfort with non-specific T-wave inversion in her lateral leads. Troponin levels were non-specifically elevated at 393.9 ng/L and TTE confirmed a small pericardial effusion. Cardiology advice had been sought, and type 2 myocardial infarction was diagnosed in the context of severe sepsis.

The patient’s clinical presentation and blood profile, following her recent surgical admission, prompted the addition of a random serum cortisol measurement which was 225 nmol/L (7–10 am reference range 185–624 nmol/L). This led to urgent short synacthen testing which failed to demonstrate adequate incrementation in serum cortisol (table 2). This raised the suspicion of an acute adrenal crisis.

Table 2.

Short synacthen test results during and after admission

Time (min)	Cortisol (U/L) during admission	Cortisol (U/L) 10 months later
0	119	77
30	129	75
60	130	80

The patient was started on intravenous hydrocortisone 100 mg four times a day and referred to endocrinology department. Response to corticosteroid treatment was rapid. Antibiotics were discontinued due to limited evidence of infection. Endocrinology reviewed the patient and requested a hormone profile (table 3).

Table 3.

Hormone profile

Test	Value	Reference
LH	49.5 U/L	10.9–58.6*
FSH	94.6 U/L	16.7–113.6*
ACTH	19 ng/L	0–46
TSH	6.41 U/L	0.34–5.6
Free T4	14.5 pmol/L	7.9–20.0
Renin	808.5 mU/L	4.9–43.6
Aldosterone	82.9 pmol/L	23.2–414.9
Renin:aldosterone ratio	0.1 mU/L

*References for perimenopausal women.

ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; LH, luteinising hormone; TSH, thyroid-stimulating hormone.

Differential diagnosis

Given the patient’s clinical presentation, pulmonary embolism and intra-abdominal collection were considered but promptly excluded on radiological imaging.

Analysis of the pericardial effusion revealed sterile exudate with mixed inflammatory cells. No malignant cells were identified. This would exclude a diagnosis of infective pericarditis or malignant pericardial effusion. Radiological imaging excluded aortic dissection or pneumopericardium as a cause for her cardiac tamponade. It was her biochemical profile and clinical shock (despite adequate fluid resuscitation and emergent pericardiocentesis) which raised the suspicion for an acute adrenal crisis.

Serum cortisol was vital in directing clinicians towards the possibility of unrecognised PAI which resulted in the adrenal crisis. The patient reported that she noticed hyperpigmentation of her elbow creases following discharge from hospital following her appendicitis. This would suggest raised circulating adrenocorticotropic hormone (ACTH).

It is difficult to know whether this patient has true idiopathic PAI (Addison’s disease) or PAI resulting from sepsis. However, it is important to note that prior to her surgical admission, the patient had a completely normal biochemical profile. This would make the diagnosis of PAI because of sepsis more likely.

Treatment

The patient fulfilled criteria for emergency pericardiocentesis following the European Society of Cardiology (ESC) guidelines: existing malignant disease, hypotension, tachycardia, rapid worsening of symptoms, cardiomegaly on chest X-ray, microvoltage in ECG, right ventricular collapse and right atrial collapse.¹ The patient did not score 0.5 points for her chest pain due to it being pleuritic in nature. This provided a score of 10, meaning the patient required urgent pericardiocentesis.¹ Whilst on CCU, 1800 mL of pericardial fluid was drained across 24 hours.

Once adrenal insufficiency was suspected, corticosteroids were initiated to treat the adrenal crisis and manage inflammatory serositis. The patient rapidly responded to treatment. Her blood pressure and pulse normalised. Sodium and potassium gradually improved, and the patient was successfully discharged with endocrinology follow-up.

Outcome and follow-up

Follow-up at 3 months confirmed complete resolution of the pericardial effusion on TTE. Her blood pressure and pulse also normalised. Repeat short synacthen testing was performed (table 2) once the patient was established on long-term hydrocortisone with confirmed established adrenal insufficiency.

Her biochemistry showed mild hyponatraemia (sodium 130 mmol/L) and hyperkalaemia (potassium 5.1 mmol/L) which suggested mineralocorticoid failure. Therefore, the patient was initiated on fludrocortisone 100 µg alongside her corticosteroids. She is under follow-up with endocrinology.

The patient was due to undergo adrenal antibody testing, but this was a non-urgent test that was postponed due to the COVID-19 pandemic. Furthermore, there was low clinical suspicion for late-onset and non-classical congenital adrenal hyperplasia (NCAH). The patient did not display phenotypical features of NCAH or 21-hydroxylase deficiency.^5–7 There were no features of hyperandrogenism and ACTH levels were not elevated.^{5 6 8}

Discussion

The patient presented with clinical and physiological evidence of cardiac tamponade on TTE which supported the need for emergent pericardiocentesis. Most cases of acute pericardial effusions in the Western World are idiopathic and presumed viral in origin.^{3 9}

PAI is a rare disorder requiring a high level of clinical suspicion. Haemodynamically significant pericardial effusions present with symptoms similar to acute adrenal crisis.¹⁰ Unrecognised and untreated acute adrenal crisis is associated with high mortality and may be the first presentation of PAI.¹⁰ Single baseline serum cortisol and ACTH levels should be taken when PAI is suspected. If initial results are abnormal, the patient should undergo prompt short synacthen testing, providing the test does not delay treatment of suspected acute adrenal crisis with systemic corticosteroids.¹¹ Our patient was managed in a high dependency care setting with close urine output and serial lactate monitoring. This supported the suitability and safety to perform short synacthen testing.

Although the patient did not have a serum baseline ACTH level recorded, her renin level of 808.5 mU/L suggested mineralocorticoid failure. This further supports a diagnosis of PAI. Individuals with secondary adrenal insufficiency, like hypothalamic disorders, would have a preserved mineralocorticoid axis.^{12 13} Furthermore, the patient had not been previously prescribed any long-term exogenous steroids that could have contributed to this presentation.¹³

The pathophysiology behind the development of cardiac tamponade due to PAI is poorly understood. It is proposed that in PAI, the deficiency of glucocorticoid and mineralocorticoid results in a hypovolaemic state with reduced right ventricular filling pressures.^{12 14} The autoimmune reaction of the pericardium will result in inflammation and increased fluid production.⁴ This fluid collection, with reduced right ventricular filling pressure, results in compression of the heart which manifests as the cardiac tamponade.^{15 16} These individuals may also experience recurrent pericardial effusions despite glucocorticoid and mineralocorticoid replacement therapy and need to be followed up closely.^{4 12}

Fortunately, our patient had no evidence of recurrence in her pericardial effusion on a repeat echocardiogram following treatment of her adrenal insufficiency. This finding is similar to a previous case report of a young woman whose pericardial effusion had complete resolution on therapeutic corticosteroid administration for adrenal insufficiency.⁴

Most cases in literature have been reported in patients with autoimmune polyglandular syndrome type II (APS 2), a rare endocrine disorder characterised by PAI, type 1 diabetes mellitus and/or autoimmune primary hypothyroidism.^17–19 Thyroid function tests should be investigated to identify hypothyroidism or a diagnosis of APS 2 as a cause of pericardial effusions.^{20 21} Cardiac tamponade with bradycardia is more suggestive of hypothyroidism.^20–22 Our patient’s thyroid function suggested sick thyroid syndrome. This, along with her tachycardia, helped exclude cardiac tamponade caused by hypothyroidism. The patient also reported normal menses prior to menopause indicating an intact gonadotropic axis. It could be suggested that symptoms of hypothyroidism are masked by the hypogonadism effects in postmenopausal women (cold intolerance, hot flushes, weight loss). However, our patient had sick thyroid syndrome and was perimenopausal with normal luteinising hormone and follicle-stimulating hormone values (table 3).²²

It has been reported previously that sepsis can be a precipitating event for acute adrenal crisis, but there is still controversy about how these are linked.^{18 23} It is proposed that sepsis causes a systemic inflammatory response that causes glucocorticoid resistance at a receptor-level.¹³ There is also evidence that a glucocorticoid insufficiency is the result of a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis which leads to a subsequent adrenal crisis.^{13 24}

In the absence of any other obvious cause for the patient’s symptoms, her haemodynamic stability on corticosteroid administration, and resolution of her pericardial effusion on follow-up imaging, it was concluded that her cardiac tamponade was secondary to untreated PAI.

Although pericardial effusion is a recognised feature of systemic autoimmune disease, cardiac tamponade as a presenting feature of PAI is infrequently reported.^{3 17 25} Furthermore, PAI does not feature in the list of aetiologies in the ESC guidelines for pericardial disease.¹ We believe this case illustrates the importance of considering a diagnosis of PAI in patients presenting with unexplained pericardial effusion. This was prompted by the features of shock not resolving following emergency pericardiocentesis. This case has suggested that serum cortisol and paired ACTH should be included within the guidelines written for the investigation and assessment of pericardial effusions and cardiac tamponade. Early recognition and treatment of acute adrenal crisis can be lifesaving for these patients.

Learning points.

• Establishing the cause of a pericardial effusion can be difficult and clinicians should be mindful of the association between cardiac tamponade and primary adrenal insufficiency (PAI).

• The diagnosis of PAI should be considered in patients presenting with unexplained pericardial effusion (especially when features of shock do not resolve following pericardiocentesis).

• Serum cortisol and paired adrenocorticotropic hormone should be measured when suspecting PAI or investigating unexplained pericardial effusion.

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