Adrenal Insufficiency in Acute Spinal Cord Injury

Abstract

Background/Objective:

A 21-year-old man with a C6 American Spinal Injury Association A spinal cord injury (SCI) developed symptomatic hypotension resistant to vasopressors and volume replacement 2 weeks after injury and was diagnosed with adrenal insufficiency by cosyntropin test. Adrenal insufficiency has been documented in chronic SCI; this case shows documented adrenal insufficiency in acute SCI.

Design:

Case report.

Results:

Secondary adrenal insufficiency complicated the medical and rehabilitative course of this patient with SCI. During 2 infectious episodes, this patient's dosage of hydrocortisone had to be doubled to control symptomatic hypotension, lethargy, diffuse weakness, and anorexia.

Conclusions:

The nonspecific symptomatology of adrenal insufficiency can be easily overlooked in patients with SCI. Low basal cortisol levels may be an important clue to this disorder. Low-dose adrenocorticotropic hormone stimulation may be more sensitive than high doses for detecting subclinical adrenal insufficiency. A high index of clinical suspicion is needed for the correct diagnosis of acute and chronic adrenal insufficiency.

INTRODUCTION

Adrenal insufficiency impairs the body's ability to respond appropriately to the physical stress of illness. The condition is difficult to recognize because of the non-specific nature of many of its symptoms, such as weight loss, weakness, anorexia, and hypotension. Diagnosis is especially difficult in persons with spinal cord injury (SCI), in whom multiple comorbidities and an impaired adrenal response to stress are common. This case report of a 21-year-old man with acute SCI and adrenal insufficiency addresses the diagnostic and therapeutic considerations.

CASE REPORT

A 21-year-old man sustained a C7 vertebral fracture and spinal cord transection secondary to a gun shot wound, which required posterior decompression and stabilization of the spine from C5 to T5 vertebral levels. The patient received the standard intravenous methylprednisolone protocol for acute SCI (1). Two weeks after injury, he developed hypotension resistant to volume resuscitation and vasopressor therapy, which resolved within 24 hours of hydrocortisone initiation. He was diagnosed with adrenal insufficiency by a cosyntropin stimulation test and was placed on oral hydrocortisone 2 times a day.

Once medically stable, the patient was admitted for acute SCI rehabilitation. The neurological examination on admission revealed normal strength for elbow flexors (C5), wrist extensors (C6), and elbow extensors (C7) and absent motor power for finger flexors (C8), finger abductors (T1), and lower extremity myotomes (L2–S1) bilaterally. His sensation was intact to pin-prick and light touch from C2 to C6 and absent from C7 to S5 dermatomes bilaterally. The rectal examination showed absent sensation, absent voluntary contraction with normal sphincter tone, and present bulbocavernosus reflex. The examination was compatible with C6 American Spinal Injury Association A tetraplegia with a C7 motor zone of partial preservation bilaterally. His past medical history was unremarkable.

During rehabilitation, the patient developed 2 distinctive episodes of impaired adrenal response to the stress induced by infectious complications—a urinary tract infection (UTI) on one occasion and pseudomembranous colitis on another. Clinically, the patient manifested symptomatic hypotension (with systolic pressures in the range of 71–77 mmHg and diastolic pressures in the range of 45–50 mmHg), lethargy, diffuse weakness, and anorexia. The general physical examination was unremarkable. The neurological examination was essentially unchanged since admission except for slightly decreased strength of functioning muscle groups, which was ascribed to diminished effort on the part of the patient.

With the UTI, the complete blood count showed an elevated white blood cell count of 18.4 × 10⁹/L (2.1 lymphocytes, 0.8 monocytes, 15.4 granulocytes, 0.1 eosinophils, 0.0 basophils). The urinalysis showed yellow cloudy urine, negative nitrates, trace leukocyte esterase, 45 white blood cells, and 9 epithelial cells, and urine culture grew more than 100,000 colony-forming units of Klebsiella pneumoniae. With the episode of pseudomembranous colitis, the work-up revealed positive Clostridium difficile toxin assay and decreased potassium at 2.9 mEq/L, and the complete blood count showed an elevated white blood cell count of 20.6 × 10⁹/L (2.3 lymphocytes, 0.9 monocytes, 17.3 granulocytes, 0.1 eosinophils, 0.0 basophils).

Before these 2 events, the diagnosis of secondary adrenal insufficiency was confirmed by laboratory work-up. The patient's evening dose of hydrocortisone was held, and the next morning, cortisol levels were measured at baseline and at 30 and 60 minutes after intravenous administration of 0.25 mg of cosyntropin (Table 1). The patient's very low morning cortisol (2 μg/dL) was already strongly suggestive of adrenal insufficiency, and his peak cortisol response of 14.8 μg/dL, (reference range, <20 μg/dL) was considered diagnostic. The patient's adrenocorticotropic hormone level was normal at 12 pg/dL, which ruled out primary insufficiency. Pituitary dysfunction was ruled out by normal thyroid-stimulating hormone and free thyroxine levels, normal follicle-stimulating hormone and luteinizing hormone levels, normal prolactin level, and normal insulin-like growth factor-I level. Magnetic resonance imaging of the sella showed an unremarkable pituitary gland.

Table 1.

Cortisol Levels (μg/dL) at Baseline and 30 and 60 Minutes after Intravenous Infusion of 0.25 mg Cosyntropin

The patient responded favorably to intravenous fluids and electrolyte correction, treatment of infections, and temporary increases in the dosage of hydrocortisone. He required temporary medical interruptions in his rehabilitation. Electrolyte values during the episodes of UTI and pseudomembranous colitis are shown in Tables 2 and 3, respectively.

Table 2.

Electrolyte Values During the Episode of UTI at Baseline (Before Increasing Steroids), During the 3 Days That Steroid Dosage Was Increased, and on Day 4 on Return to Usual Dosage of Hydrocortisone

Table 3.

Electrolyte Values During the Episode of Pseudomembranous Colitis, at Baseline (Before Increasing Steroids), During the 3 Days That Steroid Dose Was Increased, and on Day 4 on Return to Usual Dose of Hydrocortisone

DISCUSSION

Acute adrenal insufficiency should be suspected in patients with unexplained volume depletion and vascular collapse, which is often associated with hyperkalemia, acidosis, or hypoglycemia. Chronic insufficiency usually develops more insidiously with symptoms such as weakness, weight loss, anorexia, and postural hypotension (2).

The SCI in and of itself commonly causes very similar nonspecific symptoms and signs in the early postinjury period. Patients with complete tetraplegia have an interruption of efferent sympathetic activity that maintains blood pressure during upright posture. This, combined with venous pooling with limited venous return and decreased cardiac output, results in orthostatic hypotension in acute SCI. Fluid balance and homeostasis is affected by body position, with urine volumes decreasing with upright posture and increasing with recumbency in individuals with tetraplegia. In addition, fluid imbalances associated with acute infections, dehydration and altered thermoregulation, restrictions for bladder management, and diarrhea or constipation associated with ineffective bowel management programs have a direct impact on fluid and electrolyte homeostasis (3). Immobilization hypercalcemia is not uncommon in young men with acute, complete cervical SCI and usually presents with nausea/vomiting, anorexia, fatigue, lethargy, and dehydration. Depressive and adjustment disorders during acute SCI may manifest by changes in appetite and energy levels, along with affective and cognitive symptomatology.

While no documentation has been found pertaining to acute SCI, impaired adrenal reserve has been documented in patients with chronic SCI. Huang et al (4) studied 25 patients with SCI 1 year after injury and found evidence of impaired adrenocorticotropic hormone response to corticotropin-releasing hormone and insulin-induced hypoglycemia and a significantly reduced cortisol response. The patient in this report had a very low basal cortisol level. If cortisol values could be used as a screening tool for impaired adrenal function in acute SCI, those with very low levels could be confirmed with cosyntropin testing. Wang and Huang (5) tested individuals with chronic SCI, finding a high prevalence of impaired adrenal reserve, and concluded that low-dose adrenocorticotropic hormone stimulation was more sensitive than high doses for detecting subclinical adrenal insufficiency.

It is unclear to what extent and how early the SCI and/or its treatment contribute to the development of adrenal insufficiency. Additionally, the presence of preexisting subclinical adrenal insufficiency (unmasked by the cord injury and infections) cannot be excluded. The patient in this report had a positive response to supportive treatment, antimicrobial medication for underlying infections, and double doses of hydrocortisone for 3 days, after which he resumed his usual oral doses of 20 mg in the morning and 10 mg in the evening. Because the current understanding of adrenal response to life-threatening stress in SCI is undetermined, steroid treatment should be individualized for each patient and clinical situation.

CONCLUSION

Adrenal insufficiency in the presence of SCI presents unique challenges. The nonspecific symptomatology can easily be mistaken for other conditions commonly found in this patient population; therefore, a high index of clinical suspicion is needed for the correct diagnosis of acute and chronic adrenal insufficiency. Increased awareness and vigilance is recommended during acute illness, surgery, and life-threatening conditions in patients with SCI.