Introduction
The care of patients with sport-related concussion involves a thorough assessment of multiple domains as discussed in guidelines and international consensus (1,2), including vision, vestibular, neurocognitive, headache, cervical spine, sleep, mood, and others. Medical comorbidities are vital to consider in this process, as many of the abovementioned symptom domains are relatively nonspecific and could be confounded by other pathologies. Hypopituitarism has been implicated as a possible mechanism for persistent symptoms following concussion in some athletes (3–6). However, there is limited literature showing that concussion can precipitate frank adrenal insufficiency (AI) and diabetes insipidus (DI). In this case, we describe a patient presenting to a specialty concussion clinic who then received pituitary laboratory assessment, and after symptomatic worsening, necessitated emergency care directed by these laboratory studies. A brief review of the pathophysiology and clinical considerations for AI and DI in this context are additionally provided.
Case Report
A 49-year-old woman presented 7 wk after she struck her head while practicing Karate. Her predominant symptoms on presentation included right-sided headache, difficulty maintaining visual focus, dizziness/nausea, and fatigue. Her medical history included hypothyroidism and allergies/asthma for which she took daily levothyroxine and intranasal fluticasone. She struck her head on the ground and was unsure about loss of consciousness. She experienced transient numbness and tingling in her arms and legs following the impact, and slurred speech for 1 d. In addition, she endorsed intermittent clear fluid draining from her right ear when leaning forward or laying for 6 d following the impact. On further review of systems, she endorsed polydipsia and polyuria, which were persistent. She denied fever/chills, facial weakness, or hearing loss.
The patient had a history of two prior concussions, 17 years before when accidentally striking her head on a metal bar, and 2 years before when she tripped on a dock and struck her head. During these events, she recovered quickly, but was now suffering from persistent symptoms. Her headache was parietal in location, exacerbated when she looked at computer and television screens. She had difficulty focusing her vision on printed text and felt that her balance had been poor since the concussion, with occasional unsteady gait. She experienced significant dizziness with rapid changes in her gaze direction, associated with nausea. In addition, she was fatigued throughout the day, and felt that she could not think as clearly or quickly. Her mood was labile following the concussion. She did experience mild neck pain, and her exercise had been very limited due to her symptoms, such that she was only going on walks as opposed to her usual level of exercise.
The vital signs were unremarkable. Her physical examination was remarkable for mild tenderness to palpation along her cervical paraspinous muscles and restricted cervical rotation and lateral bending. She also had severe nausea/dizziness, and visual strain with extraocular movement testing prohibiting convergence and accommodation assessment, but no gross evidence of cranial neuropathy. Her external auditory canals were dry, and there was no middle ear effusion. There were no evident cutaneous striae or dorsocervical fat pad. Magnetic resonance imaging of the brain/cervical spine and CT of the head and temporal bones were normal. A basic metabolic panel was ordered, along with a pituitary function panel. The results (Table) resulted in preliminary diagnosis of AI/hypopituitarism with critically low serum cortisol, and hypernatremia. Shortly after these, laboratory results were completed, the patient called and complained of worsening headache, nausea/vomiting, and inability to sustain fluid intake. She was referred to the emergency department, where she received intravenous corticosteroids, desmopressin, and fluid resuscitation, with significant symptomatic relief.
Table -
Laboratory studies ordered after the first clinic visit
|
Value |
Normal Range |
| Sodium, serum (mmol·L−1) |
151
a
|
135 to 145 |
| Potassium, serum (mmol·L−1) |
5.0 |
3.5 to 5.0 |
| Cortisol, serum (μg·dL−1, 4 pm) |
<0.2
b
|
2.7 to 14.1 |
| Cortisol, serum (after cosyntropin test
c
) |
1.9
a
|
Referenced separately (7) |
| ACTH (pg·mL−1) |
<5.0
a
|
7.2 to 63 |
| TSH (uIU·mL−1) |
<0.015
a
|
0.6 to 3.3 |
| FSH (mIU·mL−1) |
61.7 |
1.4 to 131 |
| LH (mIU·mL−1) |
73.9 |
0.8 to 86.5 |
| Prolactin (ng·mL−1) |
14.8 |
3.0 to 19.0 |
| IGF-1 (ng·mL−1) |
152 |
44 to 227 |
| Specific gravity, urine
d
|
1.003 |
1.003 to 1.030 |
| Osmolality, urine (mOsm·kg−1) |
129a
|
150 to 1150 |
Laboratory results are shown and compared with normal ranges, as supplied by Mclendon Laboratories (University of North Carolina Hospitals, NC).
aAbnormal result.
bCritical abnormal result.
cNote, Cosyntropin stimulation test was performed at a subsequent outpatient visit with endocrinology.
dSpecific gravity is a unit-less quantity by definition.
After being stabilized and briefly observed in the hospital, she was discharged home on an oral hydrocortisone taper, and then was continued on this medication after her cosyntropin stimulation test in endocrine clinic revealed AI. Serial serum sodium and osmolality checks indicated that her fluid balance returned to normal without the need for further exogenous desmopressin. She was followed up in a specialty concussion clinic, and referral was made for vestibular therapy and visual rehabilitation. Audiometry testing was scheduled given suspicion for healed temporal bone fracture with likely transient cerebrospinal fluid otorrhea, and revealed a normal audiogram. Her levothyroxine dose was titrated slowly in the endocrinology clinic, which also correlated temporally with her cognitive symptoms.
Discussion
Existing literature suggests patients can suffer from neuroendocrine dysfunction following traumatic brain injury (TBI) (8,9). There are several reports in concussed athletes as well (3–6). However, to our knowledge, there is no literature demonstrating concussion that precipitates hypopituitarism, DI, and frank AI requiring emergency care as seen in this case.
AI can be divided into primary and secondary forms. Primary AI results when the adrenal glands are not responsive to adrenocorticotropic hormone (ACTH) released from the pituitary gland. As a result, ACTH serum levels are elevated, and serum cortisol levels decrease. Secondary AI results from inadequate secretion of ACTH from the pituitary to stimulate the adrenal glands, causing low serum cortisol levels (10). To help distinguish between primary and secondary AI, a cosyntropin stimulation test can be administered. In our patient, cosyntropin did not adequately increase the serum cortisol levels. Therefore, we felt that the patient had chronic subclinical adrenal suppression secondary to long term use of inhaled fluticasone. Her AI may have been unmasked after sustaining traumatic hypopituitarism from the concussion.
In this case, the serum ACTH level was low, likely because the patient had hypopituitarism in addition to AI from long term use of inhaled corticosteroids. Several reports indicate that inhaled corticosteroids are capable of chronic adrenal suppression (10–12). AI is usually followed by hyponatremia and hyperkalemia. Although this patient had borderline elevated serum potassium, she initially presented with hypernatremia, polydipsia, polyuria, low urine specific gravity, and low urine osmolality. This presentation is consistent with transient DI superimposed on AI, potentially caused by hypopituitarism from the head impact. Our decision to order laboratory studies was driven chiefly by the history of polydipsia, polyuria, evidence of a significant head impact (otorrhea), and history of inhaled corticosteroid use.
DI has long been identified as a potential consequence of head trauma, especially in the context of moderate and severe TBI where the majority of cases will eventually regain posterior pituitary gland function (13). DI results from either inadequate secretion of arginine vasopressin (central DI), or inadequate renal response (nephrogenic DI) (14). The clinical manifestations include the production of inappropriately dilute urine in large amounts, generating polyuria, usually accompanied by increased thirst as the patient becomes dehydrated. Measurement of decreased urine osmolality/specific gravity can be useful in diagnosis, along with elevated serum sodium. A water deprivation test also can be used to confirm diagnosis (15); however, this was not employed in the present case due to the need for emergent fluid resuscitation.
Conclusions
This case demonstrates a complicated presentation with multiple coinciding neuroendocrine conditions. It is important to consider endocrine dysfunction in patients who sustain concussion with lingering symptoms, especially in the context of chronic corticosteroid use. Symptoms, such as fatigue, cognitive “fog”, nausea, and headache, are not only commonly attributed to concussion (2) but also may have significant overlap with endocrine pathology as noted in this case. If not detected, endocrine pathology could add considerable morbidity and recovery time for patients with concussion. Comprehensive care of concussion includes detecting chronic repercussions from hypopituitarism, as these are known sequelae of this injury.
The authors declare no conflict of interest and do not have any financial disclosures.
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