Introduction

Epiglottic retroversion (ER) is a rare condition that occurs when the epiglottis is caudally displaced during inspiration, covering the rima glottidis and causing upper airway obstruction.^1–4 Dyspnea and inspiratory stridor are typical clinical signs that result from obstruction of the rima glottidis.¹ One study reported that 17% (4/24) of the dogs with ER exhibited worsening stridor or dyspnea during sleep.² Definitive diagnosis of ER requires confirmation of obstruction of the rima glottidis during inspiration by fluoroscopy or laryngoscopy.^1–4 ER is occasionally found incidentally in dogs with other causes of upper airway obstruction, such as elongated soft plate and stenotic nares.^1–3 In some cases with concurrent upper airway diseases, management of the concurrent problems can achieve sufficient resolution of ER.² However, in some dogs, ER can be the primary cause of airway obstruction and epiglottopexy or epiglottectomy is needed to resolve respiratory distress, but a high risk of postoperative complications has been reported with these techniques.^1–4 The cause of primary ER is unknown, but it could result from malacic changes in the epiglottis or the denervation of the hyoepiglotticus muscles, which control movement of the epiglottis.^1,2 Hypothyroidism-associated peripheral neuropathy has been reported to be a potential cause of ER in two dogs.¹ In these cases, surgical treatment was required because medical treatment of the hypothyroidism did not result in resolution of the ER. To the best of our knowledge, association of ER with hyperadrenocorticism (HAC) has not previously been reported in dogs. In this report, we described a case in which clinical signs of ER with concurrent HAC were resolved by medical treatment of HAC.

Case Report

A 6 yr old 2.5 kg (body condition score: 5/9) spayed female Chihuahua was referred to Miyazaki University Veterinary Teaching Hospital for a 10 mo history of chronic respiratory compromise. Worsening of clinical signs suggestive of dyspnea when excited and sleeping was reported by the owner. Other clinical signs, such as polyurea, polydipsia, and polyphagia, were not observed. Although the decreased serum thyroxine and thyroid-stimulating hormone concentrations had been confirmed by the referring veterinarian, the dog had not been treated because of absence of clinical signs of hypothyroidism.

On initial presentation, respiratory and cardiac auscultation were unremarkable with normal heart rate (120 beats per minute), respiratory rate (28 breaths per minute), and rectal temperature (37.8°C). On physical examination, hair loss around the abdomen was observed, and abdominal distension and muscle atrophy were not detected on palpation. The dog intermittently became cyanotic with increasing inspiratory efforts during physical examination because of excitement but stridor or stertor was not clearly observed even while cyanotic.

Thoracic radiographs were unremarkable, but fluoroscopic examination of the upper airway performed without any sedation or anesthesia revealed caudal displacement of the epiglottis during inspiration with inspiratory efforts (Figure 1). Midazolam HCl^a (0.2 mg/kg) and butorphanol tartrate^b (0.2 mg/kg) were administered IV for laryngoscopy. Laryngoscopic examination also confirmed a caudally displaced epiglottis during inspiration. The epiglottis was retracted rostrally with the laryngoscope. Normal movement of the arytenoid cartilages was observed, and laryngeal paralysis was ruled out.

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A complete blood count was unremarkable, but serum biochemistry revealed elevated alkaline phosphatase (ALP) concentration (2590 U/L; reference interval [RI]: <254 U/L) and hypercholesterolemia (443 mg/dL; RI: 115–337 mg/dL) and hyperglycemia (205 mg/dL; RI: 75–128 mg/dL). Urinalysis was unremarkable except for low specific gravity (1.018). Although polyuria, polydipsia, and polyphagia were not appreciated by the owner, HAC was suspected based on the elevated ALP concentration and alopecia. An adrenocorticotropic hormone (ACTH) stimulation test was performed with synthetic ACTH^c intramuscular injection (0.25 mg). Baseline serum cortisol concentration (11.1 μg/dL; RI: 1.0–6.0 μg/dL) and post-ACTH stimulation serum cortisol concentration (>50 μg/dL; RI: <20 μg/dL) were elevated. Abdominal ultrasound showed bilaterally enlarged adrenal glands (left: 5.6 mm, right: 8.1 mm) and hyperechoic liver. Based on these findings, the dog was diagnosed with ER and pituitary-dependent HAC.

Treatment with theophylline^d (10 mg/kg twice daily) and granisetron hydrochloride^e (0.08 mg/kg once daily) was initiated but had failed to resolve the respiratory compromise, and the dyspnea gradually worsened, resulting in tachypnea and weakness even on awakening. These medications were discontinued and oral trilostane^f therapy (4 mg/kg once daily) was initiated solely.

The owner reported that clinical signs of respiratory compromise at home subsided on the first day of trilostane therapy and were barely observed 7 days later. The dog became active without displaying exercise intolerance even from the first day of trilostane therapy. The dog was brought to the hospital for 7-day, follow-up examination. During physical examination, the dog was active without signs of inspiratory efforts, cyanosis, exercise intolerance, and exertion. Respiratory rate was within normal range (28 breaths per minute). Body weight was not changed (2.5 kg). The same treatment regimen for HAC was continued. No other medications were administered.

The patient was brought to the hospital for a follow-up examination 41 days after the initiation of trilostane therapy, and the owner reported that the respiratory compromise was completely resolved without showing exercise intolerance. Cyanosis was not observed during physical examination. The hair regrow around the abdomen was observed, and the body weight decreased to 2.4 kg. Body condition score was 5/9. Serum biochemistry showed significantly decreased ALP concentration (1341 U/L), baseline serum cortisol concentration (5.1 μg/dL), and post-ACTH stimulation serum cortisol concentration (10.6 μg/dL). Fluoroscopic examination was performed during tidal breathing without any sedation or anesthesia and no respiratory effort was noted. Normal position of the epiglottis on inspiration was observed during the examination (Figure 2). Ninety-eight days after the initiation of trilostane, body weight decreased to 2.3 kg (body condition score: 5/9). Serum ALP concentration (913 U/L), baseline serum cortisol concentration (1.9 μg/dL), and post-ACTH stimulation serum cortisol concentration (4.9 μg/dL) were decreased (Table 1). A Communication with the referring veterinarian by phone confirmed that the dog remained clinically well with trilostane therapy, and no clinical signs associated with ER had been observed for at least 15 mo at the time of this report.

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TABLE 1 Serum Alkaline Phosphatase Concentrations and Adrenocorti cotropic Hormone–Stimulation Test Results After the Initiation of Trilostane Treatment

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Discussion

Epiglottic retroversion is an uncommon respiratory condition in dogs.^1,4 One study reported that ∼80% of dogs with ER had concurrent or historical upper airway disease.² Surgery has been the most common treatment option for ER.^1–4 The surgical procedure consists of temporary or permanent epiglottopexy and partial or subtotal epiglottectomy.^1–4 Postoperative complications, such as postoperative aspiration pnumonia and epiglottopexy failure, have been reported.^2,3 Hypothyroidism was suspected as the cause of ER in dogs in a previous case report.¹ To the best of our knowledge, resolution of clinical signs of ER in a dog with concurrent HAC following medical management of HAC has not been reported.

We speculated that the immediate improvement of respiratory status after trilostane therapy may have been because ER had resulted from neuropathy secondary to HAC. Although HAC is not a common cause of neuropathy except facial nerve paralysis, HAC can often cause secondary hypothyroidism.⁵ Hypothyroidism is known to cause neuropathy, and two cases of ER with hypothyroidism were reported in dogs.^1,6 Even though ER in these two cases was not resolved by medical treatment, neurological abnormalities of dogs with hypothyroidism can usually improve rapidly within a few days of thyroid hormone replacement therapy, and most dogs become neurologically normal after 1–2 mo of the treatment.⁶ In this present case, respiratory signs were improved immediately after the initiation of trilostane therapy. In one study, trilostane administration decreased serum cortisol concentration within 1 hr of the first administration in dogs with pituitary-dependent HAC.⁷ Another study reported that polydipsia/polyuria or polyphagia resolved within the first week of medical treatment of HAC in more than 50% of dogs with HAC.⁸ Trilostane therapy could improve clinical signs associated with secondary hypothyroidism due to HAC, but the time frame regarding the response to treatment has not been reported. Although medical treatment of hypothyroidism did not resolve ER in dogs who had hypothyroidism without concomitant HAC in the previously reported cases,¹ the normalization of thyroid function by treating HAC with trilostane may have led to the improvement of clinical signs of ER in the present case.

In addition to the immediate response to trilostane treatment, improvement of Cushing-induced myopathy and reduction in intrathoracic fat may have gradually improved other clinical signs, including increased activity level. Muscle weakness is a major clinical sign in dogs with HAC because of enhanced protein catabolism due to hypercortisolism.⁹ The hyoepiglotticus muscle is one of the laryngeal muscles and exists between the medial surface of the ceratohyoid bone and the ventral tip of the epiglottic cartilage in dogs.¹⁰ Cushing-induced myopathy may have decreased the hyoepiglotticus muscle’s ability to hold the epiglottis cranially during respiration, causing ER. In a previous report, an attempt was made to obtain a histological sample of the hyoepiglotticus muscle from dogs with ER to investigate possible etiologies of ER. However, no muscle tissue was noted in the specimen among the inflamed mucosal and connective tissue.¹ Histopathologic evaluation of the hyoepiglotticus muscle was also not performed in the present case. Further studies are warranted to examine histological changes of the hyoepiglotticus muscle in dogs with HAC exhibiting clinical signs of ER. The weight of the patient in the present case decreased from 2.5 kg to 2.3 kg after trilostane therapy. The weight reduction may have resulted in intrathoracic fat reduction, which may have improved ventilation capacity. In addition, a decrease in fat around the upper respiratory tract can reduce negative pressure during inspiration. Thus, the weight reduction may have further contributed to the improvement of respiratory signs in the long term.

Signs of ER may fully resolve with medical management in dogs with hyperadrenocorticism. Because signs of HAC may be subtle or may be overshadowed by the signs of ER, clinicians should give the diagnosis specific consideration when evaluating dogs that are presented for signs of ER so that unnecessary surgery can be avoided in dogs with ER having HAC.

Conclusion

Clinicians should consider ER as a differential diagnosis when a dog with HAC exhibits respiratory signs. Epiglottic retroversion with concurrent HAC could potentially be resolved by medical treatment of HAC (e.g., trilostane therapy), and unnecessary epiglottic surgery would be avoided.