Case Report 1, Issue 13.3

Innovative Oral Appliance Therapy In Continuous Positive Airway Pressure-Intolerant Acromegaly-Related Obstructive Sleep Apnea

http://dx.doi.org/10.15331/jdsm.7458

Amrit Thapa, MDS1; Thanigesh Kumar N, PG Resident2; Saugat Ray, MDS3; B.S. Walia, MDS4; Mithun Mohan, PG Resident5; Sandeep Yadav, PG Resident6

1Reader & Instructor, Department of Dental Surgery & Oral Health Sciences, Armed Forces Medical College (AFMC), Pune, India; 2Postgraduate Resident, Department of Dental Surgery & Oral Health Sciences, AFMC, Pune, India; 3Associate Professor, Department of Dental Surgery & Oral Health Sciences, AFMC, Pune, India; 4Professor, Department of Dental Surgery & Oral Health Sciences, AFMC, Pune, India; 5Postgraduate Resident, Department of Dental Surgery & Oral Health Sciences, AFMC, Pune, India; 6Postgraduate Resident, Department of Dental Surgery & Oral Health Sciences, AFMC, Pune, India

ABSTRACT

Obstructive sleep apnea (OSA) is a common but underrecognized comorbidity in patients with acromegaly, largely attributed to anatomic and functional upper airway changes. Continuous positive airway pressure (CPAP) remains the first-line treatment, although many patients are unable to tolerate it. This article reports a rare case of severe OSA in a 40-year-old man with active, macroadenoma-induced acromegaly who was CPAP-intolerant and successfully treated with a titratable mandibular advancement device. The device was set at 70% of the patient’s maximum mandibular protrusion. Comprehensive upper airway evaluation was performed using polysomnography, cone-beam computed tomography, acoustic pharyngometry, ultrasonography, and validated screening tools. The pretreatment apnea–hypopnea index of 46.1 events/hour was reduced to 3 events/hour after treatment. The STOP-BANG score decreased from 7 to 4, Berlin Questionnaire score from 9/10 to 2/10, and Epworth Sleepiness Scale from 19 to 6. Cone beam computed tomography and pharyngometry confirmed improved airway dimensions. The patient tolerated the mandibular advancement device well and reported marked improvement in sleep quality and daily functioning. This case underscores the potential of titratable mandibular advancement devices as a viable, non-invasive alternative for CPAP-intolerant patients with acromegaly-associated OSA and emphasizes the importance of multidisciplinary collaboration between sleep medicine, dental specialties, and endocrinology to achieve optimal outcomes in such complex cases.

Keywords:

Acromegaly; Obstructive Sleep Apnea; Mandibular Advancement Device; Oral Appliance; CPAP Intolerance; Pituitary Adenoma

Citation:

Thapa A, Kumar TN, Ray S, Walia BS, Mohan M, Yadav S. Innovative oral appliance therapy in continuous positive airway pressure-intolerant acromegaly-related obstructive sleep apnea. J Dent Sleep Med. 2026;13(3).

INTRODUCTION 

Obstructive sleep apnea (OSA) is a prevalent but often underdiagnosed sleep-related breathing disorder characterized by repetitive upper airway obstruction during sleep. These episodes lead to intermittent hypoxia, hypercapnia, increased respiratory effort, arousals, and ultimately, fragmented sleep. The pathophysiology involves both anatomic and neuromuscular factors that reduce airway patency, especially during the relaxation of sleep. Left untreated, OSA is associated with a range of adverse consequences, including excessive daytime sleepiness, impaired cognitive function, reduced quality of life, and increased risk of cardiovascular morbidity, insulin resistance, and metabolic syndrome.1

Endocrine disorders, particularly those involving growth hormone dysregulation, play a significant role in the development and persistence of OSA. Acromegaly is a rare chronic disorder characterized by excessive secretion of growth hormone and elevated insulin-like growth factor 1 (IGF-1), most commonly caused by a pituitary adenoma.2 The sustained elevation in growth hormone and IGF-1 leads to somatic overgrowth, particularly of soft tissues and bone, affecting multiple organ systems. Common features include enlargement of the hands and feet, facial coarsening, frontal bossing, macroglossia, and prognathism. These craniofacial and oropharyngeal structural changes significantly predispose patients with acromegaly to upper airway collapse during sleep, making OSA a highly prevalent comorbidity.3

Studies report that up to 70% to 80% of patients with acromegaly have OSA, and interestingly, sleep-disordered breathing can persist even after biochemical remission of the disease.4 This persistence is likely due to irreversible structural changes in the soft tissues and skeletal framework, particularly in the tongue base, velopharynx, and craniofacial morphology. As a result, managing OSA in patients with acromegaly presents unique challenges that extend beyond the standard treatment algorithms used in the general population. Continuous positive airway pressure (CPAP) remains the first-line therapy for moderate to severe OSA.5 However, CPAP adherence is suboptimal in many patients due to discomfort, claustrophobia, and intolerance of airflow pressure.6 In patients with acromegaly, facial structural alterations and macroglossia may further reduce CPAP compliance or mask fit efficacy, prompting the need for alternative therapies. Oral appliance therapy, particularly with titratable mandibular advancement devices (MADs), has gained traction as an effective non-invasive alternative in patients with mild to moderate OSA or those intolerant to CPAP.7,8 These appliances function by repositioning the mandible forward, thereby increasing the posterior airway space and reducing pharyngeal collapse. Despite the growing use of MADs in routine OSA management, their application in patients with acromegaly remains scarcely documented due to concerns about skeletal discrepancies (eg, Class III malocclusion), macroglossia, and altered jaw dynamics. However, in carefully selected cases and with proper appliance customization, MADs may offer significant clinical benefits.

This case report presents a rare and instructive example of severe OSA in a patient with active, macroadenoma-induced acromegaly who was intolerant to CPAP therapy. A titratable mandibular advancement device (MDSA) was successfully used to manage the patient’s symptoms. To the chapter authors’ knowledge, this is the first reported case in the literature demonstrating successful OSA management in acromegaly using a titratable MDSA. The report highlights the value of multidisciplinary collaboration, comprehensive airway assessment, and individualized oral appliance therapy in managing complex cases of endocrine-related sleep-disordered breathing.
 

CASE PRESENTATION

A 40-year-old man with a known history of pituitary macroadenoma-induced acromegaly was referred to the Department of Orthodontics for evaluation and management of OSA. The diagnosis of OSA was confirmed by overnight polysomnography (PSG), revealing a pretreatment apnea-hypopnea index (AHI) of 46.1 events/hour, consistent with severe OSA (Table 1).

The patient had reported progressive symptoms since 2011, including acral enlargement, coarse facial features, increased shoe size, and difficulty removing finger rings. Magnetic resonance imaging (MRI) of the brain performed in 2017 identified a 24 × 19 × 15 mm pituitary macroadenoma located within the sella turcica (Figure 1).

Contrast-enhanced MRI of the brain revealed a large sellar mass consistent with a pituitary macroadenoma measuring approximately 24 × 19 × 15 mm. The lesion was centered within the sella turcica, causing expansion of the sellar cavity with suprasellar extension. The mass demonstrated heterogeneous contrast enhancement and resulted in compression of the normal pituitary tissue and deviation of the pituitary stalk. Superior extension of the tumor was noted in close proximity to the optic chiasm, raising concern for potential visual pathway involvement. These radiologic findings are characteristic of a pituitary macroadenoma, and in the clinical context of elevated growth hormone levels and acromegalic features, are highly suggestive of a growth hormone secreting pituitary adenoma.

Although transsphenoidal resection was recommended, the patient opted against surgical intervention and was prescribed cabergoline (0.5 mg/week), which he discontinued after 1 month without physician follow-up. In February 2023, the patient presented with an upper gastrointestinal bleed secondary to oesophageal varices. Endoscopic band ligation was performed, and abdominal ultrasonography showed coarse hepatic echotexture. A transjugular liver biopsy revealed mild portal and periportal fibrosis. Classic OSA symptoms, including loud snoring, fragmented sleep, excessive daytime sleepiness, and persistent fatigue, subsequently developed in this patient. PSG confirmed severe OSA. Although CPAP therapy was initiated, the patient reported intolerance and declined further use. He was referred to the orthodontics department for alternative management using oral appliance therapy. On clinical examination, characteristic features of acromegaly were evident, including frontal bossing, a pronounced supraorbital ridge, prognathism, coarse facial features, macroglossia, and enlargement of the hands and feet (Figure 2).

Intraoral assessment revealed wide dental arches, generalized spacing, and an Angle Class III molar relationship. Lateral cephalometric analysis demonstrated acromegaly-related mandibular prominence mild skeletal Class III discrepancy, enlarged tongue, and reduced upper airway space. Comprehensive upper airway evaluation using cone beam computed tomography (CBCT), acoustic pharyngometry, and neck ultrasonography confirmed significant upper airway narrowing and tongue hypertrophy findings consistent with the typical pathophysiology of acromegaly-associated OSA. A lateral cephalometric radiograph was obtained and analyzed using standard skeletal and dental parameters, with comparison to established normative values. Sagittal assessment revealed SNA 83°, SNB 84°, and ANB -1°, indicating a balanced maxillomandibular relationship relative to the cranial base. Vertical parameters showed a low-angle skeletal pattern (FMA 16°, mandibular plane–FH 20°), consistent with a hypodivergent growth tendency. Cranial base and mandibular angular measurements supported a horizontal growth pattern. Mild proclination of the mandibular incisors (IMPA 96°) suggested dentoalveolar compensation rather than a primary skeletal discrepancy. Despite a relatively favourable skeletal configuration, significant upper airway compromise was present, indicating that airway obstruction was predominantly related to acromegaly-associated soft tissue hypertrophy rather than conventional skeletal Class III malocclusion (Table. 2). These findings help explain the favorable airway response to mandibular advancement therapy.

CBCT evaluation demonstrated a markedly narrowed upper airway, particularly in the oropharyngeal region, when compared with normative upper airway volumes of 15 to 20 cm³ reported in healthy adults (Figure 3). 3, 4 Following appliance therapy, CBCT airway analysis revealed minimal change in total airway volume; however, a redistribution of airway dimensions was observed, characterized by an increase in the maximum cross-sectional area and an altered airway configuration. These findings suggest a favorable geometric adaptation to mandibular advancement rather than a uniform increase in overall airway volume.

In patients with acromegaly, upper airway volume is often reduced due to soft-tissue overgrowth, particularly in the tongue base and velopharyngeal segment. Acoustic pharyngometry demonstrated reduced pharyngeal cross-sectional area (CSA) and volume values below 4.5 cm² minimum CSA and 20 to 25 cm³ volume are associated with high OSA risk.5,6 The patient’s measurements fell significantly below these thresholds (Figure 4).

Ultrasound imaging (Figure 5) showed increased interlingual artery distance and tongue width, which exceeded normal ultrasound norms (tongue thickness ~4.3 ± 0.5 cm and interlingual distance ~1.2–1.5 cm).7 These findings indicated macroglossia contributing to airway obstruction.

Figures 3 through 5 visually corroborate these objective measurements, highlighting the anatomic basis for the patient’s severe OSA and supporting the choice of mandibular advancement therapy. To objectively assess the patient’s functional impairment and quality of life, validated screening tools were used to record pretreatment scores. The patient's STOP-BANG score was 7, indicating a high risk for OSA. The Berlin Questionnaire score was 9 out of 10, also reflecting a high risk. The Epworth Sleepiness Scale score was 19, consistent with severe excessive daytime sleepiness (Table 3).

Based on these findings, a diagnosis of OSA secondary to acromegaly was established. In view of the patient’s intolerance to CPAP therapy and the feasibility of mandibular advancement, a treatment plan was formulated to fabricate a custom, titratable mandibular advancement device (MDSA). Alginate impressions were obtained to prepare working models, and a George bite gauge was used to record 70% of the patient’s maximum voluntary mandibular protrusion, which was selected as the initial advancement setting. Considering the severity of OSA and the patient’s good tolerance, a nonincremental titration protocol was adopted, with mandibular advancement monitored clinically based on symptom response and patient comfort. The appliance was fabricated using a 2-mm thermoplastic sheet reinforced with self-cure acrylic resin. It incorporated titratable anterior screws embedded in the upper base, serving as the advancement mechanism, and a lower shelf platform designed to engage and maintain the mandible in an advanced position. The appliance was subsequently delivered to the patient, who received detailed instructions regarding its use, activation, and maintenance. Follow-up evaluations were conducted at 2 weeks, 1 month, and 3 months to assess adaptation, compliance, and potential adverse effects. A posttreatment overnight polysomnography (T1 PSG) was performed after 12 weeks of continuous appliance use to objectively assess therapeutic outcomes.

As part of systemic reevaluation, it was determined that the patient’s IGF-1 levels remained elevated. Repeat MRI revealed a pituitary macroadenoma measuring 31 × 20 × 23 mm, which infiltrated the sella floor and encased the right internal carotid artery and the left cavernous sinus. Visual field testing via perimetry showed no deficits. Active acromegaly and noncirrhotic portal fibrosis (NCPF) were diagnosed, for which the patient underwent laparoscopic splenectomy and splenorenal shunt surgery. Subsequently, the patient underwent transnasal transsphenoidal resection of the macroadenoma followed by Gamma Knife radiosurgery to address the residual tumor. Following MDSA treatment, the patient reported notable symptomatic improvement and enhanced sleep quality. CBCT demonstrated an increase in airway CSA from 671.44 mm² to 731.06 mm² (Figure 6). Post-treatment screening scores showed improvement across all indices: the STOP-BANG score decreased to 4,8 the Berlin Questionnaire score decreased to 2 out of 10,9 and the EPSS score improved to 6.10 Repeat PSG revealed a reduction in the AHI from 46.1 events per hour to 3 events per hour. The patient tolerated the MDSA well and reported an enhanced quality of life (Table 4).

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DISCUSSION

Sleep plays a central role in physiologic regulation, cognitive function, and metabolic balance. Circadian rhythm, governed by the hypothalamic suprachiasmatic nucleus, regulates sleep-wake cycles and endocrine processes.11 Endocrine disturbances such as acromegaly can significantly disrupt sleep and increase cardiometabolic risk.12 Acromegaly frequently coexists with OSA due to growth hormone- and IGF-1-mediated soft tissue and skeletal changes. Even biochemically controlled patients often continue to experience OSA symptoms.2 The patient described in this study exhibited hallmark features—macroglossia, mandibular prognathism, and pharyngeal soft tissue thickening—confirmed by ultrasound, CBCT, and pharyngometry. These findings align with literature showing anatomic factors as key contributors to OSA in acromegaly.6 CBCT airway analysis, acoustic pharyngometry, and ultrasonography offered a robust evaluation framework. Normative airway volumes on CBCT (15–20 cm³) 3, 4  were significantly lower in this patient, as were pharyngometry thresholds predictive of OSA (<4.5 cm² CSA, <20 cm³ volume). 5, 6

Tongue thickness and interlingual distance exceeded ultrasound norms, supporting anatomical obstruction.7 Although CPAP remains the gold standard for moderate to severe OSA,12-14 adherence is often poor because of discomfort. 15,16 This patient’s intolerance necessitated an alternative.

Guidelines by the AASM and AADSM endorse custom titratable oral appliances for CPAP-intolerant patients.17 Although their effectiveness in severe OSA is debated, emerging evidence supports their use in select cases.18, 19 Non-CPAP therapies and oral appliance therapy have shown increasing clinical relevance in the management of OSA, particularly in patients intolerant to CPAP.21, 22 Despite the patient's skeletal Class III pattern, MDSA use led to significant AHI reduction, validating its potential even in nonideal cases. Though few reports exist on MAD efficacy in acromegaly-associated OSA, the success in this study highlights the value of individualized appliance design, accurate protrusion recording, and imaging-based planning.20 Patient compliance and lack of adverse effects also support their use. Long-term monitoring is essential for evaluating dental/skeletal changes and ongoing efficacy. In complex cases, adjunctive surgical management as undertaken here can complement OSA therapy.

CONCLUSION

This case highlights the importance of identifying OSA as a critical comorbidity in acromegaly, even amidst ongoing endocrine therapy. In this patient, a titratable MDSA offered a noninvasive, well tolerated, and effective solution for severe OSA when CPAP was not feasible. Objective PSG improvement and subjective quality-of-life gains were achieved.

This report underscores the need for a multidisciplinary approach integrating endocrinology, sleep medicine, and dental specialties in managing OSA in acromegaly. Custom oral appliances may serve as a valuable alternative where CPAP is poorly tolerated. Further studies are warranted to develop standardized guidelines for this subgroup.

REFERENCES

  1. Behrents RG, Shelgikar AV, Conley RS, et al. Obstructive sleep apnea and orthodontics: an American Association of Orthodontists White Paper. Am J Orthod Dentofacial Orthop. 2019;156(1):13-28.e1. doi:10.1016/j.ajodo.2019.04.009
  2. Romijn JA. Pituitary diseases and sleep disorders. Curr Opin Endocrinol Diabetes Obes. 2016;23(4):345-351. doi:10.1097/MED.0000000000000265
  3. Alsufyani NA, Al-Saleh MA, Major PW. CBCT assessment of upper airway changes and treatment outcomes of obstructive sleep apnoea: a systematic review. Sleep Breath. 2013;17(3):911-923. doi:10.1007/s11325-012-0799-7
  4. Liistro G, Rombaux P, Belge C, et al. High Mallampati score and nasal obstruction as risk factors for obstructive sleep apnea. Eur Respir J. 2003;21(2):248-252. doi:10.1183/09031936.03.00292403
  5. Schwab RJ, Pasirstein M, Kaplan L, et al. Family aggregation of upper airway soft tissue structures in normal subjects and patients with sleep apnea. Am J Respir Crit Care Med. 2006;173(4):453-463. doi:10.1164/rccm.200412-1736OC
  6. Bosschieter PFN, Liu SYC, Chao PY, et al. Using standardized ultrasound imaging to correlate obstructive sleep apnea severity with tongue morphology. Sleep Med. 2024;120:15-21. doi:10.1016/j.sleep.2024.05.051
  7. Mukherjee S, Patel SR, Kales SN, et al. An official American Thoracic Society statement: the importance of healthy sleep. Am J Respir Crit Care Med. 2015;191(12):1450-1458. doi:10.1164/rccm.201504-0767ST
  8. Chung F, Abdullah HR, Liao P. STOP-Bang questionnaire: a practical approach to screen for obstructive sleep apnea. Chest. 2016;149(3):631-638. doi:10.1378/chest.15-0903
  9. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for sleep apnea syndrome. Ann Intern Med. 1999;131(7):485-491.
  10. Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep. 1991;14(6):540-545.
  11. Linz D, Woehrle H, Bitter T, et al. The importance of sleep-disordered breathing in cardiovascular disease. Clin Res Cardiol. 2015;104(9):705-718. doi:10.1007/s00392-015-0859-7
  12. Attal P, Chanson P. Endocrine aspects of obstructive sleep apnea. J Clin Endocrinol Metab. 2010;95(2):483-495. doi:10.1210/jc.2009-1912
  13. Thapa A, Jayan B, Nehra K, et al. Use of medical dental sleep appliance in the management of severe obstructive sleep apnoea: a case series. J Pierre Fauchard Acad India Sect. 2015;29(2-3):59-64. doi:10.1016/j.jpfa.2015.09.000
  14. Ravesloot MJL, de Vries N. Reliable calculation of the efficacy of non-surgical and surgical treatment of obstructive sleep apnea revisited. Sleep. 2011;34(1):105-110. doi:10.1093/sleep/34.1.105
  15. da Silva Paulitsch F, Zhang L. Continuous positive airway pressure for adults with obstructive sleep apnea and cardiovascular disease: a meta-analysis. Sleep Med. 2019;54:28-34. doi:10.1016/j.sleep.2018.09.030
  16. Ng SSS, Tam WWS, Lee RWW, et al. Effect of weight loss and CPAP on obstructive sleep apnea and metabolic profile. Am J Respir Crit Care Med. 2022;205(6):711-720. doi:10.1164/rccm.202106-1401OC
  17. Ramar K, Dort LC, Katz SG, et al. Clinical practice guideline for the treatment of obstructive sleep apnea with oral appliance therapy. J Clin Sleep Med. 2015;11(7):773-827. doi:10.5664/jcsm.4858
  18. Zhou N, Ho JTF, de Vries N, et al. Evaluation of drug-induced sleep endoscopy for selecting OSA patients. J Clin Sleep Med. 2022;18(4):1073-1081. doi:10.5664/jcsm.9802
  19. Gagnadoux F, Fleury B, Vielle B, et al. Titrated mandibular advancement versus CPAP for sleep apnea. Eur Respir J. 2009;34(4):914-920. doi:10.1183/09031936.00148208
  20. Johal A, Hamoda MM, Almeida FR, et al. The role of oral appliance therapy in obstructive sleep apnoea. Eur Respir Rev. 2023;32(168):220257. doi:10.1183/16000617.0257-2022
  21. Marklund M, Verbraecken J, Randerath W. Non-CPAP therapies in obstructive sleep apnea. Eur Respir J. 2012;39(5):1241-1247. doi:10.1183/09031936.00144711
  22. Sutherland K, Vanderveken OM, Tsuda H, et al. Oral appliance treatment for obstructive sleep apnea: an update. J Clin Sleep Med. 2014;10(2):215-227. doi:10.5664/jcsm.3460

SUBMISSION & CORRESPONDENCE INFORMATION

Submitted October 9, 2025
Submitted in final revised form January 4, 2026
Accepted for publication February 3, 2026

Address correspondence to: Amrit Thapa, MDS. Email: amritparul04may@gmail.com
 

DISCLOSURE STATEMENT

The authors have indicated no financial conflicts of interest relevant to this article. Written informed consent was obtained from the patient for publication of this case report and associated images. This case report complies with the ethical standards of the Declaration of Helsinki and conforms to institutional guidelines for clinical case reporting.



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