Acromegaly is a rare disease usually associated with a pituitary adenoma which secretes excess growth hormone. Characteristically, this results in hypertrophy of pharyngeal soft tissue, craniofacial deformations, macroglossia and thickening of the upper airway predisposing the patient to sleep disordered breathing (SDB) and obstructive sleep apnea (OSA)(Ramos-Levi & Marazuela,2016). Estimates vary, but 40-80% of patients diagnosed with acromegaly have also been found to have OSA compared to 5% of the general population (Galerneau et al.,2016). SDB has been associated with cardiovascular disease (Powlson & Gurnell.,2015) which is the most common cause of mortality for patients with acromegaly carrying a mortality risk 4.6 times higher than that of the general population (Mestron et al.,2004; Sherlock et al.,2014). Patients with sleep apnea report decreased quality of life associated with daytime sleepiness, fatigue, mood disturbance and depression and decline in cognitive function and executive functions (Devita et al.,2016; Silva et al., 2016; Nutt et al.,2013).
Acromegaly is an insidious progressive disease that often goes unrecognized for an estimated average of 4-10 years (Melmed,2009). A diagnosis of SDB and OSA frequently occurs well in advance of a diagnosis of acromegaly but goes unrecognized as etiologic for OSA. However, sleep apnea may also go undiagnosed or untreated both prior to and post treatment of acromegaly. Although theoretically soft tissue hypertrophy is reversible post treatment (Powlson & Gurnell.,2015), there is little data to support the prevalence of resolution or the persistence of SDB or OSA post normalization of growth hormone levels.
This study was to evaluate the prevalence of a diagnosis of OSA versus the prevalence of patients meeting criteria for SDB or OSA pre and post treatment for acromegaly who presented to a single institution.
Methods:
Fifty two patients diagnosed with acromegaly (23Males/29 Females) were interviewed pre and post treatment of acromegaly as per clinic standard of practice. Patients were identified who had an historical diagnosis of obstructive sleep apnea. Patients without a prior diagnosis were evaluated to determine if their current symptoms would meet criteria for further assessment for obstructive sleep apnea using the STOP BANG questionnaire and the Epworth Sleepiness Scale with scores in the moderate to high risk range. This process was repeated post treatment when growth hormone levels were normalized. This may have occurred after either or both surgical and medical treatments. Statistical analysis included descriptive analysis, paired and independent t test, cross tabs analysis (Chi squared, likelihood ratio and linear by linear association) using PASW 18. This study was IRB approved.
Results:
Of the 52 patients meeting criteria for acromegaly, 17 patients (32.7%, 7 Females/10 Males; mean age 51.2 years) presented with a diagnosis of sleep apnea prior to being diagnosed with acromegaly. However, a further 15 patients (28.8%, 9 females/6 males; mean age 44.5years) met criteria indicating moderate to high risk for SDB or OSA . Together, a total of 35 patients (61.5%) met criteria for SDB or OSA. Post-treatment, 6/17 patients (35.3%, 4 females/2 males) reported resolution of OSA diagnosis after disease remission. One of the 6 patients, a female, continued to meet criteria for OSA. Of those patients meeting criteria for OSA pre-treatment, 4 were newly diagnosed with OSA after treatment and 4 continued to meet criteria for OSA and were referred for polysomnography. Linear by linear association indicated increasing age was associated with a higher likelihood of meeting criteria or having a diagnosis of OSA (p=0.04) but age was not a significant factor in those diagnosed with OSA at either time-point. There was no significant difference between genders for patients diagnosed with OSA at presentation ( X2, p=0.19) however, males were more likely to have a diagnosis of OSA after treatment for acromegaly (p=0.04). There was no gender difference with respect to those meeting criteria for OSA after treatment.
Conclusion:
Both genders are known to be equally affected by acromegaly (Melmed 2009). In the general population males with higher BMI have been found to have more severe OSA (Galerneua et al., 2016). Among patients screened for both OSA and acromegaly in a large cohort of 775 patients Galerneua et al found a 0.35% incidence of undiagnosed acromegaly. However, this study suggests that younger age patients presenting with OSA may be at higher risk and perhaps should be screened for acromegaly.
Given the morphologic changes to the airway associated with acromegaly, it seems reasonable to assume that in contrast to the general population, males and females with acromegaly would be equally affected by OSA. Likewise there is no reason to believe that the regression of soft tissue swelling with disease remission should occur differentially by gender. Although this study found no gender difference in those diagnosed with OSA at presentation, post treatment there were significantly more males than females with persistent OSA. However, overall there was no significant difference in the prevalence of OSA or those meeting criteria for SDB or OSA despite ‘cure’ of acromegaly. Persistent risk may be associated with factors such as increased BMI post normalization of IGF-1 or other factors yet to be determined.
Both males and females should be evaluated for sleep apnea during physical examinations. The diagnosis of SDB or OSA may be a symptom requiring further etiologic evaluation particularly in young and female patients. Patients diagnosed with acromegaly, both males and females, regardless of age should be reassessed for SDB and OSA post treatment for acromegaly despite normalization of growth hormone levels. Further validation of these findings in larger acromegaly patient populations is needed.