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 ::  Abstract
 :: Introduction
 :: Case Report
 :: Discussion
 ::  References
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  Table of Contents     
CASE REPORT
Year : 2019  |  Volume : 65  |  Issue : 1  |  Page : 47-49

Cabergoline treatment in prolactinoma: Amelioration in obstructive and central sleep apneas


1 Department of Otolaryngology, Head and Neck Surgery, Gulhane Medical School, Ankara, Turkey
2 Department of Endocrinology, Gulhane Medical School, Ankara, Turkey

Date of Submission25-Feb-2018
Date of Decision10-May-2018
Date of Acceptance18-Jun-2018
Date of Web Publication28-Jan-2019

Correspondence Address:
Dr. M Binar
Department of Otolaryngology, Head and Neck Surgery, Gulhane Medical School, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpgm.JPGM_113_18

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 :: Abstract 


A 44-year-old male patient was admitted to the otolaryngology department with a history of progressive snoring, excessive daytime sleepiness, and reduced libido for the last 6 months. Polysomnography demonstrated the presence of moderate obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) of 24.6 events/h, consisting of 77 obstructive and 59 central apneas. The marked number of central apneas in the sleep study and urologic complaints prompted the performance of brain magnetic resonance imaging (MRI), which indicated a pituitary macroadenoma (prolactinoma). Three months after treatment with cabergoline, a control MRI showed a significant reduction in the size of the macroadenoma. The AHI was also significantly decreased (to 11.6 events/h), as were the numbers of obstructive and central apneas. The patient's complaints regarding libido were also regressed. During this treatment period, CPAP therapy has not been tolerated by the patient. Cabergoline treatment reduced the severity of both obstructive and central sleep apneas in this patient.


Keywords: Cabergoline, central sleep apnea, obstructive sleep apnea, pituitary neoplasms


How to cite this article:
Binar M, Karakoc O, Haymana C, Arslan H. Cabergoline treatment in prolactinoma: Amelioration in obstructive and central sleep apneas. J Postgrad Med 2019;65:47-9

How to cite this URL:
Binar M, Karakoc O, Haymana C, Arslan H. Cabergoline treatment in prolactinoma: Amelioration in obstructive and central sleep apneas. J Postgrad Med [serial online] 2019 [cited 2019 Feb 15];65:47-9. Available from: http://www.jpgmonline.com/text.asp?2019/65/1/47/239677





 :: Introduction Top


Obstructive sleep apnea (OSA) is associated with repetitive episodes of partial or complete upper airway collapse during sleep. Central sleep apnea (CSA) is a disorder characterized by apneic episodes during sleep with no associated ventilatory effort, and occurs more rarely than OSA.[1] We report here a case of a male patient who presented with snoring and reduced libido, diagnosed with pituitary macroadenoma and OSA with significant CSA component, and then treated with cabergoline that was effective for both sleep disorder and pituitary macroadenoma.


 :: Case Report Top


A 44-year-old male patient was admitted to our otolaryngology department with progressive snoring and excessive daytime sleepiness. After providing his detailed history, he mentioned he had experienced reduced libido for the last 6-month period. Hisotolaryngologic examination revealed normal intranasal structures and grade 1 tonsils, and his modified Mallampati score was grade 2. Endoscopy showed grade 2 (25–50%) velopharyngeal closure in the Muller maneuver, with no indications of hypopharyngeal obstruction. His body mass index (BMI) was 27.46 kg/m2. The Epworth Sleepiness Scale (ESS) score was 20 out of a total of 24. A complete polysomnography (PSG) was performed. The PSG demonstrated the presence of moderate OSA with an apnea-hypopnea index (AHI) of 24.6 events/h, consisting of 77 obstructive and 59 central apneas. The marked number of central apneas in the sleep study prompted the performance of brain magnetic resonance imaging (MRI), which indicated a pituitary tumoral lesion. The tumor measured 27 × 26 × 18 mm in size and filled the sellar-suprasellar region, forming a compression to the optic chiasm. It had both solid and cystic components and was compatible with a pituitary macroadenoma [Figure 1]a. The patient's hormone panel indicated low-testosterone levels and high-prolactin levels, whereas the other pituitary hormone levels were normal [Table 1]. The patient underwent consultations with the endocrinology, urology, and neurosurgery departments, and the decision was made to manage his pituitary macroadenoma (prolactinoma) with a dopamine agonist (cabergoline; oral tablet; beginning dose = 1 × 1 mg at 1st week; increasing 1 mg per week; 1 × 3 mg/week as the final dose), without performing any surgery. Continuous positive airway pressure (CPAP) therapy was also suggested for his OSA, but he was unable to tolerate this therapy. Three months after the treatment with cabergoline, a control MRI revealed a reduction in the size of the macroadenoma to 18.5 × 9 × 11 mm [Figure 1]b. The AHI decreased to 11.6 events/h, consisting of 31 obstructive and 8 central apneas. Total testosterone levels returned to near-normal serum levels, and the patient's complaints regarding libido significantly regressed [Table 1]. The BMI was 27.16 kg/m2 after treatment and did not differ significantly from the pretreatment value. The patient had no drug side effects such as nausea, shortness of breath, headache, dizziness, postural hypotension, and peripheral edema.
Figure 1: (a) Coronal T2 image in MRI showing pituitary macroadenoma (prolactinoma) 27 × 26 × 18 mm in size before the treatment (arrow). (b) Reduction in size of macroadenoma to 18.5 × 9 × 11 mm 3 months after the treatment (arrow)

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Table 1: The hormone levels of the patient before and after treatment

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 :: Discussion Top


The current literature is poor in terms of assessing the relationship between OSA (with a CSA component) and prolactinoma. Barbosa et al. showed that the OSA prevalence in patients with prolactinoma was similar to that of obese subjects and did not change after treatment with dopamine agonists.[2] The presence of both OSA and CSA in a prolactinoma patient makes our case extraordinary and completely separates it from previous literature. The most frequently investigated tumor associated with OSA in the pituitary gland is the growth hormone secreting tumor that results in acromegaly. The airway obstruction in acromegaly is believed to arise due to skeletal changes and soft-tissue swelling in the upper airway, which causes narrowing and airway collapse during sleep.[3] The coexistence of OSA and CSA due to prolactinoma is an unknown factor that has not been previously investigated. The possible reasons for the occurrence of OSA in patients with a prolactinoma include leptin resistance, decreased adiponectin levels, and reduction in dopaminergic tone.[2],[4] In addition, prolactinoma has been linked with obesity, metabolic syndrome, and insulin resistance, which have been also associated with OSA.[5] In the present case, following occurred together after medical treatment: 1) the size of the pituitary macroadenoma was decreased, 2) AHI was decreased to the degree of mild OSA, 3) CSA was eliminated, and 4) the affected hormone levels returned to normal levels. The patient showed no change in BMI with time that would have caused any AHI improvement at the time of postoperative PSG. Therefore, all improvements in this patient have occurred independent of obesity.

Routine evaluation of patients with central apneas by MRI is controversial. The necessity of neuroimaging in CSA was investigated in children, and the authors found that 18% of children with CSA had evidence of central nerve system pathology on MRI.[6] When no neurological findings are obvious, the number of central apneas in the PSG report seems to be a preferential factor for the decision to perform an MRI. As no consensus has been reached regarding performing MRI in OSA patients with a central apnea component, physicians should be aware of this issue.

The treatment modality for our patient was planned based on two clinical conditions: OSA with a CSA component and prolactinoma. Therefore, CPAP and cabergoline treatment were chosen as treatments in the present case. CPAP is the first line treatment modality for OSA. In addition, CPAP treatment is also first choice for patients with CSA without heart failure. As our patient was unable to use CPAP and completely quit using it after a week, other treatment alternatives such as surgical treatment, oral appliance, etc., were also considered, but none of them was appropriate for this case. He had no mechanical obstruction such as nasal deviation, nasal polyps, nasopharynx lesion, large tonsils, etc., in the upper airway that prevents using CPAP therapy. Therefore, CPAP was not contraindicated for this patient, but it was not tolerated by the patient. Besides, he had no significant retropalatal and retroglossal collapse pattern addressing upper airway surgery for the treatment of OSA. Adaptive servo-ventilation therapy could be considered if the patient had heart failure associated CSA.[7] In conclusion, the patient was compliant for only medical treatment for pituitary macroadenoma, but not compliant for OSA treatment.

Our treatment and following protocol of prolactinoma is compatible with the literature. Only the patient's control imaging was done within a shorter time than the recommended one. Although re-imaging is recommended after at least 6 months in macroprolactinomas, we performed a MRI after 3 months. The reason for this dilemma is that the patient responds well to treatment. PSG tests for OSA can be repeated in 3-month intervals during early follow-up. When we got better PSG results after 3 months follow-up, we also requested a new MRI to see if the improvement in PSG was correlated with reduction in adenoma. We performed MRI 3 months later with the reason for the perfect response in the patient's clinic and laboratory findings.

In this case, the definitive diagnosis of pituitary tumor was considered based on two important points: reduced libido and a relatively high number of central apneas observed in the PSG. Our case is the first in the English literature to report that cabergoline treatment was effective in a patient with prolactinoma who presented with both OSA and CSA. We know that the treatment of pituitary tumors is standardized and confirmed by extensive clinical trials and not by the experience of a single case. Long-term follow-up in large patient series will provide more evidence to verify this treatment effect.

Declaration of patient consent

The authors certify that appropriate patient consent was obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 :: References Top

1.
Inönü Köseoğlu H, Kanbay A, Köktürk O. [The treatment of central sleep-apnea syndrome, updated information, and review of the literature]. Tuberk Toraks 2014;62:68-78.  Back to cited text no. 1
    
2.
Barbosa FR, Silva CM, Lima GA, Warszawski L, Domingues RC, Dominic M, et al. Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists. Pituitary 2014;17:441-9.  Back to cited text no. 2
    
3.
Galerneau LM, Pépin JL, Borel AL, Chabre O, Sapene M, Stach B, et al. Acromegaly in sleep apnoea patients: A large observational study of 755 patients. Eur Respir J 2016;48:1489-92.  Back to cited text no. 3
    
4.
Pala NA, Laway BA, Misgar RA, Shah ZA, Gojwari TA, Dar TA. Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia: Response to treatment with cabergoline. Indian J Endocrinol Metab 2016;20:177-81.  Back to cited text no. 4
    
5.
Lam JC, Mak JC, Man IP MS. Obesity, obstructive sleep apnoea and metabolic syndrome. Respirology 2012;17:223-36.  Back to cited text no. 5
    
6.
Woughter M, Perkins AM, Baldassari CM. Is MRI necessary in the evaluation of pediatric central sleep apnea? Otolaryngol Head Neck Surg 2015;153:1031-5.  Back to cited text no. 6
    
7.
Aurora RN, Bista SR, Casey KR, Chowdhuri S, Kristo DA, Mallea JM, et al. Updated adaptive servo-ventilation recommendations for the 2012 AASM Guideline: “The treatment of central sleep apnea syndromes in adults: Practice parameters with an evidence-based literature review and meta-analyses.”J Clin Sleep Med 2016;12:757-61.  Back to cited text no. 7
    


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