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Original Investigation
May 7, 2020

Risk Factors for Patient-Reported Olfactory Dysfunction After Endoscopic Transsphenoidal Hypophysectomy

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 2School of Medicine, Meharry Medical College, Nashville, Tennessee
  • 3Editor, JAMA Otolaryngology-Head & Neck Surgery
  • 4Department of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 5Statistics Editor, JAMA Otolaryngology-Head & Neck Surgery
JAMA Otolaryngol Head Neck Surg. Published online May 7, 2020. doi:10.1001/jamaoto.2020.0673
Key Points

Question  What are demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative risk factors for patient-reported olfactory dysfunction after endoscopic transsphenoidal hypophysectomy?

Findings  In this cohort study of 147 patients with primary sellar lesions who underwent endoscopic transsphenoidal hypophysectomy, smoking history, acute angle between the planum sphenoidale and face of the sella turcica on sagittal imaging, and abdominal fat grafting were associated with patient-reported olfactory dysfunction. Increased number of months after the surgical procedure was associated with patient-reported normosmia.

Meaning  These findings suggest that smoking cessation counseling, cephalometric measurements of preoperative imaging, and judicious use of abdominal fat grafting may improve patient-reported olfactory outcomes after a transsphenoidal surgical procedure.


Importance  Iatrogenic olfactory dysfunction after endoscopic transsphenoidal hypophysectomy (ETSH) is an overlooked complication without elucidated risk factors.

Objective  To assess the independent prognostic role of demographic, comorbidity, cephalometric, intraoperative, histological, and postoperative parameters in patient-reported postoperative olfactory dysfunction, and to explore the association between anatomical measurements of the skull base and sinonasal cavity and postoperative olfactory dysfunction.

Design, Setting, and Participants  This retrospective cohort study in a tertiary care medical center enrolled consecutive patients with primary sellar lesions who underwent ETSH between January 1, 2015, and January 31, 2019. Patients were excluded if they underwent multiple sinonasal surgical procedures, presented with a sellar malignant neoplasm, required an expanded transsphenoidal approach, had nasal polyposis or a neurodegenerative disease, or sustained traumatic brain injury. After undergoing medical record review and telephone screening, patients were asked to participate in a 3-item telephone survey.

Main Outcomes and Measures  The primary outcome was the Clinical Global Impressions change in smell rating, a validated transitional patient-reported outcome measure. Patients rated their change in smell before and after ETSH on a 7-point Likert scale, with the following response options: (1) much better, (2) somewhat better, (3) slightly better, (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, or (7) much worse. Responses of slightly worse, somewhat worse, and much worse were surrogates for postoperative olfactory dysfunction status. Patient medical records, preoperative imaging scans, operative notes, and pathology reports were reviewed.

Results  Of the 147 patients (mean [SD] age, 54 [15] years; 79 women [54%]) who responded to the telephone survey, 42 (29%) reported olfactory dysfunction after ETSH. Median (interquartile range [IQR]) time between the ETSH completion and survey response was 31.1 (21-43) months. On multivariable analysis, abdominal fat grafting (adjusted relative risk [aRR], 2.95; 95% CI, 1.89-4.60) was associated with postoperative olfactory dysfunction, whereas smoking history (aRR, 1.54; 95% CI, 0.95-2.51) demonstrated a clinically meaningful but imprecise effect size. A more obtuse angle between the planum sphenoidale and face of the sella turcica on sagittal imaging was protective (aRR, 0.98; 95% CI, 0.96-0.99). Increased number of months after the ETSH was associated with patient-reported normosmia (aRR, 0.93; 95% CI, 0.91-0.95). In contrast, other comorbidities; intraoperative variables such as turbinate resection, nasoseptal flap, and mucosal or bone grafting; histological variables such as pathology and proliferative index; and postoperative variables such as adjuvant radiotherapy were not associated with postoperative olfactory dysfunction.

Conclusions and Relevance  This study found that abdominal fat grafting, acute skull base angle, and smoking history appeared to be clinically significant risk factors for patient-reported postoperative olfactory dysfunction. Increased time after ETSH may be associated with better olfactory outcomes.

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