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Anna Jackanich, Sherwin Tavakol, Ben A. Strickland, Martin Rutkowski, Dina Kamel, John D. Carmichael, Martin Weiss, and Gabriel Zada

OBJECTIVE

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a well-documented complication of transsphenoidal craniotomy (TSC) for sellar lesions. The authors aimed to assess their multidisciplinary approach to the diagnosis and treatment of postoperative hypocortisolemia utilizing conservative screening methods.

METHODS

The authors performed a retrospective review of 257 patients who underwent TSC for pituitary adenoma (PA) or Rathke cleft cyst (RCC) at the University of Southern California between 2012 and 2017. Patients with preoperative adrenal insufficiency, Cushing’s disease, or < 3 months of postoperative follow-up were excluded. Patient demographics, pathology, tumor characteristics, and complications were recorded. Postoperative day 1 (POD1) morning serum cortisol was assessed in all patients. Hypocortisolemia on POD1 (serum cortisol < 5 μg/dl) prompted a 7 am cortisol level measurement on POD 2 (POD2). Clinical signs and symptoms of hypocortisolemia were consistently monitored. After two serum cortisol levels < 5 μg/dl, or one serum level < 5 μg/dl plus a high clinical suspicion for HPA dysfunction, high-risk patients received glucocorticoid supplementation.

RESULTS

Data on 165 patients were included in the analysis; there were 101 women (61.2%) and 64 men (38.7%). Preoperative diagnoses included nonfunctional adenoma (n = 97, 58.7%), growth hormone–secreting adenoma (n = 37, 22.4%), RCC (n = 18, 10.9%), prolactinoma (n = 8, 4.8%), and other (n = 5, 3.0%). One hundred thirty-eight patients (63.0%) had either suprasellar extension or cavernous sinus invasion. POD1 hypocortisolemia was diagnosed in 8 patients (4.8%). Of these patients, 2 (1.2%) were clinically asymptomatic and had normalized POD2 cortisol levels. Six patients (3.6%) had clinical symptoms and POD2 cortisol levels confirming HPA axis deficiency. Of these 6 patients treated with early glucocorticoid replacement, 2 patients recovered HPA axis function during follow-up, making the incidence of new, permanent HPA axis deficiency 2.5%.

CONCLUSIONS

In the authors’ institutional review, all patients warranting postoperative glucocorticoid replacement had both complicated surgical courses and associated clinical symptoms of hypocortisolemia. The authors’ algorithm of withholding steroids until patients demonstrate clear evidence of postoperative hypocortisolemia is safe and clinically efficacious. Their data further suggest that routine postoperative cortisol screening may not be necessary following an uncomplicated operative resection, with gland preservation and the absence of clinical symptoms indicative of HPA dysfunction.

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Ben A. Strickland, Shane Shahrestani, Robert G. Briggs, Anna Jackanich, Sherwin Tavakol, Kyle Hurth, Mark S. Shiroishi, Chia-Shang J. Liu, John D. Carmichael, Martin Weiss, and Gabriel Zada

OBJECTIVE

Silent corticotroph adenomas (SCAs) are a distinct subtype of nonfunctioning pituitary adenomas (NFAs) that demonstrate positive immunohistochemistry for adrenocorticotropic hormone (ACTH) without causing Cushing’s disease. SCAs are hypothesized to exhibit more aggressive behavior than standard NFAs. The authors analyzed their institution’s surgical experience with SCAs in an effort to characterize rates of invasion, postoperative clinical outcomes, and patterns of disease recurrence and progression. The secondary objectives were to define the best treatment strategies in the event of tumor recurrence and progression.

METHODS

A retrospective analysis of patients treated at the authors’ institution identified 100 patients with SCAs and 841 patients with NFAs of other subtypes who were treated surgically from 2000 to 2019. Patient demographics, tumor characteristics, surgical and neuroimaging data, rates of endocrinopathy, and neurological outcomes were recorded. Cohorts of patients with SCAs and patients with standard NFAs were compared with regard to these characteristics and outcomes.

RESULTS

The SCA cohort presented with cranial neuropathy (13% vs 5.7%, p = 0.0051) and headache (53% vs 42.3%, p = 0.042) compared to the NFA cohort, despite similar rates of apoplexy. The SCA cohort included a higher proportion of women (SCA 60% vs NFA 45.8%, p = 0.0071) and younger age at presentation (SCA 50.5 ± 13.3 vs NFA 54.6 ± 14.9 years of age, p = 0.0082). Reoperations were comparable between the cohorts (SCA 16% vs NFA 15.7%, p = 0.98). Preoperative pituitary function was comparable between the cohorts with the exception of higher rates of preoperative panhypopituitarism in NFA patients (2% vs 6.1%, respectively; p = 0.0033). The mean tumor diameter in SCA patients was 24 ± 10.8 mm compared to 26 ± 11.3 mm in NFA patients (p = 0.05). Rates of cavernous sinus invasion were higher in the SCA group (56% vs 49.7%), although this result did not reach statistical significance. There were no significant differences in extent of resection, intraoperative CSF leak rates, endocrine or neurological outcomes, or postoperative complications. Ki-67 rates were significantly increased in the SCA cohort (2.88 ± 2.79) compared to the NFA cohort (1.94 ± 1.99) (p = 0.015). Although no differences in overall rates of progression or recurrence were noted, SCAs had a significantly lower progression-free survival (24.5 vs 51.1 months, p = 0.0011). Among the SCA cohort, progression was noted despite the use of adjuvant radiosurgery in 33% (n = 4/12) of treated tumors. Adequate tumor control was not achieved in half (n = 6) of the SCA progression cohort despite radiosurgery or multiple resections.

CONCLUSIONS

In this study, to the authors’ knowledge the largest surgical series to assess outcomes in SCAs to date, the findings suggest that SCAs are more biologically aggressive tumors than standard NFAs. The progression-free survival duration of patients with SCAs is only about half that of patients with other NFAs. Therefore, close neuroimaging and clinical follow-up are warranted in patients with SCAs, and residual disease should be considered for early postoperative adjuvant radiosurgery, particularly in younger patients.