A comparative, population-based analysis of pituitary incidentalomas vs clinically manifesting sellar masses.

PURPOSE: Sellar masses may present either with clinical manifestations of mass effect/hormonal dysfunction (CMSM) or incidentally on imaging (pituitary incidentaloma (PI)). This novel population-based study compares these two entities. METHODS: Retrospective analysis of all patients within a provincial pituitary registry between January 2006 and June 2014. RESULTS: Nine hundred and three patients were included (681 CMSM, 222 PI). CMSM mainly presented with secondary hormone deficiencies (SHDs) or stalk compression (29.7%), whereas PIs were found in association with neurological complaints (34.2%) (P < 0.0001). PIs were more likely to be macroadenomas (70.7 vs 49.9%; P < 0.0001). The commonest pathologies among CMSM were prolactinomas (39.8%) and non-functioning adenomas (NFAs) (50%) in PI (P < 0.0001). SHDs were present in 41.3% CMSM and 31.1% PI patients (P < 0.0001) and visual field deficit in 24.2 and 29.3%, respectively (P = 0.16). CMSM were more likely to require surgery (62.9%) than PI (35.8%) (P < 0.0005). The commonest surgical indications were impaired vision and radiological evidence of optic nerve compression. Over a follow-up period of 5.7 years for CMSM and 5.0 years for PI, tumour growth/recurrence occurred in 7.8% of surgically treated CMSM and 2.6% without surgery and PI, 0 and 4.9%, respectively (P = 1.0). There were no significant differences in the risk of new-onset SHD in CMSM vs PI in those who underwent surgery (P = 0.7) and those who were followed without surgery (P = 0.58). CONCLUSIONS: This novel study compares the long-term trends of PI with CMSM, highlighting the need for comprehensive baseline and long-term radiological and hormonal evaluations in both entities.

Analysis and natural history of pituitary incidentalomas.

OBJECTIVES: Pituitary incidentalomas (PI) are frequently found on brain imaging. Despite their high prevalence, little is known about their long-term natural history and there are limited guidelines on how to monitor them. METHODS: We conducted a retrospective study to compare epidemiological characteristics at presentation and the natural history of PI in population-based vs referral-based registries from two tertiary-care referral centers in Canada. RESULTS: A total of 328 patients with PI were included, of whom 73% had pituitary adenomas (PA) and 27% had non-pituitary sellar masses. The commonest indications for imaging were headache (28%), dizziness (12%) and stroke/transient ischemic attack (TIA) (9%). There was a slight female preponderance (52%) with a median age of 55 years at diagnosis; 71% presented as macroadenomas (>10mm). Of PA, 25% were functioning tumors and at presentation 36% of patients had evidence of secondary hormonal deficiency (SHD). Of the total cohort, 68% were treated medically or conservatively whereas 32% required surgery. Most tumors (87% in non-surgery and 68% in post-surgery group) remained stable during follow-up. Similarly, 84% of patients in the non-surgery and 73% in the surgery group did not develop additional SHD during follow-up. The diagnosis of non-functioning adenoma was a risk factor for tumor enlargement and a change in SHD status was associated with a change in tumor size. CONCLUSIONS: Our data suggest that most PI seen in tertiary-care referral centers present as macroadenomas and may frequently be functional, often requiring medical or surgical intervention.

Sellar Masses: An Epidemiological Study.

BACKGROUND: Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. AIM: To determine the epidemiology of SM in the province of Nova Scotia, Canada. METHODS: Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. RESULTS: A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke's cyst (6.5%; 0.5), growth hormone-secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone-secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at <1 cm, and 11 (1.1%) had functioning pituitary adenomas without discernible tumor, whereas tumor size data were unavailable in 150 (14.9%) patients. The specific pathologies and their most common presenting features were: nonfunctioning adenoma (incidental, headaches, and vision loss), prolactinomas (galactorrhea, menstrual irregularity, and headache), growth hormone-secreting adenomas (enlarging extremities and sweating), adrenocorticotropic hormone-secreting adenoma (easy bruising, muscle wasting, and weight gain) and nonpituitary lesions (incidental, headaches, and vision problems). Secondary hormonal deficiencies were common, ranging from 19.6% to 65.7%; secondary hypogonadism, hypothyroidism, and growth hormone deficiencies constituted the majority of these abnormalities. CONCLUSIONS: This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.

Morphometric changes correlate with poor psychological outcomes in patients with acromegaly.

OBJECTIVE: Acromegaly is frequently associated with altered facial appearance at the time of diagnosis. Furthermore, acromegaly is also associated with adverse psychological outcomes. We conducted a single-centre, cross-sectional study comparing patients with growth hormone vs non-functioning pituitary adenomas (NFA) to assess the association between morphometric changes and psychological outcomes and illness perception of patients with acromegaly. METHODS: A seven-step scale was developed to grade morphometric changes based on facial photographs. In addition, all patients were asked to draw an image of their own body and an image of what they considered to be an average healthy body and complete seven psychological questionnaires. We recruited 55 consecutive patients in each of the two groups who had undergone surgery with or without radiation therapy (RT). RESULTS: Our data showed that the clinician-rated morphometric scale was highly reliable in assessing facial changes, with 93/99 (Intraclass correlation coefficient (ICC)=0.95 (0.93-0.97)) graded as similar by independent raters. The mean (s.d.) grading for Acro and NFA patients on the clinician-rated morphometric scale were 3.5 (1.3) and 0.41 (0.35) respectively (P<0.0001). A higher clinician-rated morphometric score was also predictive of a poorer score on the drawing test. CONCLUSIONS: Our study demonstrates a correlation between physical changes associated with acromegaly and poor psychological outcomes, whereas no such correlation existed with modes of therapy, disease control status, RT, malignancy, initial or recent GH/IGF1 or secondary hormonal deficiency. Our data support the utility of the morphometric scale as a clinical tool for grading facial changes.

The role of morning basal serum cortisol in assessment of hypothalamic pituitary-adrenal axis.

PURPOSE: The use of morning basal serum cortisol levels as an alternative to dynamic testing for assessment of hypothalamic-pituitary-adrenal (HPA) axis has previously been reported. The purpose of this study was to determine the lower and upper cutoff values that would obviate subsequent HPA axis testing. METHODS: A single-centre, retrospective study from a tertiary care endocrinology clinic was conducted, analyzing data from 106 adult individuals referred for HPA axis testing who had undergone a 0800-0900 morning basal serum cortisol test followed by a standard dose (250 µg) adrenocorticotropin (ACTH) stimulation test. The ability of morning basal serum cortisol values to predict post-ACTH 30 or 60 minute peak cortisol value of >500 or >550 nmol/L was investigated. RESULTS: A morning basal cutoff of <128 nmol/L is sufficient for predicting a post-ACTH value<550 nmol/L, and morning basal cutoff levels of >243 nmol/L and >266 nmol/L predict peak post-ACTH values of >500 and >550 nmol/L respectively, obviating the need for dynamic testing. Regression analysis further demonstrated the log-linear relationship between morning basal and peak levels, while also finding a significant decrease in peak post-ACTH levels for patients diagnosed with secondary hypothyroidism (76 nmol/L lower, p=0.003) or secondary hypogonadism (61 nmol/L lower, p=0.02). These data suggest that the risk of cortisol deficiency is significantly higher in individuals with additional pituitary insufficiencies. The odds ratios for cortisol deficiency in patients with history of isolated secondary hypothyroidism was 3.41 (p=0.015), with isolated secondary hypogonadism was 4.77 (p=0.002) and with both was 7.45 (p=0.0002). CONCLUSION: Morning basal serum cortisol levels show promise as an effective screening test for HPA insufficiency for most patients. Clinicians should consider the high probability of HPA insufficiency in patients with one or more pituitary insufficiencies.