Cognition and psychological wellbeing in hypopituitary patients.

Hypopituitarism (HP) frequently occurs in patients presenting with sellar masses and despite recent advances in therapeutic options, HP patients consistently suffer from impaired quality of life due to psychological distress and cognitive dysfunction. These neurocognitive complications tend to persist in spite of surgical or biochemical remission of the disease making it especially challenging to segregate the effect of HP per se from other comorbidities such as the effect of tumour, surgery, radiation therapy, or complications caused by excess hormone production. Regardless, there is ample evidence to suggest that receptors for various pituitary hormones are abundantly expressed in key areas of central nervous system that are associated with memory and behaviour function and HP is also associated with poor sleep which can further exacerbate neurocognitive dysfunction. There is also evidence that hormonal replacement in HP patients partially restores these neurocognitive functions and improves sleep disorders. However, there is a need for creating better awareness among healthcare providers interacting with HP patients to enhance an earlier recognition of these disorder and their impact on quality of life despite initial remission. Importantly, there is a need to not only develop better and more cost-effective replacement therapies that would closely mimic the physiological hormonal release patterns, but also develop coping strategies for HP patients suffering from these complications.

Joint pain, physical function, and balance self-confidence in acromegaly versus nonfunctioning pituitary adenoma patients.

CONTEXT: Patients with acromegaly (PWA) experience balance issues, despite achieving biochemical remission, that may significantly impair their quality of life. OBJECTIVE: We sought to assess the prevalence of falls and balance self-confidence in PWA in comparison with a control group. Furthermore, we investigated the effect of joint pain and function as predictors for their balance self-confidence. DESIGN: Cross-sectional, case-controlled. SETTING: Tertiary care centers. PARTICIPANTS: In this case-control study, we surveyed PWA (n = 94) and nonfunctioning pituitary adenoma (PNA; n = 82) with similar age, sex, and body mass index from two Canadian centers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Data were obtained on number of falls during the past 12 months, self-confidence to maintain balance, joint pain, joint surgery, pain medication usage, and upper and lower extremity musculoskeletal disability. RESULTS: While both PWA and PNA had a similarly high risk of falls, PWA had lower self-confidence to maintain balance (P < .01). Patients with acromegaly had higher joint pain scores and more functional impairment in upper extremity, hip, knee, and ankle joints (all P < .01). In both groups, age, sex, and ankle functional score were predictors of balance self-confidence. For PWA, hip functional score was also a predictor of balance self-confidence in contrast to knee and back pain scores being predictors for the PNA group. CONCLUSIONS: We confirmed an increased prevalence of falls in both groups with diminished balance confidence in PWA. This reduced balance self-confidence seems to be related to their increased hip functional impairment in comparison with PNA.

Staged reflexive artificial intelligence driven testing algorithms for early diagnosis of pituitary disorders.

BACKGROUND: Sellar masses (SM) frequently present with insidious hormonal dysfunction. We previously showed that, by utilizing a combined reflex/reflecting approach involving a laboratory clinician (LC) on common endocrine test results requested by non-specialists, and subsequently adding further warranted tests, previously undiagnosed pituitary disorders can be identified. However, manually employing these strategies by an LC is not feasible for wider screening of pituitary disorders. OBJECTIVE: The aim of this study was to compare the accuracy and financial impact of an Artificial Intelligence (AI) based, fully computerized reflex protocol with manual reflex/reflective intervention protocol led by an LC. METHODS: We developed a proof-of-concept AI-based framework to fully computerize multi-stage reflex testing protocols for pituitary dysfunction using automated reasoning methods. We compared the efficacy of this AI-based protocol with a reflex/reflective protocol based on manually curated retrospective data in identifying pituitary dysfunction based on 12 months of laboratory testing. RESULTS: The AI-based reflex protocol, as compared with the manual protocol, would have identified laboratory tests for add-on that either directly matched or included all manual add-on tests in 92% of cases, and recommended a similar specialist referral in 90% of the cases. The AI-based protocol would have issued 2.8 times the total number of manual add-on laboratory tests at an 85% lower operation cost than the manual protocol when considering marginal test costs, technical staff and specialist salary. CONCLUSION/DISCUSSION: Our AI-based reflex protocol can successfully identify patients with pituitary dysfunction, with lower estimated laboratory cost. Future research will focus on enhancing the protocol's accuracy and incorporating the AI-based reflex protocol into institutional laboratory and hospital information systems for the detection of undiagnosed pituitary disorders.

A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer.

Background: The traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference. Methods: This is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient's choice. Our primary objective is to determine the rate of 'failure' of disease management in respective AS and surgical arms as defined by: i) AS arm - surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes. Discussion: The results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer. Registration details: This prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery.

In-Hospital Endocrinology Consultation After Transsphenoidal Surgery: Is It Always Necessary?

BACKGROUND: Patients with sellar masses undergoing transsphenoidal surgery (TSS) frequently develop endocrine dysfunction; therefore, in-hospital endocrinology consultation (IHEC) is recommended. However, we wondered whether routine endocrinology assessment of all TSS patients is always necessary. METHODS: We developed an IHEC Physician's Guide to identify patients who would require peri-operative IHEC. An analysis of all patients undergoing TSS for a sellar mass over a 4-year period was conducted to assess the predictive value of the IHEC Physician's Guide in identifying patients who required IHEC. RESULTS: A total of 116 patients underwent TSS; 24 required IHEC. As expected, the risk of endocrine complications requiring peri-operative endocrine management was significantly higher in the IHEC group versus no-IHEC group (96% vs. 1%; p < 0.001). The negative predictive value of the IHEC Physician's Guide in identifying patients who did not require IHEC was 0.99 (95% CI 0.9409-0.9997); Fisher's exact test, p < 0.001), meaning that the IHEC Physician's Guide successfully identified all but one patient who truly required IHEC. CONCLUSION: Results from our study show that most patients do not need IHEC after TSS and that those patients requiring IHEC can be reliably predicted at surgery by using a simple IHEC Physician's Guide.

Patient and tumor factors contributing to distant metastasis in well-differentiated thyroid cancer: a retrospective cohort study.

BACKGROUND: Distant metastasis in thyroid cancer significantly reduces survival in patients with well-differentiated thyroid carcinoma (WDTC). There is limited information available to clinicians regarding pathological features that confer a higher risk of distant metastasis (DM). This study aimed to identify patient and tumor factors that were associated with the development of DM over time in patients with WDTC. METHODS: A retrospective cohort analysis of patients with WDTC (n = 584) at our institution was performed between 2007 and 2017. A total of 39 patients with DM and 529 patients with no DM (NDM) were included. Patient demographics, tumor characteristics and patient survival were compared between the DM and NDM groups using a univariate analysis. Multivariate Cox-proportional hazards model was used to evaluate the risk of developing distant metastasis over time. Kaplan-Meier analysis was used to compare survival between the DM and NDM groups. RESULTS: Distant metastasis had a substantial impact on disease-specific survival (DSS) at 5 and 10-years in the DM group; 71.0% (SE 8.4%) and 46.9% (SE 11.6%) respectively, compared to 100% survival in the NDM group (p < 0.001). The DM group had significantly higher proportions of males, lymphovascular invasion (LVI), nodal metastasis (NM), large tumor size (TS), extrathyroidal extension (ETE), positive resection margins, multifocality, follicular thyroid cancer (FTC), tall cell variant of papillary thyroid cancer (PTC), and Hurthle cell carcinoma (HCC), when compared to the NDM group (p < 0.05). A TS ≥ 2 cm (Hazard Ratio (HR) 1.370), NM (HR 3.806) and FTC (HR 7.068) were associated with a significantly increased hazard of developing distant metastasis in patients with WDTC. CONCLUSIONS: TS ≥ 2 cm, NM and FTC are associated with a significantly increased propensity for developing DM in our cohort of WDTC patients.

Secondary pituitary hormonal dysfunction patterns: tumor size and subtype matter.

PURPOSE: Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM. METHODS: We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: < 1 cm, 1-1.9 cm, 2-2.9 cm, and > 3 cm. RESULTS: A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p < 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89-5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p < 0.001). CONCLUSION: Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM.

Prevalence and characteristics of sellar masses in the city of Al Ain, United Arab Emirates: 2010 to 2016.

BACKGROUND: The prevalence of sellar masses (SMs) is reported in Europe and North America but only limited data are available from the Middle East and North Africa (MENA) region. OBJECTIVES: Assess the prevalence and characteristics of SMs in Al Ain city, United Arab Emirates. DESIGN: Retrospective, descriptive multicenter study. SETTING: Three endocrine centers in Al Ain. PATIENTS AND METHODS: All patients diagnosed with SMs in the city of Al Ain, Emirate of Abu Dhabi, between 2011 and 2016 were evaluated. Cases were identified using ICD 9 and 10 codes and demographic and clinical data were collected. The prevalence rate was calculated for patients alive and residing in Al Ain city until 31 December 2016. MAIN OUTCOME MEASURES: Clinical presentations and prevalence rate. SAMPLE SIZE: 272. RESULTS: The mean (SD) age on presentation was 40.8 (14.3) years (range: 6-114 years, median: 40.0). The 170 (61.8%) females and 128 (46.5%) were native citizens of the United Arab Emirates. Two hundred and forty five (90%) patients had pituitary adenomas (PAs) while 27 (10%) had non-pituitary sellar lesions. The four most common SMs were prolactinoma (n=139, 51.1%), nonfunctioning adenoma (NFA) (n= 69, 25.4%), somatotroph adenoma (n=32, 11.8%) and craniopharyngioma (n=15, 5.5%). Patients with prolactinoma, corticotroph adenoma, and Rathke's cleft cyst had small sellar masses (<1 centimeter) while the majority of patients with other SMs had macroadenomas. Hypogonadism and growth hormone deficiency was present in 41.8% and 20.5% of the patients, respectively. Of 268 patients with available data, 82 patients underwent surgery while 25 patients received radiotherapy. At the end of 2016, 197 patients were residing in Al Ain city. The overall prevalence of SMs was 25.7/100 000 with PAs constituting most of these masses (n=177) for a prevalence of 23.1/100 000. CONCLUSIONS: This is the first study of SMs in the United Arab Emirates and the MENA region. Prolactinoma and NFA were the two most common SMs. Further studies are needed to explore the reasons for the lower prevalence of SMs in our region compared with other countries. LIMITATIONS: Retrospective design, relatively small sample size. CONFLICT OF INTEREST: None.

Primary versus Tertiary Care Follow-Up of Low-Risk Differentiated Thyroid Cancer: Real-World Comparison of Outcomes and Costs for Patients and Health Care Systems.

BACKGROUND: An unprecedented rise in the prevalence of low-risk well-differentiated thyroid cancer (TC) has been reported in several countries, which is partly due to an increased utility of sensitive imaging techniques. The outcome of these cancers has generally remained excellent and the overall 5-year survival is almost 100%. However, the extended follow-up strategy for these patients remains unclear and while the initial management is done in specialist centres some experts opt to follow them on a long-term basis while others discharge them to primary care after the initial management. The effectiveness of one strategy versus the other has not been studied. METHODS: We conducted a real-world comparison to assess the outcome of low-risk TC (AJCC stage I) with undetectable thyroglobulin (TG) 2 years after radio-iodine (I-131) therapy. The outcome from Halifax (NS, Canada) and London (ON, Canada), where all TC patients are routinely followed by the tertiary care team, was compared with that from Edmonton (AB, Canada), where patients are routinely discharged to primary care. RESULTS: All patients were diagnosed between January 1, 2006, and December 31, 2011. The mean follow-up in primary care after discharge was 62.2 months and in tertiary care it was 64.6 months (p = 0.43). Rates of recurrence were similar in both groups, i.e., 1.1% in primary care and 1.3% in tertiary care (p = 0.69). Ultrasound surveillance was conducted in 56.5% of the patients in primary care and 52.6% of the tertiary care group (p = 0.26). The rate of annual unstimulated TG testing per patient was 0.58 (range 0-14) in primary care and 0.96 (range 0-6) in tertiary care (p = 0.06). More patients in primary care (86%) than in tertiary care (29.9%) consistently had thyroid-stimulating hormone levels within the target range (p < 0.001). The mean healthcare cost, based on a single follow-up visit with a blood test and ultrasound in the primary care group was CAD 118.01 and in the tertiary care group it was CAD 164.12. CONCLUSION: Our study shows that extended follow-up of low-risk TC patients is perfectly feasible in primary care and provides significant economic benefit for the healthcare system.

PREDICTIVE MARKERS FOR POSTSURGICAL MEDICAL MANAGEMENT OF ACROMEGALY: A SYSTEMATIC REVIEW AND CONSENSUS TREATMENT GUIDELINE.

Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.

Incomplete Thyroid Ultrasound Reports for Patients With Thyroid Nodules: Implications Regarding Risk Assessment and Management.

OBJECTIVE: The purpose of this study was to determine the completeness of thyroid ultrasound (US) reports, assess for differences in report interpretation by clinicians, and evaluate for implications in patient care. MATERIALS AND METHODS: We retrospectively reviewed thyroid US examinations performed between January and June 2013 in Nova Scotia, Canada. Baseline examinations that identified a nodule were evaluated for 10 reporting elements. Reports that lacked a comment regarding malignancy risk or a recommendation for biopsy were considered unclassified and were graded by three clinical specialists in accordance with the 2015 American Thyroid Association management guidelines. Interrater agreement was assessed using the Cohen kappa statistic. A radiologist reviewed the images of unclassified nodules, and on the basis of radiologic grading, biopsy rates and pathologic findings were compared between nodules that did and did not warrant biopsy. RESULTS: Of 971 first-time thyroid US studies, 478 detected a nodule. The number of reports lacking a comment on the 10 elements ranged from 154 to 433 (32-91%). A total of 222 nodules (46%) were unclassified, and agreement in assigned grading by the clinical specialists was very poor (κ = 0.07; p < 0.05). According to radiologist grading, only 57 of 127 biopsies were performed on nodules that warranted biopsy, and 16 of 95 biopsies were performed unnecessarily. On the basis of the three clinical specialists' interpretation, 10, 31, and 33 reports were considered too incomplete to assign a grade; 40, 10, and four biopsies would have been unnecessarily ordered; and zero, three, and four cancers would have been missed. CONCLUSION: There is widespread underreporting of established elements in thyroid US reports, and this causes confusion and discrepancy among clinical specialists regarding the risk of malignancy and the need for biopsy.

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.

Reflex and reflective testing strategies for early detection of pituitary dysfunction.

OBJECTIVE: The clinical presentation of pituitary dysfunction is typically variable and may often be insidious, resulting in delayed diagnosis by up to decades. The complexity of presentation and difficulty in pattern recognition of first line hormone tests result in challenges in early diagnosis of this condition. The aim of this study was to determine the impact of reflective testing and interpretive commenting on the early detection and management of such cases from primary care. METHODS: Prospective audit over 12 months in which first line pituitary target organ hormones were identified via a reflex algorithm in the laboratory information system. Selected tests were reviewed by a laboratory clinician and decision made on reflective testing and interpretive commenting based on available clinical information and previous result trends. Patients who had a laboratory intervention were followed up to determine the clinical outcome. RESULTS: Out of 1099 patients identified, additional testing was made for 214. Interpretative comments were subsequently added to reports of 196 patients, 48 (25%) of whom were referred to endocrinology and 35 (73%) of these were directly related to the laboratory intervention. Eleven other patients had outcomes related to the intervention. Pituitary related conditions (insufficiency and/or adenoma) were found in 29 patients, 24 of which were identified as a result of laboratory intervention. CONCLUSIONS: This study highlights the clinical value of laboratory intervention in aiding early detection of pituitary dysfunction and may avoid the disease burden of delayed management.

Unusual AIP mutation and phenocopy in the family of a young patient with acromegalic gigantism.

Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy. LEARNING POINTS: Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.Unusual, previously not described AIP variant with loss of the stop codon.Phenocopy may occur in families with a disease-causing germline mutation.

Radiological Growth Patterns of Prolactinomas and Nonfunctioning Adenomas.

OBJECTIVES: To compare growth patterns of nonfunctioning and prolactin-producing pituitary macroadenomas, and to find whether their specific growth patterns are associated with clinically significant effects on vision. MATERIALS AND METHODS: From our comprehensive provincial neuropituitary registry, we retrospectively identified 35 randomly selected patients each with nonfunctioning adenomas and prolactinomas >10 mm in any dimension. MRI scans were analyzed to determine the superior and inferior growth, volume, and maximum craniocaudal height of the adenomas. Patients underwent visual field testing at diagnosis. Continuous variables were compared using Student's t test, the Mann-Whitney U test, and ANOVA. Categorical variables were compared using the chi-square test. RESULTS: The mean height of prolactinomas (23.2±11.3 mm) was similar to nonfunctioning adenomas (22.3±9.3 mm, p=0.8), and so were mean tumor volumes (prolactinoma=5.9±8 ml vs. nonfunctioning adenoma=4.8±5 ml, p=0.47). However, the mean suprasellar growth for prolactinomas was 2.9±5.3 mm and 7.3±4.7 mm for nonfunctioning adenomas (p<0.001), and the mean infrasellar growth was 10.2±8.0 and 5.0±6.6 mm, respectively (p=0.04). The inferior growth pattern of prolactinomas was associated with a significantly lower likelihood of having visual field abnormalities (11.4 vs. 57.1%, p<0.001). CONCLUSIONS: Prolactinomas have predominantly inferior growth compared to nonfunctioning adenomas and are less likely to cause vision changes.

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.

Presentation of atrial fibrillation following oral dexamethasone treatment in a NF2 patient.

Atrial fibrillation (A-fib) is the most common cardiac arrhythmia which is associated with an increased risk of mortality secondary to stroke and coronary artery disease. Intravenous glucocorticoid therapy (such as dexamethasone and hydrocortisone) is frequently used peri-operatively in patients undergoing cardiac surgery to prevent A-fib. Dexamethasone is also frequently used in patients with single or bilateral vestibular schwannomas (VS), to reduce tumor swelling both before and after radiation treatment. We describe a case of A-fib in a 50 year-old female patient with neurofibromatosis type 2 (NF-2), who was prescribed dexamethasone for post-radiation tumor edema.