Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy.

OBJECTIVE: Gender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals. METHODS: This is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes. RESULTS: There were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status. CONCLUSION: Both the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM .

The Effect of Gender-Affirming Hormone Therapy on Serum Creatinine in Transgender Individuals.

OBJECTIVE: To describe the changes in serum creatinine (Cr) levels after the initiation of gender-affirming hormone therapy (GAHT) in transgender individuals to better understand the expected changes and interpretation of laboratory values in this population. METHODS: A retrospective chart review of all adult transgender patients initiated on GAHT at Mayo Clinic from January 2011 to October 2019 was completed. Laboratory values were obtained prior to initiating GAHT and at 3, 6, and 12 months after initiating GAHT. Baseline Cr values were compared with Cr values at 3, 6, and 12 months after initiating GAHT in transgender men (TM) on testosterone and transgender women (TW) on estradiol and antiandrogens. RESULTS: A total of 84 TW (median age of 30 years) and 24 TM (median age of 23 years) were included for analysis. Following a matched pair analysis of TW, Cr values were found to be significantly decreased by -0.03 at 3 months (P = .04), -0.10 at 6 months (P < .01), and -0.07 at 12 months (P < .01) compared with baseline values. Following a matched pair analysis of TM, Cr values were found to be significantly increased, on average, by 0.14 at 3 months (P = .04), 0.21 at 6 months (P = .016), and 0.15 at 12 months (P = .003) compared with baseline values. CONCLUSION: In TW and TM, a change in Cr level was seen as early as 3 months toward their affirmed gender after initiating GAHT. Clinicians can use Cr levels established at 6 months as new baseline values, as these changes continue to persist up to 12 months.

MANAGEMENT AND OUTCOMES OF GIANT PROLACTINOMA: A SERIES OF 71 PATIENTS.

Objective: To describe outcomes of patients with giant prolactinoma (≥4 cm) and identify predictors of therapeutic response. Methods: In this retrospective study, complete biochemical and structural response were defined as prolactin (PRL) ≤25 ng/mL and no visible tumor at follow-up, respectively. Results: Giant prolactinoma (median size, 4.8 cm [range, 4 to 9.8 cm]; median PRL, 5,927 ng/mL [range, 120 to 100,000 ng/mL]) was diagnosed in 71 patients. Treatments included: dopamine agonists (DAs) (n = 70, 99%), surgery (n = 30, 42%), radiation (n = 10, 14%), and somatostatin analogs (n = 2, 3%). Patients treated with DA monotherapy were older compared with those who received subsequent therapies (47 years vs. 28 years; P = .003) but had similar initial PRL and tumor size. Surgically managed patients were younger compared with the nonsurgical group (35 years vs. 46 years; P = .02) and had lower initial PRL (3,121 ng/mL vs. 6,920 ng/mL; P = .02), yet they had similar tumor response. Hypopituitarism was more common following surgery compared to medical management: adrenal insufficiency (69% vs. 27%; P<.001), hypothyroidism (67% vs. 38%; P = .02), growth hormone deficiency (24% vs. 6%; P = .04), and diabetes insipidus (17% vs. 3%; P = .04). Therapeutic response did not correlate with sex, age, initial PRL, tumor size, or first-line therapy mode. At median follow-up of 4.8 years, the median PRL was 18.3 ng/mL (range, 0.6 to 12,680 ng/mL), and final volume was 0.9 cm3 (range, 0 to 43.0 cm3). In those with available data, 36/65 (55%) patients achieved PRL normalization, and 16/61 (26%) had no visible tumor at follow-up. Conclusion: Most patients with giant prolactinoma have excellent response to DA. Sex, age, initial PRL, and tumor size do not predict therapeutic response. Abbreviations: BRC = bromocriptine; CAB = cabergoline; CSF = cerebrospinal fluid; DA = dopamine agonist; MRI = magnetic resonance imaging; PRL = prolactin.

ENDOCRINOLOGY FELLOWS' PERCEPTION OF THEIR CONFIDENCE AND SKILL LEVEL IN PROVIDING TRANSGENDER HEALTHCARE.

OBJECTIVE: Both educational content and hours devoted to transgender health training of endocrinology fellows are suboptimal. The objective of this study was to assess the perspectives of endocrinology fellows on their training in transgender health. METHODS: We evaluated the state of comfort and knowledge of transgender healthcare among endocrinology fellows attending Endocrine University. Surveys were administered to fellows before and after their participation in a case-based session on transgender health. RESULTS: The majority of fellows felt that training in transgender health is important (95.9%, 189/197); however, only 58.9% reported inclusion of dedicated transgender content in their training programs. Fellows who had received transgender healthcare education, and those who had seen more transgender patients in their training, were more likely to be confident in treating patients with hormone therapy ( P<.001 and P<.0001, respectively). Following the case-based session, 62.4 % of fellows reported that they would change their practice, 72.8% felt that their comfort level with transgender care had improved, and 91% felt that transgender content such as that provided in the educational session should be mandatory in endocrinology training programs. Methods most desired by fellows to improve their education included lectures from visiting professors (70.3%), participation in elective rotations (62.1%), online training modules (57.9%), and attendance at meetings with transgender topics (57.4%). CONCLUSION: Transgender health education of U.S. endocrinology fellows is suboptimal. Participation in a case-based session significantly increased the comfort level of endocrinology fellows in key areas of transgender health. Abbreviation: ACGME = Accreditation Council for Graduate Medical Education.

NECESSITY OF MULTIMODAL TREATMENT OF ACROMEGALY AND OUTCOMES.

OBJECTIVE: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution. METHODS: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015. RESULTS: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not. CONCLUSION: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly. ABBREVIATIONS: CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.

PERFORMANCE OF FREE VERSUS TOTAL CORTISOL FOLLOWING COSYNTROPIN STIMULATION TESTING IN AN OUTPATIENT SETTING.

OBJECTIVE: Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation testing (CST) compared to TC and to determine the rates of discordance. METHODS: This is a cross-sectional study of 295 stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST. RESULTS: The mean age of the 295 subjects was 49.1 (16.9) years. Of 218 females, 43 were taking estrogen therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R(2) = 0.77, P<.001), 30 minutes (R(2) = 0.87, P<.001), and 60 minutes (R(2) = 0.90, P<.001). The FC cutoffs for AI were 873 and 1,170 ng/dL at 30 and 60 minutes, respectively. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 vs. 1.7, P<.001). Both TC and FC at baseline were higher in females on ET compared to those who were not and to males; however, peak TC and FC values were similar. In 3/43 females on ET, FC, and TC results were discordant (P = .003). CONCLUSION: We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in females treated with ET (7%). The FC measurements during CST in females on ET may provide a more rapid and accurate diagnosis of AI.

Impulse control disorders in patients with dopamine agonist-treated prolactinomas and nonfunctioning pituitary adenomas: a case-control study.

OBJECTIVE: We aimed to assess the prevalence of impulse control disorders (ICDs) in patients with prolactin-secreting adenomas treated with dopamine agonists (DAs), to identify associated factors and to compare it with a group of patients with nonfunctioning pituitary adenoma. SUBJECTS, DESIGN AND MEASUREMENT: In a postal survey, 77 patients from Group A (patients with prolactinomas and present or past use of DAs) and 70 patients from Group B (patients with nonfunctioning pituitary adenoma and no history of DA therapy) responded to a questionnaire on compulsive shopping, pathologic gambling, hypersexuality and punding. Associated clinical information was obtained through the survey and review of medical electronic records. RESULTS: The total ICD prevalence was 24·68% in Group A and 17·1% in Group B (P = 0·31). Group A had an increased rate of hypersexuality (P = 0·03). Subgroup analysis revealed that men in Group A had a significantly increased frequency of total ICDs when compared with men in Group B (27·7 vs 3·7%, P = 0·01). No differences in rates of total ICDs were found between women of Groups A and B (20 vs 25·6%, P = 0·78). No association with type, dose or duration of treatment with DA was noted. CONCLUSIONS: Males with prolactinomas treated with DAs were 9·9 times more likely to develop an ICD than their counterparts with nonfunctioning pituitary adenomas. Until prospective studies on the relationship of DA use in patients with prolactinoma and ICDs are available, the authors propose that patients with prolactinoma be forewarned of possible ICD development with DA therapy.

Evaluation of Variables Influencing the Measurement of Insulin-like Growth Factor-1.

OBJECTIVE: Our aim was to identify the frequency and possible clinical and analytical factors leading to "falsely" elevated insulin-like growth factor-1 (IGF-1). METHODS: We performed a retrospective review of patients with IGF-1 concentrations above the reference interval. They were selected from a database of patients who had consecutive IGF-1 measurements between the years 2007-2010. RESULTS: Out of 2,747 unique patients, 117 (4%) were found to have IGF-1 concentrations above the reference interval that were considered false-positives following a review of the clinical data. There was no relationship between the percentage of increase in IGF-1 and age, sex, body mass index (BMI), comorbidities, medication use, gonadal status, baseline growth hormone (GH), or insulin-like growth factor binding protein-3 (IGFBP-3) concentrations. An abnormal IGF-1 concentration led to performance of an oral glucose tolerance test (OGTT) for GH suppression in 21 of 117 patients (18%) and repeat IGF-1 measurements in 52 patients (44%). In 34 of 52 patients (65%) with a median follow-up of 36 months, the subsequent IGF-1 concentration was within the reference interval. CONCLUSION: Discovery of "falsely" elevated IGF-1 concentrations may lead to unnecessary testing and physician visits. Although the cause of the "falsely" elevated IGF-1 concentrations during the study period remains to be elucidated, it appears they are caused by a combination of high biological variability and method-specific assay performance issues. Clinicians should consider retesting patients with potentially spurious IGF-1 elevations after some time interval before embarking on more extensive investigations.

Genital Surgery Outcomes Using an Individualized Algorithm for Hormone Management in Transfeminine Individuals.

CONTEXT: Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender affirming providers. OBJECTIVE: To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment. DESIGN: Retrospective observational cohort study from 2017-2022. Pre- and post-operative data collected included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and post-operative complications. SETTING: Single-center tertiary referral center. PATIENTS: 183 TF individuals, grouped into estradiol continued (Group 1) vs estradiol temporarily discontinued for 2-6 weeks preoperatively (Group 2). MAIN OUTCOME MEASURE(S): Venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments. RESULTS: The majority of individuals continued estradiol perioperatively [Group 1; 138 (75.4%)]. Individuals who temporarily held estradiol preoperatively [Group 2; 45 (24.6%)] were statistically older (p < 0.01), had higher incidence of cardiometabolic comorbidities (p < 0.01), and higher Caprini scores (p < 0.01). Group 1 was statistically more likely to use oral estradiol (p < 0.01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups. CONCLUSION: An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for post-operative surgical complications while maintaining stable behavioral health measures perioperatively.

Interpretation of Abnormal Dexamethasone Suppression Test is Enhanced With Use of Synchronous Free Cortisol Assessment.

CONTEXT: Interpretation of dexamethasone suppression test (DST) may be influenced by dexamethasone absorption and metabolism and by the altered cortisol binding. OBJECTIVE: We aimed to determine the normal ranges of free cortisol during DST in participants without adrenal disorders and to identify the population of patients where post-DST free cortisol measurements add value to the diagnostic workup. DESIGN AND SETTING: Cross-sectional study conducted in a tertiary medical center. PARTICIPANTS: Adult volunteers without adrenal disorders (n = 168; 47 women on oral contraceptive therapy [OCP], 66 women not on OCP, 55 men) and patients undergoing evaluation for hypercortisolism (n = 196; 16 women on OCP). MEASUREMENTS: Post-DST dexamethasone and free cortisol (mass spectrometry) and total cortisol (immunoassay). MAIN OUTCOME MEASURES: Reference range for post-DST free cortisol, diagnostic accuracy of post-DST total cortisol. RESULTS: Adequate dexamethasone concentrations (≥0.1 mcg/dL) were seen in 97.6% volunteers and 96.3% patients. Only 25.5% of women volunteers on OCP had abnormal post-DST total cortisol (>1.8 mcg/dL). In volunteers, the upper post-DST free cortisol range was 48 ng/dL in men and women not on OCP, and 79 ng/dL in women on OCP. When compared with post-DST free cortisol, diagnostic accuracy of post-DST total cortisol was 87.3% (95% CI, 81.7-91.7); all false-positive results occurred in patients with post-DST cortisol between 1.8 and 5 mcg/dL. OCP use was the only factor associated with false-positive results (21.1% vs 4.9%, P = 0.02). CONCLUSIONS: Post-DST free cortisol measurements are valuable in patients with optimal dexamethasone concentrations and post-DST total cortisol between 1.8 and 5 mcg/dL.

Symptomatic Rathke cleft cysts: extent of resection and surgical complications.

OBJECT: Rathke cleft cysts (RCCs) are benign masses arising from the embryological Rathke pouch, and are commonly treated by transsphenoidal surgery. The authors retrospectively compared RCC extent of resection-either gross-total resection (GTR) or decompression-to the primary outcome measure, which was recurrences resulting in repeat surgery, and the secondary outcome measure, which was complications. METHODS: Seventy-four patients presenting to the neurosurgical department with RCC were analyzed retrospectively. Sixty-eight patients had a total of 78 surgical procedures, with the diagnosis of RCC confirmed by histological investigation; of these, 61 patients had adequate operative notes for the authors to evaluate extent of resection. Groups were separated into GTR (32 patients) or decompression (subtotal resection or fenestration into the sphenoid sinus; 29 patients) based on operative notes and postoperative imaging. The mean follow-up duration was 60.5 ± 72.1 months (the mean is expressed ± SD throughout). RESULTS: The average age at the time of the initial surgery was 42.8 ± 17.4 years, and 70% of patients were female. The mean cyst diameter preoperatively was 16.9 ± 17.8 mm. Eight patients had repeat surgery, our primary outcome measure; 3 repeat operations occurred in the GTR group, and 5 in the decompression group. There was no significant difference in recurrence when comparing groups (GTR 9%, decompression 17%; p = 0.36). There were no major complications; however, analysis of postoperative minor complications revealed that 11 (34%) GTRs resulted in surgical complications, whereas the decompression cohort accounted for only 3 complications (10%) (p = 0.03), with diabetes insipidus (6) and CSF leaks (5) being the most common. Gross-total resection also resulted in an increase in postoperative hyperprolactinemia compared with decompression (p = 0.03). CONCLUSIONS: It appears that RCCs require repeat surgery in 13% of cases, and attempted GTR does not appear to reduce the overall rate of recurrence. However, more aggressive resections are associated with more complications in this series.

An Approach to Nonsuppressed Testosterone in Transgender Women Receiving Gender-Affirming Feminizing Hormonal Therapy.

Nonsuppressed levels of testosterone are seen in up to a quarter of transgender women on gender-affirming feminizing hormonal treatment. Multiple factors contribute to this situation, including patient, medication, laboratory, and organ-specific concerns. We propose a stepwise approach to determine the etiology of nonsuppressed levels of testosterone in transgender women. This may lead to an appropriate feminizing hormonal therapy regimen and diagnosis of manageable medical conditions.

Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Patients with Fibromyalgia.

PURPOSE: Patients with fibromyalgia (FM) may demonstrate low cortisol concentrations during diagnostic evaluation. However, it remains unclear whether low cortisol reflects underlying pituitary dysfunction. We aimed to determine if a subset of patients with FM have concomitant secondary adrenal insufficiency (SAI) and growth hormone deficiency (GH). PATIENTS AND METHODS: This is a retrospective study of all patients with FM diagnosed with SAI based on abnormal insulin tolerance test (ITT) between June 2002 and August 2019. Patients were excluded if they had other reasons for SAI. Measurements include cortisol and GH during ITT in all patients, and peak cortisol during cosyntropin stimulation test in a subset of patients. RESULTS: We identified 22 patients (median age of 38 years (range 19-65), 18 (82%) women) diagnosed with secondary AI based on abnormal ITT (peak median cortisol level of 11 mcg/dL (range 5.4-17)). Concomitant GH deficiency was diagnosed in 19 (86%) patients. Cosyntropin stimulation test was performed in 14 (64%) patients and was normal in 11 (79%) (peak cortisol ≥18 mcg/dL). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients were started on physiologic glucocorticoid replacement, and 5 patients were started on GH replacement. Of the 13 patients with follow-up, 8 (62%) reported symptom improvement after starting treatment. CONCLUSION: Patients with FM can have concurrent SAI and GH deficiency. Cosyntropin stimulation test should not be used to exclude SAI in patients with FM. Appropriate glucocorticoid and/or GH replacement may improve symptoms in some patients.

Characteristics of Transgender Women Referred to Women's Heart Clinic.

INTRODUCTION: Transgender women have been reported to have a high burden of cardiovascular disease (CVD) and risk factors based largely on surveys. Our aim was to describe the prevalence of CVD and associated comorbidities among a cohort of older transgender women referred to cardiology as part of their gender-affirming care. METHODS: This was a retrospective, cross-sectional study of transgender women at a single institution from 2017 to 2019. RESULTS: Fifty-two consecutive patients were included. The most common reasons for referral were cardiac risk factor management (45%) and pre-operative cardiac risk stratification prior to gender-affirming surgery (35%). The mean age was 57 ± 10 years, 87% were white, and 92% had insurance coverage. Forty-eight patients (92%) were taking gender-affirming hormone therapy; 5 had undergone breast augmentation, 4 had undergone orchiectomy, and 2 had undergone vaginoplasty. The most common comorbidities were depression and/or anxiety (63%), obesity (58%), and hyperlipidemia (54%). Excluding aldosterone antagonists, 46% were on cardiac medications; changes were recommended for 25% of patients: new prescriptions in 9, dose adjustments in 5, and discontinuations in 4. According to the pooled cohort equation, the 10-year risk of atherosclerotic CVD was 9.4 ± 7.7% when the study population was calculated as male and 5.2 ± 5.1% when calculated as female (p <0.001). For patients who completed exercise testing, the functional aerobic capacity was fair (77.6 ± 21.4%) when calculated as male and average (99.5 ± 27.5%) as female (p < .0001); there was inconsistency in sex used for calculating the result on the formal report. CONCLUSIONS: Older transgender women may have an underestimated prevalence of CVD and its risk factors. More research is needed to identify cardiovascular health profiles, improve practice consistency, and establish normative values for transgender patients.

Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes.

BACKGROUND: Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. METHODS: We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. RESULTS: The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. CONCLUSIONS: Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing's syndrome.

OBJECTIVE: We sought to determine if higher resolution 3 Tesla (T) magnetic resonance imaging (MRI) with or without ovine corticotropin releasing hormone (o-CRH) stimulation would increase the sensitivity for detection of pituitary microadenomas in ACTH-dependent Cushing's syndrome (CS). DESIGN AND PATIENTS: We prospectively identified 23 patients over a 2-year period with clinical and biochemical evidence of ACTH-dependent CS with no lesion (n = 11) or equivocal lesion (n = 10) on 1.5T MRI. Subsequently, two additional MRIs were performed in random order: 3T nonstimulated MRI or 3T MRI with o-CRH in all patients. Three neuroradiologists reviewed all examinations in a randomized blinded fashion. Patients were divided into four groups, depending on the outcome of their evaluation and treatment for CS. Two patients had to be excluded, and so we report on 21 subjects. MEASUREMENTS AND RESULTS: Both 3T MRI without (P < 0.016) and with o-CRH stimulation (P < 0.013) was significantly more sensitive for detection of pituitary microadenomas than 1.5T MRI for Group 1 (definitive proof of Cushing's disease, n = 10). Group 2 (those in group 1, plus three patients where dynamic/invasive testing suggested pituitary source) also showed a significant (P < 0.012) advantage for 3T. There was no difference between the 3T and the 3T o-CRH examinations for any of the pulse sequences. We did not observe a statistically significant difference in other patient groups [patients with recurrent CD (n = 6) and patients with ectopic CS (n = 2)]. CONCLUSIONS: The results of our prospective blinded studies suggest that 3T MRI of pituitary gland should be considered in evaluation of patients with ACTH-dependent CD when 1.5T imaging is negative or equivocal.

Magnetic resonance imaging-graded hypothalamic compression in surgically treated adult craniopharyngiomas determining postoperative obesity.

OBJECT: Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma. METHODS: The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors' institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes. RESULTS: Mean age was 46 +/- 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively. Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9-26.9]) and controls (mean 29.3 [95% CI 31.9-26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5). CONCLUSIONS: Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.

Transgender Health Care Curriculum Development: A Dual-Site Medical School Campus Pilot.

Purpose: Lack of physician training contributes to health care disparities for transgender people. The limited generalizability and feasibility of published training approaches lessen their utility in lowering barriers for other institutions to adopt similar training. Methods: All first-year medical students at the Mayo Clinic Alix School of Medicine (MCASOM) in Minnesota and Arizona received a 1-h lecture introducing key concepts related to transgender people and their health disparities. Students completed a 21-question survey before and after the lecture, and 1 year later. Chi-square likelihood coefficients were used to compare responses between the three time points. Results: Eighty-six of 100 students answered the prelecture survey (86% response rate); 70 the postlecture survey; and 44 the 1-year follow-up survey. Twenty-five (29%) students had prior education in any lesbian, gay, bisexual, and transgender (LGBT+) health disparities, but this did not correlate with more favorable attitudes or knowledge. LGBT+ students and those with close LGBT+ friends had the most favorable attitudes and knowledge. The proportion of students comfortable with caring for transgender people changed significantly (76% self-reported very comfortable prelecture vs. 91% postlecture, p=0.0073) and remained at 89% 1 year later. The proportion of students comfortable with a transgender patient scenario significantly increased (67% self-reported very comfortable prelecture vs. 87% postlecture, p=0.032) even when surveyed 1 year later (95% very comfortable, p<0.0001). Conclusion: This study demonstrates that a 1-h lecture can increase the proportion of medical students who demonstrate positive attitudes and correct knowledge on transgender patient care for at least a year, and how a survey can gather essential information on student learning needs to guide training development.

A community-based study of demographics, medical and psychiatric conditions, and gender dysphoria/incongruence treatment in transgender/gender diverse individuals.

BACKGROUND: Current understanding about health care in the gender diverse population is limited by the lack of community-based, longitudinal data, especially in the USA. We sought to characterize a community-based cohort of transgender individuals including demographics, gender identities, social characteristics, psychiatric and medical conditions, and medical therapy for gender dysphoria/incongruence. PATIENTS AND METHODS: We performed a retrospective chart review of gender diverse residents of Olmsted County, Minnesota, who sought gender-specific healthcare from January 1, 1974, through December 31, 2015, using an infrastructure that links medical records of Olmsted County residents from multiple institutions. RESULTS: The number of patients seeking gender-specific healthcare increased from 1 to 2 per 5-year interval during the 1970s-1990s to 41 from 2011 to 2015 (n = 82). Forty-nine (59.8%) were assigned male sex at birth (AMAB), 31 (37.8%) were assigned female (AFAB), and 2 (2.4%) were intersex. Gender identities evolved over time in 16.3% and 16.1% of patients AMAB and AFAB, respectively, and at most recent follow-up, 8.2% and 12.9% of patients AMAB and AFAB, respectively, were non-binary. Depression affected 78%, followed by anxiety (62.2%), personality disorder (22%), and post-traumatic stress disorder (14.6%). 58.5% experienced suicidal ideation, 22% attempted suicide, and 36.6% were victims of abuse. The most prevalent medical conditions and cardiovascular (CV) risk factors included obesity (42.7%), tobacco use (40.2%), fracture [34.1% (86.2% traumatic)], hypertension (25.6%), hyperlipidemia (25.6%), and hypertriglyceridemia (15.9%). 67.3% of patients AMAB used feminizing and 48.4% of patients AFAB used masculinizing hormone therapy. When compared to US CDC National Health Statistics, there was a significantly greater prevalence of depression and anxiety but no difference in the prevalence of obesity, hypertension, hypercholesterolemia, type 2 diabetes, or stroke. CONCLUSION: Transgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.