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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.

Lucinda M Gruber,1 Sanjeev Nanda,2 Todd Nippoldt,1 Alice Y Chang,1 Irina Bancos1 1Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, Rochester, MN, USA; 2Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Irina BancosDivision of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USATel +1 507-286-1387Fax +1 507-284-5745Email bancos.irina@mayo.eduPurpose: 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.Keywords: hypothalamus-pituitary dysfunction, cosyntropin stimulation test, insulin tolerance test

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

The clinical presentation of a patient with a sellar mass can include signs and symptoms of hormonal excess, hormonal deficiency, or of the mass itself such as vision loss or headache. Alternatively a sellar mass may be discovered incidentally on brain imaging performed for an unrelated reason. Autopsy and radiology studies suggest the prevalence of incidentally found pituitary masses to be approximately 10 % of the population (Molitch, Endocrinol Metab Clin North Am 37:151–171, 2008). Clinically significant pituitary lesions are diagnosed in 1 in 1,000 people (Bancos et al., Best Pract Res Clin Endocrinol Metab 26(1):9–19, 2012). Although a wide variety of diseases can manifest as sellar or parasellar masses (Table 5.1), the vast majority of clinically apparent and incidentally found lesions are pituitary adenomas, or Rathke’s cleft cyst (Orija et al., Best Pract Res Clin Endocrinol Metab 26(1):47–68, 2012). The effects of excess hormonal secretion (prolactin (PRL), growth hormone (GH), corticotropin (ACTH), thyrotropin (TSH)) from functioning pituitary adenomas can lead to significant morbidity and increased mortality. Hypopituitarism can be a consequence of any mass lesion in the sellar or parasellar region.

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

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.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.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.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.

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

Background: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. Methods: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs

Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement. Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol < 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use. Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients achieved hypoglycemia =18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment. Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency. 1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506. 2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.

An estimated 1.4 million transgender individuals currently reside in the USA and this patient population is increasing on an annual basis (Am J Public Health 107: 1–8, 2017). Along with this census increase, there has also been an increasing number of gender confirmation surgeries being performed in the USA (American Society of Plastic Surgeons, 2016). Our primary objective was to study the effects of hormonal therapy on testicular volumetrics on transgender patients who underwent male-to-female (MtF) bottom gender confirmation surgery. Retrospective review of patients who underwent MtF bottom gender confirmation surgery. Based on World Professional Association for Transgender Health (WPATH) guidelines a minimum of 1 year of hormonal therapy was required in order to be included. Two groups were analyzed based on their hormone therapy regimen (estrogen and estrogen/progesterone). Demographics, comorbidities, body mass index (BMI), medications (and length of use), testicular volumetrics (weight, length of spermatic cord, volume), and post-operative complications (dehiscence, seroma, hematoma, infection, return to the OR) were analyzed. A total of 54 patients were analyzed. The mean age of the sample population was 37.7 (± 13.3) years old. The mean difference in BMI before and after hormonal treatment was − 0.14 (± 1.7) in the estrogen only group and + 0.3 (± 1.7) in the estrogen/progesterone (combined) group (p = 0.396). The mean weight of surgical specimens in the estrogen only and in the combined group was 30.2 (± 14.9) and 24.1 (± 8.7), respectively (p = 0.033). The spermatic chord length for patients in the estrogen group was 5.4 cm (± 1.7), and 4.5 cm (± 1.6) for patients in the combined group (p = 0.009). Of all the patients, 18 presented with minor wound dehiscence of labia majora. Analysis of complications regarding to the type of hormonal therapy they received showed no difference among patients in the estrogen only and the combined group (p = 0.859). Hormone therapy is an integral aspect of a multidisciplinary approach to transgender medicine and surgery. Further studies are required to elucidate systemic effects in detail and evaluate outcomes in a post-operative setting. Level of Evidence: Level III, risk /prognostic study.

Summary:Vaginal reconstruction and vaginoplasty are indicated in vaginal agenesis, following pelvic tumor resection, trauma, and for gender-confirmation surgery. In this article, the authors present the clinical outcomes and sexual function evaluation when using the pedicle transverse colon flap for

For transgender and gender diverse individuals, gender identity is not congruent with the sex assigned at birth. Cross sex hormone therapy (HT) and gender affirming surgery can relieve significant dysphoria associated with gender incongruence and improve health outcomes. With changes in private insurance, state and federal regulations to cover gender-affirming treatments and procedures, there has been an increasing need and demand for trained providers and centers to provide gender-affirming health care. However, there is little data to guide management of peri-operative HT with regards to limiting risks. Most surgeons follow a protocol to stop feminizing HT 2 weeks before vaginoplasty with little data that this is effective and necessary or whether this might provoke significant dysphoria peri-operatively. We sought to determine if an age-specific and route-specific peri-operative protocol for feminizing HT was associated with increased risk for complications, changes in hormone concentrations or cardiometabolic profile. At our tertiary care academic center, transgender women over the age of 50 discontinued oral estradiol 6 weeks prior to surgery to allow enough time for clotting factors to normalize but could choose to switch to transdermal estradiol until 2 weeks prior to surgery. Younger women continued estradiol until surgery. All women restarted estradiol upon discharge from the hospital. We performed a retrospective review of pre and postoperative body mass index (BMI), blood pressure (BP), estradiol (E2) and total testosterone (TT) concentrations, fasting glucose and lipids 6 months before and after vaginoplasty. Results: A total of 59 transgender women underwent vaginoplasty over 20 months. Ten women age ≥ 50 (O) had a median age of 58 [Interquartile range (IQR) 56-62]. 49 women < age 50 (Y) had a median age of 31 [IQR 27-37]. O had significantly higher BMI than Y [29.7(IQR 28.3-34.2) vs 24.6 (21.6-28.4), p

The process of gender identity development remains poorly understood. Higher prevalence of gender nonconforming identity has been reported in individuals with congenital adrenal hyperplasia, androgen insensitivity syndromes, defects in androgen biosynthesis, and structural differences in sex development, indicating that prenatal and postnatal androgen exposure plays some role in the development of gender identity. Additionally, genetics are thought to play an important role in gender identity based on the observed concordance of gender incongruence in monozygotic twin pairs and reported co-occurrence of gender nonconformity in families. Also, gender identity variance has been associated with distinct morphological characteristics of specific neuroanatomical structures, such as the interstitial nucleus of the anterior hypothalamus 3 and the central part of the bed nucleus of the stria terminalis, supporting the hypothesis that gender identity evolves as a consequence of the interaction of the developing brain and sex hormones. Gender identity development is complex and most likely stems from an intricate interaction between biological, genetic, social, and psychological factors.

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.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.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%).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.

Measuring the plasma corticotropin (ACTH) concentration is an important step in determining the underlying cause in patients with hypercortisolemia. Interfering substances in immunoassays can lead to erroneous results impacting clinical management. We describe a case series of 12 patients, the majority of whom were being investigated for possible Cushing's syndrome and in whom inconsistencies between the clinical picture and biochemical testing raised concerns of assay interference. ACTH assay interference resulted in falsely elevated ACTH concentrations using the Siemens Immulite assay and consequently led to additional unnecessary testing. Communication between physician and laboratory as well as appropriate investigation (including sample dilution, use of blocking antibodies and testing on an alternate platform) resulted in assay interference identification. Recognition of biochemical results which are clinically discrepant remains an essential step in patient assessment.

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.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.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.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.CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.

Objective To identify and characterize patterns of use among a contemporary cohort of current anabolic-androgenic steroid (AAS) users. Patients and Methods An anonymous, self-administered, 49-item questionnaire was posted on message boards of Internet websites popular among AAS users and administered via SurveyMonkey from February 1, 2015, to June 1, 2015. Thirty-seven questions were analyzed for this study. Results A total of 231 male respondents met the inclusion criteria. Most were white, were older than 25 years, were employed with above average income, and had received a formal education beyond high school. Ninety-three percent began using AAS after the age of 18 years, and 81% reported using 400 mg or more of testosterone per week. Factors associated with longer duration of use (>5 years) included higher incomes (≥$75,000, P =.003), increased testosterone dosages (>600 mg per week, P =.007), older age (≥35 years, P P P Conclusion The population of AAS users is disparate from that of other drugs of abuse. Laboratory test abnormalities and adverse effects are common and should be taken into account when counseling patients who may be using AASs.

Background The impact of sex steroids on bone health in transgender individuals is unclear. Methods A comprehensive search of several databases to 7 April 2015 was conducted for studies evaluating bone health in transgender individuals receiving sex steroids. Pairs of reviewers selected and appraised studies. A random effects model was used to pool weighted mean differences and 95% confidence intervals (CIs). Results Thirteen studies evaluating 639 transgender individuals were identified [392 male-to-female (MTF), 247 female-to-male (FTM)]. In FTM individuals and compared with baseline values before initiation of masculinizing hormone therapy, there was no statistically significant difference in the lumbar spine, femoral neck, or total hip bone mineral density (BMD) when assessed at 12 and 24 months. In MTF individuals and compared with baseline values before initiation of feminizing hormone therapy, there was a statistically significant increase in lumbar spine BMD at 12 months (0.04 g/cm2; 95% CI, 0.03 to 0.06 g/cm2) and 24 months (0.06 g/cm2; 95% CI, 0.04 to 0.08 g/cm2). Fracture rates were evaluated in a single cohort of 53 MTF and 53 FTM individuals, with no events at 12 months. The body of evidence is derived mostly from observational studies at moderate risk of bias. Conclusion In FTM individuals, masculinizing hormone therapy was not associated with significant changes in BMD, whereas in MTF individuals feminizing hormone therapy was associated with an increase in BMD at the lumbar spine. The impact of these BMD changes on patient-important outcomes such as fracture risk is uncertain.

The purpose of this study was to define an appropriate nadir growth hormone (nGH) cutoff for patients with acromegaly in remission using the Access Ultrasensitive human growth hormone (hGH) assay (Beckman Coulter, Brea, CA).This cross-sectional study included 55 acromegalic subjects and 41 healthy adult volunteers. All subjects underwent oral glucose tolerance testing (OGTT) for growth hormones (GHs). An optimal cutoff for nGH for patients with active disease versus those in remission was determined using receiver-operating curve analysis.The nGH of 0.53 ng/mL revealed a sensitivity of 97% (95% confidence interval [CI], 83-100%) and a specificity of 100% (95% CI, 82-100%). All 22 patients with acromegaly in remission suppressed GH to1 ng/mL, 20/22 (91%) suppressed to0.4 ng/mL, and 19/22 (86%) of subjects suppressed to0.3 ng/mL (the maximum nGH measured in our healthy volunteer group).When using the Access Ultrasensitive hGH assay for OGTT, a cutoff of 0.53 ng/mL was found to most accurately differentiate patients with acromegaly in remission from those with active disease.

OBJECTIVENelson-Salassa syndrome (NSS) is a rare consequence of bilateral adrenalectomy (ADX) for refractory hypercortisolism due to Cushing disease (CD). Although classically defined by rapid growth of a large, invasive, adrenocorticotropin hormone (ACTH)–secreting pituitary tumor after bilateral ADX that causes cutaneous hyperpigmentation, visual disturbance, and high levels of ACTH, clinical experience suggests more variability.METHODSThe authors conducted a retrospective chart review of all patients 18 years and older with a history of bilateral ADX for CD, adequate pituitary MRI, and at least 2 years of clinical follow-up. Statistical tests included Student's t-test, chi-square test, Fisher's exact test, multivariate analysis, and derived receiver operating characteristic curves.RESULTSBetween 1956 and 2015, 302 patients underwent bilateral ADX for the treatment of hypercortisolism caused by CD; 88 had requisite imaging and follow-up (mean 16 years). Forty-seven patients (53%) had radiographic progression of pituitary disease and were diagnosed with NSS. Compared with patients who did not experience progression, those who developed NSS were significantly younger at the time of CD diagnosis (33 vs 44 years, p = 0.007) and at the time of bilateral ADX (35 vs 49 years, p = 0.007), had larger tumors at the time of CD diagnosis (6 mm vs 1 mm, p = 0.03), and were more likely to have undergone external-beam radiation therapy (EBRT, 43% vs 12%, p = 0.005). Among NSS patients, the mean tumor growth was 7 mm/yr (SE 6 mm/yr); the median tumor growth was 3 mm/yr. Prevalence of pathognomonic symptoms was low; the classic triad occurred in 9%, while hyperpigmentation without visual field deficit was observed in 23%, and 68% remained asymptomatic despite radiographic disease progression. NSS required treatment in 14 patients (30%).CONCLUSIONSNSS is a prevalent sequela of CD after bilateral ADX and affects more than 50% of patients. However, although radiological evidence of NSS is common, it is most often clinically indolent, with only a small minority of patients developing the more aggressive disease phenotype characterized by clinically meaningful symptoms and indications for treatment. Young age at the time of CD diagnosis or treatment with bilateral ADX, large tumor size at CD diagnosis, and EBRT are associated with progression to NSS and may be markers of aggressiveness.

Context The transgender population continues to face challenges in accessing appropriate health care. Adequate training of endocrinologists in this area is a priority. Objectives Assess the status of transgender health care education in US endocrinology fellowship training programs and assess knowledge and practice of transgender health among practicing US endocrinologists. Design Mayo Clinic and the Endocrine Society developed and administered a Web-based anonymous survey to 104 endocrinology fellowship program directors (PDs; members of the Association of Program Directors in Endocrinology, Diabetes and Metabolism) and 6992 US medical doctor members of Endocrine Society. Results There were 54 total responses from 104 PDs (51.9%). Thirty-five of these 54 programs (72.2%) provide teaching on transgender health topics; however, 93.8% respondents indicated that fellowship training in this area is important. Barriers to provision of education included lack of faculty interest or experience. The most desired strategies to increase transgender-specific content included online training modules for trainees and faculty. Of 411 practicing clinician responders, almost 80% have treated a transgender patient, but 80.6% have never received training on care of transgender patients. Clinicians were very or somewhat confident in terms of definitions (77.1%), taking a history (63.3%), and prescribing hormones (64.8%); however, low confidence was reported outside of the hormonal realm. The most requested methods of education included online training modules and presentation of transgender topics at meetings. Conclusions Confidence and competence in transgender health needs to increase among endocrinologists. Strategies include the development of online training modules, expansion of formal transgender curricula in fellowship programs, and presentations at national and international meetings.

Hypopituitarism is a rare disorder with significant morbidity. To study the evidence on the association of premature mortality and hypopituitarism. A comprehensive search of multiple databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August, 2015. Eligible studies that evaluated patients with hypopituitarism and reported mortality estimates were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. We included 12 studies (published 1996–2015) that reported on 23,515 patients. Compared to the general population, hypopituitarism was associated with an overall excess mortality (weighted SMR of 1.55; 95 % CI 1.14−2.11), I 2 = 97.8 %, P = 0.000. Risk factors for increased mortality included younger age at diagnosis, female gender, diagnosis of craniopharyngioma, radiation therapy, transcranial surgery, diabetes insipidus and hypogonadism. Hypopituitarism may be associated with premature mortality in adults. Risk is particularly higher in women and those diagnosed at a younger age.

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases—MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995–2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53–1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70–1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51–2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

Objective: To identify and characterize patterns of use among a contemporary cohort of current anabolicandrogenic steroid (AAS) users. Patients and Methods: An anonymous, self-administered, 49-item questionnaire was posted on message boards of Internet websites popular among AAS users and administered via SurveyMonkey from February 1, 2015, to June 1, 2015. Thirty-seven questions were analyzed for this study. Results: A total of 231 male respondents met the inclusion criteria. Most were white, were older than 25 years, were employed with above average income, and had received a formal education beyond high school. Ninety-three percent began using AAS after the age of 18 years, and 81% reported using 400 mg or more of testosterone per week. Factors associated with longer duration of use (>5 years) included higher incomes (� $75,000, P¼.003), increased testosterone dosages (>600 mg per week, P¼.007), older age (� 35 years, P

A 50-year-old man with a history of acromegaly was referred for preoperative cardiac evaluation preceding trans-sphenoidal resection of a pituitary macroadenoma. Dobutamine stress echocardiography was negative for myocardial ischaemia. Resting left ventricular (LV) LV ejection fraction (LVEF) was 64% and there was hypertrophy of ventricular septum (18 mm) without resting LV outflow tract obstruction. With 40 µg/kg/min of dobutamine, the LVEF became hyperdynamic at 80%, and there was a maximal instantaneous LV outflow tract gradient of 77 mm Hg. There was no delayed myocardial enhancement on cardiac MRI and the pattern of hypertrophy was concentric. Acromegaly-induced cardiomyopathy can mimic hypertrophic cardiomyopathy in the setting of dobutamine provocation. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival.

OBJECTIVE: To analyze the factors associated with anterior pituitary deficits after pituitary adenoma stereotactic radiosurgery (SRS). METHODS: The tumor, pituitary stalk, and pituitary gland were segmented on the dose plans of 82 patients (secreting tumors, n = 53; nonsecreting tumors, n = 29) for dose-volume analysis. No patient had undergone prior radiation therapy and all patients had at least 12 months of endocrinological follow-up (median, 63 months; mean, 69 months; range, 13-134). RESULTS: Thirty-four patients (41 %) developed new anterior pituitary deficits at a median of 32 months (range, 2-118) after SRS.The risk of developing new anterior pituitary deficits was 16% and 45% at 2 and 5 years, respectively. Multivariate analysis of the entire group showed that poor visualization of the pituitary gland (hazard ratio [HR] = 2.63, 95% confidence interval [CI] = 1.10-6.25, P = .03) was associated with a higher rate of new anterior pituitary deficits. Dosimetric analysis of 60 patients whose pituitary gland could be clearly identified showed that increasing mean pituitary gland radiation dose correlated with new anterior pituitary deficits (HR = 1.11, 95% CI = 1.02-1.20, P = .02). New anterior pituitary deficits stratified by mean pituitary gland radiation dose: ≤7.5 Gy, 0% (0/7); 7.6 to 13.2 Gy, 29% (7/24); 13.3 to 19.1 Gy, 39% (9/23); > 19.1 Gy, 83% (5/6). CONCLUSION: New endocrine deficits after pituitary adenoma radiosurgery were correlated with increasing radiation dose to the pituitary gland. Methods that limit the radiation dose to the pituitary gland during SRS may increase the probability of preserving pituitary function.

Summary 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

The physiological role of dehydroepiandrosterone remains unclear, and there is continuing controversy on whether dehydroepiandrosterone treatment benefits adrenal-deficient and elderly people with an age-related decline in dehydroepiandrosterone. The objective of this study is to critically review published results and determine whether there is a valid case for dehydroepiandrosterone treatment with advancing age and hypoadrenalism.Oral dehydroepiandrosterone therapy in both elderly and hypoadrenal subjects achieves dehydroepiandrosterone levels comparable to young subjects. Long-term dehydroepiandrosterone replacement in elderly people demonstrated no improvement in body composition, physical performance or any metabolic parameters; however, a modest but inconsistent improvement in bone mineral density occurred at certain sites. Dehydroepiandrosterone replacement in hypoadrenalism modestly improved insulin sensitivity and altered the lipid profile, but it remains uncertain whether these changes improve any patient-important outcomes. Dehydroepiandrosterone replacement in adrenal deficiency inconsistently improves some aspects of mental health.Dehydroepiandrosterone replacement increases bone mineral density in elderly subjects; however, the effect is relatively small compared with established therapies for osteoporosis. No additional benefits have been identified for long-term dehydroepiandrosterone replacement, when used in the elderly to prevent or delay ageing. Dehydroepiandrosterone replacement may improve some metabolic variables and measures of psychological well-being in adrenal deficiency, but these benefits are not consistently sustained in long-term therapy. Long-term studies are needed to confirm sustained benefits in adrenal deficiency and establish long-term safety.

Reported biochemical remission rates have ranged widely after stereotactic radiosurgery for patients with hormone-secreting pituitary adenomas. Confounding variables include histology, radiation dose, use of pituitary-suppressive medications, and length of follow-up.A retrospective review of 46 patients with pituitary adenomas (growth hormone-secreting, n = 27; prolactin-secreting, n = 11; adrenocorticotropin-secreting, n = 8) undergoing radiosurgery between January 1990 and December 2003 was conducted. All received a tumor margin dose of 18 Gy or more and were off pituitary-suppressive medications for at least 1 month before radiosurgery. The groups were similar with regard to irradiated volume, radiation dose, and follow-up. The median endocrinological follow-up after radiosurgery was 54 months.The 4-year remission rates were 87% for patients with Cushing's disease, 67% for patients with acromegaly, and 18% for patients with prolactinomas. Patients with oversecretion of adrenocorticotropin or growth hormone were more likely to achieve remission after radiosurgery than patients with prolactinomas (hazard ratio, 4.4; 95% confidence interval, 1.1-18.2; P = 0.04). Of 44 patients with normal or partial anterior pituitary function before radiosurgery, 16 (36%) developed one or more new anterior pituitary deficits. The incidence of new anterior pituitary deficits was 26% at 4 years. No differences were noted in the incidence of new anterior deficits among the groups.There seems to be a differential sensitivity after radiosurgery for hormone-secreting pituitary adenomas. Remission rates are greater for patients with Cushing's disease and acromegaly, whereas radiosurgery is less effective in achieving biochemical remission for patients with prolactinomas.

To assess whether the type of surgical approach to the sella (sublabial transseptal vs transnasal) affects surgical outcome among patients with Cushing disease.Both procedures were performed at our institution from January 1, 1995, through January 31, 2003. From a total of 106 patients with Cushing disease who had had surgery, we identified 42 adults undergoing an initial surgery, with microadenoma (1 cm) determined by magnetic resonance imaging and a minimal follow-up of 3 months.We identified 21 patients (4 male, 17 female) for sublabial transseptal transsphenoidal microsurgery. Mean+/-SD age was 45.0+/-12.9 years (range, 27.0-69.0 years); median duration of symptoms was 2.5 years (range, 1.5-7.5 years). Median follow-up was 1.0 year (range, 0.3-11.0 years). We identified another 21 patients (5 male, 16 female) for endoscopic transsphenoidal microsurgery whose mean+/-SD age was 43.8+/-14.1 years (range, 19.0-70.0 years); median duration of symptoms was 2.4 years (range, 0.2-6.0 years). Median follow-up was 2.5 years (range, 0.3-8.7 years). Complications (cerebrospinal fluid leak and transient diabetes insipidus) and cure (86% initial cure; 76% relapse-included cure) were equivalent between the 2 procedures. However, the endoscopic approach was associated with shorter anesthesia time, less blood loss, and shorter hospital stays.The endoscopic transnasal surgical approach led to shorter total anesthesia time, less blood loss, and shorter hospital stay when compared with the sublabial transseptal approach. However, we found no difference between the 2 surgical procedures with respect to cure or complications, suggesting that outcome is more closely related to the experience of the operating team.

Cushing’s syndrome (CS), due to multiple etiologies, is a disorder associated with the ravages of cortisol excess. The purpose of this review article is to provide a historical synopsis of surgery for CS, review a recent 10-year period of operative management at a tertiary care facility, and to outline a practical approach to diagnosis and management. From 1996 to 2005, 298 patients underwent 322 operative procedures for CS at Mayo Clinic, Rochester, Minnesota. A retrospective chart review was carried out. Data was gathered regarding demographics, preoperative assessment, procedures performed, and outcomes. Data are presented as counts and percentages. Five-year survival rates were calculated where applicable by the Kaplan-Meier method. Statistical analysis was carried out with SAS, version 9 (SAS Institute, Inc., Cary, NC). Two-hundred thirty-one patients (78%) had ACTH-dependent CS and 67 patients (22%) had ACTH-independent CS. One-hundred ninety-six patients (66%) had pituitary-dependent CS and 35 patients (12%) had ectopic ACTH syndrome. Fifty-four patients (18%) had cortisol-secreting adenomas, 10 patients (3%) had cortisol-producing adrenocortical carcinomas, and 1% had other causes. Cure rates for first time pituitary operations (transsphenoidal, sublabial, and endonasal) were 80% and 55% for reoperations. Most benign adrenal processes could be managed laparoscopically. Five-year survival rates (all causes) were 90%, 51%, and 23% for adrenocortical adenomas, ectopic ACTH syndrome, and adrenocortical carcinomas, respectively. Surgery for CS is highly successful for pituitary-dependent CS and most ACTH-independent adrenal causes. Bilateral total adrenalectomy can also provide effective palliation from the ravages of hypercortisolism in patients with ectopic ACTH syndrome and for those who have failed transsphenoidal surgery. Unfortunately, to date, adrenocortical carcinomas are rarely cured. Future successes with this disease will likely depend on a better understanding of tumor biology, more effective adjuvant therapies and earlier detection. Clearly, IPSS, advances in cross-sectional imaging, along with developments in transsphenoidal and laparoscopic surgery, have had the greatest impact on today’s management of the complex patient with CS.

Context: The definitive diagnosis of Cushing’s syndrome (CS) in the setting of mild disease, as well as exclusion of CS in the setting of conditions that might mimic this clinical entity (pseudo-Cushing’s syndrome), continues to present a significant challenge to the clinician. Objective: The aim of the study was to review characteristics of the combined dexamethasone-suppressed CRH stimulation test in patients evaluated at an academic center for the possibility of mild CS. Design, Patients, and Methods: We conducted a retrospective review of 66 patients. A total of 51 patients underwent final statistical analysis: 21 (41%) had Cushing’s disease, and 30 were considered to have pseudo-CS based on the clinical scenario, comorbidities, and follow-up. Sensitivity, specificity, and diagnostic accuracy of cortisol and ACTH levels for the diagnosis of Cushing’s disease were calculated at 1 min before, and 15, 30, 45, and 60 min after CRH administration. Diagnostic cutoffs for each parameter were determined by minimizing the absolute difference between sensitivity and specificity. Diagnostic accuracy was characterized by the area under the receiver operating characteristic curve, determined using the trapezoid rule. Results: The highest diagnostic accuracy was provided by the serum ACTH level at 15 min post-CRH, in which the area under the receiver operating characteristic curve was 99.7%, and a cutoff of more than 27pg/ml(5.9pmol/liter)providedasensitivityof95%andspecificity of 97% for the diagnosis of CS. A 15-min post-CRH cortisol greater than 2.5 g/dl (70 nmol/liter) provided a sensitivity and specificity of 90 and 90%, respectively. Conclusions: Our results differ from previous studies because our data suggest that when using the combined dexamethasone-suppressed CRH stimulation test, a 15-min post-CRH ACTH value greater than 27 pg/ml (5.9 pmol/liter) had the highest diagnostic accuracy for the detection of CS. However, the sensitivity and specificity for this test were not statistically different from the sensitivity and specificity of other tests, such as those measuring post-CRH stimulated ACTH levels or post-CRH cortisol levels at other time points. Therefore, clinicians should be cautious about interpretation of suppression and stimulation tests in the diverse population of patients with hypercortisolism. (J Clin Endocrinol Metab 92: 2972–2976, 2007)

Object The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission. Methods Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)–producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor–I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22–168 months). Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6–63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2–6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4–13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years. Conclusions Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH–producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.

To determine if replacement of GH improves BMD in adult-onset GHD, we administered GH in physiologic amounts to men and women with GHD. GH replacement significantly increased spine BMD in the men by 3.8%. Introduction: Growth hormone (GH) deficiency (GHD) acquired in adulthood results in diminished BMD; the evidence that replacement of GH improves BMD is not conclusive. We therefore performed a randomized, placebo-controlled trial to determine whether GH replacement would increase lumbar spine BMD in a combined group of men and women with adult-onset GHD. Materials and Methods: We randomized 67 men and women to receive GH (n = 33) or placebo (n = 34) for 2 yr. The GH dose was initially 2 μg/kg body weight/d, increased gradually to a maximum of 12 μg/kg/d and adjusted to maintain a normal IGF-I concentration for age and sex. BMD was assessed before treatment and at 6, 12, 18, and 24 mo of treatment. Fifty-four subjects completed the protocol. Results: BMD of the lumbar spine in the entire group increased by 2.9 ± 3.9% above baseline in the GH-treated subjects, which was significantly (p = 0.037) greater than the 1.4 ± 4.5% increase in the placebo-treated subjects. In a secondary analysis, spine BMD in GH-treated men increased 3.8 ± 4.3% above baseline, which was significantly (p = 0.001) greater than that in placebo-treated men (0.4 ± 4.7%), but the change in GH-treated women was not significantly different from that in placebo-treated women. Treatment with GH did not increase total hip BMD more than placebo treatment after 2 yr. Conclusions: We conclude that GH replacement in men who have adult-onset GHD improves their spine BMD, but we cannot draw any conclusions about the effect of GH replacement on spine BMD in women with adult-onset GHD.

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.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.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).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.

To identify and characterize patterns of use among a contemporary cohort of current anabolic-androgenic steroid (AAS) users.An anonymous, self-administered, 49-item questionnaire was posted on message boards of Internet websites popular among AAS users and administered via SurveyMonkey from February 1, 2015, to June 1, 2015. Thirty-seven questions were analyzed for this study.A total of 231 male respondents met the inclusion criteria. Most were white, were older than 25 years, were employed with above average income, and had received a formal education beyond high school. Ninety-three percent began using AAS after the age of 18 years, and 81% reported using 400 mg or more of testosterone per week. Factors associated with longer duration of use (5 years) included higher incomes (≥$75,000, P=.003), increased testosterone dosages (600 mg per week, P=.007), older age (≥35 years, P.001), being married (P.001), and being self-employed (P.001). The Internet was the most common source of testosterone (53%). Ninety-three percent used at least one additional performance-enhancing drug. Seventy-seven percent had routine laboratory tests performed, and 38% reported laboratory abnormalities at some point. Nearly all experienced subjective adverse effects while using and not using testosterone. Fifty-three percent reported use of other illegal substances, most commonly (90%) beginning before AAS initiation. Ten percent had a criminal conviction, 91% of which preceded AAS use. Fifty percent were felonies.The population of AAS users is disparate from that of other drugs of abuse. Laboratory test abnormalities and adverse effects are common and should be taken into account when counseling patients who may be using AASs.

ENDOCRINE PRACTICE Vol 10 No. 3 May/June 2004 213 American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice are systematically developed statements to assist health-care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.

Objective To review the evolving approaches to surgical management of pituitary tumors during the past century, which may predict future directions. Methods We undertook a retrospective review of selected literature published during the past century and report the trends in the treatment of pituitary tumors. Results Harvey Cushing’s extraordinary influence on American neurosurgery and remarkably successful pituitary surgical series were the foundation for the development of a highly subspecialized neurosurgical operative field. Continued evolution in the treatment of pituitary tumors has been historically based on the following: (1) the development of exogenous cortisone and vasopressin; (2) the development of high-voltage and nuclear radiation therapy; (3) the experience gained from total hypophysectomy for “endocrine” driven malignant lesions and diabetic retinopathy; (4) the development of the image intensifier and television intraoperative fluoroscopic control; (5) the use of endoscopes in pituitary surgical procedures; (6) the application of the operating microscope to transsphenoidal approaches; (7) the development of the imaging modalities of computed tomographic scanning and subsequent magnetic resonance imaging; and (8) the concepts surrounding “minimally invasive” surgical techniques. Conclusion The pituitary surgical techniques of today have evolved primarily because of extraordinary past accomplishments. The approaches used continue to maximize tumor resection and preserve functioning pituitary tissue. New intraoperative imaging techniques will forge the future of the field of pituitary neurosurgery, and the expected outcomes will be improved surgical success and lower perioperative morbidity. (Endocr Pract. 2002;8:356-361)

A 67-year-old woman presented with clinical features of hypercortisolism in association with an invasive pituitary macroadenoma. Adrenocorticotropic hormone (ACTH)-dependent Cushing's disease was documented, and the resected tumor was chromophobic, weakly positive with periodic-Schiff reagent, and showed immunostaining for ACTH and beta-endorphin in a minority of adenoma cells. Both luteinizing hormone and alpha-subunit staining were also observed, but no follicle-stimulating hormone reactivity was seen. Ultrastructurally, the tumor showed typical features of a gonadotroph adenoma of female type. Immunoelectron microscopy showed that ACTH was not produced in corticotrophs, but in cells with the characteristic features of gonadotrophs. This represents the second report of a plurihormonal gonadotroph adenoma producing sufficient ACTH to result in pituitary-dependent Cushing's disease.