Use of overnight metyrapone test in suspected secondary adrenal insufficiency: A retrospective single centre-study.

OBJECTIVE: Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). Data on OMT use and its safety are scarce. We aimed to describe the indications and safety of outpatient OMT and compare OMT to the cosyntropin stimulation test (CST). DESIGN: Single-centre retrospective study of adult patients undergoing OMT between 1 April 2018 and 27 January 2023. MEASUREMENTS: OMT-related adverse events, post-OMT diagnosis of SAI, and OMT comparison to CST. RESULTS: OMT was performed in 114 patients (81, 71% women) at a median age of 48 (interquartile range 37-58). The pretest probability for SAI was low in 52 (46%) patients, moderate in 48 (42%) patients and high in 14 (12%) patients. Adverse events were reported in 7 (6.1%) patients and were mild except for one hospitalization. No baseline or OMT-related factors were associated with the development of adverse events. Prevalence of the OMT-based SAI diagnosis was 26 (23%) and 47 (46%) using 11-deoxycortisol cutoff <7 and <10 mcg/dL, respectively. Higher pretest probability was associated with the OMT-based diagnosis of SAI. Post-OMT 11-deoxycortisol cutoff of 10 mcg/dL was used most to diagnose SAI. Compared to the OMT-based diagnosis of SAI (11-deoxycortisol cutoff of 10 mcg/dL), the specificity of CST was 100%, but the sensitivity was only 52%. CONCLUSIONS: OMT was well tolerated and used in patients with low and moderate pretest probability for SAI. CST can erroneously exclude patients with SAI. Thus, OMT should be considered in selected patients with normal CST.

Treatment outcome of metastasis to the pituitary gland: a case series of 21 patients with pathological diagnosis.

OBJECTIVE: The aim of this study was to report the treatment course of histologically confirmed metastases to the pituitary gland (pituitary metastasis). METHODS: The Mayo data explorer was used to find patients with pituitary metastasis. Twenty-one patients were identified between the years 2001 and 2021, and their data were retrospectively collected. RESULTS: The most common primary cancer origin was lung in men (45%) and breast in women (33%). The median age was 66 years (IQR 56-68 years). Patients presented with headache (67% [14/21]), vision problems (86% [18/21]), anterior hypopituitarism (71% [15/21]), and arginine vasopressin deficiency (38% [8/21]). Pituitary metastases were found before the diagnosis of the primary cancer in 5 patients (24%). The mean ± SD tumor size was 2.0 ± 0.7 cm, and 90% (19/21) presented as a solitary pituitary mass with no other intracranial metastatic lesions. Common radiological features were pituitary stalk thickening (90% [19/21]), cavernous sinus involvement (71% [15/21]), and constriction at the diaphragma sellae (52% [11/21]). Transsphenoidal surgery was performed in 20 patients, and subtotal resection was most frequently attained (76% [16/21]). Fourteen patients (67%) had adjuvant radiation therapy, and 15 patients (71%) were treated with systemic therapy. The median time from surgery to the initiation of radiation therapy was 16 days (IQR 11-21 days), and that from surgery to the initiation of systemic therapy was 5.0 months (IQR 1.5-14 months). During management, headaches improved in 57% (8/14) and vision problems improved in 61% (11/18) of cases; new hypopituitarism occurred in 5 patients. Six patients developed recurrence, and the median progression-free survival was 24 months (95% CI 5.4-43 months). After recurrence, 1 patient with adenoid cystic carcinoma was treated with rescue radiotherapy twice, and 4 patients responded well to systemic therapy. The median overall survival (OS) was 25 months (95% CI 7.1-43 months). The mean OS was better in patients with neuroendocrine lung tumor (261 months) and papillary thyroid carcinoma (80 months) and worse in patients with small cell lung cancer (4 months) and unknown origin (5 months). CONCLUSIONS: Surgery with or without adjuvant radiotherapy is effective for mass reduction, rapid symptomatic improvement of vision and headaches, and definitive diagnosis. Even after local tumor control failure, some patients still benefit from radiation and/or systemic therapy.

Surgical outcomes of medically failed prolactinomas: a systematic review and meta-analysis.

PURPOSE: In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy. METHOD: A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically. RESULTS: 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I2 = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I2 = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I2 = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I2 = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I2 = 86.34%). CONCLUSIONS: This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.

Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly.

PURPOSE: Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. METHODS: Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. RESULTS: One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p < 0.0001), and scored higher in the prognostic classification (p = 0.004). Surgical remission occurred in 41.7% DG/I-A and 41.4% SG-A (p = 1.0). On multivariate analysis, absence of invasion (p = 0.009) and lower pre-operative IGF-1 index (p = 0.0002) were associated with post-surgical remission. CONCLUSION: CAM5.2 allowed distinction between DG/I-A and SG-A in most but not all cases. Histologic subtype did not predict surgical outcome. Absence of invasion and lower pre-operative IGF-1 index were the only significant predictors of post-surgical remission in this cohort.

Association Between Prolactinoma and Body Mass Index.

OBJECTIVE: Obesity is increasing worldwide, and certain endocrine disorders may contribute to weight gain. While several studies have examined the association between weight gain and prolactinomas, the results are conflicting. Therefore, this study aimed to determine if body mass index (BMI) is higher among those with prolactinomas than those without. METHODS: We identified patients ≥18 years of age referred to an endocrine clinic between 2008 and 2018 with newly diagnosed prolactinomas. We extracted the relevant information, and comparative data was obtained from the 2015-2016 National Health and Nutrition Examination Survey. RESULTS: In total, 34 cases met the inclusion criteria. One third of the patients described weight gain at presentation. Those with prolactinomas had a significantly higher BMI than the National Health and Nutrition Examination Survey population (median BMI, 29.8 kg/m2 vs 28.3 kg/m2, P = .0048). When stratified by sex, only men with prolactinomas had an increased BMI compared with the controls. Moreover, those with prolactinomas had a higher prevalence of class II obesity (BMI ≥ 35 kg/m2) than the survey population (35% vs 18%, P = .01). Among the prolactinoma patients, a correlation was observed between BMI and log-transformed prolactin levels (R2 = 0.4, P = .0002). CONCLUSION: Weight gain can be a presenting symptom for patients with newly diagnosed prolactinomas. Those with prolactinomas have a higher BMI and an increased prevalence of class II obesity. These findings suggest that patients should be counseled regarding weight issues related to prolactinomas at presentation and should be a consideration in the investigative and treatment algorithm of prolactinomas.

Bilateral pheochromocytoma: Clinical characteristics, treatment and longitudinal follow-up.

OBJECTIVE: Comprehensive data about patients with bilateral pheochromocytoma are limited. We aimed to describe the clinical presentation, genetic analysis, treatment and outcomes of patients with bilateral pheochromocytoma. DESIGN: A retrospective study at a tertiary care centre. PATIENTS: All patients with bilateral pheochromocytoma evaluated at Mayo Clinic in Rochester, Minnesota between January 1951 and December 2015. MEASUREMENTS: Tumour size, genetic testing, plasma/urine metanephrines and catecholamines. RESULTS: A total of 94 patients (51% women) were diagnosed with bilateral pheochromocytoma at a median age at first presentation of 31 years (range, 4-70). Bilateral disease was noted in 8.0% of pheochromocytoma patient overall and 37.5% of patients 18 years of younger. Most patients presented with synchronous tumours (80%). Median time to metachronous tumours was 4.5 years (range, 1-38). Genetic disease was identified in 75 (80%) patients, including MEN 2A (42.6%), VHL (19.1%), MEN 2B (9.6%) and NF1 (8.5%). Excess catecholamines were present in 97% of patients. Patients with synchronous pheochromocytoma commonly underwent simultaneous bilateral adrenalectomy (99%), and 18 (24%) had cortical-sparing surgery. Multicentric tumours were reported in 23 of 77 (30%) patients with available data. Recurrent disease was found in 9.6% of patients, and 8.5% developed metastatic disease. Median follow-up was 8.5 years. At the study conclusion, 4 patients had died due to pheochromocytoma or adrenalectomy. CONCLUSIONS: Bilateral pheochromocytoma occurred in 7.0% of adults with pheochromocytoma and 37.5% of paediatric patients. Genetic disease was identified in 80% of patients, predominantly MEN2A. Multicentric tumours were common, but most were still cured following adrenalectomy.

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.

Diagnostic Thresholds for Androgen-Producing Tumors or Pathologic Hyperandrogenism in Women by Use of Total Testosterone Concentrations Measured by Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Previously defined thresholds for total testosterone (TT) concentrations to screen for androgen-producing tumors (APTs) have used RIA, which can be less accurate in women. We aimed to define diagnostic thresholds to screen for APTs or postmenopausal pathologic hyperandrogenism using TT concentrations measured by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). METHODS: We performed a retrospective cohort study on all women with TT ≥3.5 nmol/L and all postmenopausal women presenting with hyperandrogenism between 2004 and 2014 at the Mayo Clinic in Rochester, MN. RESULTS: Of the 369 women with TT ≥3.5 nmol/L, 89 were included and subdivided into 3 groups based on their clinical diagnosis [21 (24%), APT; 16 (18%), postmenopausal pathologic hyperandrogenism; 52 (58%), polycystic ovary syndrome]. The source of the APT was more frequently ovarian (81%, n = 17) than adrenal (19%, n = 4). The diagnostic threshold using ROC analysis for TT to identify APT in women with severe biochemical hyperandrogenemia was ≥5.1 nmol/L (sensitivity, 90%; specificity, 81%). In a second analysis of a cohort of postmenopausal women only presenting with symptoms or signs of hyperandrogenism, median TT was significantly higher in the postmenopausal pathologic hyperandrogenism group (APT and ovarian hyperthecosis) vs the idiopathic hyperandrogenism group (4.9 vs 0.8 nmol/L; P < 0.01). In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was TT ≥2.2 nmol/L (sensitivity, 100%; specificity, 86%). CONCLUSIONS: The diagnostic threshold for TT concentration as measured by LC-MS/MS to identify APT in women with biochemical severe hyperandrogenemia was TT ≥5.1 nmol/L. In postmenopausal women, the diagnostic threshold for pathologic hyperandrogenism was lower (TT ≥2.2 nmol/L).

Diagnostic performance of unenhanced computed tomography and 18 F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours.

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. DESIGN: Retrospective cohort study. METHODS: Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. RESULTS: Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18 FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. CONCLUSION: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG-PET/CT could be considered as a second stage imaging study.

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.

Pheochromocytoma and paraganglioma in patients with neurofibromatosis type 1.

OBJECTIVE: Individuals with neurofibromatosis type 1 (NF1) are at an increased risk of developing a pheochromocytoma or paraganglioma (PHEO/PGL). However, the best case detection strategy is unknown. Our objectives were to describe the prevalence, clinical presentation and outcomes of PHEO/PGL associated with NF1 and formulate case detection testing recommendations for PHEO/PGL. DESIGN: A retrospective cohort study from 1959 to 2015, Tertiary medical centre. PATIENTS AND MEASUREMENTS: We studied 41 patients with NF1 and PHEO/PGL who were identified using the PHEO/PGL and NF1 databases: 3289 and 1415 patients, respectively. Our main outcome measures were prevalence of PHEO/PGL in NF1 and occurrence of bilateral, recurrent, or metastatic disease and method of PHEO/PGL detection (symptoms vs incidental vs biochemical case detection testing). RESULTS: The prevalence of PHEO/PGL in patients with NF1 was 2·9%. The 41 patients included 23 men (56%) and 18 women. The median age at diagnosis was 41·0 years (range 14-67). The median tumour size was 3·4 cm (range 0·8-9·5). Bilateral PHEO was identified in 17% (n = 7) of patients, all women. Metastatic or recurrent disease occurred in 7·3% (n = 3). In the last 25 years, PHEO/PGL was diagnosed after incidental finding on computed imaging in 31% of patients (n = 11). Only three patients (7·3%) had PHEO/PGL discovered because of biochemical case detection testing. CONCLUSION: We recommend patients with NF1 have biochemical case detection testing for PHEO/PGL every 3 years starting at age 10 to 14 years. Biochemical case detection testing should also be carried out prior to elective surgical procedures and conception.

ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION IN THE DIAGNOSIS OF ADRENAL METASTASIS IN A HIGH-RISK POPULATION.

OBJECTIVE: While the left adrenal gland is readily accessible via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), data regarding the utility of EUS-FNA in the diagnosis of adrenal lesions remain limited. We aimed to ( 1) describe the clinical context, adverse event rate, and diagnostic performance of EUS-FNA, and ( 2) compare the safety profile and diagnostic accuracy of EUS-FNA with percutaneous adrenal biopsy. METHODS: Single-center, retrospective cohort study. Medical records of patients who underwent adrenal EUS-FNA from 2005-2016 were reviewed. Biopsy outcomes were evaluated using a predefined reference standard. Results were compared to patients who underwent percutaneous biopsy (n = 419; 1994-2014) at the same institution. RESULTS: A total of 121 patients underwent EUS-FNA of 122 adrenal lesions (left [n = 121]; right [n = 1]; mean lesion size, 1.8 cm). Cytology was positive for malignancy in 35 (29%), suspicious for malignancy in 1 (1%), atypical in 1 (1%), negative for malignancy in 81 (66%), and nondiagnostic in 4 (3%). No adverse events were reported. EUS-FNA diagnosed metastasis with a sensitivity of 100%, specificity of 97.4%, positive predictive value of 91.7%, and negative predictive value of 100%. When compared to percutaneous biopsy, lesion size (1.8 cm vs. 3.7 cm; P<.001) and biopsy site (99% vs. 62% left adrenal; P<.001) were significantly different. EUS-FNA adverse event rate was lower than percutaneous biopsy (0% vs. 4%; P = .024), but nondiagnostic rates were similar (3.3% vs. 4.8%; P = .48). CONCLUSION: EUS-FNA is a sensitive technique to sample adrenal lesions in patients at high risk for adrenal metastasis with fewer adverse events compared to percutaneous biopsy. ABBREVIATIONS: CI = confidence interval CT = computed tomography EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration NPV = negative predictive value PPV = positive predictive value TUS = transabdominal ultra-sound.

SURGICAL OUTCOMES OF PROLACTINOMAS IN RECENT ERA: RESULTS OF A HETEROGENOUS GROUP.

OBJECTIVE: Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. METHODS: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. RESULTS: Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. CONCLUSION: Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.

IMAGE-GUIDED THERMAL ABLATION OF ADRENAL METASTASES: HEMODYNAMIC AND ENDOCRINE OUTCOMES.

OBJECTIVE: Image-guided thermal ablation of adrenal metastases has been increasingly used for local tumor control. This procedure has been associated with hypertensive urgency; however, endocrine complications have not been clearly described. Our objective was to assess the hemodynamic behavior and risk for adrenal insufficiency related to adrenal ablation. Additionally, we sought to understand the utility of preprocedural α-blockade to prevent periprocedural hemodynamic complications. METHODS: This was a retrospective study of patients undergoing image-guided ablation of adrenal metastases between 2003 and 2015 at our institution. We reviewed electronic medical records to obtain clinical information, including α-blockade preparation, periprocedural hemodynamic parameters, interventions, and postablation adrenal function. RESULTS: Thermal ablation was performed in 58 patients (46 men [79%]; median age, 66 years) with 60 adrenal metastases ablated in 62 sessions. Alpha-blockade was used pre-ablation in 49 (79%) sessions; it was associated with less hypertensive urgency (23 [47%] for α-blockade vs. 10 [77%] for no α-blockade; P = .048) but higher need for vasopressors (22 [45%] for α-blockade vs. 1 [8%] for no α-blockade; P = .02) during ablation. Adrenal insufficiency occurred in 13 (22%) patients, of whom 10 had history of contralateral adrenalectomy or metastases, and only 3 of 13 had a normal-appearing contralateral adrenal gland. CONCLUSION: Hemodynamic changes during ablation of adrenal metastases are common. Pre-ablation α-blockade decreases the severity of the hypertensive episode, at the expense of higher need for vasopressors periprocedurally. Adrenal function should be assessed after adrenal metastasis ablation, as adrenal insufficiency may occur after such treatment. ABBREVIATIONS: ACTH = adrenocorticotropic hormone BP = blood pressure CT = computed tomography DBP = diastolic blood pressure HR = heart rate IQR = interquartile range IV = intravenous MAP = mean arterial pressure MWA = microwave ablation RFA = radiofrequency ablation SBP = systolic blood pressure.

GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS: We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS: We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION: Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS: AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.

Procedural and clinical outcomes of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy.

OBJECTIVE: The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN: Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS: Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS: Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%. CONCLUSION: When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.

Usefulness of dynamic MRI enhancement measures for the diagnosis of ACTH-producing pituitary adenomas.

PURPOSE: The distinction between corticotropin (ACTH)-producing pituitary adenomas and occult ectopic ACTH neoplasms is a challenge and frequently complicated by the detection of nonfunctioning pituitary adenomas on dynamic magnetic resonance imaging (DMRI). Herein, we explored quantitative differences in DMRI measures from ACTH-producing pituitary adenomas. MATERIALS AND METHODS: Fifty-five patients with pathology confirmed ACTH-producing and 44 with nonfunctioning pituitary adenomas were analysed in this retrospective pilot study. The intensities of adenomas and of adjacent pituitary tissue were measured by drawing a region of interest. Time-intensity curves were then constructed, and quantitative analysis included: enhancement time, enhancement peak and prepeak slope (PPS). Multivariable logistic analysis and receiver operating characteristic curves (ROC) were used to evaluate the parameters. RESULTS: Quantitative analysis showed that tumour PPS in ACTH-producing adenomas was markedly lower than that in nonfunctioning adenomas (P = 0·0042) and that the PPS of the adjacent pituitary gland was not different (P = 0·2441). The PPS was >3·0 in 59·1% of nonfunctioning adenomas and ≤3·0 in 69·1% of ACTH-producing adenomas (P = 0·0049). Logistic analysis revealed lower tumour PPS levels (P = 0·0123, OR 1·24, 95% CI: 1·05-1·52) were associated with ACTH-producing adenomas. The optimal PPS cut-off determined by ROC analysis was 2·89, with a sensitivity of 69% and specificity of 70%. No significant difference was found between the two groups in enhancement time or enhancement peak. CONCLUSION: Enhancement parameters in DMRI can help distinguishing ACTH producing from nonfunctioning pituitary adenomas, which could be useful in the differential diagnosis between ACTH-producing pituitary adenomas and ectopic ACTH syndrome complicated with nonfunctioning pituitary adenoma.

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.

A single-institution experience in image-guided thermal ablation of adrenal gland metastases.

PURPOSE: To assess safety, technical success, local control, and survival associated with percutaneous image-guided adrenal ablation. MATERIALS AND METHODS: Adult patients with adrenal metastases who underwent percutaneous image-guided adrenal ablation during the years 2003-2012 were identified. There were 32 patients with 37 adrenal tumors identified. Technical success, safety, local control, and survival were analyzed according to standard criteria. RESULTS: In 32 patients (25 men and 7 women; mean age, 66 y; age range, 44-88 y) with 37 adrenal tumors, 35 ablation procedures were performed. One patient with an 8.2-cm tumor underwent planned cryoablation debulking fully anticipating untreated margins owing to close proximity of the pancreas (ie, the intent was to diminish tumor burden rather than a curative intervention). Of the 36 patients treated with curative intent, technical success was achieved in 35 (97%) tumors. Follow-up imaging was performed on 34 of 37 tumors (excluding patients with intentional debulking [n = 1], technical failure [n = 1], and absence of follow-up [n = 1]). Local recurrence developed in 3 (8.8%) of 34 tumors. Local tumor control was achieved in 31 lesions at a mean of 22.7 months of follow-up. Recurrence-free survival and overall survival at 36 months were 88% and 52%, respectively, with a median survival of 34.5 months. A Common Terminology Criteria for Adverse Events version 4 grade 3 or 4 complication was observed in three (8.6%) ablation procedures. CONCLUSIONS: Image-guided ablation is safe and effective for local control of metastatic adrenal tumors and provides a minimally invasive alternative to surgical resection in appropriately selected patients.