Citations

SummaryObjectiveThe 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.DesignSingle‐centre, retrospective cohort study.Patients and MeasurementsMedical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard.ResultsBiopsy 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%.ConclusionWhen 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.

Objective The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07–3.27; P = 0.02). Conclusions Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

OBJECT This study was undertaken to analyze the predisposing factors, clinical presentation, therapeutic management, and clinical recovery in patients with pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and functional outcomes. METHODS The authors performed a retrospective analysis of consecutive cases involving patients treated at Mayo Clinic between 1992 and 2013. Patients were included in the study only if they had 1) abrupt onset of severe headache or visual disturbance in the presence of a pituitary adenoma and 2) radiological or surgical confirmation of a pituitary mass. The primary endpoints of analysis were the visual (ocular motility, visual fields, and visual acuity), endocrine, and functional outcomes (using the modified Rankin Scale). RESULTS Eighty-seven patients were identified (57 males and 30 females, mean age 50.9 years, range 15–91 years). Twenty-two patients (25.3%) had a known pituitary adenoma. Hypertension was the most common associated factor (39%). Headache was the most frequent presenting symptom (89.7%), followed by visual abnormalities (47.1%). Cranial nerve palsies were present in 39% and visual field defects in 34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by CT scan. Sixty-one patients (70.1%) underwent surgery during acute hospitalization (median time from apoplexy 5 days, IQR 3–10 days), 8 (9.2%) had delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4 (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization. The average duration of follow-up was 44.2 ± 43.8 months. All survivors were independent and had complete resolution or substantial improvement in eye movements and visual fields at the last follow-up. Many patients needed long-term hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily desmopressin was needed in 23% of all surgical patients at 3 months (versus none of the medically treated) and this requirement decreased slightly over time. Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no statistically significant differences in any of the outcome measures across the treatment groups. CONCLUSIONS The outcome of most patients with pituitary apoplexy is excellent. Selected patients can be managed conservatively, and patients with severe neuro-ophthalmological deficits treated with early surgery can achieve an excellent recovery.

Context: Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause. Objective and Design: The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion. Setting: The study was performed at the Mayo Center for Clinical and Translational Science. Participants: The participants were 24 postmenopausal women (aged 50–77 years with body mass index of 19–32 kg/m2). Interventions: This was a randomized, double-blind, placebo-controlled, parallel-cohort treatment study with placebo (PL) (n = 14) or the antiestrogen fulvestrant (FUL) (n = 10) for 3 weeks, followed by infusion of l-arginine with saline, GHRH, ghrelin, or both peptide secretagogues. Outcomes: GH concentrations were measured over 6 hours with 10-minute sampling and mass spectrometry measures of testosterone, E2, and estrone. Results: Concentrations of testosterone, E2, estrone, SHBG, IGF-I, LH, and FSH were not influenced by antiestrogen treatment. In contrast, GH rose from 0.096 ± 0.018 (PL) to 0.23 ± 0.063 μg/L (FUL, P = .033), and IGF-I binding protein type 3 (IGFBP-3) from 3.6 ± 0.18 to 4.0 ± 2.0 mg/L (P = .041). Conversely, prolactin fell from 7.1 ± 0.69 (PL) to 5.5 ± 0.57 μg/L (FUL) (P = .05), and IGF-I binding protein type 1 (IGFBP-1) fell from 44 ± 9.4 to 27 ± 4.3 μg/L (P = .048). Moreover, FUL vs PL potentiated mean GH responses to l-arginine/saline (P = .007), l-arginine/ghrelin (P = .008), and l-arginine/GHRH + ghrelin (P = .031), but not l-arginine/GHRH. Conclusion: The potent antiestrogen, FUL, amplifies fasting and secretagogue-driven GH secretion and IGFBP-3 concentrations in postmenopausal women without altering SHBG or sex steroid levels. FUL also suppresses prolactin and IGFBP-1, without altering IGF-I. Thus, a major antiestrogen mediates 3 actions of estrogen: agonism (GH), neutral effects (sex steroids), and estrogen antagonism (prolactin and IGFBP-1).

SummaryPurposeThe 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 methodsFifty‐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.ResultsQuantitative 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.ConclusionEnhancement 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.

AbstractBackgroundTo assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy.MethodsA cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed.ResultsMedian follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26–23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03–6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05–9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8–6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient).ConclusionCVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

Although the autoantigen involved in Graves’ hyperthyroidism is known to be the TSH receptor (TSHr), whether this antigen plays a primary role in the pathogenesis of Graves’ ophthalmopathy (GO) is unclear. We sought to determine whether fibroblasts derived from orbital adipose/connective tissue are capable of differentiating into adipocytes that bear immunoreactive and functional TSHr. In addition, we assessed relative levels of TSHr gene expression in normal and GO orbital adipose/connective tissue specimens.GO and normal orbital preadipocyte fibroblasts, cultured under conditions known to stimulate adipocyte differentiation, showed evidence of adipogenesis and positive immunostaining for TSHr protein. In addition, significantly more cAMP was produced in response to TSH stimulation in the differentiated cultures than in undifferentiated cultures derived from the same individuals’ cells. Other studies demonstrated relatively greater TSHr gene expression in GO than in normal orbital tissue specimens.These results indicate that orbital preadipocyte fibroblasts increase their TSHr expression with differentiation and suggest that these cells play an important role in the pathogenesis of GO. Furthermore, our studies support the concept that TSHr may be an important target antigen in this condition. Factors that stimulate adipocyte differentiation and TSHr expression in the orbit in GO have yet to be defined.

Summary Objective We aimed to assess the prevalence of impulse control disorders ( ICD s) in patients with prolactin‐secreting adenomas treated with dopamine agonists ( DA s), 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 DA s) 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 ICD s when compared with men in Group B (27·7 vs 3·7%, P = 0·01). No differences in rates of total ICD s 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 DA s 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 ICD s are available, the authors propose that patients with prolactinoma be forewarned of possible ICD development with DA therapy.

Secondary causes of hypertension can affect over 10% of those patients diagnosed with hypertension, and the workup can encompass a wide variety of pathologies. Here we present a case of secondary hypertension found in a young physician who, fortunately, had both of these two entities diagnosed via fortuitous imaging performed for non-diagnostic reasons. This case involves a relatively common cause of secondary hypertension (renovascular) and a more obscure cause (paraganglioma). We outline evidencebased surgical and perioperative management of paragangliomas, as well as the medical management of renovascular hypertension. This case is unique in that it involves both elements of secondary hypertension and presents difficult management decisions.

To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E2; women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu ( P = 0.019) and dual-peptide stimulation ( P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E2/T exposure elevated nadir GH concentrations during saline infusion ( P = 0.003), whereas dual-peptide infusion did so independently of T/E2 and sex difference ( P = 0.001). All three of sex difference ( P = 0.001), sex steroid treatment ( P = 0.005), and double-peptide stimulation ( P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men ( P = 0.016). E2/T augmented peak GH recovery during saline infusion ( P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment ( P = 0.012) and peptide infusion ( P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain.