Benign Adrenocortical Tumors and the Detection of Nonadrenal Neoplasia.

CONTEXT: Patients with adrenocortical tumors have been frequently observed to have nonadrenal neoplasia. OBJECTIVE: To investigate whether patients with benign adrenocortical tumors have a higher likelihood of having nonadrenal neoplasia detected. DESIGN AND PARTICIPANTS: Case-control study of patients with benign adrenocortical tumors (cases; n = 400) and normal adrenal glands (controls; n = 400), who underwent repeated abdominal cross-sectional imaging. MAIN OUTCOMES: Primary analyses: association between case-control status and benign abdominal neoplasia detected via cross-sectional imaging. Secondary analyses: association between case-control status and tumors detected via other imaging modalities. RESULTS: The mean interval of abdominal imaging was 4.7 (SD = 3.8) years for cases and 5.9 (4.8) years for controls. Cases were more likely to have detected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas (8.5% vs. 4.5%, adjusted OR = 2.22, 95% CI (1.11, 4.63)) compared with controls. In secondary analyses, cases were more likely to have detected thyroid nodules (25.5% vs. 17.0%, adjusted OR = 1.77, 95% CI (1.15, 2.74)), hyperparathyroidism or parathyroid adenomas (3.5% vs. 1.3%, adjusted OR = 3.00, 95% CI (1.00, 11.64)), benign breast masses (6.0% vs. 3.3%, adjusted OR = 3.25, 95% CI (1.28, 8.78)), and benign prostatic hyperplasia (20.5% vs. 5.3%, adjusted OR = 3.20, 95% CI (1.14, 10.60)). Using a composite outcome, cases had higher odds of detection of the composite of IPMN, thyroid nodules, parathyroid tumors, benign breast masses, and prostate hyperplasia (adjusted OR = 2.36, 95% CI: 1.60, 3.50) when compared with controls. CONCLUSIONS: Patients with benign adrenocortical tumors had higher odds of detected pancreatic IPMN, as well as thyroid nodules, parathyroid tumors, benign breast masses, and prostate hyperplasia compared with patients with normal adrenal glands. These associations may have important implications for patient care and healthcare economics, regardless of whether they reflect incidental discoveries due to imaging detection or frequency bias, or a common risk for developing multiple neoplasia.

The Lateralizing Asymmetry of Adrenal Adenomas.

CONTEXT: It is presumed that the incidence of adrenal adenomas is symmetric between the left and right adrenal gland; however, anecdotal observations suggest a potential lateralizing asymmetry. OBJECTIVE: To investigate the symmetry in detection of adrenal adenomas and relevance to patient care. DESIGN: Cross-sectional and longitudinal studies. POPULATION AND SETTING: One thousand three hundred seventy-six patients with abdominal computed tomography or magnetic resonance imaging demonstrating benign-appearing adrenal adenomas. MAIN OUTCOME: Location and size of adrenal adenomas. RESULTS: Left-sided adenomas were discovered in 65% of patients, right-sided in 21%, and bilateral adenomas in 14%. Among unilateral adenomas, 75% were left-sided. Left-sided adenomas were more prevalent than right-sided adenomas in each size category except the largest: <10 mm, 87%; 10 to 19 mm, 74%; 20 to 29 mm, 72%; ≥30 mm, 56% (P < 0.0001 for each category, except P = 0.19 when ≥30 mm). Among those with bilateral adenomas, the left-sided adenoma was significantly larger than the right one in 61% of patients (P < 0.001). There were no significant differences in the baseline prevalence or incidence of cardiometabolic diseases between patients with left-sided vs right-sided adenomas during 5.10 (4.2) years of follow-up. CONCLUSIONS: Adrenal adenomas are substantially more likely to be identified on the left adrenal than the right. This observation may be due to detection bias attributed to the location of the right adrenal, which may preclude identification of right-sided adenomas until they are substantially larger. These findings suggest the potential for an underrecognition of right-sided adenomas that may also impair the accurate detection of bilateral adrenal diseases.

Heparin-Induced Thrombocytopenia in Healthy Individuals with Continuous Heparin Infusion.

The risk for developing heparin-induced thrombocytopenia in healthy individuals is thought to be low, but monitoring recommendations remain controversial. Therefore, a retrospective cohort study was conducted to identify the incidence of thrombocytopenic events in a healthy research population exposed and re-exposed to continuous intravenous (IV) unfractionated heparin. The Division of Sleep Medicine and the Centre for Clinical Investigations at Brigham and Women's Hospital, Boston, Massachusetts, United States, instituted a standardized platelet monitoring procedure for all research protocols that involved heparin to detect platelet count decreases. Protocol-related frequent blood sampling required use of continuous IV unfractionated heparin infusion (5,000 unit/L in 0.45% saline at 40 mL/h) to maintain line patency over extended periods of IV access. From the years 2009 to 2012, a total of 273 healthy volunteers enrolled in Sleep Medicine research protocols met study criteria as having been exposed and/or re-exposed to continuously infused intravenous heparin for at least 4 hours. The mean continuous heparin exposure time was 88 ± 82 SD hours with a total of 397 heparin exposure and re-exposure events. Platelet count measurements were obtained on 629 occasions, representing a range from 2 to 9 draws per participant. No platelet count decrease of more than 50% was detected. There were no detected adverse bleeding or thrombotic events. In this retrospective study of healthy volunteers involved in a rigorously applied inpatient platelet monitoring protocol, heparin exposure and re-exposure did not lower platelet concentration and, therefore, does not appear to be associated with increased risk of HIT in this population.

Striatin Gene Polymorphic Variants Are Associated With Salt Sensitive Blood Pressure in Normotensives and Hypertensives.

BACKGROUND: Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms. METHODS: We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-). RESULTS: The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; ß = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems. CONCLUSIONS: These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention.

Angiotensin-Converting Enzyme Inhibition and Parathyroid Hormone Secretion.

BACKGROUND: Prior studies suggest that renin-angiotensin-aldosterone system (RAAS) inhibitors decrease parathyroid hormone (PTH) secretion. OBJECTIVE: To evaluate the effect of angiotensin-converting enzyme inhibitors (ACEi) on serum PTH in participants with and without primary hyperparathyroidism (P-HPT). METHODS: An open-label, single-arm, pilot study whereby participants with and without P-HPT had PTH were evaluated before and after 1 week of maximally tolerated lisinopril therapy. RESULTS: A total of 12 participants with, and 15 participants without, P-HPT successfully completed the protocol. Following 1 week of lisinopril, participants with P-HPT had a decrease in systolic blood pressure (SBP) (-6.4 mmHg, P < 0.01), an increase in plasma renin activity (PRA) (+1.50 ng/mL/h, P = 0.06), and a decrease in PTH (79.5 (21.6) to 70.9 (19.6) pg/mL, ∆ = -8.6 pg/mL, P = 0.049); however, serum and urine calcium did not change. In contrast, although 1 week of lisinopril significantly decreased SBP and increased PRA among participants without P-HPT, there were no changes in PTH or calcium. CONCLUSION: In this short pilot investigation, 1 week of maximally titrated ACEi did not impact PTH in participants without P-HPT, but resulted in a modest and marginally significant reduction of PTH but not calcium, among participants with P-HPT. This trial is registered with ClinicalTrials.gov NCT01691781.

Where is the leak in the pipeline? Investigating gender differences in academic promotion at an academic medical centre.

BACKGROUND: Women are still under-represented in the senior ranks of academic medicine. As local surveys represent a critical initial step in addressing the challenges of gender disparities in academic promotion within institutions, we surveyed faculty at an academic medical centre to identify factors to improve the academic advancement of women. METHODS: We conducted an electronic survey of all full-time faculty members in a Department of Medicine assessing academic rank and factors important in consideration for promotion. RESULTS: 106 faculty members (46 %) responded to the survey; 40 % of the respondents were women. There was a statistically significant gender gap in faculty rank (p = 0.002), with only 2 of 17 full professor positions occupied by women. Among faculty who had not yet requested promotion, women were more likely to report that they did not think an academic promotion would benefit them (69 vs. 32 % in men, p = 0.01), and to report a lack of encouragement for requesting promotion (50 vs. 29 %, p = 0.08). CONCLUSIONS: Targeting the perceived value of academic promotion among women faculty, increasing junior faculty mentorship and modifying annual review processes could address gender disparities in academic medicine ranks.