Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism.

BACKGROUND: Primary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. METHODS: A retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. RESULTS: We included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP). In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician. In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). CONCLUSIONS: AVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.

Imaging features of intra-abdominal and intra-pelvic causes of hirsutism.

Hirsutism is a relatively common disorder which affects approximately 5% to 15% of women. It is defined by excessive growth of terminal hair in women, which primarily affects areas dependent on androgens, such as the face, abdomen, buttocks, and thighs. Hirsutism can be caused by a variety of etiologies, which are most often not lifethreatening. However, in some cases, hirsutism can be an indicator of more serious underlying pathology, such as a neoplasm, which may require further elucidation with imaging. Within the abdomen and pelvis, adrenal and ovarian pathologies are the primary consideration. The goal of this manuscript is to review the etiologies and imaging features of various intra-abdominal and intra-pelvic causes of hirsutism.

Complications related to thyroidectomy among patients with hyperthyroidism: Exploring the potential for ambulatory surgery.

BACKGROUND: Total thyroidectomy for hyperthyroidism is typically followed by overnight admission to monitor for complications including thyrotoxicosis. Outpatient thyroid surgery is increasingly common, but its safety in patients with hyperthyroidism has not been well studied. METHODS: This retrospective study reviewed 183 patients with hyperthyroidism who underwent total thyroidectomy from 2015 to 2022 at one urban, academic center. The main outcomes were rates of thyroid storm, surgical complications, and 30-day ED visits and readmissions. RESULTS: Among 183 patients with hyperthyroidism (mean age, 45 ± 14.5 years; 82.5% female), there were no cases of thyroid storm and complications included recurrent laryngeal nerve (RLN) palsy (7.0%), symptomatic hypocalcemia (4.4%), and hematoma (1.6%). ED visits were present in 1.1% and no patients were readmitted. CONCLUSION: Total thyroidectomy was not associated with thyroid storm and <6% of patients required inpatient management. Ambulatory total thyroidectomy for hyperthyroidism warrants further consideration through identification of predictive factors for postoperative complications.

Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort.

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p = 0.81 and p = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test (p = 0.016) and multivariate Cox regression (HR 0.48, p = 0.09 for White and HR 0.36, p = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test (p = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study.

Perioperative Management of Metastatic Paraganglioma-Pheochromocytoma of the Humerus with the Aid of Regional Anesthesia.

A 38-year-old female with a past history of pheochromocytoma and subsequent malignant paraganglioma presented with right arm pain after a fall. Imaging demonstrated a malunited humeral shaft associated with a large cortical destructive lesion and extraosseous extension. Here, we report the use of a multidisciplinary team approach including an endocrinologist, anesthesiologist, and orthopedic surgeon in the perioperative management of a patient with metastatic paraganglioma undergoing a surgical resection of the humerus, internal fixation, reconstruction, and placement of endoprosthesis. The challenges of perioperative anesthetic management and the use of regional anesthesia, especially peripheral nerve block for perioperative pain management, are highlighted.

Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults.

Administration of metformin increases healthspan and lifespan in model systems, and evidence from clinical trials and observational studies suggests that metformin delays a variety of age-related morbidities. Although metformin has been shown to modulate multiple biological pathways at the cellular level, these pleiotropic effects of metformin on the biology of human aging have not been studied. We studied ~70-year-old participants (n = 14) in a randomized, double-blind, placebo-controlled, crossover trial in which they were treated with 6 weeks each of metformin and placebo. Following each treatment period, skeletal muscle and subcutaneous adipose tissue biopsies were obtained, and a mixed-meal challenge test was performed. As expected, metformin therapy lowered 2-hour glucose, insulin AUC, and insulin secretion compared to placebo. Using FDR<0.05, 647 genes were differentially expressed in muscle and 146 genes were differentially expressed in adipose tissue. Both metabolic and nonmetabolic pathways were significantly influenced, including pyruvate metabolism and DNA repair in muscle and PPAR and SREBP signaling, mitochondrial fatty acid oxidation, and collagen trimerization in adipose. While each tissue had a signature reflecting its own function, we identified a cascade of predictive upstream transcriptional regulators, including mTORC1, MYC, TNF, TGFß1, and miRNA-29b that may explain tissue-specific transcriptomic changes in response to metformin treatment. This study provides the first evidence that, in older adults, metformin has metabolic and nonmetabolic effects linked to aging. These data can inform the development of biomarkers for the effects of metformin, and potentially other drugs, on key aging pathways.

Subclinical hypothyroidism and cardiovascular risk: recommendations for treatment.

The definition of subclinical hypothyroidism (SCH) is solely biochemical: a serum free T4 level within the reference range in the presence of an elevated serum thyroid-stimulating hormone (TSH) level. While overt hypothyroidism is associated with an increased cardiovascular disease risk, SCH, the mildest form of hypothyroidism, may also be associated with an increased cardiovascular disease risk, but to a lesser degree. Recent evidence points to a significant trend toward an increase in cardiovascular risk at higher TSH levels, with TSH levels ≥10 mIU/L associated with increased cardiovascular morbidity and mortality. It is generally recommended to treat with thyroid hormone those individuals with SCH and TSH values ≥10 mIU/L. Treatment of patients with SCH and TSH values <10 is controversial but may be considered in selected patients.

Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53.

We have previously found that nonenzymatically glycated collagen I (GC), mimicking diabetic microenvironment, can induce senescent phenotype in early passage human umbilical vein endothelial cells (HUVECs). In the present study, we explored the functional involvement of cell cycle checkpoint pathways in initiating GC-induced premature endothelial cell senescence. When compared with native collagen, early passage HUVECs showed increased p53, p21(CIP1) (p21), and p16(INK4a) (p16) mRNA expression after exposure to GC. Twenty-four hours after transfection of p16, p21, and p53-enhanced green fluorescent protein (EGFP) recombinant plasmids, HUVECs entered G(1)-phase cell cycle arrest. By days 3 and 5, HUVECs transfected with p16-EGFP showed an increased proportion of senescent cells, and this increase was more prominent in the GFP-positive cell population, which exhibited 68% of senescent cells. Transfection of p21 also induced senescence but only by day 5. Cotransfection of p16 and p21 showed no additive effect. Transfection of p21 or p53 induced apoptosis in HUVECs. Next, we suppressed endogenous p53, p21, p16, or retinoblastoma (Rb) gene expression through small interference RNA strategy and investigated their influence in p16- and p21-initiated endothelial cell senescence. Analysis indicated that suppression of p53 expression can abolish senescence induced by p16 overexpression. Paradoxically, this effect was not observed when p21 was suppressed. On the other hand, suppression of Rb eliminated senescence initiated by either p16 or p21 overexpression. In summary, the p53/p21 pathway is mainly responsible for GC-induced apoptosis, but the coordinated activation of the p53/p21 and p16 pathway is responsible for GC-induced endothelial cell senescence through a Rb-dependent mechanism.