Hypertension resolution after adrenalectomy for primary hyperaldosteronism: Which is the best predictive model?

BackgroundWe aimed to compare the predictive performance of three distinct clinical models purported to predict the resolution of aldosteronoma-associated hypertension after adrenalectomy.MethodsA tri-institutional database of aldosteronoma patients who underwent adrenalectomy between 2004 and 2019 was retrospectively reviewed. The three models of interest incorporate various preoperative clinical factors, such as age and sex. The predictive accuracy, as measured by area under the curve of receiver operator characteristic, was estimated. Receiver operator characteristic was evaluated across the whole cohort, then stratified by treatment location.ResultsA total of 200 patients were included (91 American, 109 French). The clinicodemographic variables between groups were similar; the French cohort had a lower mean body mass index (P = .02). The overall complete clinical resolution of hypertension after adrenalectomy for the entire data set was 45.5% (n = 91). The regression coefficients in the Utsumi et al (2014) Japanese model produced a superior overall area under the curve (0.78, 95% confidence interval [CI] [0.71–0.84]). This model also performed best when the cohort was stratified by treatment location (French area under the curve = 0.74, 95% CI [0.64–0.83], US area under the curve = 0.82, 95% CI [0.72–0.91]).ConclusionWhen comparing three predictive models of aldosteronoma-associated hypertension resolution after adrenalectomy, the Utsumi et al model demonstrated the highest predictive validity across all cohorts. Counseling based on this model regarding probability of cure is recommended.     

Identification of borderline thyroid tumors by gene expression array analysis

BACKGROUND:

A subset of follicular lesions of the thyroid is encapsulated similar to follicular adenomas but with partial nuclear features suggestive of papillary thyroid carcinoma (PTC), raising the possibility of biologically borderline tumors.

METHODS:

Gene expression profiling and advanced significance analyses were performed on 50 histologically unequivocal benign and malignant tumors, and a list of 61 differentially expressed genes was generated. By using this 61‐gene list, unsupervised hierarchical and K‐means cluster analyses were performed on 40 additional tumors, including 15 histologically borderline tumors, 11 benign tumors, and 14 PTCs.

RESULTS:

Analysis revealed 3 distinct tumor groups—benign, malignant, and intermediate. Tumors in the intermediate group (n = 15) were mostly histologic borderline tumors and had an expression profile overlapping with the benign and malignant groups. Twenty‐seven genes were expressed differentially between the benign and intermediate groups, including the cyclic AMP response element‐binding protein/p300‐interactivator with glutamic acid/aspartic acid‐rich carboxy‐terminal domain 1 or CITED1 gene and the fibroblast growth factor receptor 2 or FGFR2 gene. Fourteen genes were expressed differentially between the intermediate group and malignant tumors, notably overexpression of the met proto‐oncogene and of the high‐mobility group adenine/thymine‐hook 2 or HMGA2 gene in malignancies. Mutations of the v‐raf murine sarcoma viral oncogene homolog B1 or BRAF gene were identified in 4 of 14 malignant tumors but not in benign or intermediate tumors. Patients who had either histologically or molecularly borderline tumors did not have metastasis or recurrences.

CONCLUSIONS:

Gene expression profiling supported the finding that encapsulated thyroid follicular lesions with partial nuclear features of PTC are biologically borderline tumors that are distinct molecularly from benign and malignant tumors. Cancer 2009. © 2009 American Cancer Society.     

Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome

Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.     

Seroprevalence study in forestry workers of a non-endemic region in eastern Germany reveals infections by Tula and Dobrava�CBelgrade hantaviruses

Highly endemic and outbreak regions for human hantavirus infections are located in the southern, southeastern, and western parts of Germany. The dominant hantavirus is the bank vole transmitted Puumala virus (PUUV). In the eastern part of Germany, previous investigations revealed Tula virus (TULV) and Dobrava-Belgrade virus (DOBV) infections in the respective rodent reservoirs. Here, we describe a seroprevalence study in forestry workers from Brandenburg, eastern Germany, using IgG ELISA and immunoblot tests based on recombinant TULV, DOBV, and PUUV antigens. Out of the 563 sera tested, 499 from male and 64 from female workers, we found 41 out of the 499 (8.2%) sera from men (mean age 47 years) and 10 out of 64 (15.6%) from the women (mean age 48 years) anti-hantavirus-positive. The majority of the 51 seropositive samples reacted exclusively in the TULV (n=22) and DOBV tests (n=17). Focus reduction neutralization assay investigations on selected sera confirmed the presence of TULV- and DOBV-specific antibodies in the forestry workers. These investigations demonstrated a potential health threat for forestry workers and also the average population in non-endemic geographical regions where TULV and DOBV are circulating in the corresponding reservoir hosts. The infections in this region might be frequently overlooked due to their unspecific and mild symptoms.     

Robot-assisted adrenalectomy

Currently laparoscopic adrenalectomy (LA) is regarded as the preferred surgical approach for the management of most adrenal surgical disorders. Despite the benefits of LA, the procedure has shortcomings that are shared by other laparoscopic techniques. Commonly noted problems include the absence of 3-dimensional perception, reduced dexterity, and poor ergonomics for the surgeon. Recently, robotic technology has been introduced into laparoscopic clinical practice. The requirement for precise surgery in adrenalectomy is important, and the introduction of robotically assisted LA offers new possibilities. This review summarizes current available data regarding robotic adrenalectomy, including its indications, advantages, limitations, and comparison with conventional laparoscopic adrenalectomy. See the videos, Supplemental Digital Content 1, http://links.lww.com/SLE/A33, Supplemental Digital Content 2, http://links.lww.com/SLE/A34 and Supplemental Digital Content 3, http://links.lww.com/SLE/A35.     

Parathyroid carcinoma,atypical parathyroid adenoma,or parathyromatosis?

BACKGROUND: Parathyroid carcinoma, atypical parathyroid adenoma, and parathyromatosis can be differentiated relatively easily from typical parathyroid adenomas, but distinguishing them from each other is more difficult. METHODS: A retrospective study of 28 consecutive patients with parathyroid carcinoma, 7 patients with atypical parathyroid adenoma, and 13 patients with parathyromatosis who were treated at the University of California at San Francisco Medical Center between 1966 and 2005 was performed. Patient demographics and clinical characteristics, indication for surgery, intraoperative findings, histopathologic characteristics, disease recurrence or persistence, site of invasion/metastases, and survival were compared in the 3 groups. RESULTS: Parathyroid carcinoma (19 of 28 patients) and atypical adenoma (4 of 7 patients) were significantly more common in men, whereas parathyromatosis was more common in women (10 of 13 patients) (P = .02). A palpable neck mass and hoarseness were almost exclusively present in patients with parathyroid carcinoma. Prior to the first parathyroid surgery, patients with parathyroid carcinoma were found to have higher blood calcium levels (>/=14 mg/dL in 16 of 26 patients [62%]), whereas only 1 of 6 patients with atypical adenoma (17%) and no patients with parathyromatosis were found to have profound hypercalcemia (P < .01). Intraoperatively, patients with parathyroid carcinoma and atypical adenoma presented with single lesions, whereas patients with parathyromatosis had multiple small lesions. Histopathologic findings were well defined in parathyroid carcinoma, but some findings overlapped in the 3 tumors studied. CONCLUSIONS: Patients with parathyroid carcinoma often differ from those with atypical parathyroid adenoma or parathyromatosis at the time of presentation because patients with parathyroid carcinoma have more profound hypercalcemia as well as invasive tumors. However, at times it is difficult to distinguish between these conditions both clinically and by final histologic examination.     

Cyclooxygenase-2-linked attenuation of hypoxia-induced pulmonary hypertension and intravascular thrombosis

Exogenous prostacyclin is effective in reducing pulmonary vascular resistance in some forms of human pulmonary hypertension (PH). To explore whether endogenous prostaglandins played a similar role in pulmonary hypertension, we examined the effect of deleting cyclooxygenase (COX)-gene isoforms in a chronic hypoxia model of PH. Pulmonary hypertension, examined by direct measurement of right ventricular end systolic pressure (RVESP), right ventricular hypertrophy (n = 8), and hematocrit (n = 3), was induced by 3 weeks of hypobaric-hypoxia in wild-type and COX-knockout (KO) mice. RVESP was increased in wild-type hypoxic mice compared with normoxic controls (24.4 +/- 1.4 versus 13.8 +/- 1.9 mm Hg; n = 8; p < 0.05). COX-2 KO mice showed a greater increase in RVESP following hypoxia (36.8 +/- 2.7 mm Hg; p < 0.05). Urinary thromboxane (TX)B(2) excretion increased following hypoxia (44.6 +/- 11.1 versus 14.7 +/- 1.8 ng/ml; n = 6; p < 0.05), an effect that was exacerbated by COX-2 gene disruption (54.5 +/- 10.8 ng/ml; n = 6). In contrast, the increase in 6-keto-prostacyclin(1alpha) excretion following hypoxia was reduced by COX-2 gene disruption (29 +/- 3 versus 52 +/- 4.6 ng/ml; p < 0.01). Tail cut bleed times were lower following hypoxia, and there was evidence of intravascular thrombosis in lung vessels that was exacerbated by disruption of COX-2 and reduced by deletion of COX-1. The TXA(2)/endoperoxide receptor antagonist ifetroban (50 mg/kg/day) offset the effect of deleting the COX-2 gene, attenuating the hypoxia-induced rise in RVESP and intravascular thrombosis. COX-2 gene deletion exacerbates pulmonary hypertension, enhances sensitivity to TXA(2), and induces intravascular thrombosis in response to hypoxia. The data provide evidence that endogenous prostaglandins modulate the pulmonary response to hypoxia.