11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature.

Background and Objectives: 11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of. Design and Methods: We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021. Results: We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions. Conclusions: 11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable. Systematic Review Registration: Open Science Framework, 10.17605/OSF.IO/NR7UV.

Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma?

INTRODUCTION: Molecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC. METHODS: In this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry. RESULTS: One-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001). DISCUSSION: The implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).

[Evaluation of parathyroid function in presternal subcutaneous grafting after total parathyroidectomy for renal hyperparathyroidism]. / Evaluación de la función paratiroidea en el injerto subcutáneo preesternal tras paratiroidectomía total en el hiperparatiroidismo renal.

INTRODUCTION: In the setting of total parathyroidectomy (TPT) and parathyroid transplantation (PTx) for renal hyperparathyroidism (RHP), we evaluated long-term parathyroid graft function after subcutaneous presternal transplantation (SCPTx). HYPOTHESIS: Parathyroid glands are surrounded by fatty tissue. Therefore, we postulated that subcutaneous implantation of parathyroid tissue after TPT for RHP could be at least as effective as intramuscular grafting and would avoid the complications of the latter technique. MATERIAL AND METHOD: We performed a study in a university hospital and its dialysis unit. DESIGN: Prospective open efficacy study of a postoperative diagnostic monitoring method of intact parathyroid hormone (iPTH) in a cohort of surgical patients without loss to follow-up. PATIENTS AND INTERVENTIONS: Thirty-five patients (19 women and 16 men) underwent TPT and SCPTx for RHP at the Department of General Surgery and Department of Nephrology, Donostia Hospital, San Sebastián, Gipuzkoa, Spain, from January 2002 to December 2005. Follow-up ranged from 6 to 42 months (mean, 15.4 months). Graft function was evaluated by measurement of plasma iPTH levels before surgery and 24 hours and 1, 3, 5, 15, 30, 60, 100 and 150 weeks after surgery. Reference values for PTH in our laboratory were 20-65 pg/mL. RESULTS: The mean preoperative iPTH values were 1245 +/- 367.9 pg/mL (mean +/- SD) (range, 493-2160). After TPT and SCPTx, iPTH levels became undetectable in all patients at 24 hours. A value of 50 pg/mL was established as the criterion for adequate parathyroid graft function. The following values were obtained: 15.54 +/- 10.61 pg/mL (mean +/- SD) (range, 6-44) after 1 week, 57.2 +/- 1.9 pg/mL (mean +/- SD) (range, 43-74) after 5 weeks, 64.21 +/- 9.73 pg/mL (mean +/- SD) (range, 11.3-89) after 15 weeks, 75.12 +/- 9.05 pg/mL (mean +/- SD) (range, 24.6-104.2) after 30 weeks, 101.63 +/- 19.85 pg/mL (mean +/- SD) (range, 65-143) after 60 weeks, 121.63 +/- 27.85 pg/mL (mean +/- SD) (range, 62-179) after 100 weeks, 63 +/- 19.85 pg/mL (mean +/- SD) (range, 68-723) after 150 weeks and 102 +/- 18.65 pg/mL (mean +/- SD) (range, 68-113) after 200 weeks. The prevalence of hypoparathyroidism (serum iPTH level of < 20 pg/mL with a normal or low serum calcium concentration) was 2 out of 35 patients (5.71%) by week 60, with recovery of normal values by week 100. Graft-related recurrence occurred in one out of 35 patients (2.85%). CONCLUSIONS: SCPTx after TPT and PTx for secondary RHP is an adequate method to replace muscular forearm parathyroid transplantation and avoid its complications. The functional results of TPT and SCPTx compare favorably with published data on other surgical techniques proposed for the treatment of RHP. Long-term follow-up of this series is currently being performed.

Parathyroid subcutaneous pre-sternal transplantation after parathyroidectomy for renal hyperparathyroidism. Long-term graft function.

BACKGROUND: In the setting of total parathyroidectomy (TPT) and parathyroid transplantation (PTx) for renal hyperparathyroidism (RHP), we evaluated long-term parathyroid graft function after subcutaneous pre-sternal transplantation (SCPTx). Because parathyroid glands are surrounded by fatty tissue, we postulated that results of subcutaneous implantation of parathyroid tissue after total parathyroidectomy for renal hyperparathyroidism could be at least as successful as intramuscular grafting, but without its complications. PATIENTS AND METHODS: The study, a prospective open efficacy study of postoperative (po) diagnostic monitoring of intact parathyroid hormone (iPTH) on a cohort of surgical patients, was conducted within a university hospital with a dialysis unit. Thirty five patients (19 women and 16 men) operated on for renal hyperparathyroidism underwent TPT and SCPTx for RHP at the Department of General Surgery and the Department of Nephrology. Donostia Hospital. San Sebastián. Gipuzkoa. Spain, from January 2002 to December 2005. Follow-up ranges from 6 months to 42 months (median: 15.4 months). The main outcome measure was evaluation of graft function by measurement of iPTH plasma level, based on serum levels of iPTH before operation and 24 h and 1, 3, 5, 15, 30, 60, 100, and 150 weeks after surgery. RESULTS: Average preoperative iPTH values were 1,341.52 + 367.78 pg/ml (mean +/- SD) (range: 493-2,180). After TPT and PSCTx, iPTH levels became undetectable in all patients at 24 h. A level of 50 pg/ml was established as the criterion of adequate parathyroid graft function. Values obtained at the various time intervals were as follows: 14.14 + 7.73 1 pg/ml (mean +/- SD) (range: 6-36) after 1 week, 53 + 77.33 pg/ml (mean +/- SD) (range: 35-74) after 5 weeks, 62.95 + 20.93 pg/ml (mean +/- SD) (range: 11-89) after 15 weeks, 77.54 + 18.84 pg/ml (mean +/- SD) (range: 24.6-104.2) after 30 weeks, 109.29 + 50.22 pg/ml (mean +/- SD) (range: 54-327) after 60 weeks, 134.21 + 128.64 pg/ml (mean +/- SD) (range: 43-712) after 100 weeks, and 122.84 + 117.54 pg/ml (mean +/- SD) (range: 68-723) after 150 weeks. Prevalence of hypoparathyroidism (intact parathyroid hormone serum level < 20 pg/ml with a normal or low serum calcium concentration) was 2/35 (5.71%) by week 60 and recovered by week 100. Graft-related recurrence was 2.85% (1/35). CONCLUSIONS: Subcutaneous pre-sternal transplantation (SCPTx) after TPT and PTx for secondary (RHP) is an adequate method to replace muscular forearm parathyroid transplantation and avoid its complications. Functioning results of total parathyroidectomy and presternal subcutaneous grafting compare favorably with the published data on other surgical techniques proposed for the treatment of renal hyperparathyroidism. Results of long-term follow-up exceed previously reported results.