Abstract
Context
Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.
Case report
A 46-year-old ...woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 µg/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.
Discussion
We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.
Conclusion
Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
Abstract
Context
Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using ...immunoassay.
Objective
To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening.
Methods
A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings.
Results
The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements.
Conclusion
Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.
Abstract
Context
Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare ...worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula.
Objective
Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.
Methods
Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint.
Results
Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin.
Conclusion
The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.
Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic ...symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.
Objective
Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of ...Brazilian children with PPGL.
Patients and Methods
This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4‐19). The median time of follow‐up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation‐dependent probe amplification and/or target next‐generation sequencing panel.
Results
Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects median (range), 12 (4‐16) vs. 15.5 (14‐19) years; P = .027. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL.
Conclusions
Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.
Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications.
Primary objective: to describe the frequency of adverse skeletal related events (SREs) ...in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset.
In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled.
SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0–246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio HR, 0.536 95 % CI, 0.309–0.932; P = .027) and absence of liver metastases (HR, 0.638 95 % CI, 0.410–0.992; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 95 % CI, 0.3877–0.806; P = .002), absence of liver metastases (HR, 0.618 95 % CI, 0.396–0.965; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 95 % CI, 0.405–0.884; P = .010), and MIBG radionuclide therapy (HR, 0.444 95 % CI, 0.274–0.718; P = .001) were associated with a reduced risk of death.
SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome.
•What is the SREs frequency in PPGL with BM?•Retrospective multicenter study: 31 % of PPGL patients with BM experienced SREs.•mOS was 5 years, with 67 % of SREs occurring within the first year of BM diagnosis.•Prognosis was not negatively affected by SREs.•SREs are observed frequently and early in patients with PPGL who have BM.
Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism ...(PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.
Abstract
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the ...highest degree of heritability among endocrine tumors. Currently, ~40% of individuals with PPGLs have a genetic germline and there are at least 12 different genetic syndromes related to these tumors. Metastatic PPGLs are defined by the presence of distant metastases at sites where chromaffin cells are physiologically absent. Approximately 10% of pheochromocytomas and ~40% of sympathetic paragangliomas are linked to metastases, explaining why complete surgical resection is the first-choice treatment for all PPGL patients. The surgical approach is a high-risk procedure requiring perioperative management by a specialized multidisciplinary team in centers with broad expertise. In this review, we summarize and discuss the most relevant aspects of perioperative management in patients with pheochromocytomas and sympathetic paragangliomas.
Abstract
Context
The role of hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcomes remains controversial.
Objective
To investigate the impact of hormone ...parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcomes.
Methods
We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. The bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index, aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), and relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 − nondominant RASI) * 100.
Results
A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had the worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure was significantly more frequent in the patients with CS >50% 98.41% vs 42.86% (P < .001) and 41.94% vs 0% (P < .001). CS correlated with high aldosterone at diagnosis (P < .001) and low postoperative aldosterone levels at 1 month (P = .019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs 16.67%, P = .014). In multivariable analysis, a CS >50% was associated with complete biochemical cure odds ratio (OR) 125, 95% confidence interval (CI) 11.904-5000; P = .001 and hypertension remission (OR 12.19, 95% CI 2.074-250; P = .023).
Conclusion
A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral primary aldosteronism and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.
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