Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas

Objective: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6%-16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone SIT (DSIT) by applying both tests on the same subjects. Methods: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls, with normal adrenal imaging. Serum cortisol, aldosterone and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean+2SD values from the controls, we defined the upper normal limits (UNL) for cortisol, aldosterone and PRC for both the SIT and DSIT. Results: In the controls, the post-DSIT aldosterone levels and the ARR were approximately 2-fold and 3-fold lower respectively than the corresponding post-SIT values (all p=0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion. Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. Conclusions: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk for developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant autonomous cortisol secretion.

Adrenal imaging: anatomy and pathology (literature review)

This literature review focuses on the normal adrenal gland anatomy and typical imaging features necessary to evaluate benign and malignant lesions. In particular, adenoma, pheochromocytoma, metastases and adrenocortical carcinoma were discussed as some of the most common lesions. For this purpose, a review of relevant local and international literature sources up to January 2021 was conducted.In many cases, adrenal incidentalomas have distinctive features allowing characterization using noninvasive methods. It is possible to suspect a malignant nature and promptly refer the patient for the necessary invasive examinations in some cases. ­Computed tomography, especially with intravenous contrast enhancement, is the primary imaging modality because it enables differential diagnosis. Magnetic resonance tomography remains a sensitive method in lesion detection and follow-up but is not very specific for determining the malignant potential. Positron emission computed tomography also remains an additional method and is used mainly for differential diagnosis of malignant tumors, detecting metastases and recurrences after surgical treatment. Ultrasound has a limited role but is nevertheless of great importance in the pediatric population, especially newborns. Promising techniques such as radiomics and dual-energy CT can expand imaging capabilities and improve diagnostic accuracy.Because adrenal lesions are often incidentally detected by imaging performed for other reasons, it is vital to interpret such findings correctly. This review should give the reader a broad overview of how different imaging modalities can evaluate adrenal pathology and guide radiologists and clinicians.

Aldosterone signaling defect in young infants: single-center report and review

Background Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. Methods A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. Results A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240–1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. Conclusion Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.

Leydigcelhyperplasie: een zeldzame oorzaak van hyperandrogenisme bij een menopauzale vrouw

Leydig cell hyperplasia: an atypical cause of postmenopausal hyperandrogenism We present a case of a 64-year old postmenopausal patient with new onset hirsutism, acne and clitoromegaly. Her medical history includes a non-secreting adrenal incidentaloma. Biochemical evaluation withheld an elevated testosterone with normal dehydroepiandrosterone sulphate (DHEAS). Other adrenal biochemical tests were normal and adrenal imaging was unaltered. Imaging of the ovaries was unremarkable. Due to the normal DHEAS, ovarian etiology was suspected, for which a bilateral oophorectomy was performed. Pathological examination showed bilateral Leydig cell hyperplasia, a benign though rare cause of postmenopausal hyperandrogenism. Postmenopausal hyperandrogenism is caused by of a group of gynaecological and endocrinological disorders. In case of rapid onset and severe symptoms of hirsutism or virilization an androgen-secreting neoplastic disorder should be suspected. Normal DHEAS is suggestive for an ovarian etiology. Imaging is necessary to differentiate between adrenal and ovarian causes, though normal imaging of the ovaries does not rule out ovarian pathology. Definitive diagnosis is often based on pathological examination after oophorectomy.

Giant bilateral adrenal lipoma in a patient with congenital adrenal hyperplasia

Summary Apart from adrenal myelolipomas, adrenal lipomatous tumors are rare and only seldom described in the literature. We present the case of a 50-year-old man, with a classical form of congenital adrenal hyperplasia (CAH), which was well treated with prednisolone and fludrocortisone. The patient presented with pollakisuria and shortness of breath while bending over. On MRI, fat-equivalent masses were found in the abdomen (14 × 19 × 11 cm on the right side and 10 × 11 × 6 cm on the left side). The right adrenal mass was resected during open laparotomy and the pathohistological examination revealed the diagnosis of an adrenal lipoma. Symptoms were subdued totally postoperatively. This is the first report of a bilateral adrenal lipoma in a patient with CAH that we are aware of. Learning points Macronodular hyperplasia is common in patients with congenital adrenal hyperplasia (CAH). Solitary adrenal tumors appear in approximately 10% of adult CAH patients and are often benign myelolipomas. The Endocrine Society Clinical Practice Guideline does not recommend routine adrenal imaging in adult CAH patients. Adrenal imaging should be performed in CAH patients with clinical signs for an adrenal or abdominal mass. Adrenal lipoma is rare and histopathological examinations should rule out a differentiated liposarcoma.

Diagnostic accuracy of adrenal imaging for subtype diagnosis in primary aldosteronism: systematic review and meta-analysis

ObjectivesAccurate subtype classification in primary aldosteronism (PA) is critical in assessing the optimal treatment options. This study aimed to evaluate the diagnostic accuracy of adrenal imaging for unilateral PA classification.MethodsSystematic searches of PubMed, EMBASE and the Cochrane databases were performed from 1 January 2000 to 1 February 2020, for all studies that used CT or MRI in determining unilateral PA and validated the results against invasive adrenal vein sampling (AVS). Summary diagnostic accuracies were assessed using a bivariate random-effects model. Subgroup analyses, meta-regression and sensitivity analysis were performed to explore the possible sources of heterogeneity.ResultA total of 25 studies, involving a total of 4669 subjects, were identified. The overall analysis revealed a pooled sensitivity of 68% (95% CI: 61% to 74%) and specificity of 57% (95% CI 50% to 65%) for CT/MRI in identifying unilateral PA. Sensitivity was higher in the contrast-enhanced (CT) group versus the traditional CT group (77% (95% CI 66% to 85%) vs 58% (95% CI 50% to 66%). Subgroup analysis stratified by screening test for PA showed that the sensitivity of the aldosterone-to-renin ratio (ARR) group was higher than that of the non-ARR group (78% (95% CI 69% to 84%) vs 66% (95% CI 58% to 72%)). The diagnostic accuracy of PA patients aged ≤40 years was reported in four studies, and the overall sensitivity was 71%, with 79% specificity. Meta-regression revealed a significant impact of sample size on sensitivity and of age and study quality on specificity.ConclusionCT/MRI is not a reliable alternative to invasive AVS without excellent sensitivity or specificity for correctly identifying unilateral PA. Even in young patients (≤40 years), 21% of patients would have undergone unnecessary adrenalectomy based on imaging results alone.

Surgical Outcomes Among Primary Aldosteronism Patients Without Visible Adrenal Lesions

Context Many patients with unilateral primary aldosteronism (PA) have normal adrenal imaging, but little is known about their outcome following adrenalectomy. Objective To evaluate biochemical and clinical outcomes after adrenalectomy in patients with unilateral PA and normal-appearing adrenal imaging. Design Retrospective cohort study of patients seen between January 2006 and May 2018. Setting A Canadian tertiary care PA referral center. Patients Consecutive individuals with PA, normal cross-sectional adrenal imaging, and lateralizing adrenal vein sampling (AVS) who underwent adrenalectomy during the study period. Primary Outcome Biochemical response to adrenalectomy graded according to the Primary Aldosteronism Surgical Outcome criteria. Results A total of 40 patients were included. Biochemical outcomes were available for 33 people (mean age, 54.7 years; 91% male; median follow-up, 2.7 months), with 28 (85%) showing a complete or partial response and 5 (15%) with no response. Clinical outcomes were available for 36 people (mean age, 54.6 years; 86% male; median follow-up, 9.8 months), with 31 (86%) demonstrating a complete or partial response and 5 (14%) with no response. Conclusions The prognosis after adrenalectomy is highly favorable for patients with unilateral PA and normal-appearing adrenal imaging. Patients with lateralizing disease should be considered for surgery despite apparently normal adrenal imaging.

PREVALENCE AND CHARACTERISTICS OF ADRENAL TUMORS AND MYELOLIPOMAS IN CONGENITAL ADRENAL HYPERPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: The prevalence of adrenal tumors in congenital adrenal hyperplasia (CAH) is uncertain. Our objective was to estimate the prevalence and characteristics of adrenal tumors and myelolipoma in CAH, and investigate clinical features of this population. Methods: We carried out systematic searches in Medline Ovid and Embase for articles published until January, 2020. Studies with confirmed CAH, biochemically and/or genetically, were included. The two authors independently extracted data from each study. Results: Six cohort studies were included in the prevalence calculation. In addition, 32 case reports on adrenal myelolipomas and CAH were included. The prevalence of adrenal tumors in CAH was 29.3%. When only studies with genetically verified cytochrome P450, Family 21, subfamily A, polypeptide 2 gene ( CYP21A2) mutations were included the prevalence was 23.6%. The prevalence of myelolipoma in CAH was 7.4% (verified CYP21A2 mutations 8.6%). The proportion of myelolipoma in the adrenal tumors was 25.4% (genetically verified 36.6%). The median (range) age at tumor diagnosis was 36.0 (12 to 60) years and there were more tumors in males than in females (37.9% versus 22.1%; P<.05). In patients with myelolipomas, 93.5% had an undiagnosed or poorly managed CAH. Conclusion: Patients with CAH had a high prevalence of adrenal tumors, particularly myelolipomas. Those with myelolipomas had a high frequency of late-diagnosed or poorly controlled CAH. Adrenal imaging may be considered in patients with CAH, especially if abdominal pain is present. Abbreviations: ACTH = adrenocorticotropic hormone; CAH = congenital adrenal hyperplasia; CT = computed tomography; CYP21A2 = cytochrome P450, Family 21, subfamily A, polypeptide 2 gene; HU = Hounsfield units; MRI = magnetic resonance imaging; 21-OHD = 21-hydroxylase deficiency; 17-OHP = 17-hydroxyprogesterone; SV = simple virilizing

Reversibility of Acute Adrenal Insufficiency after hip Replacement: A Case Series

Background: Acute adrenal insufficiency is a rare but potentially lethal condition that is important to identify promptly and treat with replacement therapy. It can be due to adrenal hemorrhage that can occur after major orthopedic surgery. Few data are available about potential recovery of adrenal function, as well as both timing and modality of cortisone acetate withdrawal, probably due to the assumption that adrenal failure is definitive. A not massive adrenal damage can justify a partial, or potentially complete, recovery of adrenal function. Methods: We had recently described a case of acute adrenal insufficiency, which developed shortly after hip replacement; the patient was able to discontinue cortisone acetate treatment 46 months after the diagnosis and remained untreated up to five years later. We found other two cases of acute adrenal insufficiency that developed about one week after major orthopedic surgery. We followed such patients for about three years, repeatedly reassessing adrenal imaging and cortisol response to 250 µg ACTH test, in order to ascertain the real need of lifetime substitutive treatment with cortisone acetate. Results: Acute adrenal insufficiency partially reverted during the follow up for both patients. We observed a reduction in adrenal glands’ volume and a progressive improvement of cortisol basal levels, without response (or with a poor one) to ACTH stimulation, as well as with ACTH basal levels persistently above the normal range after 36 and 28 months respectively after the acute event. Conclusions: The present finding suggests that patients developing acute adrenal insufficiency after major orthopedic surgery must undergo long-term surveillance, in order to establish if steroid replacement has to be continued, or if it can be safely withdrawn.