A case of primary aldosteronism with secondary hyperparathyroidism and bilateral adrenal tumors

Feasibility of single-port laparoscopic partial adrenalectomy with selective adrenal venous sampling and high-resolution ultrasound for unilateral aldosterone-producing adenomas

Primary aldosteronism (PA) is the most common detectable cause of secondary hypertension. The majority of patients have either an adrenal aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH) demanding different therapeutic approaches. Screening tests and imaging cannot reliably distinguish between a unilateral or bilateral PA. This review article gives an overview concerning etiology, diagnostics, and therapeutic options of PA, and reviews the indication, the technique, and relevance of selective adrenal venous sampling (AVS) in the context of the current literature and the authors' experience. AVS can verify or exclude a unilaterally dominated secretion with a high success rate. Patients with PA and a unilateral APA can be treated curatively by adrenalectomy. AVS is an established diagnostic examination for differentiation of unilateral from bilateral adrenal disease in patients with PA. · Selective adrenal venous sampling (AVS) is a safe, reliable, and minimally invasive method to detect a unilateral or bilateral adrenal adrenal gland disease.. · Verification of lateralization by AVS has direct therapeutic relevance for patients with primary aldosteronism (PA).. · AVS can be performed with low radiation exposure, without contrast medium, and with a high success rate when performed by an experienced interventional radiologist.. · Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 - 666.

BackgroundCoexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature.Case presentationA 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years.ConclusionsThis is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management.

According to some authors, a higher incidence of subclinical hypercortisolemia is found among patients with bilateral benign adrenal tumors than in those with unilateral tumors. It is still unknown whether all patients with bilateral adrenal tumors and subclinical hypercortisolemia should undergo surgery, and, if so, which tumor should be removed first. The aim of the study was to investigate whether unilateral adrenalectomy can lead to resolution of hypercortisolemia in patients with bilateral adrenal tumors and to improvement of their clinical status. The study group consisted of 25 patients with bilateral benign adrenal tumors and subclinical hypercortisolemia. In 24 patients, unilateral adrenalectomy was performed. The adrenal gland was selected for removal on the basis of scintigraphy and/or tumor diameter. Cortisol concentrations were measured before the surgery and at 1 and 6 months after the surgery at 8:00 AM, 10:00 PM, and after dexamethasone suppression. The morning blood levels of adrenocorticotropic hormone, dehydroepiandrosterone, 17‑hydroxyprogesterone, glycated hemoglobin, and lipid profile were determined. In all surgical patients, hypercortisolemia resolved after the surgery. However, only in 14 patients (58%), the clinical improvement was evident (improved control of diabetes and hypertension, body mass loss). Although subclinical hypercortisolemia resolved after surgery in all patients with bilateral adrenal tumors, only patients with poorly controlled diabetes and hypertension and a rapid increase in body mass benefited from the surgery.

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling

BACKGROUND: Reports of the synchronous glucocorticoid-mineralocorticoid activity in patients with Cushing’s syndrome and primary hyperaldosteronism have been found in the literature for fifty years, but there are few evidence-based studies on this issue. AIM: To study mineralocorticoid and glucocorticoid secretion in patients with unilateral, bilateral tumours and bilateral hyperplasia of the adrenal cortex exploring urine and blood steroid metabolomes by chromatography methods. MATERIALS AND METHODS: 114 patients with corticotrophin-independent Cushing’s syndrome, autonomous cortisol secretion and primary hyperaldosteronism were examined. The state of the pituitary-adrenal cortex system was assessed by classical methods of immunochemical analysis and functional tests. The corticosteroid metabolomics was studied in biological fluids using high-performance liquid chromatography and gas chromatography-mass spectrometry. In accordance with functional activities and type of hyperplasia, all the patients were divided into 8 subgroups: Cushing’s syndrome and corticosteroma (n = 19), Cushing’s syndrome and bilateral adenomas (n = 9), Cushing’s syndrome and bilateral macronodular hyperplasia (n = 8); autonomus cortisol secretion and unilateral adrenal adenoma (n = 19), autonomus cortisol secretion and bilateral adenomas (n = 14) and autonomus cortisol secretion with bilateral macronodular hyperplasia (n = 11); primary hyperaldosteronism with unilateral aldosteroneproducing adrenal adenoma (n = 15) and bilateral hyperplasia (n = 19). The group of healthy subjects was a control group (n = 22). Family hyperaldosteronism and adrenocortical cancer were excluded. Patients’ urinary corticosteroid excretion and blood steroid levels were compared using the nonparametric Mann–Whitney test. RESULTS: Chromatographic methods have shown the presence of mineralocorticoid and glucocorticoid co-secretion in the patients with primary hyperaldosteronism: increased urine excretion of free cortisol 51 (27–90) ng/ml (p = 0.001) and its metabolite tetrahydrocortisol — 850 (720–994) μg/24 h (p = 0.0002) in the patients with Conn syndrome. As well as free cortisol 35 (32–72) µg/24 h (p = 0.002), tetrahydrocortisol — 1036 (490–1482) µg/24 h (p = 0.0049), 5α-tetrahydrocortisol — 1194 (411–1873) µg/24 h (p = 0.0048), 5α-tetrahydrocorticosterone — 339 (172–356) µg/24 h (p = 0.0008) in the patients with bilateral adrenal hyperplasia and hyperaldosteronism in comparison with the healthy persons. Glucocorticoid-mineralcorticoid activity was found among the patients with autonomous cortisol secretion and bilateral adrenal tumours: by increased levels of 18-hydroxycorticosterone in blood — 2.7 (1.3–3.5) ng/ml (p = 0.002). The patients with autonomous cortisol secretion and a single tumour had an increase of 18-hydroxycorticosterone in urine — 35 (33–55) µg/24 h (p = 0.0048) in comparison with the healthy subjects. The group of patients with corticotrophin-independent Cushing’s syndrome and unilateral corticosteroma was distinguished from the control group by high level of 18-hydroxycorticosterone in blood — 2.4 (1.0–4.3) ng/ml (p = 0.001) and urine — 42 (30–123) µg/24 h (p = 0.003). CONCLUSIONS: Mixed glucocorticoid and mineralocorticoid activity of adrenal cortical tumor cells was revealed among the patients with Cushing’s syndrome, with autonomous cortisol secretion and primary hyperaldosteronism using chromatographic methods.

The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes. A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020. The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9). Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

ABSTRACTPurpose: Adrenalectomy has the potential to cure or improve the control of hypertension in patients with primary hyperaldosteronism due to unilateral adrenal adenoma (Conn's syndrome). This study assesses the patients' perception of, and costs associated with, laparoscopic adrenalectomy for Conn's syndrome. Materials and Methods: Clinical, radiological, operative, and pathological data were collected on patients undergoing adrenalectomy for Conn's syndrome over 8-years period in a UK tertiary referral center. Results: Thirty-eight patients (17M:21F, age 34–79 yrs, median 54 yrs) operated between Jan2005-Sept2012 had lateralization based on CT scans (n = 30) and/or MRI scans (n = 18) and confirmed on selective adrenal venous sampling (n = 25). Laparoscopic adrenalectomy was performed in all patients, with two cases requiring conversion to open operation. Median operative time was 105 min (range: 27–315). Costs were estimated as £19k for preoperative investigations, £20k for in-hospital stay, £53k for operating theatre use and £29k for disposable surgical instruments, with average £3499/patient (national tariff for adrenalectomy in 2015/2016 £3624). Follow-up at a mean of 30 months postoperatively using a visual analogue scale and a standardized questionnaire showed significantly improved quality of life (QoL) post-operatively. Majority of patients (85%) reported taking none or fewer anti-hypertensive medications (median reduction of 2 antihypertensive drugs). All patients stated that they would definitely have the operation again in preference to anti-hypertensive medications and they would recommend the operation to friends/relatives. Conclusions: Laparoscopic adrenalectomy for Conn's syndrome has a positive impact on hypertension control, leads to improved QoL and its costs are covered in the NHS financial model.

Hypertension Editors' Picks: Hyperaldosteronism.

Misdiagnosis of Two Cases of Primary Aldosteronism Owing to Failure of Computed Tomography to Detect Adrenal Microadenoma

Bilateral adrenal neuroblastoma (NB) is rare and is mainly stage 4S. Its incidence, presenting features, management, and outcome have not been fully defined yet. We searched the Italian NB Registry (RINB) for stage 4S NB infants with bilateral adrenal primary tumor to compare them with stage 4S NB with unilateral tumor. Between 1979 and 2016, the RINB enrolled 3731 NB patients aged 0-18 years including 317 infants (8.5%) diagnosed with stage 4S NB. Eleven/317 (3.5%) had a bilateral adrenal primary tumor (Group 1) and 190/317 (59.9%) had a unilateral tumor (Group 2). Group 1 infants were significantly younger (51 vs. 89 days) but were comparable with Group 2 for any other presenting features. In the absence of specific protocols, upfront treatment was based on symptoms, size of adrenal tumors, and biology, and consisted of observation in 5 cases, radiotherapy in one, chemotherapy in 2, and surgery in 3. Five/11 developed progression and 2 of them, both with MYCN amplification, died. The 5-year EFS rates of Group 1 and 2 were 54.5% vs. 73.3% (P=.14) and 5-year OSs were 81.8% and 89.4%, respectively (P=.44). Our data support the hypothesis that 4S NB infants with bilateral adrenal tumors can have favorable outcome with personalized therapeutic approach. The three patients with MYCN amplified tumor benefited from upfront aggressive chemotherapy, in accordance with current protocols. Because of the rarity of this intriguing form of neuroblastoma, collaborative prospective studies are warranted, especially in view of gaining a better insight on its biological and genetic features.

In a patient with primary aldosteronism, in which the postural endocrine tests suggested the presence of an aldosteronoma rather than hyperplasia, bilateral adrenal tumours were found by computer tomography. Adrenal scintigraphy using 6-131I-iodomethyl-19-norcholesterol (NP59) during dexamethasone suppression showed early unilateral adrenal visualization on the left side. After removal of the left adrenal gland, which contained a 2 x 2 x 2 cm adenoma, the blood pressure and aldosterone levels returned to normal. A CT-scan, performed 1 year after the pre-operative CT-scan, showed no change in size of the right adrenal tumour, consistent with a non-functioning adenoma. In this patient, the NP59 scan adequately distinguished a non-functioning from an aldosterone-producing adrenal tumour.

Adrenal-preserving laparoscopic surgery in selected patients with bilateral adrenal tumors

Approximately 10% of cases of hypertension in Japan are caused by primary aldosteronism (PA), amounting to about 4 million patients in total. Primary aldosteronism due to unilateral aldosterone hypersecretion is potentially curable by adrenalectomy. The clinical benefits of identifying and treating PA have been reported internationally, but its cost-effectiveness is unclear. We examined whether diagnosing and treating hidden PA in hypertensive population was cost-effective compared with suboptimal treatment. Our hypothetical patient was a 50-year-old man diagnosed with stage I-III hypertension. We established a Markov decision model based on plausible clinical pathways and prognoses of PA. We applied cost-effectiveness analysis comparing a comprehensive diagnostic strategy for PA (measurement of plasma aldosterone/renin ratio, 2 loading tests, imaging, and selective adrenal venous sampling) with a suboptimal strategy to manage hypertension by medication unless the typical signs of PA or other complication were manifest. Outcome measures were expected costs, expected effectiveness, and incremental cost-effectiveness ratio. The robustness of the findings was established by one-way and scenario sensitivity analyses. The comprehensive PA diagnostic strategy increased the expected costs by 64 004 JPY and expected life-years by 0.013 compared with standard treatment. The incremental cost-effectiveness ratio for the diagnosis of PA was 4 923 385 JPY per year. Our findings were sensitive to the outcomes of screening and treatment, and the costs of continuous or periodic medication for hypertension and the treatment of stroke and its complications.

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.