Conn's Adenoma Research Articles

Adrenal lesions do matter in the course of primary aldosteronism: a comparative analysis of Conn's adenoma vs bilateral adrenal hyperplasia

Adrenal lesions do matter in the course of primary aldosteronism: a comparative analysis of Conn's adenoma vs bilateral adrenal hyperplasia

Adrenal Venous Sampling Could Be Omitted before Surgery in Patients with Conn's Adenoma Confirmed by Computed Tomography and Higher Normal Aldosterone Concentration after Saline Infusion Test.

Purpose: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. Methods: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). Results: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. Conclusions: AVS could be omitted before surgery in patients with typical Conn´s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT.

THE EXPLORATION OF THE RENINE ANGIOTENSIN SYSTEM IN NEPHROLOGY: EXPERIENCE OF THE NEPHROLOGY DEPARTMENT OF THE HEDI CHAKER UNIVERSITY HOSPITAL CENTER OF SFAX

Objective: Plasma renin and aldosterone assays are useful in clinical practice for the aetiological assessment of arterial hypertension (hypertension) and / or a disturbance of the electrolyte balance. The objective of our work is to describe the main indications exploration of the renin aldosterone system, its results, its diagnostic and etiological impact. Design and method: We conducted a retrospective study of 40 patients who received a renin / aldosterone dosage, collected in the Nephrology department at the Hédi Chaker CHU in Sfax for a period of 6 years from January 2014 until December 2020. Results: These are 21 women and 19 men with a sex ratio of 1.1. Hypertension was present in 82.5% of cases. The dosage indication was: hypertension with hypokalaemia in 52.5%, hypertension in young subjects in 20%, resistant hypertension and hypertension with incidentaloma in each 7, 5% of cases, and incidentaloma without HTA in each 5% of cases and in one case hypokalaemia without HTA. Aldosterone was elevated in 52.5% of cases. Renin was normal in 67.5% of cases, low in 25% and high in 7.5% of cases. The aldosterone / renin ratio was normal in 60% of cases, elevated, decreased and invalid in respectively 27.5%, 2.5% and 10%. The etiological investigation revealed: primary hyperaldosteronism in 42.5% of cases secondary to a Conn adenoma in 20% of cases, to adrenal hyperplasia in 17.5% of cases and with normal imaging in 5% of cases. Secondary hyperaldosteronism was confirmed in association with Liddle syndrome and renal artery stenosis in 2.5% of cases each. The other etiologies were pheochromocytoma in 12.5% of cases, Takayusu’s disease, tubulopathy in 2.5% of cases each. The dosage was non-contributory in 7.5% of cases and normal in 25% of cases. Conclusions: The exploration of the renin angiotensin aldosterone system has several indications, mainly in hypertension with hypokalaemia. It can help make the etiological diagnosis and guide therapeutic management.

Minimally invasive treatment of conn's adenoma: real world cases in tertiary oncology center

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

ARTERIAL HYPERTENSION IN A PATIENT OPERATED FOR CONN ADENOMA: ABOUT A CASE

Objective: Conn's adenoma is a rare cause of high blood pressurr. It is the second surgically curable cause of hypertension after renal artery stenosis. Its recurrence after surgery remains rare. Design and method: We report a case. Results: Mr B.M, 60 years old, with a history of diabetes, hypertensive and right adrenalectomy for Conn's adenoma, admitted for investigation of dysphagia and high blood pressure. On examination, the blood pressure was 17/10, the pulses are present and symmetrical. Skin examination revealed sclerodactyly, subcutaneous calcinosis and raynaud's syndrome. The blood ionogram showed hypokalaemia while the renal workup noted chronic renal failure. Urinary cortisol and plasma cortisol were normal. The adrenal CT scan showed a left adrenal nodule. A contralateral recurrence of Conn's adenoma associated with CREST syndrome was strongly suspected. The decision was to intensify the antihypertensive treatment. Conclusions: Hypertension can be multifactorial: metabolic syndrome, Conn's adenoma and systemic disorder. A recurrence of an operated Conn's adenoma should be systematically sought in the presence of persistent elevated blood pressure levels.

MANAGEMENT OF PRIMARY HYPERADOSTERONISM : DON'T WAIT UNTIL IT'S TOO LATE

Introduction: Arterial hypertension by primary hyperaldosteronism is the most frequent cause of endocrine hypertension. It is responsible for 10% of endocrine arterial hypertension. In our context, there is a delay in the diagnosis of primary hyperaldosteronism because it is under traked and also because of the high cost of check-ups. The aim of our study is to highlight the challenges in the management of these patients. This observational study i Material And Method: ncludes patients admitted at the department of endocrinology of Sheikh Khalifa Ibn Zayd universitary hospital for primary aldosteronism between January 2019 and January 2021. Primary hyperaldosteronism was dened according to the Consensus on Primary Hyperaldosteronism of The French Society of Endocrinology (SFE), in collaboration with the French Society of Hypertension (SFHTA) and the French Association of Endocrine Surgery (AFCE). For all patients, we collected demographic characteristics, familial history of hypertension and cardiovascular diseases, patient's history of hypertension and its complications. We performed biological assessments and imaging investigations. We included 10 patients .The mean age of patients Results: was 42.5 years (+/-12.06). 7/10 of patients was males. We found a family history of hypertension in 7/10 of the cases . The mean age of onset of arterial hypertension was 36.4 years (+/-7,87) . Grade 3-hypertension was found in 4/10 of the cases. Hypokalemia was found in 6/10 of the cases. The etiological investigation found bilateral adrenal hyperplasia in 4/10 of the cases. Among them 5/10 have performed catheterization of the adrenal veins, which revealed lateralization of aldosterone secretion. Conn's adenoma was found in 4/10 of the cases and unilateral adrenal hyperplasia in 2/10 of the cases. Our study illustrate the value of screening for Conclusion: primary hyperaldosteronism in young subjects with severe hypertension associated with hypokalemia and also given the curable and reversible nature of hypertension.

Hypertension is not always cured after unilateral adrenalectomy in patients with endocrine secondary hypertension

It is commonly accepted that adrenalectomy cures hypertension in secondary endocrine hypertensions. The purpose of this study was to evaluate the percentage of cure of hypertension after adrenal surgery in three causes of endocrine hypertension: Conn's adenoma, pheochromocytoma and cortisolic adenoma. Patients with hypertension with a radiological and hormonal check-up confirming the diagnosis of endocrine hypertension by Conn's adenoma (55 cases), pheochromocytoma (39 cases) or cortisolic adenoma (15 cases) have had unilateral adrenal surgery. Before the surgery, patients were treated with anti-anhypertensive drugs specific to each cause allowing the control of blood pressure in home blood pressure monitoring in 89% of subjects. In the 3 months following surgery, blood pressure was reassessed by home monitoring after stopping antihypertensive drugs. Healing of hypertension was observed in 69% of pheochromocytomas, 60% of Conn's adenomas and 40% of cortisolic adenomas. In subjects with Conn's adenoma the healing characteristics are: age less than 40 years, female sex, normalization of blood pressure before surgery with spironolactone treatment and normality of the opposite adrenal gland on CT. For pheochromocytoma, parameters linked with hypertension healing were normalization of blood pressure before surgery with specific medical treatment and age less than 40 years. For cortisol adenoma, young age at surgery is also linked with healing hypertension. This work indicates that in secondary hypertensions, adrenal surgery does not achieve a cure in all patients in the months following surgery. The characteristics that predict the cure of hypertension are the effectiveness of medical treatment before surgery, and a patient's age of less than 40 years.

Endocrine hypertension in an internal medicine department

Endocrine arterial hypertension (HT) is rare; its overall prevalence does not exceed 4% of hypertensive patients. Research interest in endocrine HT is due to the severity of some life-threatening, potentially curable and reversible forms of HT. We aimed to determine the clinical, paraclinical, etiological and therapeutic profile of secondary endocrine HT in patients treated in our department of internal medicine. Twenty-seven patients were diagnosed with endocrine HT; 11 males and 16 females, mean age 42 years old. HT duration ranged from one month to 24 years. 13 cases of neuroendocrine tumors were diagnosed: 11 pheochromocytoma and 2 para-ganglioma. Patients with neuroendocrine tumors had the classic triad of diaphoresis, headache and palpitation associated with cathecholamine/metanephrine excess. The tumor was localized by magnetic resonance or 123 I–MIBG imaging and the diagnosis was confirmed by pathological examination after surgery. We diagnosed 6 cases of Conn adenoma, 5 cortical carcinomas, 1 pulmonary cancer's adrenal metastasis, 1 adrenal hyperplasia and 1 hyperaldosteronism secondary to treatment with Ergoloid. The diagnosis was confirmed by hormone dosage evidencing elevated plasma aldosterone levels and decreased plasma renin activity in cases of Conn adenoma and adrenal hyperplasia, hyper-cortisolemia in cases of cortical adenoma, cortical carcinoma and pulmonary cancer's adrenal metastasis. The tumor was localized by CT scan and the diagnosis was confirmed by pathological examination after surgery. Blood pressure normalization was found among 16 patients after surgery. Endocrine HT has many etiologies possibly responsible for high morbidity and mortality, especially when not properly diagnosed or treated. The potentially curable nature of endocrine HT in more than two thirds of cases, demonstrates the importance of early diagnosis of every severe HT resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

ENDOCRINE HYPERTENSION (HYPERTENSION) IN A DEPARTMENT OF INTERNAL MEDICINE

Objective: The aim of our study was to determine the clinical, paraclinical, etiological and therapeutic profile of secondary HTA of endocrine origin in patients treated in internal medecine department at the University Hospital Sahloul in Tunisia. Design and method: This study investigated various clinicalpathological factors of 27 patients who were diagnosed with endocrine HTA in patients hospitalized in internal medecine department at the University Hospital Sahloul in Tunisia. Results: There were 11 male and 16 female patients. The mean age was 42 years. HTA's average duration of evolution ranged from one month to 24 years. There were 13 cases of neuroendocrine tumors: 11 cases of pheochromocytoma and 2 cases of paraganglioma. Patients with Neuroendocrine tumors had the classic triad of diaphoresis, headache and palpitation associated with cathecholamine/metanephrine excess. The tumor was localized by magnetic resonance imaging(MRI) or 123 I –MIBG imaging and the diagnosis was confirmed by pathological examination after surgery. We have found 6 cases of Conn adenoma, 5 cases of cortical carcinoma, one case of pulmonary cancer's adrenal metastasis, one case of adrenal hyperplasia and one case of hyperaldosteronism secondary to treatment with Ergoloid. The diagnosis was confirmed by hormone dosage which showed elevated plasma aldosterone levels and decreased plasma renin activity in cases of Conn adenoma and adrenal hyperplasia, hypercortisolemia in cases of cortical adenoma, cortical carcinoma and pulmonary cancer's adrenal metastasis. The tumor was localized by CT scann and the diagnosis was confirmed by pathological examination after surgery. Blood pressure normalization was found among16 patients after surgery. Conclusions: HTA of endocrine origin has many etiology witch could have high morbidity and mortality, especially when not properly diagnosed or treated. The potentially curable nature of HTA in more than two thirds of cases, demostrates the importance of early diagnosis of each severe HTA resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

Evaluation of Biochemical Conditions Allowing Bypass of Confirmatory Testing in The Workup of Primary Aldosteronism: A Retrospective Study in a French Hypertensive Population.

The diagnostic workup for primary aldosteronism includes a screening step using the aldosterone-to-renin ratio (ARR) and a confirmatory step based on dynamic testing of aldosterone secretion autonomy. International guidelines suggest that precise clinical and biochemical conditions may allow the bypassing of the confirmatory step, however, data which validate hormone thresholds defining such conditions are lacking. At our tertiary center, we retrospectively examined a cohort of 173 hypertensive patients screened for PA by the ARR, of whom 120 had positive screening and passed a saline infusion test (SIT) or a captopril challenge test (CCT). Fifty-nine had PA, including 34 Conn adenomas and 25 with idiopathic aldosteronism (IA). Using a threshold of 160 pmol/l, post-SIT plasma aldosterone concentration (PAC) identified PA with 86.4% sensitivity, 94.7% specificity, and a negative predictive value of 92.3%. Of those subjects with a high ARR and a PAC above 550 pmol/l, 93% had a positive SIT, while 100% of subjects with a high ARR, but a PAC under 240 pmol/l had a negative SIT. Our results thus validate the biochemical conditions defined in the French and US guidelines for bypassing the confirmatory step in the workup for PA diagnosis.

Molecular genetics of Conn adenomas in the era of exome analysis

Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism (PA), the most common form of secondary hypertension. Exome analysis of APA has allowed the identification of recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3in more than 50% of sporadic cases. These gain of function mutations in ion channels and pumps lead to increased and autonomous aldosterone production. In addition, somatic CTNNB1mutations have also been identified in APA. The CTNNB1mutations were also identified in cortisol-producing adenomas and adrenal cancer, but their role in APA development and the mechanisms specifying the hormonal production or the malignant phenotype remain unknown. The role of the somatic mutations in the regulation of aldosterone production is well understood, while the impact of these mutations on cell proliferation remains to be established. Furthermore, the sequence of events leading to APA formation is currently the focus of many studies. There is evidence for a two-hit model where the somatic mutations are second hits occurring in a previously remodeled adrenal cortex. On the other hand, the APA-driver mutations were also identified in aldosterone-producing cell clusters (APCC) in normal adrenals, suggesting that these structures may represent precursors for APA development. As PA due to APA can be cured by surgical removal of the affected adrenal gland, the identification of the underlying genetic abnormalities by novel biomarkers could improve diagnostic and therapeutic approaches of the disease. In this context, recent data on steroid profiling in peripheral venous samples of APA patients and on new drugs capable of inhibiting mutated potassium channels provide promising preliminary data with potential for translation into clinical care.

How can cortisol-normalized adrenal venous sampling miss some Conn's adenoma

How can cortisol-normalized adrenal venous sampling miss some Conn's adenoma

Genetics of tumors of the adrenal cortex.

This review describes the molecular alterations observed in the various types of tumors of the adrenal cortex, excluding Conn adenomas, especially the alterations identified by genomic approaches these last five years. Two main forms of bilateral adrenocortical tumors can be distinguished according to size and aspect of the nodules: primary pigmented nodular adrenal disease (PPNAD), which can be sporadic or part of Carney complex and primary bilateral macro nodular adrenal hyperplasia (PBMAH). The bilateral nature of the tumors suggests the existence of an underlying genetic predisposition. PPNAD and Carney complex are mainly due to germline-inactivating mutations of PRKAR1A, coding for a regulatory subunit of PKA, whereas PBMAH genetic seems more complex. However, genome-wide approaches allowed the identification of a new tumor suppressor gene, ARMC5, whose germline alteration could be responsible for at least 25% of PBMAH cases. Unilateral adrenocortical tumors are more frequent, mostly adenomas. The Wnt/beta-catenin pathway can be activated in both benign and malignant tumors by CTNNB1 mutations and by ZNRF3 inactivation in adrenal cancer (ACC). Some other signaling pathways are more specific of the tumor dignity. Thus, somatic mutations of cAMP/PKA pathway genes, mainly PRKACA, coding for the catalytic alpha-subunit of PKA, are found in cortisol-secreting adenomas, whereas IGF-II overexpression and alterations of p53 signaling pathway are observed in ACC. Genome-wide approaches including transcriptome, SNP, methylome and miRome analysis have identified new genetic and epigenetic alterations and the further clustering of ACC in subgroups associated with different prognosis, allowing the development of new prognosis markers.

Lipofuscin Accumulation in Cortisol-Producing Adenomas With and Without PRKACA Mutations.

The adrenal cortex accumulates lipofuscin granules with age. Lipofuscin accumulation is also seen in adrenocortical tumors associated with Cushing syndrome (CS), particularly those with PRKAR1A mutations, such as in primary pigmented nodular adrenocortical disease (PPNAD). We investigated the presence of lipofuscin in cortisol-producing adenomas (CPAs) responsible for CS with and without the PRKACA (pLeu206Arg) somatic mutation. Ten paraffin-embedded sections of CPAs from cases with overt CS with (n=4) and without (n=6) a PRKACA mutation were microscopically examined through three detection methods, the hematoxylin-Eosin (H & E) staining, the Fontana Masson (FM) staining using light microscopy, and lipofuscin autofluorescence, using confocal laser scanning microscopy (CLSM). Sections were examined quantitatively according to the intensity of the pigmentation, as well as qualitatively based on the total number of granular pigments at all visual fields per tissue slide. Tissues from CPAs were compared to peritumoral adjacent tissues (n=5), to Conn adenomas (n=4), and PPNAD (n=3). CPAs had significantly higher number of lipofuscin-pigment granules compared to peritumoral adrenal tissue and Conn adenomas (46.9±9.5 vs. 3.8±4.8, p=0.0001). The presence of the PRKACA mutation did not increase the chances of pigmentation in the form of lipofuscin granules within CPAs associated with CS. Thus, all CPAs leading to CS accumulate lipofuscin, which presents like pigmentation sometimes seen macroscopically but always detected microscopically. PPNAD caused by PRKAR1A mutations is the best known adrenal lesion leading to CS associated with intense lipofuscin pigmentation and this was confirmed here; CPAs harboring PRKACA mutations did not have statistically significantly more pigmentation than CPAs without mutation, but a larger study might have shown a difference.

Posterior retroperitonoscopic adrenalectomy; a back door access with an unusually rapid learning curve.

Posterior retroperitonoscopic adrenalectomy (PRA) has become a standard approach to the adrenal gland. The aim of this study was to report an initial experience with the procedure following a proper preparatory phase highlighting the rapidity, safety and effectiveness by which it could be introduced into a surgeon's practice. Between May 2015 and July 2016, 14 PRAs were performed in 14 patients (9 females and 5 males). The average age was 46years, BMI: 25.5kg/m2, and ASA score: 2. Indications included: incidenatloma (n=5), Conn's adenoma (n=5), and Cushing's adenoma (n=4). Lesions were on average 3.3cm in size. Outcomes of interest included: operative time (OT), conversion rate, postoperative morbidity and mortality rates, and the length of hospital stay. Mean OT was 87.5min (range 35-150min). A significant reduction in OT occurred after the sixth procedure and was progressive thereafter. After the tenth case, the OT became less than 1h. No conversion was required. No intra- or post-operative complications occurred, and mortality was zero. All patients commenced oral intake and ambulated following full recovery from anesthesia. The mean length of hospital stay was 3days (range 2-6days). PRA offers a direct access to the adrenal gland allowing for target-oriented dissection. Cognitive reorientation to the anatomy of this back door access and an adequate learning curve could be rapidly achieved by experienced and properly prepared laparoscopic surgeons.

325 - Predictive factors of hypertension persistence after adrenalectomy in Conn adenoma

325 - Predictive factors of hypertension persistence after adrenalectomy in Conn adenoma

Adrenal Molecular Imaging.

The major workload in the field of adrenal imaging comprises patients with adrenal tumors incidentally depicted by imaging performed for other reasons than adrenal disease. These so-called 'incidentalomas' are generally managed by CT and MRI, and molecular imaging techniques are required only for a few patients. PET/CT with 18F-fluorodeoxyglucose (18F-FDG) is useful for establishing whether an adrenal metastasis is the only lesion, and therefore is available for surgical resection, or if the disease is disseminated. 18F-FDG PET/CT may be applied to differ benign from malignant incidentalomas and can be helpful in the imaging of pheochromocytoma and adrenocortical cancer (ACC). 11C-metomidate PET/CT can differentiate adrenocortical from nonadrenocortical tumors and a suspected ACC may be characterized and staged before surgery. 11C-metomidate PET/CT is currently also used to help diagnose Conn's adenomas in primary aldosteronism, but further development is needed. Scintigraphy with 123I/131I-metaiodobenzylguanidine (MIBG) remains the mainstay for molecular imaging of pheochromocytoma and is mandatory in patients for whom 131I-MIBG therapy is considered. A PET tracer for the imaging of pheochromocytoma is the norepinephrine analogue (11)C-hydroxyephedrine that can be used to characterize equivocal lesions and for the follow-up and diagnosis of recurrent malignant disease. Other specialized PET tracers for the imaging of pheochromocytoma are 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluorodopamine.

P-161: Conn adenoma revealed by malignant hypertension

Objectifs L’hyperaldosteronisme primaire (HAP) est l’une des causes les plus frequentes d’hypertension arterielle (HTA) secondaire. Elle doit etre systematiquement evoquee devant toute HTA avec hypokaliemie. L’HTA maligne est rare au cours de l’HAP et souvent elle complique une HTA essentielle meconnue ou sous traitee. Methodes Nous allons rapporter un cas pour illustrer ce sujet. Resultats Nous rapportons l’observation d’un jeune patient âge de 31 ans sans antecedents notables, admis pour exploration d’une HTA maligne avec une PAS a 25 cmHg et une PAD a 12 cmHg et un retentissement visceral avec un œdeme papillaire, une cardiomyopathie hypertensive a fonction systolique conservee et une insuffisance renale avec une clairance a 53 ml/min. A la biologie : une hypokaliemie a 3,4 mmom/l avec une kaliurese elevee 40 mmol/24h. Devant l’urgence therapeutique, un traitement par nicardipine par voie IV a ete initie avec une stabilisation de la TA. Devant le jeune âge, l’absence d’ATCD familiaux d’HTA et l’HTA d’emblee severe, une cause secondaire a ete evoquee. Une stenose de l’artere renale a ete eliminee par une echographie doppler des arteres renales normale ainsi que le pheochromocytome par un dosage des derives methoxyles des catecholamines. Le reste du bilan hormonal a mis en evidence une hyperaldosteronemie avec un rapport aldosterone / renine superieur a 23 confirmant le diagnostic d’HAP. Le diagnostic d’adenome de Conn a ete par la suite retenu sur la presence d’un nodule de 8 mm de la surrenale gauche au scanner. Devant ces donnees le patient a ete opere avec la decouverte en peroperatoire d’un adenome de la surrenale gauche qui a ete reseque. L’evolution a ete marquee par la stabilisation de la TA sous un seul traitement antihypertenseur (arret des 2 antihy-pertenseurs). Conclusion L’HTA maligne au cours de l’adenome de Conn est rarement rapportee. Il est aussi important de faire la difference entre l’HAP et l’hyperaldosteronisme secondaire souvent retrouve dans le cas de l’HTA maligne. Ceci est du a une hyperactivite du systeme renine-angiotensine-aldosterone. Le mecanisme physiopathologique exact de cette HTA maligne au cours de l’HAP reste inexplicable devant les rares cas rapportes dans la litterature. Pour reconforter ce diagnostic, la bonne evolution apres traitement chirurgical est souvent constatee comme c’est le cas de notre patient.

Copy number variations alter methylation and parallel IGF2 overexpression in adrenal tumors.

Overexpression of insulin growth factor 2 (IGF2) is a hallmark of adrenocortical carcinomas and pheochromocytomas. Previous studies investigating the IGF2/H19 locus have mainly focused on a single molecular level such as genomic alterations or altered DNA methylation levels and the causal changes underlying IGF2 overexpression are still not fully established. In the current study, we analyzed 62 tumors of the adrenal gland from patients with Conn's adenoma (CA, n=12), pheochromocytomas (PCC, n=10), adrenocortical benign tumors (ACBT, n=20), and adrenocortical carcinomas (ACC, n=20). Gene expression, somatic copy number variation of chr11p15.5, and DNA methylation status of three differential methylated regions of the IGF2/H19 locus including the H19 imprinting control region were integratively analyzed. IGF2 overexpression was found in 85% of the ACCs and 100% of the PCCs compared to 23% observed in CAs and ACBTs. Copy number aberrations of chr11p15.5 were abundant in both PCCs and ACCs but while PCCs retained a diploid state, ACCs were frequently tetraploid (7/19). Loss of either a single allele or loss of two alleles of the same parental origin in tetraploid samples resulted in a uniparental disomy-like genotype. These copy number changes correlated with hypermethylation of the H19 ICR suggesting that the lost alleles were the unmethylated maternal alleles. Our data provide conclusive evidence that loss of the maternal allele correlates with IGF2 overexpression in adrenal tumors and that hypermethylation of the H19 ICR is a consequence thereof.

Nuclear imaging in the diagnosis of primary aldosteronism.

Purpose of reviewPrimary aldosteronism is increasingly recognized as a common secondary cause of hypertension. Successful demonstration of a unilateral cause (e.g. a classical ‘Conn's adenoma’) offers the potential for curative adrenalectomy. Adrenal vein sampling (AVS), in conjunction with cross-sectional imaging, remains the ‘gold standard’ for distinguishing unilateral and bilateral disease, but is technically demanding and frequently unsuccessful or inconclusive. As such, alternative strategies for lateralization, including nuclear medicine techniques, are being developed and brought into clinical practice.Recent findingsMetomidate, a potent ligand of CYP11B1 and CYP11B2, can be C11H3-labelled as a PET tracer and has been shown to offer a rapid noninvasive alternative to AVS for localizing unilateral aldosterone-producing adenomas.SummaryIncreasing experience with 11C-metomidate PET-CT supports its use as an adjunct to AVS when this has failed, is ambiguous, or cannot be undertaken.