Unilateral Secretion Research Articles

Impact of Cortisol-Cosecretion on Adrenal Venous Sampling Results in Primary Aldosteronism: Study of 225 Cases.

Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn's Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing's syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance.

Intraprocedural cortisol testing improves adrenal vein cannulation success and diagnostic accuracy in assessment of primary aldosteronism, in a medium throughput centre

Primary aldosteronism is the most common cause of secondary hypertension. Identifying individuals who have unilateral secretion from aldosterone secreting adenomas allows adrenalectomy. Surgical treatment when feasible may be superior to medical management with improved cardiovascular outcomes and reduced medication dependence. Adrenal vein sampling (AVS) is required to biochemically lateralise aldosterone secretion prior to adrenalectomy. However, diagnostic success of AVS is variable and can be poor even at tertiary centres; failure is largely due to unsuccessful adrenal vein cannulation. Intra-procedural rapid semiquantitative cortisol testing (RCT) identifies correct catheter placement in real time. We compared diagnostic success rates of AVS before and after the introduction of intraprocedural cortisol testing at the Royal Adelaide Hospital—a medium throughput tertiary centre (average 6.2 procedures a year over the last 8 years). We observed an increase in success rate from 63% to 94%. Intraprocedural cortisol testing also led to a net financial saving of ~$100 AUD per procedure. RCT is likely to be cost effective if pre-RCT success rate is less than 78%. Procedure time and number of samples collected, however, were increased with RCT. This suggests that intraprocedural cortisol testing will improve success in low to medium throughput centres and may make AVS feasible in less specialised centres.

Evaluation of Adrenal Vein Sampling Use and Outcomes in Patients With Primary Aldosteronism

BackgroundPrimary aldosteronism (PA) occurs in 10%-20% of patients with resistant hypertension. Guidelines recommend adrenal vein sampling (AVS) to identify patients for surgical management. We evaluate the use of AVS in managing PA to better understand the selection and outcomes of medical versus surgical treatment. MethodsA retrospective review was performed, and patients were divided into those who did (AVS) and did not have AVS (non-AVS). Demographics, aldosterone and renin levels, blood pressure, comorbidities, and antihypertensive medications were recorded. Reasons to defer AVS and medical versus surgical decision-making were examined and groups were compared. ResultsWe included 113 patients; 39.8% (45/113) had AVS, whereas 60.2% (68/113) did not. Groups were similar in age, body mass index, and initial systolic blood pressure (SBP).In patients who underwent AVS, 31 of 45 (68.9%) had unilateral secretion and were referred for surgery, whereas 13 of 45 (28.9%) had bilateral secretion. Of the 31 referred for surgery, 26 underwent laparoscopic adrenalectomy, all cured; four refused surgery; and one counseled toward medical management by their physician.In 68 non-AVS patients, 6 (8.8%) underwent adrenalectomy without sampling and 2 with no clinical improvement. The remaining deferrals were because of normal or bilateral adrenal nodules on imaging (8/68, 11.8%); medical management due to poor surgical candidacy (12/68, 17.6%); patient refusal of intervention (13/68, 19.1%); or reasons not stated (28/68, 41.1%). At the follow-up, patients who underwent AVS had lower median SBP (135.4 mmHg versus 144.7 mmHg, P = 0.0241) and shorter follow-up (17.7 mo versus 54.0 mo, P < 0.0001). Surgically managed patients had biochemical resolution of PA with normalization of potassium levels (3.6 to 4.7mEq/L, P < 0.00001). ConclusionsAVS correctly selects patients for surgical management avoiding unnecessary surgery. However, despite guidelines, AVS is not always pursued as part of PA treatment, potentially excluding surgical candidates.

Adrenal Venous Sampling for Assessment of Autonomous Cortisol Secretion.

Autonomous cortisol secretion (ACS) can be unilateral or bilateral irrespective of the presence of an adrenal tumor. A reliable method to distinguish between unilateral and bilateral ACS is lacking. Evaluate the use of adrenal venous sampling (AVS) to distinguish between unilateral and bilateral ACS. This was a prospective study of AVS in patients with adrenal tumors who received a diagnosis of ACS or adrenal Cushing syndrome (CS). Unilateral secretion was defined as >2.3-fold difference in cortisol levels between the two adrenal veins. Metanephrine levels were used to ascertain correct catheter position. Results were correlated with findings on CT and iodine-131-cholesterol scintigraphy. Thirty-nine patients underwent AVS; there were no complications. The procedure was inconclusive in six patients and repeated with success in one, giving a success rate of 85%, and leaving 34 procedures for evaluation (adrenal CS, n = 2; ACS, n = 32). Of 14 patients with bilateral tumors, 10 had bilateral and 4 had unilateral overproduction. Of 20 patients with unilateral tumors, 11 had lateralization to the side of the tumor and the remaining had bilateral secretion. Cholesterol scintigraphy findings were concordant with those of AVS in 13 of 18 cases (72%) and discordant in 5 (28%). Laterality of ACS does not always correspond to findings on CT images. AVS is a safe and valuable tool for differentiation between unilateral and bilateral cortisol secretion and should be considered when operative treatment of ACS is a possibility.

Technical Aspects of Adrenal Vein Sampling

The most common cause of secondary hypertension is primary aldosteronism, with a prevalence of approximately 30% when screened by specialized hypertension clinics. Adrenal venous sampling is considered the standard for reliably distinguishing between unilateral and bilateral hormone secretion, with unilateral secretion being surgically curable. Success of adrenal vein sampling relies on appropriate patient selection, patient preparation, and recognition and catheterization of both adrenal veins. However, this procedure may prove technically challenging, particularly for inexperienced operators. This video (see Fig; available online at www.jvir.org) is designed to provide the viewer with details on the technical aspects of adrenal vein sampling by using the sequential technique in an immersive format with real-time table-top teaching. Indications, patient preparation, equipment selection, technique, and quality assurance are reviewed in detail, with the goal of providing practitioners an opportunity to successfully incorporate this procedure into their practice.

Long-term follow up after adrenalectomy for primary hyperaldosteronism

Purpose: Primary hyperaldosteronism sub-types have a radically different management: adrenalectomy for adrenal aldosterone unilateral secretion and medical therapy for bilateral secretion. Our aim was to prove higher long term postoperative blood pressure (BP) in patients with histological defined hyperplasia compared to patients with histological adenoma. Methods: We retrospectively included patients with biological primary hyperaldosteronism, an unilateral nodule on computed tomography (CT) and who underwent adrenalectomy between 2005 to 2009. This was the period before using routinely adrenal venous sampling in our institution. We compared long-term postoperative BP between pre-operative suspected patients of unilateral secretion but with final histological diagnosis of adenoma (group 1) and those with hyperplasia (group 2). Results: 41 patients underwent adrenalectomy (mean age 53.9±12.2). Mean peripheral aldosterone/renin ratio was 229.4. 6 patients (15%) had adrenal hyperplasia as post-operative histological diagnosis (group 2). No difference was observed pre-operatively between the two groups in term of clinical and biological characteristics (mean BP group 1: 136.7±15.8 / 81.8±12.1 mmHg vs group 2: 137.5±9.6 / 85±5.8 mmHg; mean kalemia group 1: 2.9±0.5 mmol/l vs group 2: 3.0±0.5 mmol/l; p=NS). Nodule size on CT was higher in group 1 (18.9mm ±8.7; n=35) than in group 2 (11.7mm ±1.5; n=6) (p=0.05). Post-operative mean follow-up was 4.6 years. Long-term postoperative mean BP was higher in group 2 (137.0±14.8 / 87.0±17.2 mmHg) than in group 1 (127.2±7.4 / 76.1±7.8 mmHg) (p=0.03). Postoperative mean antihypertensive drug score was 0.6±0.7 in group 1 and 2.2±2.4 in group 2 (p=0.002). Long-term mean kalemia was similar in the two groups (group 1: 4.4±0.4 mmol/l vs group 2: 4.0±0.4 mmol/l; p=NS). Conclusions: Long term follow-up after adrenalectomy shows higher BP and antihypertensive drug score in patients with hyperplasia than patients with adenoma. This data confirm that nowadays adrenal venous sampling is essential before adrenal surgery whatever nodule size on CT to prove unilateral secretion.

Systematic Review: Diagnostic Procedures to Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism

Computed tomography (CT), magnetic resonance imaging (MRI), and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion as a cause of primary aldosteronism. This distinction is crucial because unilateral primary aldosteronism can be treated surgically, whereas bilateral primary aldosteronism should be treated medically. To determine the proportion of patients with primary aldosteronism whose CT or MRI results with regard to unilateral or bilateral adrenal abnormality agreed or did not agree with those of AVS. PubMed, MEDLINE, EMBASE, and Cochrane Library, 1977 to April 2009. Studies describing adults with primary aldosteronism who underwent CT/MRI and AVS were included. Of 472 initially identified studies, 38 met the selection criteria; extractable data were available for 950 patients. The CT/MRI result was considered accurate when AVS showed unilaterally increased aldosterone secretion on the same side as the abnormality seen on CT/MRI or when AVS showed symmetric aldosterone secretion and CT/MRI revealed bilateral or no unilateral abnormality. In 37.8% of patients (359 of 950), CT/MRI results did not agree with AVS results. If only CT/MRI results had been used to determine lateralization of an adrenal abnormality, inappropriate adrenalectomy would have occurred in 14.6% of patients (where AVS showed a bilateral problem), inappropriate exclusion from adrenalectomy would have occurred in 19.1% (where AVS showed unilateral secretion), and adrenalectomy on the wrong side would have occurred in 3.9% (where AVS showed aldosterone secretion on the opposite side). The lack of follow-up data in the included articles made it impossible to confirm that adrenalectomies were performed appropriately. When AVS is used as the criterion standard test for diagnosing laterality of aldosterone secretion in patients with primary aldosteronism, CT/MRI misdiagnosed the cause of primary aldosteronism in 37.8% of patients. Relying only on CT/MRI may lead to inappropriate treatment of patients with primary aldosteronism.

Diagnosis of Surgically-Treatable Forms of Primary Aldosteronism

Primary aldosteronism (PA) is a common form of endocrine hypertension in which aldosterone production is inappropriate and at least partially autonomous of the renin-angiotensin system. Recent studies using the plasma aldosterone/plasma renin activity (PRA) ratio (ARR) as a screening test for both hypokalaemic and normokalaemic hypertensives have reported a high prevalence of this disease, with PA accounting for up to 12% of hypertensive patients. Therefore, PA is considered the most common identifiable, specifically treatable and potentially curable form of hypertension. Of particular interest is the identification of the different subtypes of PA, since some of them benefit from surgical treatment, whereas others require medical treatment with mineralocorticoid receptor antagonists. Herein, we review the diagnostic strategies used to identify surgically-treatable forms of PA, i.e. those forms that display unilateral secretion of aldosterone and benefit from unilateral adrenalectomy. In particular, we compare the different imaging strategies, the role of hormonal tests and the indication and interpretation of adrenal venous sampling. Keywords: mineralocorticoid hypertension, mineralocorticoid receptor, ACTH, Adrenal Imaging, computed tomography, Ancillary Hormonal Tests, 18hydroxycorticosterone, Adrenal Venous Sampling (AVS)

Adrenal Vein Sampling: How to Make It Quick, Easy, and Successful

Adrenal vein sampling has a reputation as a difficult procedure. However, it is being performed more frequently at some institutions due to the realization that primary aldosteronism is more common than previously believed. At the author's institution, adrenal vein sampling with computed tomographic (CT) and laboratory correlation has been performed more than 800 times in the past 10 years. Adrenal vein sampling is used to determine whether autonomous hormone production is unilateral or bilateral; unilateral secretion can be treated with surgery. The venous drainage of each adrenal gland is predominantly via a central vein. Recognition of the right adrenal vein is the crux of adrenal vein sampling. CT is useful in planning adrenal vein sampling by demonstrating the anatomy and positions of the adrenal veins. A small amount of contrast material is injected gently and slowly into the adrenal vein; it is not necessary to perform formal venography to outline the entire gland. To confirm that the vein is draining the majority of adrenal cortical blood, the adrenal vein sample should have a significantly higher level of cortisol than a peripheral sample. Adrenal glands that are producing aldosterone demonstrate an aldosterone-cortisol ratio that is higher than the peripheral value.

Surgical approach to nipple discharge: a ten-year experience.

The actual relationship between malignancy and secreting breast has not yet been extensively verified, mainly in patients with nipple discharge but without evidence of a breast lump. This study was carried out in 1,251 consecutive patients to evaluate the reliability of cytology combined with galactography in order to assess the relationship of malignant and premalignant lesions with discharge without the presence of a breast lump. Those patients with bilateral discharge were approached endocrinologically, whereas the patients (433) with unilateral secretion were evaluated by cytology, mammography, fine needle biopsy, and galactography. Of 194 patients without a breast lump, 94 with positive cytology were surgically treated after mammogalactography. Surgical treatment included ductgalactophorectomy in 53, segmentectomy in 23, microdochectomy in 13, and mastectomy in 5 patients. Pathologic findings showed a solitary papilloma in 49 cases, minimal breast cancer in 20, fibrocystic disease in 11, papillomatosis in 7, lobular cancer in 5, and, finally, a duct ectasia in 2. In the patients with secreting breast but without lump, cytological analysis in addition to galactography seems to be useful in identifying minimal breast cancer and in detecting premalignant lesions like papillomatosis.

Surgical approach to nipple discharge: A ten-year experience

The actual relationship between malignancy and secreting breast has not yet been extensively verified, mainly in patients with nipple discharge but without evidence of a breast lump. This study was carried out in 1,251 consecutive patients to evaluate the reliability of cytology combined with galactography in order to assess the relationship of malignant and premalignant lesions with discharge without the presence of a breast lump.Those patients with bilateral discharge were approached endocrinologically, whereas the patients (433) with unilateral secretion were evaluated by cytology, mammography, fine needle biopsy, and galactography. Of 194 patients without a breast lump, 94 with positive cytology were surgically treated after mammogalactography. Surgical treatment included ductgalactophorectomy in 53, segmentectomy in 23, microdochectomy in 13, and mastectomy in 5 patients.Pathologic findings showed a solitary papilloma in 49 cases, minimal breast cancer in 20, fibrocystic disease in 11, papillomatosis in 7, lobular cancer in 5, and, finally, a duct ectasia in 2.In the patients with secreting breast but without lump, cytological analysis in addition to galactography seems to be useful in identifying minimal breast cancer and in detecting premalignant lesions like papillomatosis.

Apparent Left Ventricular Aneurysm Due to Unilateral Secretion of Tc-99m Pertechnetate in a Nursing Mother with Breast Cancer

Apparent Left Ventricular Aneurysm Due to Unilateral Secretion of Tc-99m Pertechnetate in a Nursing Mother with Breast Cancer

Plasma noradrenaline and dopamine in renin‐mediated hypertension

Noradrenaline (NA) and dopamine (DA) have opposite effects on the kidney; NA causes vasoconstriction and increased sodium reabsorption while DA promotes vasodilation and natriuresis. In 15 patients investigated for renin-mediated hypertension measurements of plasma renin activity (PRA), NA and DA concentrations were made in arterial and renal venous blood from both kidneys before and after acute stimulation of renin release by i.v. dihydralazine. Nine patients had unilateral renin secretion and were classified as renin-positive, while the remaining six patients were renin-negative. Renin-positive patients had higher arterial and renal venous PRA, NA and DA levels than the negative ones. In the renin-positive group V-A differences for NA and DA were present on both sides despite unilateral secretion of renin. NA but not DA levels were higher in the renin-secreting kidney, which can partly be explained by the reduced plasma flow to the involved kidney. After dihydralazine the arterial NA and DA rose similarly in renin-positive and renin-negative patients, while PRA rose only in the renin-positive cases. In the renin-positive patients where stimulation of renin secretion caused a marked increase of the PRA gradient on the affected side only, renal gradients for NA and DA increased bilaterally. The increase in DA was more pronounced than that of NA yielding a rise in DA/NA ratio on the affected side. Arterial PRA was positively correlated to the plasma concentrations of NA and DA. V-A differences for PRA and NA or DA were positively correlated on the involved renin-secreting side. In summary, patients with renin-dependent hypertension have elevated plasma NA and DA concentrations. Stimulation of renin release by dihydralazine increases the DA/NA ratio in arterial and renal venous blood indicating release of 'precursor dopamine' from noradrenergic fibres and/or activation of dopaminergic nerves. There seems to be a relationship between renal nerve activity and renin release in renin-dependent hypertension.

Human Chorionic Gonadotropin β-Subunit in Human Semen

The level of human seminal chorionic gonadotropin beta-subunit (hCG beta) was determined by radioimmunoassay (RIA). The mean hCG beta level in 34 normal men was 3.7 +/- 1.6 ng/ml, which was much higher than that in serum. The mean hCG beta level for 20 patients with mild oligozoospermia (20-39 x 10(6) sperm/ml) was 2.5 +/- 0.8 ng/ml, that for 34 patients with severe oligozoospermia (1-19 x 10(6) sperm/ml) was 1.7 +/- 0.5 ng/ml, and that for 21 azoospermia was 1.5 +/- 0.6 ng/ml. Thus, the decrease of sperm count was correlated with the decrease of hCG beta. In 17 cases to which testicular biopsy was applied together with sperm counting, the seminal hCG beta level was found to positively correlate with the germinal cell index (the ratio germinal cell count/Sertoli cell count) and with the testicular volume. The level of seminal hCG beta was also found to correlate negatively with the levels of seminal LH and FSH and positively with the level of seminal testosterone. These findings suggest that the production of seminal hCG beta is a process of spermatogenesis and closely related to spermatogenesis. The level of hCG beta in serum was too low to detect, and no relation to that in seminal plasma could be investigated. However, in 6 cases with testicular tumor, the hCG beta level in serum was high, whereas that in seminal plasma was rather low probably because of unilateral secretion. Enhanced production of hCG beta by tumor tissues and the destruction of the blood-testis barrier by proliferation of tumor cells seemed to be one of the causes of this high hCG beta level in serum. The hCG beta levels in 13 vasectomized seminal plasma and the prostatic fluid samples collected from 3 normal men were 1.5 ng/ml, which was similar to those in azoospermic patients. These findings suggest that the seminal hCG beta level consists of the hCG beta secreted by the testis and about 1.5 ng/ml of hCG beta from the prostate. Based on these results, seminal hCG beta is thought to be secreted by the prostate and the process of spermatogenesis and the value of seminal hCG beta may serve as an effective index for the testicular function.

Unilateral Secretion of Tears in Facial Paralysis

Unilateral Secretion of Tears in Facial Paralysis