Adrenal venous sampling in primary aldosteronism: lessons from over 600 single-operator procedures.

Adrenal vein sampling (AVS) is a recommended if not required final diagnostic step in the investigation of primary aldosteronism, the most common cause of remediable secondary hypertension. Successful adrenal vein sampling is operator-dependent. Having performed over 600 such procedures at our centre over 20 years, our single-operator experience is described in detail for the purpose of training future radiologists as well as for use by those who are planning to start an AVS programme of their own. This updated review considers new developments in primary aldosteronism disease understanding that are relevant for AVS performance and protocols, along with technical enhancements that may be used for special cases. Detailed understanding of variant anatomy and tips for successful cannulation are keys to success, along with an endocrinology and clinical chemistry partnership for continuous quality control. A successful AVS programme offers patients a hope for cure of resistant hypertension.

Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood.

PURPOSE: Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. METHODS: Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. RESULTS: The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. CONCLUSIONS: GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. IMPLICATIONS FOR CANCER SURVIVORS: GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

Pharmacotherapy decisions among postmenopausal women attending a group medical consultation or a one-on-one specialist consultation at an osteoporosis center: an observational cohort study.

Group medical visits for osteoporosis can improve access to care while being highly accepted by patients. In this study, a similar proportion of women planned to initiate pharmacotherapy after attending a group or traditional one-on-one osteoporosis consultation, indicating that the group consultation model does not produce unexpected treatment decisions. INTRODUCTION: Group medical consultations for osteoporosis are time-efficient and highly accepted by patients, but effects on treatment decisions are unknown. We aimed to compare women's decisions to initiate or decline osteoporosis pharmacotherapy after attending either a group or transitional one-on-one osteoporosis consultation. METHODS: In this observational study, we prospectively evaluated postmenopausal women referred to an osteoporosis clinic who attended a group medical visit and compared their decisions regarding pharmacologic osteoporosis treatment with retrospective data from a cohort of women who attended a traditional consultation. Both consultation types involved interaction with a specialist physician, individualized fracture risk estimation (using FRAX®), and education regarding fracture consequences and available osteoporosis medications. Both forms of consultation emphasized shared decision-making; however, group consultation attendees did not receive personalized treatment recommendations from the physician. RESULTS: We reviewed the records of 125 women (median age 63 years) who attended a group consultation and 83 women (median age 64 years) who attended a traditional consultation between 2016 and 2019. Twenty-four (19%) of the group cohort and 16 (19%) of the traditional cohort were at high 10-year risk of major osteoporotic fracture (FRAX® ≥ 20.0%). A similar proportion planned to initiate pharmacologic therapy after the group and traditional consultations (23% vs 16%, p = 0.22); these proportions were comparable among women at high risk (42% vs 50%, p = 0.75) and moderate risk (19% vs 15%, p = 0.77), but a higher proportion of low-risk women planned to initiate therapy after the group consultation (18% vs 0%, p = 0.009). CONCLUSION: Patient decisions to initiate pharmacologic treatment made during a group visit are similar to those made during traditional one-on-one consultation. The group consultation model represents an alternative to one-on-one assessment for delivering osteoporosis consultative services.

Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Very high rate of false positive biochemical results when screening for pheochromocytoma in a large, undifferentiated population with variable indications for testing.

OBJECTIVE: Pheochromocytoma/Paraganglioma (PPGL) is a rare tumor with non-specific presentations overlapping common entities like anxiety, hypertension, acute illness and episodic "spells." Assessment of urine normetanephrine or metanephrine (UNM-UMN) in real-life, where PPGL is very rare and PPGL mimics extremely common, may show overlap in results with loss of specificity depending on the reference range. We determined the extent to which UNM-UMN are high in people undergoing screening for PPGL. DESIGN AND METHODS: Retrospective review of all UNM-UMN performed in a central lab serving Southern Alberta over 8 years. RESULTS: After excluding pediatric ages and patients with CKD, there were 12,572 unique patients with 14,383 measures of UNM-UMN. 85 patients (0.7%) had markedly high UNM-UMN compatible with likely PPGL. Depending on the age category (in decades), 10-22% of all UNM results were above the upper reference limit(URL), particularly between ages of 40-60. Less than 3% had elevations in both UNM and UMN. Of those with high UNM, 99% were less than 3-fold the URL. Based on the population data, a potential new reference range for UNM is suggested, which may be more appropriate to the types of patient who undergo this form of testing. CONCLUSIONS: There is an extraordinarily high prevalence of high UNM seen in real-life use of the test. However, the vast majority of high UNM are unlikely to be PPGL given the disease rarity and the massive number of tests ordered. This suggests the current laboratory URL may be too low (poor specificity) and/or the reference range may not be appropriate to the type of patient being screened for PPGL. Depending on the frequency of use of any screening test in a population, if the disease is rare and the specificity of the test is poor, a high rate of false positive results will be expected.

Diffuse, fracturing systemic skeletal histiocytosis of unknown type: a novel metabolic bone disease.

We describe a novel disease of diffuse skeletal histiocytosis associated with multiple fragility fractures and high osteoclast activity. Clinical, radiographic, biochemical, genetic, and histopathological investigations were performed to characterize the diagnosis of an Asian man who presented with hip fracture and diffuse skeletal lytic lesions. After excluding malignancy and other common metabolic bone diseases, open bone biopsy yielded several pathological samples all showing extensive skeletal histiocytosis likely to explain the diffuse axial and appendicular lytic lesions. Rare disorders such as Langerhans histiocytosis, Erdheim-Chester disease, and diffuse cystic skeletal angiomatosis were excluded through careful pathological examination and lack of CD1a and S-100 staining. Whole exome sequencing did not yield diagnostic findings to explain this likely acquired disease. High markers of osteoclast activity suggested excessive focal bone resorption but normalized after zoledronic acid treatment. A novel disease of skeletal histiocytosis with high bone turnover is differentiated from other histiocytic and lytic skeletal diseases.

Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay.

OBJECTIVES: Recent guidelines recommend a diagnosis of adrenal insufficiency when a stimulated peak cortisol level falls below 500nmol/L. This may not be valid using a highly specific cortisol immunoassay or liquid chromatography-mass spectroscopy (LCMS/MS). We sought to determine the diagnostic threshold for adrenal insufficiency using a new and widely available, highly specific cortisol immunoassay. DESIGN: All patients having a dynamic test of adrenal reserve had results measured using the historical cortisol assay (Roche Cortisol) and the newer assay (Roche Cortisol II). MEASUREMENTS: Subjects were categorized according to the traditional assay (normal>500nmol/L) with clinical case adjudication where necessary. Results from Cortisol II assay were concomitantly measured along with cortisol levels measured by LCMS/MS. ROC curve analysis was performed to generate new diagnostic thresholds. RESULTS: The Roche Cortisol II compared favourably with measures by LCMS/MS, generating cortisol levels approximately 30% lower than the older immunoassay. Many normal subjects had peak cortisols as low as 300nmol/L with Cortisol II. The optimized diagnostic threshold for adrenal insufficiency was 350nmol/L with a sensitivity of 91% and specificity 97%. Use of the old diagnostic threshold with the Cortisol II assay would have inappropriately doubled the rate of patient-classification as adrenal insufficient. CONCLUSIONS: Transition to a more specific cortisol assay requires revision of diagnostic thresholds for dynamic tests of adrenal insufficiency. With the Roche Cortisol II assay, a cut-off of 350nmol/L should replace the traditional 500nmol/L although some healthy subjects may be very close to this level.

Defining contralateral adrenal suppression in primary aldosteronism: implications for diagnosis and outcome.

OBJECTIVE: Unilateral primary aldosteronism (PA) should have a contralaterally normal and therefore suppressed adrenal zona glomerulosa. However, there is no validated definition of adrenal suppression. We created two biochemical hypotheses of adrenal suppression based upon measurements taken during adrenal vein sampling (AVS) to determine whether either proved useful for interpretation of AVS or prediction of hypertension outcome in operated cases. DESIGN: Retrospective database analysis. PATIENTS: Ninety-nine cases of PA from a tertiary hypertension unit. MEASUREMENTS: Hypothesis 1 was the proportional suppression of the uninvolved/lowest adrenal(aldo/cortisol) to IVC(aldo/cortisol) ratio pre- and post cosyntropin. Hypothesis 2 was the absolute decrease in the uninvolved adrenal(aldo/cortisol) ratio after cortrosyn injection. ROC analysis performed using lateralization and hypertension resolution as the outcomes of interest. RESULTS: Hypothesis 1 proved highly predictive of lateralization with a ROC AUC of 0.958, P < 0.0001, giving adrenal(aldo/cortisol):IVC(aldo/cortisol) <1.4 as the optimized criterion (sensitivity 90%, specificity 94%). For blood pressure outcomes in the surgical subgroup (n = 52), hypertension resolution was most commonly seen among subjects with adrenal suppression by both definitions although there was significant overlap with subjects requiring ongoing medication. CONCLUSIONS: Post cosyntropin suppression of the uninvolved adrenal-to-IVC ratio is a highly useful definition of adrenal suppression that accurately predicts unilateral PA. This may be particularly useful in a case where AVS fails to catheterize one of the adrenal veins but suppression is seen on the other side. Adrenal suppression may also predict blood pressure outcome, however, a much larger PA database is likely necessary to determine the relative contribution of this predictor.