Adrenal Crisis: Still a Deadly Event in the 21st Century Puar, Troy H.K., MBBS, MRCP (UK); Stikkelbroeck, Nike M.M.L., MD, PhD; Smans, Lisanne C.C.J., MD, PhD ...
The American journal of medicine,
03/2016, Volume:
129, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable ...condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about “sick day rules,” patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations.
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.
Abstract
Background
Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic disease is an important cause of ...MEN1-related mortality. Especially small nonfunctional (NF) pNETs pose a challenge to the treating physician and more information is needed regarding their natural course. We assessed long-term natural history of small NF-pNETs and its modifiers in the Dutch MEN1 population.
Patients and Methods
Retrospective longitudinal observational cohort study of patients with small (<2 cm) NF-pNETs from the Dutch national MEN1 database, which includes >90% of the Dutch MEN1 population. Modifiers of long-term natural course were analyzed using linear mixed-models analysis.
Results
Growth rate of the 115 included small NF-pNETs from 99 patients was slow (0.4 mm/y; 95% confidence interval, 0.15 to 0.59). Seventy percent of the tumors was stable and a subgroup of 30% of the tumors was growing (1.6 mm/y; 95% confidence interval, 1.1 to 2.0). No differences in clinical characteristics were identified between growing and stable tumors. Within the subgroup of growing tumors, germline missense mutations were significantly associated with accelerated growth compared with nonsense and frameshift mutations.
Conclusion
The majority of small NF-pNETs are stable at long-term follow-up, irrespective of the underlying MEN1 genotype. A subgroup of tumors is slowly growing but cannot be identified on clinical grounds. In this subgroup, tumors with missense mutations exhibited faster growth. Additional events appear necessary for pNETs to progress. Future studies should be aimed at identifying these molecular driving events, which could be used as potential biomarkers.
The size of 115 small NF-pNETs from 99 MEN1 patients was followed over time. Most tumors were stable. In the subgroup of growing tumors a genotype-phenotype correlation was seen.
To assess self-management in patients receiving glucocorticoid replacement therapy for primary or secondary adrenal failure before and 6 months after a glucocorticoid education group meeting.
All ...patients with primary or secondary adrenal insufficiency, treated at the Department of Medicine, Division of Endocrinology, were invited by their endocrinologist to participate in a 3-h glucocorticoid education group meeting, consisting of a lecture about the disease and glucocorticoid doses adjustments in case of stress, followed by an instruction on how to inject hydrocortisone i.m. Finally, all participants could practise the i.m. injection and discuss their experience with (imminent) adrenal crises with other patients and the health care providers. Two weeks before the meeting and 6 months after the meeting, patients were asked to fill out a questionnaire about how they would act in six different conditions (e.g. febrile illness or vomiting).
Of the 405 patients who were invited, 246 patients (61%) participated. At baseline the response by the participants on the questionnaire was 100% (n=246) and at follow-up 74% (n=183). At follow-up, significantly more participants (P≤0.005) gave the correct answers to how to act in different situations (e.g. self-administration of a glucocorticoid injection and phone contact in case of vomiting/diarrhoea without fever). Moreover, the use of self-management tools, such as having a 'medicine passport (travel document with information about disease and medication) (P=0.007) or SOS medallion (P=0.0007)', increased.
A glucocorticoid education group meeting for patients with adrenal failure seems helpful to improve self-management and proper use of stress-related glucocorticoid dose adjustment.
Summary
Background
An adrenal crisis (AC) is a potential life‐threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes, and risk factors of AC ...in AI.
Methods
Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified, and all medical records were assessed by two independent investigators. The observed frequency of AC was determined as incidence rate, calculated as the number of AC divided by person‐years (PY). In addition, precipitating factors and risk factors were assessed.
Results
We observed an incidence rate of 5·2 AC (95% CI 4·3–6·3) per 100 PY in primary adrenal insufficiency (PAI, a total of 111 patients), and 3·6 AC (95% CI 3·1–4·1) per 100 PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients with an established diagnosis of tertiary (glucocorticoid‐induced) adrenal insufficiency (a total of 28 patients) had 15·1 AC (95% CI 11·0–19·9) per 100 PY. The most important risk factor was the existence of comorbidity. Gastro‐enteritis and other infections were the most common precipitating factors for AC.
Conclusion
AC still occurs relatively frequent in patients with AI, mostly precipitated by infections and particularly in patients with high comorbidity. This should be taken into account in the education and follow‐up of patients with AI.
Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been ...associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies have examined the vitamin D status in HIV-infected patients. This study will specifically focus on the effects of antiretroviral agents on vitamin D status. Furthermore, the effect of vitamin D status on CD4 cell recovery after initiation of HAART will be evaluated. Among 252 included patients the prevalence of vitamin D deficiency (<35 nmol/liter from April to September and <25 nmol/liter from October to March) was 29%. Female sex, younger age, dark skin, and NNRTI treatment were significant risk factors in univariate analysis, although in multivariate analyses skin pigmentation remained the only independent risk factor. Median 25(OH)D(3) levels were significantly lower in white NNRTI-treated patients 54.5(27.9-73.8) nmol/liter compared to white PI-treated patients 77.3 (46.6-100.0) nmol/liter, p = 0.007, while among nonwhites no difference was observed. Both PI- and NNRTI-treated patients had significantly higher blood PTH levels than patients without treatment. Moreover, NNRTI treatment puts patients at risk of elevated PTH levels (>6.5 pmol/liter). Linear regression analysis showed that vitamin D status did not affect CD4 cell recovery after initiation of HAART. In conclusion, 29% of the HIV-1-infected patients had vitamin D deficiency, with skin color as an independent risk factor. NNRTI treatment may add more risk for vitamin D deficiency. Both PI- and NNRTI-treated patients showed higher PTH levels and might therefore be at risk of bone problems. Evaluation of 25(OH)D(3) and PTH levels, especially in NNRTI-treated and dark skinned HIV-1-infected patients, is necessary to detect and treat vitamin D deficiency early.
Context:
Patients with pheochromocytomas and paragangliomas (PGLs) may have brown adipose tissue (BAT) activation induced by catecholamine excess. 18F-fluorodeoxyglucose (18F-FDG) positron emission ...tomography (PET)/computed tomography (CT) can be used for the localization of both PGLs and BAT. It is unknown whether BAT is specifically affected by altered cellular energy metabolism in patients with SDHx- and VHL-related PGLs.
Objective:
The objective of the study was to determine endocrine and paracrine effects of catecholamine excess on BAT activation in patients with PGLs as detected by 18F-FDG PET/CT, taking into account genetic variation.
Design:
Patients with PGLs who were fully genetically characterized underwent presurgical 18F-FDG PET/CT imaging for tumor localization and to quantify BAT activation.
Setting:
The study was conducted at a single Dutch tertiary referral center.
Patients and Intervention:
Seventy-three patients, aged 52.4 ± 15.4 years, with a body mass index of 25.2 ± 4.1 kg/m2, mean ± SD, were grouped into sporadic, cluster 1 (SDHx, VHL) and cluster 2 (RET, NF1, MAX) mutations.
Main Outcome Measures:
18F-FDG mean standard uptake values were assessed in predefined BAT locations, including perirenal fat.
Results:
Twenty-one of 73 patients (28.8%) exhibited BAT activation. BAT activation was absent in all six patients with nonsecreting PGLs. No difference in 18F-FDG uptake by perirenal fat on the side of the pheochromocytoma and the contralateral side was observed (mean standard uptake value of 0.80 vs 0.78, respectively, P = .42). The prevalence of BAT activation did not differ between sporadic (28.9%), cluster 1 (40.0%), and cluster 2 patients (15.4%, P= .36).
Conclusion:
Patients with PGLs exhibit a high prevalence of BAT activation on 18F-FDG PET/CT. This is likely due to systemic catecholamine excess. BAT activation is not associated with specific germline mutations.
Context:
Testicular adrenal rest tumors (TART) are one of the major long term complications in patients with congenital adrenal hyperplasia. Although several adrenal-like properties have been ...assigned to these benign lesions, the etiology has not been confirmed yet.
Objective:
The aim of this study was to describe TART in more detail by analyzing several (steroidogenic) characteristics that may be classified as adrenal cortex or Leydig cell specific.
Methods:
Gene expression analysis by qPCR was performed for 14 genes in TART tissue (n = 12) and compared with the expression in healthy control fibroblasts (nonsteroidogenic control). In addition, a comparison was made with the expression levels in testis tissue (n = 9) and adrenal tissue (n = 13).
Results:
Nearly all genes were highly expressed in TART tissue, including all genes that encode the key steroidogenic enzymes. TART expression levels are in the majority almost identical to those found in adrenal tissue. The expression of adrenal cortex specific genes (CYP11B1, CYP11B2, and MC2R) in both TART and adrenal tissue is approximately 1000–10 000 times higher compared to that in testes samples. In addition, the Leydig cell markers INSL3 and HSD17B3 were not only found in testes, but also in TART, both at significantly higher levels than in the adrenal (p < 0.01).
Conclusion:
Our study shows for the first time that TART have multiple steroidogenic properties, which include not only the expression of adrenal cortex but also of Leydig cell markers. Therefore, the origin of these tumors might be a more totipotent embryonic cell type.
Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in ...mitochondrial function and catecholamine content in PGL tumors.
Respiratory chain enzyme assays and (1)H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X.
In SDHx-related PGLs, a significant decrease in complex II activity (P < 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P < 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P < 0.001) and decrease in ATP/ADP/AMP accumulation (P < 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P < 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues.
This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation.
Adrenal vein sampling is used to establish the origins of excess production of adrenal hormones in primary aldosteronism. Correct catheter positioning is confirmed using adrenal vein measurements of ...cortisol, but this parameter is not always reliable. Plasma metanephrine represents an alternative parameter. The objective of our study was to determine the use of plasma metanephrine concentrations to establish correct catheter positioning during adrenal vein sampling with and without cosyntropin stimulation. We included 52 cosyntropin-stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and metanephrine concentrations were measured in adrenal and peripheral venous samples. Success rates of sampling, using an adrenal to peripheral cortisol selectivity index of 3.0, were compared with success rates of metanephrine using a selectivity index determined by receiver operating characteristic curve analysis. Among procedures assessed as selective using cortisol, the adrenal to peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol (94.0 versus 15.5; P<0.0001). There were significant positive relationships between adrenal to peripheral vein ratios of cortisol and metanephrine for cosyntropin-stimulated samplings but not for nonstimulated samplings. Receiver operating characteristic curve analysis indicated a plasma metanephrine selectivity index cutoff of 12. Using this cutoff, concordance in sampling success rates determined by cortisol and metanephrine was substantially higher in cosyntropin-stimulated than in nonstimulated samplings (98% versus 59%). For the latter procedures, sampling success rates determined by metanephrine were higher (P<0.01) than those determined by cortisol (91% versus 56%). In conclusion, metanephrine provides a superior analyte compared with cortisol in assessing the selectivity of adrenal vein sampling during procedures without cosyntropin stimulation.
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